TITLE OF THESIS BEENA 5 june -...

CChhaapptteerr 22

SSyynntthheessiiss aanndd BBiioollooggiiccaall AAccttiivviittyy EEvvaalluuaattiioonn ooff MMeettrroonniiddaazzoollee

BBaasseedd CCoommppoouunnddss

Chapter 2 Synthesis and Biological Activity Evaluation of Metronidazole Based Compounds

105

22..11 IInnttrroodduuccttiioonn The 5-nitroimidazoles are a well-established group of protozoal and bactericidal

agents.1 The importance of imidazole can be realized by the fact that many drugs in use today contain this moiety and several nitroimidazole derivatives such as metronidazole (1), tinidazole (2), ornidazole (3), secnidazole (4) and ronidazole (5) have been used for the treatment of serious infections caused by anaerobic bacteria and protozoa.2-4

N N

NO2

OH

3 (Ornidazole)

4 (Secnidazole)

2 (Tinidazole)1 (Metronidazole)

N N

NO2

OH

Cl

N N

NO2

OH

N N

NO2

OO

NH25 (Ronidazole)

N N

NO2

SO

O

NHN

NO2

6 (Azomycin)

Initially, azomycin (6)5 was discovered as an antibacterial and antiprotozoal agent and later it was replaced by metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole) which was more effective against bacterial and protozoal infections.6 MTZ has been used effectively in the treatment of anaerobic infections7 and prophylactically in gynaecological and colonic surgery.8 MTZ has been a drug of choice for the treatment of anti-infectious diseases against protozoa such as Trichomonas vaginalis,9 Entamoeba histolytica,10 Giardia intestinalis11 and infections caused by Gram-negative anaerobes such as bacteroides and Gram-positive anaerobes such as clostridia. Due to its role as a second-line defense against Helicobacter pylori infections,12,13 metronidazole has been included in the ‘‘essential medicines’’ list by the World Health Organization.14 MTZ has extensively been used for the treatment of anaerobic infections


106

after bowel surgery and infections caused by Clostridium difficile.15 MTZ has also been used for the radiosensitization16 of hypoxic tumors and Crohn’s disease. Since its discovery in 1959, MTZ has been among the top 100 most prescribed drugs in the US and one of the 10 most drugs used during pregnancy.17 MTZ is quickly and completely absorbed after oral administration and penetrates body tissues and secretions such as saliva, breast milk, semen and vaginal secretions. The drug is metabolized mainly in the liver and is excreted in the urine. However, resistance to this compound have been demonstrated in trichomonads18 and Bacteroides fragilis,19 in both natural and in vitro under drug pressure-induced populations. Anaerobic bacteria and protozoa develop resistance to metronidazole by reducing or abolishing the activity of elements of this series of electron transport reactions, resulting in an insufficient rate of accumulation of reduced metabolites or by increasingly futile cycling, once oxygen is known to alter the effectiveness of metronidazole.

Nitroimidazole based compounds have also been studied for their potential role in the treatment of tuberculosis and these efforts resulted in the discovery of many potent anti-TB agents and out of these, two compounds PA824 (7) and OPC67683 (8) are currently in the clinical trials.20,21 Most of the antitubercular drugs interferes with aerobic growth and are less effective for hypoxia so they are taken for longer duration of time.22 It has been known for almost 15 years that under low oxygen conditions M. tb cultures become sensitive on treatment with MTZ.23,24 The 4-nitroimidazoles based on MTZ originally synthesized as radiosensitizing agents,25 were later found to have significant activity against M. tb.26,27 From a large number of 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole derivatives, compound 2-ethyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (9, CGI-17341) emerged as an interesting compound with potent in vitro and in vivo activity against M. tb strains. The nitroimidazole (S)-2-nitro-6-(4-(trifluoromethoxy)-benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (7, PA824),28 is a promising new


107

class of compound which shows antitubercular activity under hypoxic conditions, with no cross resistance to current TB drugs and efficacy in the mouse model of TB infection. PA824 is currently being developed as a drug molecule by the Global Alliance for TB Drug Development.29

N

NO

O2NN

NO

O2N

O

N

O

OCF3

7 (PA 824) 9 (CGI 17341)8 (OPC 67683)

N

NO

O2N

O

OCF3

MTZ shows cytotoxicity due to its ability to form nitroradical anion by the reduction of nitro group (figure 2.1).30 The activated nitro group undergoes further reduction to generate a nitrosoimidazole which reacts with sulphydryl groups and DNA.31-33 This group further gets reduced to amine via hydroxylamine intermediate. In the presence of oxygen, however, the nitroradical anion rapidly gets reoxidized to its respective parent drug before nitroso intermediates can be formed.34 Despite the resulting oxidative stress, this futile cycle is believed to render metronidazole treatment safe in man. However, there are still concerns regarding its potential carcinogenicity.35

RNO2 RNHOH RNH2e e

2He 2 e

2 HO2 O2

Nitrocompound

Nitroanionradical

RNO

Nitrosocompound

Hydronitroxideradical

Hydroxyl amine AmineSuperoxideradical anion Superoxide

radical anion

O2

H

O2

RNO2e H

(R-NO)H

Figure 2.1: Nitroreductive metabolic pathways36


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22..22 CChheemmiissttrryy aanndd BBiioollooggiiccaall AAccttiivviittyy ooff TTrriiaazzoolleess Azides, the most important precursor of triazoles have been used in rubber

vulcanisation, polymer cross linking, tire-cored adhesives and foaming of plastics. Azides have also been used as pharmaceuticals, pesticides and herbicides.

CuSO4

[CuLn]+

R1 CuLn

N N NR

R1 CuLnN

NR

N

N N N

R1 CuLn

R

N N N

R1

R

N N NCuLn

R1

R

Reducing agent

R1 H

-H++H+

Figure 2.2: Catalytic cycle for azide-alkyne coupling37

Rolf Huisgen in 1960’s studied the 1,3-dipolar cycloaddition of azides and alkynes to give 1,2,3-triazoles.38 Later, Meldal39 and Sharpless40 independently discovered the more efficient and regioselective copper catalyzed azide-alkyne cycloaddition (CuAAC) to form 1,4-disubstituted triazole with increased reaction rate and lowered reaction temperature and the reaction is known as “click chemistry”. While the reaction can be performed using commercial sources of copper(I) salts such as cuprous bromide or iodide, the reaction works much better using a mixture of copper(II) (e.g. copper(II) sulfate) and a reducing agent (e.g. sodium ascorbate) to produce Cu(I) in situ.


109

The copper-catalyzed reaction is thought to proceed in a stepwise manner starting with the generation of copper(I) acetylide (figure 2.2). Due to the reliability and generality of the copper(I)-catalyzed azide-alkyne cycloaddition to generate N-heterocyclic pharmocophores, the reaction has been utilized for various aspects of drug discovery. Triazoles are used as fungicides, herbicides, light stabilizers, fluorescent whiteners, optical brightening agents and corrosion retardants. Triazole derivatives are also known for their antimicrobial, cytostatic, virostatic and anti-inflamatory activities and has been found in many biologically active molecules such as rufinamide (10, antiepileptic drugs),41 tazobactam (11, antibiotic),42 vancomycin analogs (12, antibiotic),43 syn-TZ2PA6 (13, AChE inhibitor)44.

O OO

NH

HN HN

ONH

O

H2N

ONH

HN

HO

Cl

HOOC

O

HN

OHOH

OOH

O

O

HO OHOH

NNN

R1R2

HO N

NH

NNN

N NH2

H2N

12 (Vancomycin analogs) 13 (syn-TZ2PA6)

NN N

H

O NF

F

NS

O

H

HO O

OO

N NN

10 (Rufinamide)

11 (Tazobactam)

22..33 PPrreesseenntt IInnvveessttiiggaattiioonn In recent year’s concept of hybrid molecules have been used successfully and

many compounds have entered into clinical trials.45 Hybrid molecules are defined as chemical entities with two (or more than two) structural domains having different biological functions. Both entities of the hybrid molecule are not necessarily acting on the same biological target. We anticipated that hybrid molecule containing metronidazole and other biologically active pharmacophores such as triazoles (65-125), styrene (126-195)


110

and thiazolidinone (197-203) will lead to a molecule of biomedical importance (figure 2.3). For this we decided to functionalize hydroxyl and methyl functionality of MTZ in such a way that MTZ can be covalently linked to these pharmacophores (figure 2.3).

N

N

O2N

NNN R

R1

NN

NO2NN N

R

N N

NO2

NS

O

R

N N

NO2OH

NN N

NS

O

NN

NO2OH

N N

NO2OH

(65-125)

(126-195)

(197-203) Figure 2.3: Metronidazole based hybrids under study

22..44 RReessuullttss aanndd DDiissccuussssiioonn The structure activity relationship study conducted on MTZ revealed that NO2

group is most essential for activity while substitution at alcoholic OH and methyl group can lead to molecule with improved activity. The hydroxyl group of MTZ has been exploited in a great deal and a number of structurally diverse compounds with improved activity have been reported. We exploited OH group of MTZ and number of MTZ-triazoles were synthesized and their antibacterial and antiamoebic activities were studied.


111

The synthesis of MTZ-triazole conjugates were accomplished in the sequence of reactions as depicted in scheme 2.4. Synthesis of MTZ-triazole hybrids started with the preparation of substituted alkynes (scheme 2.1 and scheme 2.2) and 1-(2-azido-ethyl)-2-methyl-5-nitro-1H-imidazole (64) by literature methods (scheme 2.3).39,46, Alkynes 14-38 were synthesized using Williamsons ether synthesis starting from various substituted phenols and propargyl bromide under basic conditions (scheme 2.1).47 These compounds were characterized by various spectroscopic techniques and data corresponds to literature reported values.47-63

14, R = Ph15, R = 2-MePh16, R = 3-MePh17, R = 4-MePh18, R = 2-NO2Ph19, R = 4-NO2Ph20, R = 2-CHOPh21, R = 4-CHOPh22, R = 2-ClPh23, R = 4-ClPh24, R = 4-BrPh25, R = 4-EtPh26, R = 4-i-PrPh

(14-38)Br

R OHO R

K2CO3, Dry DMF, RT, 8-10 h

27, R = 4-n-PrPh28, R = 4-t-BuPh29, R = 4-MeCOPh30, R = 2,3-MePh31, R = 2-COOMePh32, R = 2,4-ClPh33, R = 2,6-ClPh34, R = 3-Me,4-ClPh35, R = 2,4,6-t -BuPh36, R = CH2Ph37, R = 1-Napthyl38, R = 2-Napthyl

Scheme 2.1

Alkylation of amines with propargyl bromide leads to the formation of compounds having terminal alkyne chain (39-61) as depicted in scheme 2.2. Reaction of primary amines with propargyl bromide results into formation of mono and disubstituted products in all the cases. The monoalkylated product was separated by column chromatography and then reacted with azido derivative of MTZ (scheme 2.3) to form triazoles (scheme 2.4). The compounds were characterised by using different spectroscopic tools.64-67


112

39, R = Ph40, R = 2-FPh41, R = 3-FPh42, R = 4-FPh43, R = 2-ClPh44, R = 3-ClPh45, R = 4-ClPh46, R = 4-BrPh47, R = 2-MePh48, R = 4-MePh49, R = 4-EtPh50, R = 4-i-PrPh51, R = 2-OMePh

Major (70-80%) Minor (20-30%)(39-61)

BrR NH2 HN R

N RK2CO3, Dry DMF

52, R = 2,3-ClPh53, R = 2,5-ClPh54, R = 2,4,5-ClPh55, R = 2,6-MePh56, R = CH2Ph57, R = CH2CH2Ph58, R = 2-Amino-pyridyl59, R = 3-Amino-pyridyl60, R = 3,5-OMePh61, R = Morpholino

RT, 8-10 h

Scheme 2.2

Figure 2.4: IR spectrum of compound 49

The IR specta of compound 49 (figure 2.4) displayed band at 3399 cm-1 due to N–H stretching of secondary amine. A very weak stretching band between 2100–2260 cm-1 was due to C≡C stretching of alkyne. In the 1H NMR spectrum of compound 49 (figure 2.5) triplet and quartret at δ 1.19 and 2.55 were characteristic of the ethyl group. Triplet at δ 2.21 was assigned to the CH while the corresponding doublet appeared at


113

δ 3.92 for the CH2 group. A broad peak at δ 3.76 was observed for NH. Aromatic protons appeared as doublets at δ 6.64 and 7.06.

Figure 2.5: 1H NMR spectrum of compound 49

Figure 2.6: 13C NMR spectrum of compound 49


114

In the 13C NMR spectrum of compound 49 (figure 2.6) nine peaks were observed. Signals at δ 15.84 and 27.91 were due to the carbons of ethyl group. The signal for aliphatic carbon attached to nitrogen appeared at δ 33.88. The triply bonded carbons appeared at δ 71.15 and 81.20. The remaining peaks at higher chemical shift at δ 113.67, 128.53, 134.50 and 144.69 were due to aromatic carbons.

N N

NO2OTs

N N

NO2N3

N N

NO2OH

62 63 64

p-TsCl NaN3, DMF, 0 oC70–80 oC, 1 hPyridine, RT, 12 h

Scheme 2.3

The hydroxyl group of MTZ was converted to tosylate, an easily leaving group, by reaction of MTZ with p-toluenesulfonyl chloride (p-TsCl) in pyridine (scheme 2.3). The resulting compound 63 on treatment with sodium azide gave 1-(2-azidoethyl)-2-methyl-5-nitro-1H-imidazole (64).

N N

NO2N3

N N

NO2NN N

NHR

O RN N

NO2NN N

O R

N N

NO2NN N

R

R

HN R

113, R = CH2OH114, R = CH2CH2OH115, R = CH2Br116, R = CH2OMe117, R = CH2OCOEt118, R = CH2OTHP119, R = Ph

64(65-89) (90-112)

t-BuOH : H2O (1:1)Sodium ascorbateCuSO4.5H2O

t -BuOH : H2O (1:1)Sodium ascorbateCuSO4.5H2O

(113-125)

90, R = Ph91, R = 2-FPh92, R = 3-FPh93, R = 4-FPh94, R = 2-ClPh95, R = 3-ClPh96, R = 4-ClPh97, R = 4-BrPh98, R = 2-MePh99, R = 4-MePh100, R = 4-EtPh101, R = 4-i-PrPh102, R = 2-OMePh

65, R = Ph66, R = 2-MePh67, R = 3-MePh68, R = 4-MePh69, R = 2-NO2Ph70, R = 4-NO2Ph71, R = 2-CHOPh72, R = 4-CHOPh73, R = 2-ClPh74, R = 4-ClPh75, R = 4-BrPh76, R = 4-EtPh77, R = 4-i-PrPh

78, R = 4-n-PrPh79, R = 4-t-ButPh80, R = 4-MeCOPh81, R = 2,3-MePh82, R = 2-COOMePh83, R = 2,4-ClPh84, R = 2,6-ClPh85, R = 3-Me,4-ClPh86, R = 2,4,6-t-ButPh87, R = CH2Ph88, R = 1-Napthyl89, R = 2-Napthyl

103, R = 2,3-ClPh104, R = 2,5-ClPh105, R = 2,4,5-ClPh106, R = 2,6-MePh107, R = CH2Ph108, R = CH2CH2Ph109, R = 2-Amino-pyridyl110, R = 3-Amino-pyridyl111, R = 3,5-OMePh112, R = Morpholino

120, R = 2-Pyridyl121, R = 3-Pyridyl122, R = 1-Cyclohexanol123, R = (CH3)3Si124, R = n-Propyl125, R = n-Butyl

t-BuOH : H2O (1:1)Sodium ascorbateCuSO4.5H2O

Scheme 2.4


115

Reactions of compound 64 with terminal alkynes in presence of sodium ascorbate and CuSO4.5H2O in t-BuOH/H2O (1:1) (scheme 2.4) lead to the formation of desired hybrid molecules in good yield (65-125). All the compounds were purified over silica gel column. The structures of the compounds were confirmed by spectroscopic techniques. In the IR spectra the characteristic N=O stretching bands for all compounds were observed at 1502-1599 and 1358-1372 cm-1 regions. In the 1H NMR spectra, the imidazole CH3

protons resonates as singlet at about δ 1.7-2.0, CH2CH2 protons appeared at δ 4.7-5.2. The imidazole and triazole ring protons appeared as singlets at δ 7.7-8.2.


In the IR spectrum of compound 72 (figure 2.7) peak at 1683 cm-1 was assigned to CHO and N=O stretching bands appeared at 1524 and 1370 cm-1. The 1H NMR spectrum of compound 72 (figure 2.8) showed a singlet at δ 1.84 due to the methyl group present at 2-position of the imidazole ring. Triplets at δ 4.76 and 4.92 were due to the methylene protons of the alkyl linker between imidazole and triazole rings. A singlet was observed at δ 5.32 for the OCH2 group. Doublets at δ 7.23 and 7.95 with J = 8 Hz clearly indicates para substitution in the aromatic ring. Peaks at δ 8.09 was due to the CH proton of the


116

imidazole nucleus and a peak at δ 8.20 was characteristic of the proton of the triazole nucleus and singlet at δ 9.93 was due to the aldehydic proton. The 13C NMR (figure 2.9) showed fourteen signals in all. Peak at δ 12.68 was assigned to the methyl carbon, while peaks at δ 46.10 and 48.77 were assigned to the two methylene carbons flanked between two nitrogens. Peak at δ 61.19 was assigned to the methylene carbon attached to oxygen atom and peak at δ 151.15 was due to the carbon of imidazole nucleus attached to methyl group. Signal at δ 162.73 was assigned to the aromatic carbon attached to oxygen atom and peak at δ 191.31 was due to the CHO group. Remaining signals appeared at δ 115.19, 125.61, 129.82, 131.73, 133.16, 138.32 and 142.41. Mass spectra of compound 72 (figure 2.10) showed molecular ion peak at m/z 357.18 [M + H]+.



117


Figure 2.10: ESI-MS of compound 72


118

The methyl of the triazole is another group that can be functionalized and we carried out a systematic study and prepared many styryl derivatives by reacting MTZ-triazole (65, 119, 120, 122, 113, 124 and 125) with substituted benzaldehydes in presence of strong base.68

N

N

O2N

NNN

R1

N

N

O2N

NNN

R1

N

N

O2N

NNN

R1

NN

O2N

NNN

R1

NN

O2N

NNN

R1

NN

O2N

NNN

R1

ON

OH

NN

O2N

NNN

R1

OH

126, R1 = H127, R1 = 4-Me128, R1 = 4-Et129, R1 = 4-n-Pr130, R1 = 4-i-Pr



(126-135)

156, R1 = H157, R1 = 4-Me158, R1 = 4-Et159, R1 = 4-n-Pr160, R1 = 4-i-Pr161, R1 = 4-n-Bu162, R1 = 4-t -Bu163, R1 = 4-F164, R1 = 4-Br165, R1 = 4-Cl

166, R1 = H167, R1 = 4-Me168, R1 = 4-Et169, R1 = 4-n-Pr170, R1 = 4-i-Pr171, R1 = 4-n-Bu172, R1 = 4-t-Bu173, R1 = 4-F174, R1 = 4-Br175, R1 = 4-Cl



(136-145) (146-155)

(156-165) (166-175) (176-185) (186-195)

NN

O2N

NNN R

65, R = CH2OPh119, R = Ph120, R = 2-Pyridyl122, R = 1-Cyclohexanol113, R = CH2OH124, R = n-Propyl125, R = n-Butyl

NN

O2N

NNN R

R1

Substituted benzaldehydesDMSO, Dry MeOHNaOMe, 40 oC,12 h

(126-195)

131, R1 = 4-n-Bu132, R1 = 4-t-Bu133, R1 = 4-F134, R1 = 4-Br135, R1 = 4-Cl



Scheme 2.5


119




120




121

In the IR spectrum of compound 178 (figure 2.11) peaks at 1556 and 1386 cm-1 were due to N=O stretching. In the 1H NMR (figure 2.12) a triplet at δ 0.80, sextet at δ 1.46 and again a triplet at δ 2.49 were assigned to n-propyl chain attached to triazole nucleus. While a triplet and quartet at δ 1.25 and 2.67 were due to the ethyl group at para position of the aromatic ring. Peaks at δ 4.82 and 4.92 were due to the two types of methylene protons. Doublets at δ 6.04 and 7.71 were because of the trans substituted vinylic protons (J = 15.4 Hz). The singlet at 6.97 was due to the proton of the imidazole nucleus. Doublet at δ 7.23 and 7.38 indicates para substitution of the aromatic ring. The most downfield peak at δ 8.15 is characteristic of the proton of the triazole nucleus. In the 13C NMR of compound 178 (figure 2.13) eighteen peaks were observed in all. Five peaks at δ 13.58, 15.27, 22.46, 27.31 and 28.78 correspond to the carbons of the ethyl and n-propyl groups. Two peaks at δ 46.05 and 49.74 were assigned to the methylene carbons between imidazole and triazole rings. Peaks at δ 108.47 and 135.44 were assigned to the alkene carbons. Peaks at δ 127.80 and 128.47 were assigned to the CH protons of aromatic ring. Peaks at δ 121.86, 132.31, 138.03, 141.44, 146.80, 149.04 and 151.31 were due to remaining peaks of aromatic, triazole and imidazole rings. The ESI-MS of compound 178 (figure 2.14) clearly shows a [M + H]+ peak at m/z 381.26.

The thiazolidinones are associated with a broad spectrum of biological activities such as antiretroviral,69,70 antimicrobial,71 antimalarial,72 antidiarrhoeal,73 anti-yellow fever virus,74 antiarrhythmic,75 anticancer,76 anticonvulsant,77 anti-inflammatory78 and antituberculosis.79 1,3-Thiazolidin-4-ones are prepared using three components an aldehyde or ketone, an amine and a mercapto-acid, either in a one- or two-step process. The reactions proceed by initial formation of an imine (the nitrogen of amine attacks the carbonyl), which undergoes attack by sulfur nucleophile, followed by intramolecular cyclization on elimination of water. In order to synthesize MTZ-thiazolidinone hybrids the azide group of compound 64 was reduced to amine functionality using PPh3 as


122

reducing agent as depicted in scheme 2.6 (Staudinger reduction). The compound 196 on reaction with substituted benzaldehydes and thioglycolic acid in the presence of N,N-dicyclohexyl carbodiimide (DCC) and dry THF as solvent lead to the formation of 1,3-thiazolidin-4-one derivative. DCC was used as a dehydrating agent during the reaction.80

N N

NO2

N3 N N

NO2

NN N

NO2

NH2S

O

R

64 196197, R = H198, R = 4-Me199, R = 4-Et200, R = 2-Br201, R = 4-Br202, R = 4-Cl203, R = 4-F

Dry THF, PPh320 oC, 3 h

Substituted benzaldehydeDry THF, 0 oC, 5 min

Conc. HCl, Reflux, 5 h HSCH2COOHDCC, 1 h, RT(197-203)

Scheme 2.6



123




124


The IR spectrum of compound 202 (figure 2.15) showed peak at 1683 cm-1 for C=O stretching. The symmetrical and asymmetrical stretching for NO2 group appeared at 1528 and 1386 cm-1. In the 1H NMR spectrum of compound 202 (figure 2.16), singlet at δ 2.48 was assigned to the methyl protons attached to imidazole ring. One of the protons of the CH2 of thiazolidinone nucleus appear as multiplet at δ 3.15-3.23 while the other hydrogen appeared as double doublet at δ 3.79 with J = 15.6 and 1.8 Hz. Multiplets at δ 3.65-3.73 and 4.27-4.41 were assigned to the methylene protons present between the imidazole and thiazolidinone rings. The signal at δ 5.35 was characteristic of the methine proton attached to phenyl ring. Aromatic protons appeared as doublets at δ 7.18 and 7.32. The signal at δ 7.87 was assigned to the proton of the imidazole nucleus. In the 13C NMR of compound 202 (figure 2.17) thirteen signals appeared in all, the methyl carbon appeared at δ 13.87. The methylene and methine carbon of thiazolidinone appeared at


125

δ 42.66 and 63.64. The methylene carbons between the imidazole and thiazolidinone rings appeared at δ 32.31 and 42.78. The three carbons of imidaozle nucleus were assigned at δ 133.17, 136.84 and 150.68. The aromatic carbons appeared at δ 128.56, 129.45, 135.54 and 138.13. Peak at δ 171.85 was assigned to the carbonyl carbon of the thiazolidinone nucleus. The ESI-MS of compound 202 showed m/z peaks at 367.13 and 369.13 corresponding to [M + H]+ and [M + 2]+ in 3:1 ratio which confirms the presence of one chlorine atom in the molecule.

22..55 BBiioollooggiiccaall AAccttiivviittyy Some of the synthesized metronidazole derivatives were tested for their in vitro

biological activity. The metronidazole triazole showed a good level of activity against Gram-positive (S. aureus and S. epidermidis) and Gram-negative (E. coli and P. aeruginosa) bacterial strains. These compounds were also found to be active against E. histolytica. The MTZ-triazoles (65-125) were found to be inactive against M. tb H37Rv at >50 µg/mL concentration.

22..55..11 IInn VViittrroo AAnnttiibbaacctteerriiaall AAccttiivviittyy Antimicrobial susceptibility testing was carried out using National Committee for

Clinical Laboratory Standards (NCCLS) micro dilution assay. Briefly, the bacterial strains were grown in standard media until exponential growth was achieved. Tests were performed in a 96-well microtiter plate in a final volume of 100 µL. Test compounds were dissolved in 5% DMSO at an initial concentration of 500 µg and serially diluted in plate. Each well was then inoculated with ~ 2-5 x 105 bacterial cells and incubated at 37 oC for 24 h with shaking at 200 rpm. One well containing cells and 5% DMSO without any test compound (growth control), and one well containing only growth medium (sterility control) were used as controls. Growth of bacteria was determined using Power wave 200 microplate scanning spectrophotometer (Bio-Tek Instruments, Winooski, VT,


126

USA). Percent survival was calculated using growth without any compound as 100% survival. IC50 values are calculated using Grafit 4.0 software (Erithacus Software Ltd., Horley, Surrey, UK).

Table 2.1: In vitro antibacterial activity of metronidazole-triazole hybrids

Compd N N

NO2NN N

R

IC50 (µg/mL)

E. coli

P. aeruginosa

S. aureus

E. epidermidis R

65 CH2OPh 0.670 0.130 NA NA 66 CH2O-2-MePh 0.028 NA NA NA 67 CH2O-3-MePh 0.067 0.068 0.260 NA 68 CH2O-4-MePh 0.060 0.030 0.130 NA 72 CH2O-4-CHOPh 0.070 0.070 NA NA 74 CH2O-4-ClPh 0.003 0.020 0.130 NA 113 CH2OH 0.091 0.180 0.350 0.350 119 Ph 0.130 0.130 NA NA 120 2-Pyridyl 0.120 0.180 0.130 NA 121 3-Pyridyl NA NA 0.310 NA 122 1-Cyclohexanol NA 0.180 NA NA Ref Tetracycline 0.090 0.060 0.120 0.080 NA: Not active upto 500 µg/mL

Table 2.1 shows the IC50 values of the active compounds against the four bacterial strains used. Compound 113 has shown potent antibacterial activity against both Gram-positive as well as Gram-negative bacteria with IC50 value of 0.091-0.35 µg/mL. Introduction of one more CH2 group between OH and CH2 of compound 113, results in total loss of antibacterial activity of the compound (114). Similarly substitution of OH by OCOEt (117), OMe (116), tetrahydropyran (118) or Br (115) functional group in compound 113 leads devoid of antibacterial activity of the compounds. Compound 72 having CHO group at the para position of the phenyl ring exhibit potent antibacterial activity against Gram-negative (E. coli and P. aeruginosa), while it has been inactive against Gram-positive bacteria. Substitution at para position of the phenyl ring by methyl


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(68), CHO (72) or chloro (74) groups showed very good antibacterial activity. Presence of NO2 group at any position of the phenyl ring results in the devoid of antibacterial activity of the compounds (69 and 70). It is clear from table 2.1 that substitution at ortho position of the phenyl ring has negative effect on the antibacterial activity and unsubstituted phenyl ring containing compound also shows good antibacterial activity (65). Similarly, compounds having phenyl or pyridyl groups directly attached with the triazole ring exhibit potent antibacterial activity (119-121). All of these compounds have also been tested against G. candidum, C. galbrata and C. albicans and found to be inactive.

22..55..22 IInn VViittrroo AAnnttiiaammooeebbiicc AAccttiivviittyy Ten compounds were evaluated for antiamoebic activity in vitro using HK-9 strain

of E. histolytica. The IC50 values in µM are shown in table 2.2. The results were estimated as the percentage of growth inhibition compared with the untreated controls and plotted as probit values as a function of the drug concentration. All the ten compounds showed good antiamoebic activity and eight compounds (65, 72, 74, 113, 117, 118, 119 and 120) were more active than the reference compound MTZ. Compound 120 with a 2-pyridyl moiety was the most active. Compounds in which there was a para substituent in the aromatic ring (72 and 74) were found to be active but a meta methyl substituted compound (67) was less active.

22..55..33 HHeemmoollyyttiicc SSttuuddiieess In order to study toxicity of these compounds hemolysis of selected compounds

(67, 68, 72, 74, 107 and 113) was investigated using human red blood cells (hRBCs) upto 1000 µg/mL concentration. Compounds 67, 68, 72 and 74 were 1.7, 0.31, 2, 2.2 % hemolytic at the highest concentration tested. Thus, all the compounds were found to be


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non-hemolytic and extremely safe, can be taken up as lead molecules for further development.

Table 2: In vitro antiamoebic activity of metronidazole-triazole hybrids

Compd N N

NO2NN N

R

IC

50 (µM) SD

R 65 CH2OPh 0.6070 88.78 x 10

-6

67 CH2O-3-MePh 92.3600 14.00 x 10-6

72 CH2O-4-CHOPh 0.0710 2.54 x 10-3

74 CH2O-4-ClPh 0.0870 60.57 x 10-6

113 CH2OH 0.0223 89.35 x 10-6

114 CH2CH2OH 2.3600 85.80 x 10-6

117 CH2OCOEt 0.1290 82.01 x 10-6

118 CH2OTHP 0.1490 223.80 x 10-6

119 Ph 0.2180 19.97 x 10-6

120 2-Pyridyl 0.0084 36.26 x 10-6

Ref Metronidazole 1.3020 20.06 x 10-6

22..55..44 IInn VViittrroo CCyyttoottooxxiicciittyy SSccrreeeenniinngg Some of the MTZ-styryl derivatives when screened against Hela cell line were

found to be cytotoxic at 50 µM concentration. The IC50 of compound 137, 145 and 175 were 0.370, 0.389 and 0.392, respectively.

22..66 EExxppeerriimmeennttaall SSeeccttiioonn

22..66..11 AAnnaallyyttiiccaall MMeetthhooddss All of the chemicals used in the synthesis were purchased from Sigma-Aldrich

and were used as such. Thin layer chromatography (Merck TLC silica gel 60 F254) was used to monitor the progress of the reactions. The compounds were purified by silica gel


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column (60-120 mesh). Melting points were determined on EZ-Melt automated melting point apparatus, Stanford Research Systems, and are uncorrected. IR (KBr/film/nujol) spectra were recorded using Perkin-Elmer FT-IR spectrophotometer and the values are expressed as υmax cm−1. Mass spectral data were recorded in Thermo Finnigan LCQ Advantage max ion trap mass spectrometer/Data system. The 1H NMR and 13C NMR spectra were recorded on Bruker Spectrospin spectrometer at 300 MHz and 75.5 MHz and on Jeol ECX spectrospin at 400 MHz and 100 MHz, using TMS as an internal standard. The chemical shift values are recorded on δ scale and the coupling constants (J) are in Hz. Elemental analysis were performed on a Carlo Erba Model EA-1108 elemental analyzer and data of C, H and N is within ±0.4% of calculated values.

22..66..22 SSyynntthheessiiss aanndd CChhaarraacctteerriizzaattiioonn ooff CCoommppoouunnddss Typical procedure: Synthesis of 2-(prop-2-ynyloxy)benzaldehyde (20) and

related compounds (14-38): To a mixture of ortho-hydroxybenzaldehyde (500 mg, 4.09 mmol) and anhydrous K2CO3 (1.69 g, 12.28 mmol) in dry DMF (5 mL), a solution of propargyl bromide (535.7 mg, 4.5 mmol) in dry DMF (2 mL) was added dropwise (scheme 2.1). The reaction mixture was stirred at room temperature for 8-10 h. The progress of the reaction was monitored by thin layer chromatography and after completion the reaction, mixture was poured into ice cold water and extracted thrice with chloroform. The organic layer was washed with cold water thrice to remove DMF. The chloroform layer was dried over anhydrous Na2SO4 and excess of solvent was removed under reduced pressure. The crude product thus obtained was purified over silica gel column using EtOAc:Hexane as an eluent to afford compound 20 in good yield. Yield 90%; mp 69-70 oC (lit. 66-68 oC); IR (cm-1, KBr): 3271, 2120 (C≡C), 1689; 1H NMR (300 MHz, CDCl3) δ: 2.59 (t, 1H, J = 2.4 Hz, C≡CH), 4.86 (d, 2H, J = 2.4 Hz, OCH2), 7.11 (d, 1H, J = 8.0 Hz, ArH), 7.14 (d, 1H, J = 8.5 Hz, ArH), 7.60 (dt, 1H, J = 8.5, 1.5


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Hz, ArH), 7.90 (dd, 1H, J = 7.7 Hz, 1.8 Hz, ArH), 10.50 (s, 1H, CHO); 13C NMR (75 MHz, DMSO-d6) δ: 56.4, 78.6, 79.0, 114.3, 121.5, 124.8, 127.8, 136.2, 159.5, 188.9.

1-Ethyl-4-(prop-2-ynyloxy)benzene (25): Yield 75%; 1H NMR (400 MHz, CDCl3) δ: 1.21 (t, J = 7.3 Hz, 3H, CH2CH3), 2.50 (t, J = 2.9 Hz, 1H, C≡CH), 2.59 (q, J = 7.3 Hz, 2H, CH2CH3), 4.66 (d, J = 2.9 Hz, 2H, OCH2), 6.90 (dd, J = 6.6, 2.9 Hz, 2H, ArH), 7.12 (dd, J = 8.8, 2.9 Hz, 2H, ArH).

1-iso-Propyl-4-(prop-2-ynyloxy)benzene (26): Yield 82%; 1H NMR (400 MHz, CDCl3) δ: 1.22 (d, J = 6.6 Hz, 6H, CH(CH3)2), 2.50 (t, J = 2.2 Hz, 1H, C≡CH), 2.86 (septet, J = 6.6 Hz, 1H, CH(CH3)2), 4.66 (d, J = 2.2 Hz, 2H, OCH2), 6.91 (dd, J = 6.6, 2.2 Hz, 2H, ArH), 7.16 (dd, J = 6.6, 2.2 Hz, 2H, ArH).

1,2-Dimethyl-3-(prop-2-ynyloxy)benzene (30): Yield 90%; IR (cm-1, film): 3293, 2922, 2865, 2122 (C≡C), 1584, 1473, 1370, 1304, 1256, 1235, 1192, 1103, 1015; 1H NMR (400 MHz, CDCl3) δ: 2.16 (s, 3H, CH3), 2.27 (s, 3H, CH3), 2.48 (t, J = 2.2 Hz, 1H, C≡CH), 4.68 (d, J = 2.9 Hz, 2H, OCH2), 6.82 (d, J = 7.3 Hz, 2H, ArH), 7.03-7.07 (m, 1H, ArH).

2,4-Dichloro-1-(prop-2-ynyloxy)benzene (32): Yield 82%; 1H NMR (400 MHz, CDCl3) δ: 2.50 (t, J = 2.9 Hz, 1H, C≡CH), 4.77 (d, J = 2.9 Hz, 2H, OCH2), 7.02 (d, J = 8.8 Hz, 1H, ArH), 7.20 (dd, J = 8.8 Hz, 2.9 Hz, 1H, ArH), 7.39 (d, J = 2.2 Hz, 1H, ArH).

1,3-Dichloro-2-(prop-2-ynyloxy)benzene (33): Yield 88%; 1H NMR (400 MHz, CDCl3) δ: 2.54 (t, J = 2.9 Hz, 1H, C≡CH), 4.78 (d, J = 2.9 Hz, 2H, OCH2), 7.03 (d, J = 8.0 Hz, 1H, ArH), 7.30 (d, J = 8.0 Hz, 2H, ArH).

Typical procedure: Synthesis of N-(prop-2-ynyl)aniline (39) and related compounds (40-61): To a mixture of aniline (500 mg, 5.36 mmol) and anhydrous K2CO3 (2.22 g, 16.10 mmol) in dry DMF (5 mL), a solution of propargyl bromide (702.56 mg,


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5.9 mmol) in dry DMF (2 mL) was added dropwise (scheme 2.2). The reaction mixture was stirred at room temperature for 8-10 hour. The progress of the reaction was monitored by thin layer chromatography. TLC of the reaction showed three close spots corresponding to the unreacted aniline, the monosubstituted secondary amine and the disubstituted tertiary amine. After completion, the reaction mixture was poured into ice cold water and extracted thrice with chloroform (3 x 10 mL). The organic layer was washed with cold water thrice (3 x 30 mL) to remove DMF. The chloroform layer was dried over anhydrous Na2SO4 and excess of solvent was removed under reduced pressure. The crude product thus obtained was purified over silica gel column using EtOAc:Hexane as an eluent to afford compound 39 as major product. Yield 70%; 1H NMR (300 MHz, CDCl3): 2.21 (1H, C≡CH), 3.93 (s, 2H, NCH2), 4.12 (s, 1H, NH), 6.67-6.81 (m, 3H, ArH), 7.19-7.24 (m, 2H, ArH); 13C NMR: 33.6, 71.3, 81.0, 113.5, 118.7, 129.2, 146.8.

2-Fluoro-N-(prop-2-ynyl)aniline (40): Yield 77%; 1H NMR (400 MHz, CDCl3) δ: 2.23 (t, J = 2.2 Hz, 1H, C≡CH), 3.98 (d, J = 2.2 Hz, 2H, CH2), 4.15 (brs, 1H, NH), 6.68-6.73 (m, 1H, ArH), 6.78-6.83 (m, 1H, ArH), 6.96-7.06 (m, 2H, ArH).

3-Fluoro-N-(prop-2-ynyl)aniline (41) Yield 73%; 1H NMR (400 MHz, CDCl3) δ: 2.23 (t, J = 2.9 Hz, 1H, C≡CH), 3.91 (s, 2H), 4.00 (brs, 1H), 6.36-6.40 (m, 1H, ArH), 6.43-6.49 (m, 2H, ArH), 7.10-7.16 (m, 1H, ArH).

4-Fluoro-N-(prop-2-ynyl)aniline (42): Yield 78%; 1H NMR (400 MHz, CDCl3) δ: 2.21 (t, J = 2.2 Hz, 1H, C≡CH), 3.72 (brs, 1H), 3.90 (d, J = 2.2 Hz, 2H), 6.61-6.66 (m, 2H, ArH), 6.89-6.95 (m, 2H, ArH).

2-Chloro-N-(prop-2-ynyl)aniline (43): Yield 71%; 1H NMR (400 MHz, CDCl3) δ: 2.23 (t, J = 2.2 Hz, 1H, C≡CH), 4.01 (d, J = 2.2 Hz, 2H), 4.55 (brs, 1H), 6.69-6.73 (m, 1H), 6.77 (d, J = 8.0 Hz, 1H, ArH), 7.17-7.20 (m, 1H, ArH), 7.25-7.28 (m, 1H, ArH).


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4-Chloro-N-(prop-2-ynyl)aniline (45): Yield 80%; 1H NMR (400 MHz, CDCl3) δ: 2.22 (s, 1H), 3.91 (s, 3H), 6.61 (dd, J = 6.6, 2.2 Hz, 2H, ArH), 7.16 (dd, J = 6.6 Hz, 2.2 Hz, 2H, ArH).

4-Bromo-N-(prop-2-ynyl)aniline (46): Yield 77%; 1H NMR (400 MHz, CDCl3) δ: 2.22 (t, J = 2.2 Hz, 1H, C≡CH), 3.90 (d, J = 2.2 Hz, 2H), 6.54-6.58 (m, 2H, ArH), 7.27-7.31 (m, 2H, ArH).

2-Methyl-N-(prop-2-ynyl)aniline (47): Yield 70%; 1H NMR (400 MHz, CDCl3) δ: 2.16 (s, 3H, CH3), 2.24 (t, J = 2.2 Hz, 1H, C≡CH), 3.75 (brs, 1H, NH), 3.98 (d, J = 2.9 Hz, 2H, NCH2), 6.70-6.76 (m, 2H, ArH), 7.08 (d, J = 7.3 Hz, 1H, ArH), 7.15-7.19 (m, 1H, ArH).

4-Ethyl-N-(prop-2-ynyl)aniline (49): Yield 75%; IR (cm-1, film): 3399, 3292, 3020, 2963, 2928, 2871, 1617, 1560, 1542, 1519, 1459, 1313, 1260, 1185, 1127, 909, 823; 1H NMR (400 MHz, CDCl3) δ: 1.19 (t, J = 7.3 Hz, 3H, CH2CH3), 2.21 (t, J = 2.2 Hz, 1H, C≡CH), 2.55 (q, J = 7.3 Hz, 2H, CH2CH3), 3.76 (brs, 1H, NH), 3.92 (d, J = 2.2 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H, ArH), 7.06 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3) δ: 15.84, 27.91, 33.88, 71.15, 81.20, 113.67, 128.53, 134.50, 144.69.

4-iso-Propyl-N-(prop-2-ynyl)aniline (50): Yield 72%; 1H NMR (400 MHz, CDCl3) δ: 1.12 (d, J = 7.3 Hz, 6H, CH(CH3)2), 2.21 (t, J = 2.2 Hz, 1H, C≡CH), 2.82 (septet, J = 7.3 Hz, 1H, CH(CH3)2), 3.76 (brs, 1H, NH), 3.92 (d, J = 2.2 Hz, 2H), 6.64 (dd, J = 8.8, 2.2 Hz, 2H, ArH), 7.08 (dd, J = 8.0, 2.2 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): 24.16, 33.15, 33.83, 71.16, 81.23, 113.52, 127.08, 139.10, 144.77.

2-Methoxy-N-(prop-2-ynyl)aniline (51): Yield 74%; 1H NMR (300 MHz, CDCl3): 2.27 (t, J = 2.4 Hz, 1H, C≡CH), 2.57 (t, J = 4.5 Hz, 4H, CH2N), 3.29 (d, J = 2.4 Hz, 2H, C≡CCH2), 3.75 (t, J = 4.5 Hz, 4H, CH2O).


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2,6-Dimethyl-N-(prop-2-ynyl)aniline (55): Yield 74%; 1H NMR (400 MHz, CDCl3) δ: 2.19 (t, J = 2.9 Hz, 1H, C≡CH), 2.32 (s, 6H, 2CH3), 3.35 (brs, 1H, NH), 3.78 (d, J = 2.9 Hz, 2H), 6.87 (dd, J = 7.3 Hz, 7.3 Hz, 1H), 7.00 (d, J = 7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 18.40, 37.32, 71.49, 82.08, 122.79, 128.76, 130.12, 144.52.

N-Benzylprop-2-yn-1-amine (56): Yield 77%; 1H NMR (400 MHz, CDCl3) δ: 1.20 (s, 1H), 1.49 (s, 4H), 7.19 (s, 5H, ArH).

N-Phenethylprop-2-yn-1-amine (57): Yield 32%; 1H NMR (400 MHz, CDCl3) δ: 2.20 (t, J = 2.2 Hz, 1H, C≡CH), 2.82 (t, J = 7.3 Hz, 2H), 2.97 (t, J = 7.3 Hz, 2H), 3.44 (d, J = 2.9 Hz, 2H), 3.46 (brs, 1H, NH), 7.27 (d, J = 7.3 Hz, 3H, ArH), 7.28-7.30 (m, 2H, ArH).

Synthesis of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-methylbenzene

sulfonate (63): To a stirred solution of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol, (62; 5 g, 0.029 mol) in anhydrous pyridine (75 mL), para-toluenesulfonylchloride (11.13 g, 0.0584 mol) was added and the reaction mixture was stirred at room temperature overnight (12 h). The solid precipitated was filtered and crystallized from ethanol to give pale yellow shining needle like crystals of compound 63 (scheme 2.3). Yield 85% (pale yellow solid); mp 151 oC (lit mp 153 oC)81; IR: 1596, 1526, 1460, 1430, 1366, 1174, 898; 1H NMR (CDCl3) δ: 2.45 (s, 3H, CH3), 2.52 (s, 3H, CH3), 4.37 (t, 2H, NCH2), 4.54 (t, 2H, OCH2), 7.30 (d, J = 8.3 Hz, 2H, ArH), 7.60 (d, J = 8.3 Hz, 2H, ArH), 7.79 (s, 1H); 13C NMR (CDCl3) δ: 13.91, 21.01, 44.61, 68.38, 127.21, 129.24, 131.5, 133.04, 138.03, 145.22, 151.57.

Synthesis of 1-(2-azidoethyl)-2-methyl-5-nitro-1H-imidazole (64)82,83: To a stirred solution of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-methylbenzene sulfonate (63; 8 g, 0.0245 mol) in dry DMF (40 mL), sodium azide (4.79 g, 0.0737 mol) was added at 0 oC. Then the reaction mixture was heated at 70-80 oC for 1 hour (scheme 2.3). The


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temperature of the reaction mixture was brought to room temperature and added cold water. It was extracted thrice with chloroform (3 x 40 mL) and the organic layer was washed several times with cold water to remove DMF. The organic solvent was removed under reduced pressure and to the residue hexane was added to get compound 64 as off white coloured crystalline solid. Yield 78%; mp 56-58 oC; 1H NMR (CDC13) δ: 2.44 (s, 3H, CH3), 3.79 (dd, J = 5.6, 5.3 Hz, CH2), 4.45 (dd, J = 5.7, 5.3 Hz, CH2), 7.98 (s, 1 H); I3C NMR δ: 14.5, 45.5, 50.8, 133.4, 136.7, 151.3.

Typical procedure: Synthesis of metronidazole-triazole conjugates (65-125): To a vigorously stirred solution of 1-(2-azido-ethyl)-2-methyl-5-nitro-1H-imidazole (64), (2.5 mmol) and appropriate alkyne (2.5 mmol) in tert-butyl alcohol was added a solution of CuSO4.5H2O (0.51 mmol) and sodium ascorbate (1.02 mmol) in distilled water (scheme 2.4). The amount of tert-butyl alcohol and distilled water was kept 1:1 (v/v). The deep yellow mixture was stirred vigorously at room temperature and progress of reaction was monitored by thin layer chromatography. After 2 h reaction was completed and crude

reaction mixture was extracted with CHCl3 (3 × 10 mL) and dried over anhydrous

Na2SO4. Excess of solvent was removed under vaccuo. The crude mixture was purified over SiO2 column using ethyl acetate/hexane as an eluent.

1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-phenoxymethyl-1H-[1,2,3]triazole (65): Yield 54%; mp 146-148 oC; IR (KBr, cm-1): 3128, 2932, 1527, 1466, 1428, 1367, 1252, 1196, 1151, 1049, 884; 1H NMR (300 MHz, DMSO-d6) δ: 1.80 (s, 3H, CH3), 4.71 (t, J = 5.4 Hz, 2H, NCH2), 4.85 (t, J = 5.4 Hz, 2H, NCH2), 5.12 (s, 2H, OCH2), 6.92-7.01 (m, 3H, ArH), 7.26-7.31 (m, 2H, ArH), 8.04 (s, 1H), 8.11 (s, 1H); ESI-MS (m/z): 329.23 [M + H]+; Anal. calcd for C15H16N6O3: C, 54.87; H, 4.91; N, 25.60; found: C, 54.98; H, 5.08; N, 25.79.


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1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-o-tolyloxymethyl-1H-[1,2,3]triazole (66): Yield 60%; mp 134-136 oC; IR (KBr, cm-1): 3128, 2924, 2854, 1526, 1461, 1430, 1268, 1243, 1193, 1120, 1052, 1006; 1H NMR (300 MHz, DMSO-d6) δ: 1.74 (s, 3H, CH3), 2.09 (s, 3H, CH3), 4.69-4.71 (m, 2H, NCH2), 4.83-4.85 (m, 2H, NCH2), 5.10 (s, 2H, OCH2), 6.81-6.86 (m, 1H, ArH), 7.03-7.06 (m, 1H, ArH), 7.11-7.13 (m, 2H, ArH), 8.03 (s, 1H), 8.08 (s, 1H); ESI-MS (m/z): 343.22 [M + H]+; Anal. calcd for C16H18N6O3: C, 56.13; H, 5.30; N, 24.55; found: C, 56.33; H, 5.55; N, 24.73.

1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-m-tolyloxymethyl-1H-[1,2,3]triazole (67): Yield 58%; mp 108-110 oC; IR (KBr, cm-1): 3131, 3030, 2924, 2873, 1608, 1585, 1528, 1510, 1465, 1364, 1262, 1192, 1155, 1039, 824; 1H NMR (300 MHz, DMSO-d6) δ: 1.82 (s, 3H, CH3), 2.22 (s, 3H, CH3), 4.74 (brs, 2H, NCH2), 4.88 (brs, 2H, NCH2), 5.10 (s, 2H, OCH2), 6.77-6.91 (m, 2H, ArH), 7.09-7.21 (m, 2H, ArH), 8.08 (s, 1H), 8.12 (s, 1H); ESI-MS (m/z): 343.20 [M + H]+.

1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-p-tolyloxymethyl-1H-[1,2,3]triazole (68): Yield 52%; mp 142 oC; IR (KBr, cm-1): 2924, 2854, 1538, 1509, 1465, 1369, 1266, 1235, 1190, 1155, 1047; 1H NMR (300 MHz, DMSO-d6) δ: 1.78 (s, 3H, CH3), 2.21 (s, 3H, CH3), 4.70 (brs, 2H, NCH2), 4.82 (brs, 2H, NCH2), 5.05 (s, 2H, OCH2), 6.85 (d, J = 8 Hz, 2H, ArH), 7.05 (d, J = 8 Hz, 2H, ArH), 8.02 (s, 1H), 8.07 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6): 12.73, 20.05, 48.73, 60.87, 114.56, 125.23, 129.49, 129.78, 133.23, 138.34, 143.26, 151.19, 155.74; ESI-MS (m/z): 343.22 [M + H]+; Anal. calcd for C16H18N6O3: C, 56.13; H, 5.30; N, 24.55; found: C, 56.33; H, 5.45; N, 24.77.

1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-(2-nitro-phenoxymethyl)-1H-[1,2,3] triazole (69): Yield 66%; mp 144-146 oC; IR (KBr, cm-1): 3012, 1603, 1526, 1469, 1430, 1358, 1281, 1265, 1253, 1190, 1144, 1092, 1035, 972; 1H NMR (300 MHz, DMSO-d6) δ: 1.93 (s, 3H, CH3), 4.79-4.84 (m, 4H, NCH2CH2N), 5.34 (s, 2H, OCH2), 7.06-7.11 (m, 1H,


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ArH), 7.23-7.26 (m, 1H, ArH), 7.51 (s, 1H, ArH), 7.53-7.58 (m, 1H, ArH), 7.84-7.87 (m, 1H), 7.99 (s, 1H); ESI-MS (m/z): 374.21 [M + H]+.

1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-(4-nitro-phenoxymethyl)-1H-[1,2,3]triazole (70): Yield 54%; mp 196-198 oC; IR (KBr, cm-1): 3127, 2916, 1593, 1502, 1457, 1361, 1259, 1186, 1044, 1106; 1H NMR (300 MHz, CDCl3) δ: 1.99 (s, 3H, CH3), 4.82 (brs, 4H, NCH2CH2N), 5.26 (s, 2H, OCH2), 7.04 (d, J = 9 Hz, 2H, ArH), 7.36 (s, 1H), 8.00 (s, 1H), 8.21 (d, J = 9 Hz, 2H, ArH); HRMS calcd for C15H15N7O5: 373.3238, found: 373.3228 [M]+.

2-{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-ylmethoxy}-benzal-dehyde (71): Yield 60%; mp 180-182 oC; IR (KBr, cm-1): 3141, 3031, 2870, 1679, 1599, 1534, 1475, 1370, 1261, 1241, 1187, 1049, 1004; 1H NMR (300 MHz, DMSO-d6) δ: 1.78 (s, 3H, CH3), 4.72 (brs, 2H, NCH2), 4.87 (brs, 2H, NCH2), 5.33 (s, 2H, OCH2), 7.08-7.13 (m, 1H, ArH), 7.38-7.41 (m, 1H, ArH), 7.65-7.72 (m, 2H, ArH), 8.04 (s, 1H), 8.19 (s, 1H), 10.33 (s, 1H, CHO); HRMS calcd for C16H16N6O4: 356.3363; found: 356.3358 [M]+.

4-{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-ylmethoxy}-benzal-dehyde (72): Yield 60%; mp 170-172 oC; IR (KBr, cm-1): 2924, 2854, 1683, 1601, 1577, 1524, 1454, 1370, 1261, 1221, 1172, 826; 1H NMR (300 MHz, DMSO-d6) δ: 1.84 (s, 3H, CH3), 4.76 (t, 2H, NCH2), 4.92 (t, 2H, NCH2), 5.32 (s, 2H, OCH2), 7.23 (d, J = 8 Hz, 2H, ArH), 7.95 (d, J = 8 Hz, 2H, ArH), 8.09 (s, 1H), 8.20 (s, 1H), 9.93 (s, 1H, CHO); 13C NMR (75.5 MHz, DMSO-d6): 12.68, 46.10, 48.77, 61.19, 115.19, 125.61, 129.82, 131.73, 133.16, 138.32, 142.41, 151.15, 162.73, 191.31; ESI-MS (m/z): 357.18 [M + H]+; Anal. calcd for C16H16N6O4: C, 53.93; H, 4.53; N, 23.58; found: C, 54.09; H, 4.70; N, 23.78.


137

4-(2-Chloro-phenoxymethyl)-1-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3] triazole (73): Yield 63%; mp 140-142 oC; IR (KBr, cm-1): 3133, 2924, 1525, 1501, 1460, 1430, 1366, 1264, 1195, 1037; 1H NMR (300 MHz, CDCl3) δ: 1.98 (s, 3H, CH3), 4.79 (s, 4H, NCH2CH2N), 5.15 (s, 2H, OCH2), 6.66-6.69 (m, 1H, ArH), 6.74-6.75 (m, 1H, ArH), 7.01-7.04 (d, J = 8.4 Hz, 1H, ArH), 7.33 (s, 1H), 8.00 (s, 1H); ESI-MS (m/z): 363.32 [M + H]+, 365.35 [M + 2]+.

4-(4-Chloro-phenoxymethyl)-1-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3] triazole (74): Yield 57%; mp 103-106 oC; IR (KBr, cm-1): 3128, 2927, 1526, 1495, 1464, 1428, 1368, 1267, 1245, 1196, 1050; 1H NMR (300 MHz, DMSO-d6) δ: 1.78 (s, 3H, CH3), 4.70 (brs, 2H, NCH2), 4.83 (brs, 2H, NCH2), 5.11 (s, 2H, OCH2), 7.02 (d, J = 9 Hz, 2H, ArH), 7.32 (d, J = 8 Hz, 2H, ArH), 8.02 (s, 1H), 8.09 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6): 12.7, 46.1, 48.8, 61.1, 116.54, 124.6, 125.4, 129.2, 133.2, 138.3, 142.8, 151.2, 156.7; ESI-MS (m/z): 363.18 [M + H]+, 365.21 [M + 2]+; Anal. calcd for C15H15ClN6O3: C, 49.66; H, 4.17; N, 23.17; found: C, 49.89; H, 4.28; N, 23.42.

4-((4-Bromophenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (75): Yield 55%; mp 138-139 oC; IR (film, cm-1): 3127, 2924, 2854, 1701, 1526, 1487, 1460, 1425, 1363, 1263, 1239, 1190; 1H NMR (300 MHz, DMSO-d6) δ: 1.84 (s, 3H, CH3), 4.76 (t, J = 5.4 Hz, 2H, NCH2), 4.91 (t, J = 5.4 Hz, 2H, NCH2), 5.19 (s, 2H, OCH2), 7.04 (d, J = 9 Hz, 2H, ArH), 7.51 (d, J = 8.7 Hz, 2H, ArH), 8.11 (s, 1H), 8.17 (s, 1H); ESI-MS (m/z): 407.23 [M + H]+, 409.15 [M + 2]+.

4-((4-Ethylphenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (76): Yield 60%; mp 143-144 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.14 (t, J = 7.5 Hz, 3H, CH2CH3), 1.79 (s, 3H, CH3), 2.53 (q, J = 7.5 Hz, 2H, CH2CH3), 4.71 (t, J = 5.4 Hz, 2H, NCH2), 4.85 (t, J = 5.7 Hz, 2H, NCH2), 5.08 (s, 2H, OCH2), 6.90 (d, J = 8.4


138

Hz, 2H, ArH), 7.11 (d, J = 8.4 Hz, 2H, ArH), 8.05 (s, 1H), 8.08 (s, 1H); ESI-MS (m/z): 356.43 [M + H]+.

4-((4-iso-Propylphenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (77): Yield 62%; mp 147-149 oC; IR (KBr, cm-1): 3131, 2958, 2924, 1747, 1700, 1650, 1611, 1511, 1430, 1364, 1264, 1241, 1191, 1147; 1H NMR (300 MHz, CDCl3) δ: 1.21 (d, J = 6.9 Hz, 6H, CH(CH3)2), 1.95 (s, 3H, CH3), 2.86 (septet, J = 6.9 Hz, 1H, CH(CH3)2), 4.79 (s, 4H, 2NCH2), 5.16 (s, 2H, OCH2), 6.87 (d, J = 8.7 Hz, 2H, ArH), 7.14 (d, J = 8.4 Hz, 2H, ArH), 7.14 (d, J = 8.4 Hz, 2H, ArH), 7.33 (s, 1H), 8.0 (s, 1H); ESI-MS (m/z): 371.24 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-((4-propylphenoxy)methyl)-1H-1,2,3-triazole (78): Yield 59%; mp 125-126 oC; IR (film, cm-1): 3401, 3127, 2924, 2853, 1603, 1529, 1466, 1427, 1363, 1263, 1190, 1148, 1047; 1H NMR (300 MHz, CDCl3) δ: 0.89-0.95 (m, 3H, CH2CH2CH3), 1.57-1.62 (m, 2H, CH2CH2CH3), 1.95 (s, 3H, CH3), 2.24-2.54 (m, 2H, CH2CH2CH3), 4.80 (s, 4H, 2NCH2), 5.15 (s, 2H, OCH2), 6.86 (dd, J = 8.4, 2.4 Hz, 2H, ArH), 7.08 (dd, J = 8.4, 2.4 Hz, 2H, ArH), 7.33 (s, 1H), 8.0 (s, 1H); ESI-MS (m/z): 371.28 [M + H]+.

4-((4-tert-Butylphenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (79): Yield 64%; mp 141-142 oC; IR (film, cm-1): 3135, 3108, 2962, 2868, 1608, 1527, 1513, 1466, 1429, 1363, 1260, 1244, 1188, 1148; 1H NMR (300 MHz, CDCl3) δ: 1.29 (s, 9H, (CH3)3), 1.95 (s, 3H, CH3), 4.79 (s, 4H, 2NCH2), 5.16 (s, 2H, OCH2), 6.87 (d, J = 8.7 Hz, 2H, ArH), 7.29 (d, J = 9 Hz, 2H, ArH), 7.35 (s, 1H), 7.99 (s, 1H); ESI-MS (m/z): 385.26 [M + H]+.

1-(4-{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-ylmethoxy}-phenyl)-ethanone (80): Yield 54%; mp 168-170 oC; IR (KBr, cm-1): 3115, 2918, 1673, 1602,


139

1526, 1481, 1460, 1367, 1259, 1192, 1173, 1042; 1H NMR (300 MHz, DMSO-d6) δ: 1.76 (s, 3H), 2.49 (s, 3H), 4.68 (brs, 2H), 4.84 (brs, 2H, NCH2), 5.22 (s, 2H, OCH2), 7.08 (d, J = 8 Hz, 2H), 7.90 (d, J = 8 Hz, 2H), 8.03 (s, 1H), 8.12 (s, 1H); HRMS calcd for C17H18N6O4: 370.3629; found: 370.3618 [M]+.

4-((2,3-Dimethylphenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (81): Yield 58%; mp 144-146 oC; IR (film, cm-1): 3128, 2923, 1703, 1656, 1584, 1525, 1461, 1429, 1372, 1269, 1251, 1198, 1093; 1H NMR (300 MHz, CDCl3) δ: 1.95 (s, 3H, CH3), 2.11 (s, 3H, CH3), 2.30 (s, 3H, CH3), 4.81 (s, 4H, NCH2CH2N), 5.16 (s, 2H, OCH2), 6.76-6.82 (m, 2H, ArH), 7.02-7.07 (m, 1H, ArH), 7.30 (s, 1H), 8.0 (s, 1H); ESI-MS (m/z): 357.24 [M + H]+.

Methyl-2-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methoxy) benzoate (82): Yield 64%; mp 152-153 oC; IR (film, cm-1): 3118, 1721, 1594, 1525, 1462, 1423, 1366, 1259, 1087; 1H NMR (300 MHz, DMSO-d6) δ: 1.83 (s, 3H, CH3), 3.82 (s, 3H, COOCH3), 4.77 (t, J = 4.8 Hz, 2H, NCH2), 4.93 (t, J = 4.5 Hz, 2H, NCH2), 5.27 (s, 2H, OCH2), 7.07-7.12 (m, 1H, ArH), 7.35 (d, J = 8.4 Hz, 1H, ArH), 7.56-7.61 (m, 1H, ArH), 7.70 (d, J = 7.5 Hz, 1H, ArH), 8.11 (s, 1H), 8.14 (s, 1H); ESI-MS (m/z): 387.27 [M + H]+.

4-((2,4-Dichlorophenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H- 1,2,3-triazole (83): Yield 67%; mp 120-121 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.76 (s, 3H, CH3), 4.71 (t, J = 5.4 Hz, 2H, NCH2), 4.87 (t, J = 5.4 Hz, 2H, NCH2), 5.25 (s, 2H, OCH2), 7.32-7.41 (m, 2H, ArH), 7.57-7.58 (m, 1H, ArH), 8.05 (s, 1H), 8.14 (s, 1H); ESI-MS (m/z): 397.20 [M + H]+, 399.18 [M + 2]+, 401.20 [M + 4]+.

4-((2,6-Dichlorophenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (84): Yield 68%; mp 170-171 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.93


140

(s, 3H, CH3), 4.79 (t, J = 5.7 Hz, 2H, NCH2), 4.94 (t, J = 5.7 Hz, 2H, NCH2), 5.15 (s, 2H, OCH2), 7.28 (d, J = 8.1 Hz, 1H, ArH), 7.56 (d, J = 8.1 Hz, 2H, ArH), 8.12 (s, 1H), 8.29 (s, 1H); ESI-MS (m/z): 397.15 [M + H]+, 399.18 [M + 2]+, 401.18 [M + 4]+.

4-((4-Chloro-3-methylphenoxy)methyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethyl)-1H-1,2,3-triazole (85): Yield: 70%; mp 139-140 oC; IR (film, cm-1): 3132, 2923, 1575, 1525, 1461, 1429, 1364, 1265, 1241, 1192, 1169, 1033; 1H NMR (300 MHz, DMSO-d6) δ: 1.78 (s, 3H, CH3), 2.29 (s, 3H, CH3), 4.71 (t, J = 4.8 Hz, 2H, NCH2), 4.85 (t, J = 4.5 Hz, 2H, NCH2), 5.11 (s, 2H, OCH2), 6.86 (dd, J = 9 Hz, 3 Hz, 1H, ArH), 7.01 (d, J = 3 Hz, 1H, ArH), 7.30 (d, J = 8.7 Hz, 1H, ArH), 8.05 (s, 1H), 8.10 (s, 1H); ESI-MS (m/z): 376.25 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-((2,4,6-tri-tert-butylphenoxy)methyl)-1H-1,2,3-triazole (86): Yield 77%; mp 199-200 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.29 (s, 9H, (CH3)3), 1.38 (s, 18H, 2(CH3)3), 1.83 (s, 3H, CH3), 4.75 (s, 4H, 2NCH2), 4.91 (s, 2H, OCH2), 7.25 (s, 2H, ArH), 8.07 (s, 1H), 8.13 (s, 1H); ESI-MS (m/z): 497.48 [M + H]+.

4-(Benzyloxymethyl)-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (87): Yield 58%; mp 104-106 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.88 (s, 3H, CH3), 4.48-4.56 (m, 4H, 2NCH2), 4.75-4.87 (m, 4H, 2OCH2), 7.36 (brs, 5H, ArH), 8.06 (s, 2H); ESI-MS (m/z): 343.21 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-((naphthalen-1-yloxy)methyl)-1H-1,2,3-triazole (88): Yield 60%; mp 168-169 oC; IR (film, cm-1): 3127, 2916, 1577, 1524, 1459, 1429, 1371, 1267, 1238, 1198, 1096, 1052; 1H NMR (300 MHz, DMSO-d6) δ: 1.87 (s, 3H, CH3), 4.80-4.81 (m, 2H, NCH2), 4.94 (s, 2H, NCH2), 5.37 (s, 2H, OCH2), 7.19 (d, J =


141

7.2 Hz, 1H, ArH), 7.48-7.56 (m, 4H), 7.93 (d, J = 6.9 Hz, 1H), 8.12-8.15 (m, 2H), 8.27 (s, 1H); ESI-MS (m/z): 379.29 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-((naphthalen-2-yloxy)methyl)-1H-1,2,3-triazole (89): Yield 62%; mp 186-187 oC; IR (KBr, cm-1): 2924, 1629, 1460, 1363, 1263, 1216, 1190, 1016; 1H NMR (300 MHz, DMSO-d6) δ: 1.81 (s, 3H, CH3), 4.72-4.74 (m, 2H, NCH2), 4.85-4.87 (m, 2H, NCH2), 5.25 (s, 2H, OCH2), 7.15-7.19 (m, 1H, ArH), 7.34-7.39 (m, 1H, ArH), 7.45-7.50 (m, 2H, ArH), 7.80-7.85 (m, 3H, ArH), 8.05 (s, 1H), 8.17 (s, 1H); ESI-MS (m/z): 379.26 [M + H]+.

N-((1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (90): Yield 62%; mp 137-138 oC; IR (KBr, cm-1): 3132, 2958, 2928, 2869, 1611, 1583, 1525, 1510, 1461, 1431, 1371, 1268, 1241, 1198, 1176, 1150, 1116, 1051, 1006, 884, 862; 1H NMR (300 MHz, DMSO-d6) δ: 1.79 (s, 3H, CH3), 3.30 (s, 1H, NH), 4.70-4.71 (m, 2H, NCH2), 4.82-4.83 (m, 2H, NCH2), 5.07 (s, 2H, CH2NH), 6.90 (d, J = 7.8 Hz, 3H), 7.07 (d, J = 7.8 Hz, 2H, ArH), 8.03 (s, 1H), 8.08 (s, 1H); ESI-HRMS calcd. for C15H17N7O2: 327.1444; Found: 327.8076 [M]+.

2-Fluoro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (91): Yield 65%; mp 110-111 oC; IR (KBr, cm-1): 3368, 3106, 2858, 1623, 1527, 1461, 1365, 1332, 1294, 1265, 1191, 1153, 1115, 1051, 823; 1H NMR (300 MHz, DMSO-d6) δ: 1.72 (s, 3H, CH3), 4.33 (d, J = 6 Hz, 2H, CH2NH), 4.65 (t, J = 5.1 Hz, 2H, NCH2), 4.78 (t, J = 5.1 Hz, 2H, NCH2), 5.97 (t, J = 6 Hz, 1H, NH), 6.53-6.55 (m, 1H, ArH), 6.64 (t, J = 8.1 Hz, 1H, ArH), 6.91 (t, J = 7.8 Hz, 1H, ArH), 6.99 (dd, J = 7.8, 4.2 Hz, 1H, ArH), 7.83 (s, 1H), 8.01 (s, 1H); ESI-HRMS calcd. for C15H16FN7O2: 345.1350; Found: 345.0865 [M]+.


142

3-Fluoro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (92): Yield 55%; mp 139-140 oC; 1H NMR (400 MHz, CDCl3) δ: 1.94 (s, 3H, CH3), 4.33 (brs, 1H, NH), 4.40 (s, 2H, CH2NH), 4.77 (s, 4H, NCH2CH2N), 6.27-6.31 (m, 1H, ArH), 6.37 (dd, J = 8.0, 1.5 Hz, 1H, ArH), 6.40-6.45 (m, 1H, ArH), 7.07-7.13 (m, 1H, ArH), 7.15 (s, 1H), 7.97 (s, 1H); ESI-MS (m/z): 346.19 [M + H]+.

4-Fluoro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (93): Yield 57%; mp 138-139 oC; IR (KBr, cm-1): 3375, 3160, 3113, 3033, 2838, 1612, 1558, 1528, 1510, 1460, 1363, 1262, 1220, 1191, 1155, 1114, 1051; 1H NMR (400 MHz, CDCl3) δ: 1.92 (s, 3H, CH3), 4.11 (brs, 1H, NH), 4.37 (s, 2H, CH2NH), 4.76 (s, 4H, NCH2CH2N), 6.53-6.56 (m, 2H, ArH), 6.86-6.90 (m, 2H, ArH), 7.13(s, 1H), 7.97 (s, 1H); ESI-MS (m/z): 346.20 [M + H]+.

2-Chloro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)

aniline (94): Yield 59%; mp 146-142 oC; IR (nujol, cm-1): 3380, 3110, 3033, 2924, 2854, 1595, 1560, 1530, 1515, 1460, 1424, 1367, 1320, 1262, 1190, 1153, 1092, 1052, 1037; 1H NMR (300 MHz, DMSO-d6) δ: 1.74 (s, 3H, CH3), 4.39 (d, J = 6 Hz, 2H, CH2NH), 4.65 (t, J = 5.1 Hz, 2H, NCH2), 4.78 (t, J = 5.1 Hz, 2H, NCH2), 5.88 (t, J = 6 Hz, 1H, NH), 6.55-6.65 (m, 2H, ArH), 7.05-7.10 (m, 1H, ArH), 7.23 (d, J = 7.8 Hz, 1H, ArH), 7.83 (s, 1H), 8.01 (s, 1H); ESI-HRMS calcd. for C15H16ClN7O2: 361.1054; Found: 361.1448 [M]+, 363.1243 [M + 2]+.

3-Chloro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (95): Yield 60%; mp 101-102 oC; IR (KBr, cm-1): 3382, 3112, 3075, 2851, 1599, 1528, 1461, 1424, 1367, 1323, 1262, 1190, 1154, 1086, 1051, 986; 1H NMR (300 MHz, DMSO-d6) δ: 1.76 (s, 3H, CH3), 4.27 (d, J = 5.4 Hz, 2H, CH2NH), 4.67 (d, J = 3.3 Hz, 2H, NCH2), 4.79 (s, 2H, NCH2), 6.45-6.60 (m, 3H, ArH), 7.02-7.07 (m, 1H, ArH), 7.86 (s, 1H), 8.02 (s, 1H); ESI-MS (m/z): 362.24 [M + H]+, 364.26 [M + 2]+.


143

4-Chloro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (96): Yield 61%; mp 151-152 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.94 (s, 3H, CH3), 4.20 (brs, 1H, NH), 4.39 (d, J = 5.1 Hz, 2H, CH2NH), 4.76 (s, 4H, NCH2CH2N), 6.53 (d, J = 8.8 Hz, 2H, ArH), 7.12 (d, J = 8.8 Hz, 2H, ArH), 7.11 (s, 1H), 7.97 (s, 1H); ESI-HRMS calcd. for C15H16ClN7O2: 361.1054; Found: 361.5812 [M]+, 363.2341 [M + 2]+

4-Bromo-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (97): Yield 62%; mp 145-146 oC; 1H NMR (300 MHz, CDCl3) δ: 1.93 (s, 3H, CH3), 4.23 (brs, 1H, NH), 4.38 (d, J = 5.1 Hz, 2H, CH2NH), 4.76 (s, 4H, NCH2CH2N), 6.49 (d, J = 8.8 Hz, 2H, ArH), 7.12 (s, 1H), 7.25 (dd, J = 8, 1.4 Hz, 2H, ArH), 7.97 (s, 1H); ESI-MS (m/z): 406.13 [M + H]+, 408.17 [M + 2]+.

2-Methyl-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)

aniline (98): Yield 58%; mp 151-152 oC; IR (nujol, cm-1): 3111, 3074, 2924, 2855, 1604, 1523, 1459, 1367, 1314, 1258, 1188, 1050, 742; 1H NMR (300 MHz, DMSO-d6) δ: 1.72 (s, 3H, CH3), 2.05 (s, 3H, CH3), 4.30 (d, J = 5.7 Hz, 2H, CH2NH), 4.60-4.65 (m, 2H, NCH2), 4.75-4.76 (m, 2H, NCH2), 5.40 (t, J = 5.7 Hz, 1H, CH2NH), 6.44-6.47 (m, 2H, ArH), 6.91-6.93 (m, 2H, ArH), 7.76 (s, 1H), 7.99 (s, 1H); ESI-HRMS calcd. for C16H19N7O2: 341.1600; Found: 341.0375 [M]+.

4-Methyl-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (99): Yield 63%; IR (KBr, cm-1): 2923, 2852, 1699, 1617, 1524, 1465, 1363, 1263, 1190, 1148, 1045, 822; 1H NMR (300 MHz, DMSO-d6) δ: 1.77 (s, 3H, CH3), 2.14 (s, 3H, CH3), 4.22 (d, J = 6 Hz, 2H, CH2NH), 4.65-4.71 (m, 2H, NCH2), 4.74-4.82 (m, 2H, NCH2), 5.83 (t, J = 6 Hz, 1H, CH2NH), 6.49 (d, J = 8 Hz, 2H, ArH), 6.87 (d, J = 8 Hz, 2H, ArH), 7.82 (s, 1H), 8.04 (s, 1H); ESI-HRMS calcd. for C16H19N7O2: 341.1600; Found: 341.5826 [M]+.


144

4-Ethyl-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) aniline (100): Yield 62%; mp 92-93 oC; IR (KBr, cm-1): 3119, 3019, 2957, 2927, 2862, 1700, 1617, 1525, 1462, 1426, 1363, 1287, 1261, 1189, 1140, 1047, 867; 1H NMR (300 MHz, DMSO-d6) δ: 1.09 (t, J = 7.5 Hz, 3H, CH2CH3), 1.76 (s, 3H, CH3), 2.42 (q, J = 7.5 Hz, 2H, CH2CH3), 4.23 (s, 2H, CH2NH), 4.66 (t, J = 4 Hz, 2H, NCH2), 4.78 (t, J = 4 Hz, 2H, NCH2), 5.85 (brs, 1H, CH2NH), 6.49 (d, J = 8.4 Hz, 2H, ArH), 6.89 (d, J = 8.4 Hz, 2H, ArH), 7.82 (s, 1H), 8.02 (s, 1H); ESI-MS (m/z): 356.31 [M + H]+.

4-iso-Propyl-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (101): Yield 62%; mp 140-143 oC; IR (KBr, cm-1): 2928, 2859, 1518, 1471, 1431, 1359, 1258, 1234, 1187, 1139, 1031; 1H NMR (300 MHz, CDCl3) δ: 1.15 (d, J = 7.3 Hz, 6H, CH(CH3)2), 1.75 (s, 3H, CH3), 2.85 (septet, J = 7.3 Hz, 1H, CH(CH3)2), 4.21 (t, J = 4 Hz, 2H, CH2NH), 4.65 (t, J = 4 Hz, 2H, NCH2), 4.75 (t, J = 4 Hz, 2H, NCH2), 5.81 (brs, 1H, NH), 6.58 (d, J = 8.8 Hz, 2H, ArH), 7.01 (d, J = 8.8 Hz, 2H, ArH), 7.81 (s, 1H), 8.03 (s, 1H); ESI-MS (m/z): 370.35 [M + H]+.

2-Methoxy-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (102): Yield 60%; mp 153-154 oC; IR (KBr, cm-1): 2925, 2854, 1601, 1514, 1460, 1427, 1363, 1262, 1223, 1190, 1148, 1027, 910; 1H NMR (300 MHz, CDCl3) δ: 1.93 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 4.46 (s, 2H, CH2NH), 4.75-4.78 (m, 4H, NCH2CH2N), 4.86 (brs, 1H, NH), 6.53-6.59 (m, 1H, ArH), 6.68-6.86 (m, 2H, ArH), 7.15-7.18 (m, 1H, ArH), 7.29 (s, 1H), 7.97 (s, 1H); ESI-MS (m/z): 358.28 [M + H]+.

2,3-Dichloro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (103): Yield 62%; mp 148-149 oC; IR (KBr, cm-1): 3363, 3108, 2857, 1584, 1529, 1502, 1460, 1424, 1366, 1321, 1261, 1221, 1189, 1151, 1181, 1041, 899; 1H NMR (300 MHz, DMSO-d6) δ: 1.74 (s, 3H, CH3), 4.42 (d, J = 5.7 Hz, 2H, CH2NH), 4.65 (t, J = 4.5 Hz, 2H, NCH2), 4.78 (t, J = 4.5 Hz, 2H, NCH2), 6.29 (t, J = 5.7 Hz, 1H,


145

CH2NH), 6.59 (d, J = 8.4 Hz, 1H, ArH), 6.79 (dd, J = 8.1, 1.2 Hz, 1H, ArH), 7.05-7.11 (m, 1H, ArH), 7.82 (s, 1H), 8.01 (s, 1H); ESI-MS (m/z): 396.18 [M + H]+, 398.17 [M + 2]+, 400.17 [M + 4]+.

2,5-Dichloro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (104): Yield 57%; mp 143-145 oC; IR (KBr, cm-1): 3306, 3129, 1599, 1517, 1458, 1426, 1363, 1287, 1264, 1190, 1136, 1041; 1H NMR (300 MHz, DMSO-d6) δ: 1.74 (s, 3H, CH3), 4.41 (d, J = 6 Hz, 2H, CH2NH), 4.65-4.68 (m, 2H, NCH2), 4.78-4.81 (m, 2H, NCH2), 6.24 (t, J = 6 Hz, 1H, CH2NH), 6.60 (dd, J = 8.4 Hz, 2.4 Hz, 1H, ArH), 6.69 (d, J = 2.4 Hz, 1H, ArH), 7.24 (d, J = 8.4 Hz, 1H, ArH), 7.86 (s, 1H), 8.01 (s, 1H); ESI-MS (m/z): 396.21 [M + H]+, 398.20 [M + 2]+, 400.21 [M + 4]+.

2,4,5-Trichloro-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (105): Yield 74%; mp 169-170 oC; 1H NMR (400 MHz, CDCl3) δ: 1.98 (s, 3H, CH3), 4.45 (d, J = 5.1 Hz, 2H, CH2NH), 4.79 (s, 4H, NCH2CH2N), 4.84 (t, J = 5.9 Hz, 1H, CH2NH), 6.71 (s, 1H, ArH), 7.18 (s, 1H), 7.35 (s, 1H, ArH), 7.98 (s, 1H); ESI-MS (m/z): 430.16 [M + H]+, 432.18 [M + 2]+, 434.19 [M + 4]+, 436.21 [M + 6]+.

2,6-Dimethyl-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (106): Yield 69%; mp 152-153 oC; IR (KBr, cm-1): 3383, 3130, 3070, 2926, 1525, 1474, 1459, 1426, 1369, 1269, 1196, 1147, 1099; 1H NMR (300 MHz, DMSO-d6) δ: 1.73 (s, 3H, CH3), 2.18 (s, 6H, 2CH3), 4.14 (s, 2H, CH2NH), 4.65 (t, J = 5.4 Hz, 2H, NCH2), 4.76-4.79 (m, 3H), 6.67-6.72 (m, 1H, ArH), 6.89 (d, J = 7.2 Hz, 2H, ArH), 7.81 (s, 1H), 8.03 (S, 1H); ESI-HRMS calcd. for C17H21N7O2: 355.1757; Found: 356.7510 [M]+.

N-Benzyl-1-(1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanamine (107): Yield 55% (sticky solid); IR (nujol, cm-1): 3379, 2924, 2855, 1525,


146

1460, 1366, 1257, 1187, 1148, 1038; 1H NMR (300 MHz, DMSO-d6) δ: 1.87 (s, 3H, CH3), 3.62 (s, 4H, CH2NHCH2), 4.71 (t, J = 4.2 Hz, 2H, NCH2), 4.81 (t, J = 4.2 Hz, 2H, NCH2), 7.21-7.26 (m, 1H, ArH), 7.30-7.32 (m, 4H, ArH), 7.85 (s, 1H), 8.04 (s, 1H); ESI-MS (m/z): 342.28 [M + H]+.

N-((1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-2-phenylethanamine (108): Yield 52%; mp 79-80 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.86 (s, 3H, CH3), 2.76 (brs, 3H), 3.86 (s, 4H, CH2NHCH2), 4.70-4.72 (m, 2H, NCH2), 4.82 (s, 2H, NCH2), 7.19-7.22 (m, 3H, ArH), 7.26-7.29 (m, 2H, ArH), 7.87 (s, 1H), 8.04 (s, 1H); ESI-HRMS calcd. for C17H21N7O2: 355.1757; Found: 355.8252 [M]+.

N-((1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)pyridine-2-amine (109): Yield 51%; mp 154-155 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.75 (s, 3H, CH3), 4.41 (d, J = 5.1 Hz, 2H, NHCH2), 4.64 (brs, 2H, NCH2), 4.75 (brs, 2H, NCH2), 6.45 (d, J = 6.9 Hz, 2H, ArH), 6.92 (brs, 1H, NH), 7.31-7.36 (m, 1H, ArH), 7.79 (s, 1H), 7.94 (s, 1H), 8.0 (s, 1H); ESI-HRMS calcd. for C14H16N8O2: 328.1396; Found: 328.2912 [M]+.

N-((1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)pyridin-3-amine (110): Yield 50%; mp 148-150 oC; 1H NMR (300 MHz, DMSO-d6) δ: 1.73 (s, 3H, CH3), 4.43 (s, 2H, NCH2), 4.65 (brs, 2H, NCH2), 4.71 (brs, 2H, NCH2), 6.43 (d, J = 7 Hz, 2H, ArH), 6.89 (brs, 1H, NH), 7.32-7.37 (m, 1H, ArH), 7.80 (s, 1H), 7.98 (s, 1H), 8.03 (s, 1H); ESI-MS (m/z): 329.41 [M + H]+.

3,5-Dimethoxy-N-((1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methyl)aniline (111): Yield 69%; mp 136-138 oC; 1H NMR (400 MHz, CDCl3) δ: 1.95 (s, 3H, CH3), 3.73 (s, 6H, 2OCH3), 4.19 (brs, 1H, NH), 4.39 (s, 2H, CH2NH), 4.76 (s, 4H,


147

NCH2CH2N), 5.80 (d, J = 2 Hz, 2H, ArH), 5.90-5.91 (m, 1H, ArH), 7.16 (s, 1H), 7.98 (s, 1H); ESI-MS (m/z): 388.29 [M + H]+.

4-((1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl) morpholine (112): Yield 58%; IR (nujol, cm-1): 3402, 3127, 3065, 2924, 2854, 1528, 1459, 1376, 1268, 1198, 1117, 1054; 1H NMR (300 MHz, DMSO-d6) δ: 1.85 (s, 3H, CH3), 2.32 (t, J = 4.2 Hz, 4H, 2NCH2), 2.50 (s, 2H, NCH2), 3.53 (t, J = 4.5 Hz, 4H, OCH2), 4.69-4.73 (m, 2H, NCH2), 4.79-4.82 (m, 2H, NCH2), 7.84 (s, 1H), 8.04 (s, 1H); ESI-MS (m/z): 322.31 [M + H]+.

{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-yl}-methanol (113): Yield 64%; mp 152-154 oC; IR (KBr, cm-1): 3341, 3127, 2924, 1525, 1457, 1430, 1371, 1268, 1197, 1147, 1012, 825; 1H NMR (300 MHz, CDCl3) δ: 2.01 (s, 3H, CH3), 2.12 (brs, 1H, OH), 4.78-4.80 (m, 6H), 7.28 (s, 1H), 8.0 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6): 12.76, 46.19, 48.54, 54.83, 123.54, 133.14, 138.30, 148.35, 151.23; HRMS calcd for: C9H12N6O3: 252.2302, Found: 253.2310 [M + H]+.

2-{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-yl}-ethanol (114): Yield 57%; mp 115-116 oC; IR (KBr, cm-1): 3325, 3127, 2924, 1530, 1463, 1428, 1365, 1265, 1192, 1152, 1052; 1H NMR (300 MHz, DMSO-d6) δ: 1.82 (s, 3H, CH3), 2.69 (t, 2H, J = 5.8 Hz, CH2CH2OH), 3.51 (brs, 1H, OH), 3.55 (q, 2H, CH2CH2OH), 4.66-4.67 (m, 2H, NCH2), 4.73-4.75 (m, 2H, NCH2), 7.72 (s, 1H), 8.02 (s, 1H); EI-MS (m/z): 267.18 [M + H]+.

4-Bromomethyl-1-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazole (115): Yield 52%; mp 108-110 oC; IR (KBr, cm-1): 3127, 2947, 1526, 1461, 1429, 1369, 1268, 1199, 1117, 1028, 1008; 1H NMR (300 MHz, DMSO-d6) δ: 1.83 (s, 3H, CH3), 3.73 (s,


148

2H, CH2Br), 4.59-4.81 (m, 4H, 2NCH2), 7.95 (s, 1H), 8.03 (s, 1H); ESI-MS (m/z): 315.10 [M + H]+, 317.11 [M + 2]+.

4-Methoxymethyl-1-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazole (116): Yield 67%; mp 116-118 oC; IR (KBr, cm-1): 3129, 2926, 1628, 1527, 1463, 1371, 1267, 1198, 1102, 1051, 953; 1H NMR (300 MHz, DMSO-d6) δ: 1.83 (s, 3H, CH3), 3.20 (s, 3H, OCH3), 4.83 (s, 2H, NCH2), 4.69-4.71 (m, 2H, NCH2), 4.80 (s, 2H, OCH2), 7.95 (s, 1H), 8.02 (s, 1H); ESI-MS (m/z): 267.20 [M + H]+.

Propionicacid-1-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-ylmethyl ester (117): Yield 58%; mp 116-118 oC; IR (KBr, cm-1): 3118, 3073, 2979, 1732, 1530, 1467, 1425, 1372, 1263, 1174, 1143; 1H NMR (300 MHz, DMSO-d6) δ: 1.02 (t, J = 6 Hz, 3H, CH2CH3), 1.83 (s, 3H, CH3), 2.32 (q, J = 6 Hz, 2H, CH2CH3), 4.68-4.72 (m, 2H, NCH2), 4.82-4.85 (m, 2H, NCH2), 5.09 (s, 2H, OCH2), 8.01 (s, 1H), 8.06 (s, 1H); ESI-MS (m/z): 309.21 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-((tetrahydro-2H-pyran-2-yloxy) methyl)-1H-1,2,3-triazole (118): Yield 60%; IR (KBr, cm-1): 3423, 2931, 2861, 1526, 1461, 1429, 1366, 1267, 1190, 1148, 1018; 1H NMR (300 MHz, DMSO-d6) δ: 1.30-1.36 (m, 2H), 1.44 (brs, 2H), 1.55-1.58 (m, 2H), 2.39 (s, 3H, CH3), 3.74-3.82 (m, 1H), 4.37-4.40 (m, 2H), 4.46-4.55 (m, 2H), 4.81-4.83 (m, 2H), 4.92-4.96 (m, 2H), 7.79 (s, 1H), 8.04 (s, 1H); ESI-MS (m/z): 337.22 [M + H]+.

1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-4-phenyl-1H-[1,2,3]triazole (119): Yield 59%; mp 178-180 oC; IR (KBr, cm-1): 3124, 1527, 1460, 1367, 1263, 1192, 1149, 1082, 825, 771; 1H NMR (300 MHz, DMSO-d6) δ: 1.92 (s, 3H, CH3), 4.77 (brs, 2H, NCH2), 4.88 (brs, 2H, NCH2), 7.31-7.36 (m, 3H, ArH), 7.75-7.77 (m, 2H, ArH), 8.06 (s, 1H), 8.43 (s, 1H); HRMS calcd for C14H14N6O2: 298.3002; found: 298.3001 [M]+.


149

2-{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-yl}-pyridine (120): Yield 58%; mp 194-196 oC; IR (KBr, cm-1): 2924, 2854, 1597, 1531, 1461, 1424, 1367, 1268, 1191, 1087, 1043, 997; 1H NMR (300 MHz, DMSO-d6): 1.89 (s, 3H, CH3), 4.76-4.78 (m, 2H, NCH2), 4.87-4.89 (m, 2H, NCH2), 7.30-7.35 (m, 1H, ArH), 7.84-7.89 (m, 1H, ArH), 7.97-8.00 (m, 1H, ArH), 8.03 (s, 1H), 8.50 (s, 1H), 8.54-8.56 (m, 1H, ArH); 13C NMR (75.5 MHz, DMSO-d6) δ: 12.90, 46.05, 48.95, 119.38, 123.09, 124.22, 133.20, 137.23, 138.40, 147.43, 149.62, 151.13; ESI-MS (m/z): 300.11 [M + H]+.

3-{1-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethyl]-1H-[1,2,3]triazol-4-yl}-pyridine (121): Yield 53%; mp 180-182 oC; IR (KBr, cm-1): 2923, 2853, 1510, 1458, 1364, 1186, 1067; 1H NMR (300 MHz, CDCl3) δ: 2.06 (s, 3H, CH3), 4.84-4.93 (m, 4H, NCH2CH2N), 7.36-7.40 (m, 1H, ArH), 7.59 (s, 1H), 8.03 (s, 1H), 8.11-8.15 (m, 1H, ArH), 8.59-8.61 (m, 1H, ArH), 8.94 (s, 1H, ArH); EI-MS (m/z): 300.11 [M + H]+.

1-(1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)cyclohexanol (122): Yield 68%; mp 15-152 oC; 1H NMR (300 MHz, DMSO-d6): 1.33-1.37 (m, 1H), 1.50-1.59 (m, 3H), 1.61-1.80 (m, 6H), 1.94 (s, 3H, CH3), 2.28 (s, 1H, OH), 4.78 (s, 4H, NCH2CH2N), 7.10 (s, 1H), 8.0 (s, 1H); ESI-MS (m/z): 321.21 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-(trimethylsilyl)-1H-1,2,3-triazole (123): Yield 60%; mp 189-191 oC; 1H NMR (300 MHz, DMSO-d6): 0.20 (s, 9H, Si(CH3)3), 1.54 (s, 3H, CH3), 4.47 (t, J = 4.2 Hz, 2H, NCH2), 4.62 (t, J = 4.5 Hz, 2H, NCH2), 7.72 (s, 1H), 7.83 (s, 1H); ESI-MS (m/z): 295.31 [M + H]+.

1-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (124): Yield 75%; mp 121-122 oC; 1H NMR (400 MHz, CDCl3) δ: 0.93 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.63 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.94 (s, 3H, CH3), 2.64 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.76 (s, 4H, NCH2CH2N), 6.91 (s, 1H), 8.0 (s,


150

1H); 13C NMR (100 MHz, CDCl3) δ: 13.30, 13.64, 22.70, 27.39, 46.68, 49.39, 121.55, 133.82, 149.11, 151.42; ESI-MS (m/z): 265.24 [M + H]+.

4-Butyl-1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (125): Yield 72%; mp 122-124 oC; 1H NMR (400 MHz, CDCl3) δ: 0.92 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.32 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.54-1.62 (m, 2H, CH2CH2CH2CH3), 1.94 (s, 3H, CH3), 2.66 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.76 (s, 4H, NCH2CH2N), 6.91 (s, 1H), 8.02 (s, 1H); ESI-MS (m/z): 279.21 [M + H]+.

Typical procedure for the synthesis of (E)-1-(2-(5-nitro-2-styryl-1H-imidazol-

1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (126) and related compounds (127-195): To a stirred solution of compound 65 (200 mg, 0.609 mmol) in DMSO (5 mL) benzaldehyde (64.6 mg, 0.609 mmol) was added. The reaction mixture was cooled to 0 oC and a solution sodium methoxide (98.7 mg, 1.829 mmol) in dry MeOH (5 mL) was added. The reaction mixture was further stirred at 40 oC for 12 h. The solid obtained was filtered and purified by column chromatography to obtain compound 126. Yield 47%; mp 179-180 oC; IR (film, cm-1): 2923, 2852, 1491, 1459, 1429, 1379, 1264, 1243, 1192, 1050; 1H NMR (400 MHz, CDCl3) δ: 4.87 (t, J = 5.1 Hz, 2H, NCH2), 4.97 (t, J = 5.1 Hz, 2H, NCH2), 4.99 (s, 2H, OCH2), 6.18 (d, J = 15.4 Hz, 1H, CH=CH), 6.82 (d, J = 7.3 Hz, 2H, ArH), 6.92-6.96 (m, 1H, ArH), 7.21-7.25 (m, 2H, ArH), 7.36-7.42 (m, 4H, ArH), 7.46-7.48 (m, 2H, ArH), 7.75 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 417.32 [M + H]+.

(E)-1-(2-(2-(4-Methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (127): Yield 53%; mp 214-215 oC; IR (film, cm-1): 3111, 3077, 2917, 2850, 1725, 1626, 1601, 1528, 1515, 1496, 1450, 1435, 1406, 1382, 1365, 1301, 1265, 1245, 1195, 1213, 1173, 1078, 1042; 1H NMR (400 MHz, CDCl3) δ: 2.36 (s, 3H, CH3), 4.85 (t, J = 5.2 Hz, 2H, NCH2), 4.95 (t, J = 5.2 Hz, 2H, NCH2), 4.98 (s, 2H, OCH2), 6.12 (d, J =


151

16.1 Hz, 1H, CH=CH), 6.82 (d, J = 8.0 Hz, 2H, ArH), 6.92-6.96 (m, 1H, ArH), 7.18-7.22 (m, 2H, ArH), 7.23 (d, J = 1.5 Hz, 1H, ArH), 7.25 (s, 1H, ArH), 7.35-7.37 (m, 3H), 7.72 (d, J = 16.1 Hz, 1H, CH=CH), 8.14 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 21.48, 45.83, 50.00, 61.54, 108.27, 114.57, 121.26, 123.65, 127.71, 129.47, 129.73, 132.01, 135.51, 140.61, 141.50, 145.26, 151.19, 157.92; ESI-MS (m/z): 430.25 [M + H]+.

(E)-1-(2-(2-(4-Ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (128): Yield 62%; mp 212-213 oC; IR (film, cm-1): 3110, 2919, 2850, 1523, 1449, 1386, 1240, 1195, 1053; 1H NMR (400 MHz, CDCl3) δ: 1.23 (t, J = 8.0 Hz, 3H, CH2CH3), 2.66 (q, J = 8 Hz, 2H, CH2CH3), 4.86 (t, J = 5.8 Hz, 2H, NCH2), 4.95 (t, J = 5.8 Hz, 2H, NCH2), 4.98 (s, 2H, OCH2), 6.12 (d, J = 15.4 Hz, 1H, CH=CH), 6.82 (d, J = 8.0 Hz, 2H, ArH), 6.92-6.95 (m, 1H, ArH), 7.22 (d, J = 7.3 Hz, 4H, ArH), 7.37 (d, J = 4.4 Hz, 2H, ArH), 7.40 (s, 1H), 7.73 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 15.27, 28.79, 45.85, 50.01, 61.56, 108.34, 114.59, 121.27, 123.67, 127.82, 128.55, 129.47, 132.28, 135.51, 141.55, 145.27, 146.89, 151.20, 157.93; ESI-MS (m/z): 445.28 [M + H]+.

(E)-1-(2-(5-Nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (129): Yield 51%; mp 207-208 oC; IR (film, cm-1): 3086, 2958, 2869, 2430, 1603, 1495, 1428, 1380, 1307, 1265, 1245, 1170, 1192, 1049, 1078; 1H NMR (400 MHz, CDCl3) δ: 0.94 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.64 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.59 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.85 (t, J = 5.8 Hz, 2H, NCH2), 4.95 (t, J = 5.8 Hz, 2H, NCH2), 4.99 (s, 2H, OCH2), 6.13 (d, J = 15.4 Hz, 1H, CH=CH), 6.81-6.83 (m, 2H, ArH), 6.91-6.95 (m, 1H, ArH), 7.18-7.22 (m, 3H, ArH), 7.24 (s, 1H, ArH), 7.37 (d, J = 2.2 Hz, 2H, ArH), 7.39 (s, 1H), 7.73 (d, J = 16.1 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 459.36 [M + H]+.


152

(E)-1-(2-(2-(4-iso-Propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (130): Yield 47%; mp 208-209 oC; IR (film, cm-1): 3093, 2958, 2337, 2352, 1601, 1445, 1385, 1306, 1267, 1242, 1194, 1171, 1079, 1052, 1033, 1014, 967, 819, 750; 1H NMR (400 MHz, CDCl3) δ: 1.25 (d, J = 6.6 Hz, 6H, CH(CH3)2), 2.91 (septet, J = 6.6 Hz, 1H, CH(CH3)2), 4.86 (t, J = 5.1 Hz, 2H, NCH2), 4.95 (t, J = 5.1 Hz, 2H, NCH2), 4.99 (s, 2H, OCH2), 6.12 (d, J = 15.4 Hz, 1H, CH=CH), 6.82 (d, J =8.0 Hz, 2H, ArH), 6.91-6.95 (m, 1H, ArH), 7.21 (s, 1H, ArH), 7.22-7.24 (m, 2H, ArH), 7.27 (s, 1H, ArH), 7.38 (d, J = 5.1 Hz, 2H, ArH), 7.41 (s, 1H), 7.73 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 459.30 [M + H]+.

(E)-1-(2-(2-(4-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (131): Yield 65%; mp 189-190 oC; IR (film, cm-1): 3129, 2954, 2926, 2857, 1601, 1515, 1497, 1450, 1434, 1389, 1305, 1267, 1243, 1193, 1171, 1079, 1015, 1033, 969, 855, 818, 750, 691; 1H NMR (400 MHz, CDCl3) δ: 0.93 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.35 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.59-1.62 (m, 2H, CH2CH2CH2CH3), 2.61 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.86 (t, J = 5.9 Hz, 2H, NCH2), 4.95 (t, J = 5.9 Hz, 2H, NCH2), 4.99 (s, 2H, OCH2), 6.12 (d, J = 15.4 Hz, 1H, CH=CH), 6.82 (d, J = 8.8 Hz, 2H, ArH), 6.92-6.96 (m, 1H, ArH), 7.19 (s, 1H, ArH), 7.21 (s, 1H, ArH), 7.23 (d, J = 1.5 Hz, 1H, ArH), 7.25-7.26 (m, 1H, ArH), 7.37 (d, J = 2.2 Hz, 2H, ArH), 7.39 (s, 1H), 7.73 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.91, 22.32, 33.32, 35.56, 45.84, 50.01, 61.56, 108.31, 114.59, 121.27, 123.66, 127.75, 129.09, 129.47, 132.24, 135.51, 141.59, 145.42, 145.63, 151.22, 157.93; ESI-MS (m/z): 473.29 [M + H]+.

(E)-1-(2-(2-(4-tert-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (132): Yield 47%; mp 177-178 oC; IR (film, cm-1): 2923, 2852, 1458, 1377, 1263, 1188, 1033, 821, 753; 1H NMR (400 MHz, CDCl3) δ: 1.31 (s, 9H, C(CH3)3),


153

4.86 (t, J = 5.1 Hz, 2H, NCH2), 4.95 (t, J = 5.9 Hz, 2H, NCH2), 5.00 (s, 2H), 6.12 (d, J = 15.4 Hz, 1H, CH=CH), 6.82 (d, J = 8.0 Hz, 2H, ArH), 6.91-6.95 (m, 1H, ArH), 7.20-7.24 (m, 2H, ArH), 7.38 (s, 1H, ArH), 7.41 (s, 4H), 7.73 (d, J = 16.1 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 473.30 [M + H]+.

(E)-1-(2-(2-(4-Fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (133): Yield 44%; mp 182-183 oC; IR (film, cm-1): 2921, 2851, 1449, 1379, 1254, 1192, 1173, 1032; 1H NMR (400 MHz, CDCl3) δ: 4.87-4.88 (m, 2H, NCH2), 4.93-4.97 (m, 2H, NCH2), 5.0 (s, 2H, OCH2), 6.07 (d, J = 15.4 Hz, 1H, CH=CH), 6.81-6.84 (m, 2H, ArH), 6.90-6.96 (m, 2H, ArH), 7.08 (s, 1H), 7.22 (d, J = 8.8 Hz, 2H, ArH), 7.36 (d, J = 7.3 Hz, 1H, ArH), 7.42 (d, J = 8.8 Hz, 1H, ArH), 7.45-7.47 (m, 1H, ArH), 7.69 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 435.27 [M + H]+.

(E)-1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-

triazole (134): Yield 52%; mp 223-224 oC; IR (film, cm-1): 2921, 2851, 1516, 1458, 1377, 1263, 1181, 1059, 970; 1H NMR (400 MHz, CDCl3) δ: 4.86 (t, J = 5.8 Hz, 2H, NCH2), 4.96 (t, J = 5.8 Hz, 2H, NCH2), 4.99 (s, 2H, OCH2), 6.15 (d, J = 16.1 Hz, 1H, CH=CH), 6.82 (d, J = 7.3 Hz, 2H, ArH), 6.92-6.96 (m, 1H, ArH), 7.22 (d, J = 7.3 Hz, 2H, ArH), 7.31 (s, 1H), 7.33 (d, J = 3.7 Hz, 2H, ArH), 7.50 (s, 1H), 7.52 (d, J = 1.5 Hz, 1H, ArH), 7.65 (d, J = 15.4 Hz, 1H, CH=CH), 8.13 (s, 1H); ESI-MS (m/z): 495.18 [M + H]+, 497.17 [M + 2]+.

(E)-1-(2-(2-(4-Chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-(phenoxymethyl)-1H-1,2,3-triazole (135): Yield 51%; mp 211-212 oC; IR (film, cm-1): 3079, 2918, 2850, 1450, 1383, 1271, 1243, 1194, 1172, 1049; 1H NMR (400 MHz, CDCl3) δ: 4.86 (t, J = 5.8 Hz, 2H, NCH2), 4.97 (t, J = 5.1 Hz, 2H, NCH2), 4.99 (s, 2H, OCH2), 6.12 (d, J = 15.4 Hz, 1H, CH=CH), 6.82 (d, J = 8 Hz, 2H, ArH), 6.94 (t, J = 7.3 Hz, 1H), 7.22 (d, J = 7.3 Hz, 2H,


154

ArH), 7.35 (d, J = 5.8 Hz, 3H, ArH), 7.39 (d, J = 8 Hz, 2H, ArH), 7.67 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 451.23 [M + H]+, 453.24 [M + 2]+.

(E)-1-(2-(5-Nitro-2-styryl-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (136): Yield 63%; mp 230-231 oC; IR (film, cm-1): 2922, 1440, 1380, 1261, 1187; 1H NMR (400 MHz, CDCl3) δ: 4.91 (t, J = 5.1 Hz, 2H, NCH2), 4.99 (t, J = 5.1 Hz, 2H, NCH2), 6.20 (d, J = 15.4 Hz, 1H, CH=CH), 7.25 (s, 1H, ArH), 7.29 (s, 1H, ArH), 7.30 (s, 1H, ArH), 7.32-7.35 (m, 3H, ArH), 7.39-7.41 (m, 2H, ArH), 7.49 (s, 1H), 7.55-7.57 (m, 2H, ArH), 7.67 (d, J = 15.4 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 387.25 [M + H]+.

(E)-1-(2-(2-(4-Methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (137): Yield 51%; mp 237-238 oC; IR (film, cm-1): 3082, 1516, 1449, 1430, 1378, 1275, 1260, 1176, 1199; 1H NMR (400 MHz, DMSO-d6) δ: 2.29 (s, 3H, CH3), 4.88 (t, J = 5.8 Hz, 2H, NCH2), 5.03 (t, J = 5.8 Hz, 2H, NCH2), 6.58 (d, J = 16.1 Hz, 1H, CH=CH), 7.10 (d, J = 8 Hz, 2H, ArH), 7.24-7.62 (m, 1H, ArH), 7.28-7.32 (m, 2H), 7.41 (d, J = 8 Hz, 2H, ArH), 7.47 (d, J = 15.4 Hz, 1H, CH=CH), 7.54 (s, 1H, ArH), 7.56 (d, J = 1.5 Hz, 1H, ArH), 8.22 (s, 1H), 8.46 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 20.99, 45.20, 49.41, 110.79, 122.24, 125.13, 127.59, 127.70, 128.67, 129.20, 130.42, 132.40, 135.16, 138.48, 139.17, 146.64, 150.47; ESI-MS (m/z): 401.28 [M + H]+.

(E)-1-(2-(2-(4-Ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (138): Yield 56%; mp 230-231 oC; IR (film, cm-1): 3081, 2924, 1448, 1384, 1272, 1182; 1H NMR (400 MHz, DMSO-d6) δ: 1.15 (t, J = 7.3 Hz, 3H, CH2CH3), 2.57 (q, J = 7.3 Hz, 2H, CH2CH3), 4.88 (t, J = 5.9 Hz, 2H, NCH2), 5.02 (t, J = 5.9 Hz, 2H, NCH2), 6.56 (d, J = 15.4 Hz, 1H, CH=CH), 7.11 (d, J = 8.0 Hz, 2H, ArH), 7.21-7.25 (m, 1H, ArH), 7.27-7.31 (m, 2H, ArH), 7.41 (d, J = 8.0 Hz, 2H, ArH), 7.47 (d, J =15.4 Hz, 1H, CH=CH), 7.54 (s, 1H), 7.56 (d, J = 1.5 Hz, 1H, ArH), 8.22 (s, 1H), 8.47 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 15.38, 28.02, 45.23, 49.42, 110.84, 122.23, 125.13,


155

127.67, 127.99, 128.65, 130.42, 132.64, 135.15, 144.41, 146.65, 150.46; ESI-MS (m/z): 415.32 [M + H]+.

(E)-1-(2-(5-Nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (139): Yield 38%; mp 219-220 oC; IR (film, cm-1): 2926, 1447, 1382, 1272, 1182; 1H NMR (400 MHz, CDCl3) δ: 0.95 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.65 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.59 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.90 (t, J = 5.1 Hz, 2H, NCH2), 4.98 (t, J = 5.1 Hz, 2H, NCH2), 6.15 (d, J = 15.4 Hz, 1H, CH=CH), 7.15 (d, J = 8 Hz, 2H, ArH), 7.28-7.30 (m, 3H, ArH), 7.32 (d, J = 8 Hz, 2H, ArH), 7.48 (s, 1H), 7.55 (dd, J = 7.3, 2.2 Hz, 2H, ArH), 7.65 (d, J = 15.4 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 429.26 [M + H]+.

(E)-1-(2-(2-(4-iso-Propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (140): Yield 59%; mp 230-231 oC; IR (film, cm-1): 3084, 2957, 2924, 1438, 1383, 1273, 1184; 1H NMR (400 MHz, DMSO-d6) δ: 1.17 (d, J = 6.6 Hz, 6H, CH(CH3)2), 2.86 (septet, J = 7.3 Hz, 1H, CH(CH3)2), 4.88-4.89 (m, 2H, NCH2), 5.01-5.04 (m, 2H, NCH2), 6.53 (d, J = 15.4 Hz, 1H, CH=CH), 7.13 (d, J = 8.0 Hz, 2H, ArH), 7.23-7.25 (m, 1H, ArH), 7.27-7.30 (m, 2H, ArH), 7.41 (d, J = 8.8 Hz, 2H, ArH), 7.47 (d, J = 16.1 Hz, 1H, CH=CH), 7.54 (d, J = 1.5 Hz, 1H, ArH), 7.56 (d, J = 1.5 Hz, 1H, ArH), 8.22 (s, 1H), 8.48 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 23.64, 33.29, 45.27, 49.44, 110.84, 122.22, 125.15, 126.51, 127.69, 128.63, 130.42, 132.76, 135.14, 138.43, 146.67, 149.96, 150.46; ESI-MS (m/z): 429.26 [M + H]+.

(E)-1-(2-(2-(4-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (141): Yield 38%; mp 229-230 oC; 1H NMR (400 MHz, CDCl3) δ: 0.94 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.36 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.58-1.64 (m, 2H, CH2CH2CH2CH3), 2.62 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.90 (t, J = 5.9 Hz, 2H, NCH2), 4.98 (t, J = 5.9 Hz, 2H, NCH2), 6.15 (d, J = 15.4 Hz, 1H, CH=CH), 7.15 (d, J =


156

8.0 Hz, 2H, ArH), 7.28-7.29 (m, 2H, ArH), 7.30 (d, J = 3.7 Hz, 2H, ArH), 7.33 (s, 1H, ArH), 7.48 (s, 1H), 7.55 (d, J = 1.5 Hz, 1H, ArH), 7.56 (d, J = 2.2 Hz, 1H, ArH), 7.65 (d, J = 15.4 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 443.35 [M + H]+.

(E)-1-(2-(2-(4-tert-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (142): Yield 55%; mp 184-185 oC; 1H NMR (400 MHz, CDCl3) δ: 1.32 (s, 9H, C(CH3)3), 4.91 (t, J = 5.1 Hz, 2H, NCH2), 4.98 (t, J = 5.8 Hz, 2H, NCH2), 6.14 (d, J = 16.1 Hz, 1H, CH=CH), 7.29 (d, J = 7.3 Hz, 2H, ArH), 7.35 (dd, J = 8.8, 2.2 Hz, 4H, ArH), 7.50 (s, 1H), 7.56 (dd, J = 7.3, 2.2 Hz, 2H, ArH), 7.66 (d, J = 15.4 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 443.38 [M + H]+.

(E)-1-(2-(2-(4-Fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (143): Yield 53%; mp 181-182 oC; IR (film, cm-1): 3119, 3089, 2920, 1598, 1518, 1487, 1449, 1381, 1273, 1261, 1227, 1187, 1039; 1H NMR (400 MHz, CDCl3) δ: 4.91-4.92 (m, 2H, NCH2), 4.96-5.0 (m, 2H, NCH2), 6.05 (d, J = 15.4 Hz, 1H, CH=CH), 7.30 (d, J = 7.3 Hz, 1H, ArH), 7.34-7.37 (m, 2H, ArH), 7.42-7.45 (m, 2H, ArH), 7.48 (d, J = 8 Hz, 1H, ArH), 7.54-7.56 (m, 1H, ArH), 7.60 (d, J = 15.4 Hz, 1H, CH=CH), 7.40-7.76 (m, 2H, ArH), 8.03 (s, 1H), 8.15 (s, 1H); ESI-MS (m/z): 405.28 [M + H]+.

(E)-1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (144): Yield 64%; mp 270-271 oC; IR (film, cm-1): 3409, 3111, 3083, 2922, 1521, 1487, 1450, 1431, 1381, 1271, 1199, 1073; 1H NMR (400 MHz, DMSO-d6) δ: 4.88 (t, J = 5.1 Hz, 2H, NCH2), 5.04 (t, J = 5.8 Hz, 2H, NCH2), 6.66 (d, J = 16.1 Hz, 1H, CH=CH), 7.24-7.27 (m, 1H), 7.29-7.31 (m, 1H, ArH), 7.43 (d, J = 15.4 Hz, 1H, CH=CH),7.44 (s, 5H, ArH), 7.50-7.51 (m, 1H), 7.52-7.53 (m, 1H), 8.24 (s, 1H), 8.44 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 45.28, 49.42, 112.69, 122.22, 122.51, 125.04, 127.68, 128.63, 129.42, 130.34, 131.45, 134.34, 135.06, 136.81, 138.55, 146.63, 149.97; ESI-MS (m/z): 467.24 [M + H]+, 469.26 [M + 2]+.


157

(E)-1-(2-(2-(4-Chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole (145): Yield 38%; mp 272-273 oC; IR (film, cm-1): 3085, 2922, 2852, 1519, 1485, 1449, 1433, 1378, 1271, 1259, 1187, 1178, 1086, 1011; 1H NMR (400 MHz, DMSO-d6) δ: 4.87 (t, J = 5.8 Hz, 2H, NCH2), 5.03 (t, J = 5.1 Hz, 2H, NCH2), 6.64 (d, J = 15.4 Hz, 1H, CH=CH), 7.23-7.25 (m, 1H), 7.26 (s, 1H, ArH), 7.28-7.30 (m, 2H, ArH), 7.31 (s, 1H, ArH), 7.44 (d, J = 16.1 Hz, 1H, CH=CH), 7.49-7.50 (m, 2H), 7.52-7.53 (m, 2H), 8.22 (s, 1H), 8.44 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 45.26, 49.41, 112.22, 122.22, 125.03, 127.68, 128.52, 128.62, 129.18, 130.34, 133.70, 134.01, 135.05, 136.73, 138.54, 146.62, 149.97; ESI-MS (m/z): 421.28 [M + H]+, 423.29 [M + 2]+.

(E)-2-(1-(2-(5-Nitro-2-styryl-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)pyridine (146): Yield 62%; mp 208-209 oC; IR (film, cm-1): 3076, 2920, 2851, 1603, 1518, 1490, 1461, 1446, 1428, 1378, 1304, 1260, 1190, 1157, 1081, 1038, 996, 961, 821, 784; 1H NMR (400 MHz, CDCl3) δ: 4.93 (t, J = 5.1 Hz, 2H, NCH2), 5.00 (t, J = 5.1 Hz, 2H, NCH2), 6.20 (d, J = 15.4 Hz, 1H, CH=CH), 7.15-7.18 (m, 1H, ArH), 7.30-7.32 (m, 3H, ArH), 7.36-7.38 (m, 2H, ArH), 7.59-7.61 (m, 1H, ArH), 7.65(d, J = 15.4 Hz, 1H, CH=CH), 7.84 (d, J = 8.0 Hz, 1H, ArH), 7.94 (s, 1H, ArH), 8.16 (s, 1H), 8.49 (d, J = 3.7 Hz, 1H, ArH); ESI-MS (m/z): 388.26 [M + H]+.

(E)-2-(1-(2-(2-(4-Methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (147): Yield 58%; mp 237-238 oC; IR (film, cm-1): 3087, 2916, 2848, 1596, 1516, 1485, 1443, 1379, 1361, 1265, 1227, 1194, 1082, 1038, 996; 1H NMR (400 MHz, CDCl3) δ: 2.35 (s, 3H, CH3), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 4.99 (t, J = 5.9 Hz, 2H, NCH2), 6.17 (d, J = 15.4 Hz, 1H, CH=CH), 7.11 (d, J = 8.0 Hz, 2H, ArH), 7.15-7.18 (m, 1H), 7.28 (d, J = 8 Hz, 2H, ArH), 7.60-7.62 (m, 1H), 7.65 (s, 1H), 7.85 (d, J = 6.6 Hz, 1H, ArH), 7.94 (s, 1H), 8.15 (s, 1H), 8.49 (d, J = 3 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3) δ: 21.47, 45.88, 50.11, 108.34, 120.18, 122.96, 123.09, 127.66, 129.50, 131.99,


158

135.51, 136.72, 140.29, 141.45, 149.12, 149.30, 149.39, 151.21; ESI-MS (m/z): 402.25 [M + H]+.

(E)-2-(1-(2-(2-(4-Ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (148): Yield 58%; mp 200-201 oC; IR (film, cm-1): 2925, 1603, 1516, 1444, 1377, 1263, 1189, 1037; 1H NMR (400 MHz, CDCl3) δ: 1.24 (t, J = 7.3 Hz, 3H, CH2CH3), 2.65 (q, J = 7.3 Hz, 2H, CH2CH3), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 4.99 (t, J = 5.9 Hz, 2H, NCH2), 6.16 (d, J = 15.4 Hz, 1H, CH=CH), 7.14 (d, J = 8.0 Hz, 2H. ArH), 7.16-7.18 (m, 1H), 7.30 (d, J = 8.0 Hz, 2H, ArH), 7.59-7.65 (m, 2H), 7.84 (d, J = 8.0 Hz, 1H, ArH), 7.95 (s, 1H), 8.15 (s, 1H), 8.49 (d, J = 3.0 Hz, 1H, ArH); ESI-MS (m/z): 416.34 [M + H]+.

(E)-2-(1-(2-(5-Nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (149): Yield 43%; mp 129-130 oC; IR (film, cm-1): 2924, 2852, 1604, 1521, 1446, 1378, 1267, 1187; 1H NMR (400 MHz, CDCl3) δ: 0.95 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.64 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.58 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 4.99 (t, J = 5.9 Hz, 2H, NCH2), 6.16 (d, J = 15.4 Hz, 1H, CH=CH), 7.12 (d, J = 8.0 Hz, 2H, ArH), 7.14-7.18 (m, 1H, ArH), 7.30 (d, J = 8.0 Hz, 2H, ArH), 7.58-7.65 (m, 2H), 7.84 (d, J = 8.0 Hz, 1H, ArH), 7.94 (s, 1H), 8.15 (s, 1H), 8.49 (d, J = 5.1 Hz, 1H, ArH); ESI-MS (m/z): 430.26 [M + H]+.

(E)-2-(1-(2-(2-(4-iso-Propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (150): Yield 55%; mp 224-225 oC; IR (film, cm-1): 3081, 2922, 2851, 1603, 1446, 1379, 1270, 1190, 963,818, 784; 1H NMR (400 MHz, CDCl3) δ: 1.25 (d, J = 6.6 Hz, 6H, CH(CH3)2), 2.90 (septet, J = 7.3 Hz, 1H, CH(CH3)2), 4.92 (t, J = 4.4 Hz, 2H, NCH2), 4.99 (t, J = 4.4 Hz, 2H, NCH2), 6.15 (d, J = 15.4 Hz, 1H, CH=CH), 7.14-7.18 (m, 3H, ArH), 7.31 (d, J = 8.0 Hz, 2H, ArH), 7.58-7.65 (m, 2H, ArH), 7.83 (d, J = 8.0 Hz, 1H, ArH), 7.94 (s, 1H), 8.15 (s, 1H), 8.49 (d, J = 5.9 Hz, 1H, ArH); ESI-MS (m/z): 430.28 [M + H]+.


159

(E)-2-(1-(2-(2-(4-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (151): Yield 36%; mp 207-208 oC; IR (film, cm-1): 3079, 2923, 2852, 1604, 1521, 1446, 1378, 1303, 1269, 1203, 1037, 963, 821, 784; 1H NMR (400 MHz, CDCl3) δ: 0.95 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.36 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.53-1.63 (m, 2H, CH2CH2CH2CH3), 2.60 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 4.99 (t, J = 5.9 Hz, 2H, NCH2), 6.16 (d, J = 15.4 Hz, 1H, CH=CH), 7.12 (d, J = 8.0 Hz, 2H, ArH), 7.15-7.18 (m, 1H, ArH), 7.29 (d, J = 8.0 Hz, 2H, ArH), 7.58-7.65 (m, 2H, ArH), 7.84 (d, J = 8.0 Hz, 1H, CH=CH), 7.94 (s, 1H), 8.15 (s, 1H), 8.49 (d, J = 5.1 Hz, 1H, ArH); ESI-MS (m/z): 444.37 [M + H]+.

(E)-2-(1-(2-(2-(4-tert-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (152): Yield 47%; mp 207-208 oC; IR (film, cm-1): 2919, 2850, 1519, 1440, 1373, 1183, 978, 813, 783, 736; 1H NMR (400 MHz, CDCl3) δ: 1.32 (s, 9H, C(CH3)3), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 4.98 (t, J = 5.9 Hz, 2H, NCH2), 6.15 (d, J = 16.1 Hz, 1H, CH=CH), 7.14-7.17 (m, 1H), 7.32 (s, 4H), 7.58-7.60 (m, 1H), 7.63 (d, J = 15.4 Hz, 1H, CH=CH), 7.84 (d, J = 8.0 Hz, 1H, ArH), 7.95 (s, 1H), 8.15 (s, 1H), 8.49 (d, J = 5.1 Hz, 1H, ArH); ESI-MS (m/z): 444.35 [M + H]+.

(E)-2-(1-(2-(2-(4-Fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (153): Yield 32%; mp 188-189 oC; IR (film, cm-1): 2927, 1596, 1508, 1420, 1363, 1259, 1227, 1188, 1080, 1036; 1H NMR (400 MHz, CDCl3) δ: 4.92-4.94 (m, 2H, NCH2), 4.98-5.0 (m, 2H, NCH2), 6.06 (d, J = 15.4 Hz, 1H, CH=CH), 6.96-7.0 (m, 1H, ArH), 7.16-7.19 (m, 1H, ArH), 7.32-7.36 (m, 2H, ArH), 7.58 (d, J = 15.4 Hz, 1H, ArH), 7.62-7.65 (m, 1H, ArH), 7.83-7.87 (m, 1H, ArH), 7.91 (s, 1H), 7.94 (d, J = 4.4 Hz, 1H, ArH), 8.15 (s, 1H), 8.55-8.56 (m, 1H, ArH); ESI-MS (m/z): 406.30 [M + H]+.

(E)-2-(1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (154): Yield 40%; mp 212-213 oC; IR (film, cm-1): 3369, 3131, 3086, 1597,


160

1535, 1524, 1458, 1448, 1379, 1269, 1232, 1079; 1H NMR (400 MHz, CDCl3) δ: 4.92-4.93 (m, 2H, NCH2), 4.98-4.99 (m, 2H, NCH2), 6.11 (d, J = 15.4 Hz, 1H, CH=CH), 7.20 (d, J = 8 Hz, 3H, ArH), 7.41 (d, J = 8 Hz, 2H, ArH), 7.54 (d, J = 15.4 Hz, 1H, CH=CH), 7.62-7.66 (m, 1H, ArH), 7.82 (d, J = 8 Hz, 1H, ArH), 7.93 (s, 1H), 8.15 (s, 1H), 8.48 (d, J = 2.9 Hz, 1H, ArH); ESI-MS (m/z): 466.23 [M + H]+, 468.28 [M + 2]+.

(E)-2-(1-(2-(2-(4-Chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) pyridine (155): Yield 80%; mp 210-211 oC; 1H NMR (400 MHz, CDCl3) δ: 4.92-4.94 (m, 2H, NCH2), 4.98-4.99 (m, 2H, NCH2), 6.10 (d, J = 15.4 Hz, 1H, CH=CH), 7.17-7.20 (m, 2H, ArH), 7.29 (s, 1H), 7.56 (d, J = 15.4 Hz, 1H, CH=CH), 7.61-7.65 (m, 1H, ArH), 7.82-7.84 (m, 1H, ArH), 7.91-7.95 (m, 1H, ArH), 8.07 (s, 1H), 8.14-8.16 (m, 1H, ArH), 8.48-8.49 (m, 1H, ArH), 8.55-8.56 (m, 1H, ArH); ESI-MS (m/z): 422.25 [M + H]+, 444.28 [M + H]+.

(E)-1-(1-(2-(5-Nitro-2-styryl-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (156): Yield 46%; mp 206-207 oC; IR (film, cm-1): 3276, 2923, 2853, 1742, 1529, 1458, 1375, 1265, 1220, 1197, 1065; 1H NMR (400 MHz, CDCl3) δ: 1.16-1.19 (m, 1H), 1.35-1.40 (m, 2H), 1.49-1.52 (m, 1H), 1.54 (brs, 1H), 1.56 (brs, 2H), 1.61 (brs, 1H), 1.68-1.69 (m, 1H), 1.72-1.74 (m, 1H), 1.94 (s, 1H), 4.84 (t, J = 5.9 Hz, 2H, NCH2), 4.95 (t, J = 5.9 Hz, 2H, NCH2), 6.08 (d, J = 16.1 Hz, 1H, CH=CH), 7.12 (s, 1H), 7.35-7.48 (m, 3H, ArH), 7.45-7.47 (m, 2H, ArH), 7.73 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 409.23 [M + H]+.

(E)-1-(1-(2-(2-(4-Methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (157): Yield 39%; mp 214-216 oC; 1H NMR (400 MHz, CDCl3) δ: 1.17-1.26 (m, 1H), 1.36-1.40 (m, 2H), 1.48-1.51 (m, 1H), 1.55 (brs, 2H), 1.61 (brs, 2H), 1.68-1.69 (m, 1H), 1.72-1.75 (m, 1H), 1.91 (s, 1H), 2.37 (s, 3H, CH3), 4.83 (t, J = 5.1 Hz, 2H, NCH2), 4.94 (t, J = 5.9 Hz, 2H, NCH2), 6.03 (d, J = 15.4 Hz, 1H, CH=CH), 7.10 (s, 1H),


161

7.20 (d, J = 7.3 Hz, 2H, ArH), 7.35 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 423.29 [M + H]+.

(E)-1-(1-(2-(2-(4-Ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (158): Yield 47%; mp 204-205 oC; IR (film, cm-1): 3368, 2927, 2853, 1444, 1379, 1262, 1190, 1059; 1H NMR (400 MHz, CDCl3) δ: 1.16-1.19 (m, 2H), 1.25 (t, J = 7.3 Hz, 3H, CH2CH3), 1.35-1.39 (m, 2H), 1.49-1.52 (m, 1H), 1.54 (brs, 1H), 1.57 (brs, 2H), 1.68-1.69 (m, 1H), 1.71-1.75 (m, 1H), 1.97 (s, 1H), 2.67 (q, J = 7.3 Hz, 2H, CH2CH3), 4.83 (t, J = 5.9 Hz, 2H, NCH2), 4.94 (t, J = 5.9 Hz, 2H, NCH2), 6.02 (d, J = 15.4 Hz, 1H, CH=CH), 7.12 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H, ArH), 7.38 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 437.31 [M + H]+.

(E)-1-(1-(2-(5-Nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)

cyclohexanol (159): Yield 46%; mp 197-198 oC; IR (film, cm-1): 2930, 2856, 1624, 1458, 1379, 1263, 1192, 1037, 970, 822, 739; 1H NMR (400 MHz, CDCl3) δ: 0.94 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.16-1.22 (m, 2H), 1.36-1.38 (m, 2H), 1.50-1.54 (m, 2H), 1.59-1.62 (m, 2H), 1.64-1.68 (m, 2H), 1.71-1.74 (m, 2H), 1.89 (s, 1H), 2.61 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.83 (t, J = 5.1 Hz, 2H, NCH2), 4.94 (t, J = 5.9 Hz, 2H, NCH2), 6.02 (d, J = 16.1 Hz, 1H, CH=CH), 7.11 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H, ArH), 7.37 (d, J = 8.8 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 451.30 [M + H]+.

(E)-1-(1-(2-(2-(4-iso-Propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (160): Yield 48%; mp 204-206 oC; IR (film, cm-1): 2924, 2852, 1458, 1370, 1262, 1190, 1057, 974, 823; 1H NMR (400 MHz, CDCl3) δ: 1.15-1.18 (m, 1H), 1.26 (d, J = 7.3 Hz, 6H, CH(CH3)2), 1.34-1.39 (m, 2H), 1.48-1.51 (m, 1H), 1.53 (brs, 1H), 1.55-1.56 (m, 3H), 1.67-1.68 (m, 1H), 1.70-1.73 (m, 1H), 1.89 (s, 1H), 2.93 (septet, J = 7.3 Hz, 1H,


162

CH(CH3)2), 4.83 (t, J = 5.1 Hz, 2H, NCH2), 4.94 (t, J = 5.1 Hz, 2H, NCH2), 6.02 (d, J = 15.4 Hz, 1H, CH=CH), 7.12 (s, 1H), 7.26 (d, J = 8.0 Hz, 2H, ArH), 7.38 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 451.33 [M + H]+.

(E)-1-(1-(2-(2-(4-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (161): Yield 53%; mp 191-192 oC; IR (film, cm-1): 3293, 2924, 2852, 2368, 1527, 1459, 1376, 1265, 1191, 1057, 974, 825; 1H NMR (400 MHz, CDCl3) δ: 0.93 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.15-1.19 (m, 2H), 1.30-1.40 (m, 4H), 1.47-1.52 (m, 2H), 1.53-1.55 (m, 2H), 1.60-1.64 (m, 2H), 1.67-1.73 (m, 2H), 1.89 (s, 1H), 2.63 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.83 (t, J = 5.9 Hz, 2H, NCH2), 4.94 (t, J = 5.9 Hz, 2H, NCH2), 6.01 (d, J = 15.4 Hz, 1H, CH=CH), 7.11 (s, 1H), 7.20 (d, J = 8.0 Hz, 2H, ArH), 7.36 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 465.38 [M + H]+.

(E)-1-(1-(2-(2-(4-tert-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (162): Yield 62%; mp 206-207 oC; IR (film, cm-1): 3360, 2928, 2851, 2095, 1627, 1528, 1454, 1370, 1312, 1257, 1223, 1190, 1160, 1058, 1008, 974, 874, 824, 793; 1H NMR (400 MHz, CDCl3) δ: 1.14-1.17 (m, 1H), 1.33 (s, 9H, C(CH3)3), 1.35-1.38 (m, 2H), 1.48-1.51 (m, 1H), 1.53 (brs, 1H), 1.56 (brs, 3H), 1.66-1.67 (m, 1H), 1.70-1.73 (m, 1H), 1.89 (s, 1H), 4.83 (t, J = 5.9 Hz, 2H, NCH2), 4.94 (t, J = 5.1 Hz, 2H, NCH2), 6.02 (d, J = 15.4 Hz, 1H, CH=CH), 7.13 (s, 1H), 7.38-7.44 (m, 4H, ArH), 7.71 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 21.71, 25.09, 31.12, 34.90, 37.83, 46.04, 49.92, 69.44, 108.41, 121.00, 125.96, 127.60, 131.93, 135.49, 138.04, 141.23, 151.18, 153.79, 156.64; ESI-MS (m/z): 465.40 [M + H]+.

(E)-1-(1-(2-(2-(4-Fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (163): Yield 45%; mp 219-220 oC; IR (film, cm-1): 2928, 2857, 1602, 1436,


163

1379, 1262, 1226, 1187; 1H NMR (400 MHz, CDCl3) δ: 1.17-1.21 (m, 2H), 1.39 (s, 2H), 1.52-1.58 (m, 4H), 1.68-1.75 (m, 2H), 1.98 (s, 1H), 4.84 (t, J = 5.8 Hz, 2H, NCH2), 4.95 (t, J = 5.1 Hz, 2H, NCH2), 5.97 (d, J = 15.4 Hz, 1H, CH=CH), 6.92 (d, J = 8.8 Hz, 2H, ArH), 7.08-7.12 (m, 2H, ArH), 7.43-7.47 (m, 2H, ArH), 7.68 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 427.36 [M + H]+.

(E)-1-(1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (164): Yield 54%; mp 214-215 oC; 1H NMR (400 MHz, CDCl3) δ: 1.19-1.24 (m, 2H), 1.37-1.41 (m, 2H), 1.52-1.59 (m, 4H), 1.68-1.74 (m, 2H), 2.04 (s, 1H, OH), 4.84 (t, J = 5.1 Hz, 2H, NCH2), 4.95 (t, J = 5.1 Hz, 2H, NCH2), 6.06 (d, J = 15.4 Hz, 1H, CH=CH), 7.10 (s, 1H), 7.32 (d, J = 8.8 Hz, 2H, ArH), 7.53(d, J = 8.8 Hz, 2H, ArH), 7.65 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 487.28 [M + H]+, 489.29 [M + 2]+.

(E)-1-(1-(2-(2-(4-Chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) cyclohexanol (165): Yield 68%; mp 215-217 oC; IR (film, cm-1): 3403, 2925, 2853, 1637, 1440, 1376, 1262, 1190; 1H NMR (400 MHz, CDCl3) δ: 1.18-1.22 (m, 2H), 1.36-1.41 (m, 2H), 1.52-1.56 (m, 3H), 1.68-1.74 m, 3H), 1.97 (s, 1H, OH), 4.84 (t, J = 5.8 Hz, 2H, NCH2), 4.95 (t, J = 5.1 Hz, 2H, NCH2), 6.04 (d, J = 15.4 Hz, 1H, CH=CH), 7.10 (s, 1H), 7.36-7.41 (m, 4H, ArH), 7.66 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 443.25 [M + H]+, 445.24 [M + 2]+.

(E)-(1-(2-(5-Nitro-2-styryl-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methanol (166): Yield 56%; mp 161-162 oC; IR (film, cm-1): 2923, 2857, 1625, 1429, 1377, 1263, 1190, 1032; 1H NMR (400 MHz, DMSO-d6) δ: 4.23 (d, J = 5.8 Hz, 2H, CH2OH), 4.81 (t, J = 5.1 Hz, 2H, NCH2), 4.98 (t, J = 5.8 Hz, 2H, NCH2), 5.06 (t, J = 5.8 Hz, 1H, CH2OH), 6.60 (d, J = 16.1 Hz, 1H, CH=CH), 7.36-7.39 (m, 2H, ArH), 7.41-7.43 (m, 1H), 7.56 (d, J = 15.4 Hz, 1H, CH=CH), 7.60 (d, J = 6.6 Hz, 2H, ArH), 7.90 (s,1H), 8.22 (s, 1H);


164

13C NMR (100 MHz, DMSO-d6) δ: 45.24, 49.02, 54.83, 112.01, 123.55, 127.65, 128.75, 129.43, 134.99, 135.27, 138.22, 138.51, 148.27, 150.16; ESI-MS (m/z): 341.34 [M + H]+.

(E)-(1-(2-(2-(4-Methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (167): Yield 59%; mp 200-201 oC; 1H NMR (400 MHz, DMSO-d6) δ: 2.32 (s, 3H, CH3), 4.23 (d, J = 5.8 Hz, 2H, CH2OH), 4.80 (t, J = 5.8 Hz, 2H, NCH2), 4.96 (t, J = 5.8 Hz, 2H, NCH2), 5.06 (t, J = 5.8 Hz, 1H, CH2OH), 6.54 (d, J = 15.4 Hz, 1H, CH=CH), 7.21 (d, J = 8 Hz, 2H, ArH), 7.49 (d, J = 8 Hz, 2H, ArH), 7.52 (d, J = 16.1 Hz, 1H, CH=CH), 7.89 (s, 1H), 8.20 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 21.00, 45.18, 49.00, 54.83, 110.91, 123.51, 127.63, 129.34, 132.55, 135.05, 138.29, 138.42, 139.25, 148.24, 150.39; ESI-MS (m/z): 355.26 [M + H]+.

(E)-(1-(2-(2-(4-Ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (168): Yield 48%; mp 180-181 oC; IR (film, cm-1): 2920, 2850, 1458, 1378, 1263, 1189, 1219, 1032; 1H NMR (400 MHz, CDCl3) δ: 1.25 (t, J = 7.0 Hz, 3H, CH2CH3), 1.66 (t, J = 5.9 Hz, 1H, CH2OH), 2.68 (q, J = 7.3 Hz, 2H, CH2CH3), 4.58 (d, J = 5.9 Hz, 2H, CH2OH), 4.85 (t, J = 5.1 Hz, 2H, NCH2), 4.95 (t, J = 5.1 Hz, 2H, NCH2), 6.08 (d, J = 15.4 Hz, 1H, CH=CH), 7.23 (s, 1H), 7.26 (s, 2H, ArH), 7.39 (d, J = 8.0 Hz, 2H, ArH), 7.72 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 369.28 [M + H]+.

(E)-(1-(2-(5-Nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (169): Yield 48%; mp 189-190 oC; IR (film, cm-1): 3117, 2923, 2853, 1736, 1626, 1448, 1380, 1265, 1191, 1032, 822; 1H NMR (400 MHz, CDCl3) δ: 0.95 (t, J = 6.6 Hz, 3H, CH2CH2CH3), 1.66 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 1.72 (t, J = 5.9 Hz, 1H, CH2OH), 2.61 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.58 (d, J = 5.9 Hz, 2H, CH2OH), 4.82 (t, J = 5.1 Hz, 2H, NCH2), 4.95 (t, J = 5.1 Hz, 2H, NCH2), 6.08 (d, J = 15.4 Hz, 1H,


165

CH=CH), 7.22 (d, J = 8.0 Hz, 2H, ArH), 7.27 (s, 1H), 7.38 (d, J = 8.0 Hz, 2H, ArH), 7.72 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 383.29 [M + H]+.

(E)-(1-(2-(2-(4-iso-Propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (170): Yield 43%; mp 174-175 oC; IR (film, cm-1): 3352, 2960, 2924, 2852, 1630, 1523, 1459, 1379, 1264, 1189, 1053; 1H NMR (400 MHz, CDCl3) δ: 1.26 (d, J = 6.6 Hz, 6H, CH(CH3)2), 1.71 (t, J = 5.9 Hz, 1H, CH2OH), 2.93 (septet, J = 6.6 Hz, 1H, CH(CH3)2), 4.58 (d, J = 5.9 Hz, 2H, CH2OH), 4.85 (t, J = 5.8 Hz, 2H, NCH2), 4.95 (t, J = 5.9 Hz, 2H, NCH2), 6.09 (d, J = 16.1 Hz, 1H, CH=CH), 7.26 (s, 1H), 7.27 (s, 1H), 7.28 (s, 1H), 7.40 (d, J = 8.8 Hz, 2H, ArH), 7.72 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 383.30 [M + H]+.

(E)-(1-(2-(2-(4-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (171): Yield 45%; mp 178-180 oC; IR (film, cm-1): 2925, 1379, 1263, 1191, 772; 1H NMR (400 MHz, CDCl3) δ: 0.93 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.36 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.61-1.63 (m, 2H, CH2CH2CH2CH3), 1.74 (t, J = 5.9 Hz, 1H, CH2OH), 2.63 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.58 (d, J = 6.6 Hz, 2H, CH2OH), 4.85 (t, J = 5.9 Hz, 2H, NCH2), 4.95 (t, J = 5.9 Hz, 2H, NCH2), 6.08 (d, J = 15.4 Hz, 1H, CH=CH), 7.22 (d, J = 8.0 Hz, 2H, ArH), 7.27 (s, 1H), 7.38 (d, J = 8.0 Hz, 2H, ArH), 7.72 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 397.32 [M + H]+.

(E)-(1-(2-(2-(4-tert-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (172): Yield 52%; 1H NMR (400 MHz, CDCl3) δ: 1.33 (s, 9H, C(CH3)3), 2.02 (s, 1H, OH), 4.84 (s, 2H, CH2OH), 4.90 (t, J = 5.8 Hz, 2H, NCH2), 4.98 (t, J = 5.8 Hz, NCH2), 6.14 (d, J = 15.4 Hz, 1H, CH=CH), 7.29 (d, J = 7.3 Hz, 2H, ArH), 7.55 (dd, J = 7.3, 2.0 Hz, 2H, ArH), 7.50 (s, 1H), 7.66 (d, J = 15.4 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 397.35 [M + H]+.


166

(E)-(1-(2-(2-(4-Fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (173): Yield 57%; mp 160-162 oC; IR (film, cm-1): 2922, 2852, 1443, 1380, 1278, 1184, 970, 821, 764; 1H NMR (400 MHz, CDCl3) δ: 3.85 (s, 1H, OH), 4.58 (d, J = 3.6 Hz, 2H, CH2OH), 4.86-4.87 (m, 2H, NCH2), 4.93-4.97 (m, 2H, NCH2), 5.95 (d, J = 15.4 Hz, 1H, CH=CH), 6.93 (d, J = 8 Hz, 2H, ArH), 7.08-7.13 (m, 1H, ArH), 7.41-7.45 (m, 2H, ArH), 7.69 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 359.28 [M + H]+.

(E)-(1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (174): Yield 61%; mp 222-223 oC; IR (film, cm-1): 2921, 1623, 1420, 1027, 996; 1H NMR (400 MHz, CDCl3) δ: 1.71 (t, J = 5.9 Hz, 1H, CH2OH), 4.59 (d, J = 5.9 Hz, 2H, CH2OH), 4.85 (t, J = 5.9 Hz, 2H, NCH2), 4.96 (t, J = 5.9 Hz, 2H, NCH2), 6.12 (d, J = 15.4 Hz, 1H, CH=CH), 7.25 (s, 1H), 7.33 (d, J = 8.8 Hz, 2H, ArH), 7.54 (d, J = 8.0 Hz, 2H, ArH), 7.66 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 419.12 [M + H]+, 421.14 [M + 2]+.

(E)-(1-(2-(2-(4-Chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl) methanol (175): Yield 51%; mp 221-222 oC; IR (film, cm-1): 2919, 2850, 1433, 1380, 1264, 1226, 1189, 1091, 1007, 968, 813; 1H NMR (400 MHz, CDCl3) δ: 1.72 (t, J = 5.9 Hz, 1H, CH2OH), 4.59 (d, J = 6.6 Hz, 2H, CH2OH), 4.85 (t, J = 5.9 Hz, 2H, NCH2), 4.96 (t, J = 5.9 Hz, 2H, NCH2), 6.10 (d, J = 15.4 Hz, 1H, CH=CH), 7.25 (s, 1H), 7.39 (dd, J = 8.8 Hz, 2.9 Hz, 4H, ArH), 7.68 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 375.22 [M + H]+, 377.24 [M + 2]+.

(E)-1-(2-(5-Nitro-2-styryl-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (176): Yield 42%; mp 177-178 oC; IR (film, cm-1): 2922, 2851, 1449, 1380, 1264, 1195, 913, 742; 1H NMR (400 MHz, CDCl3) δ: 0.79 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.46 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.49 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.8 Hz, 2H,


167

NCH2), 4.93 (t, J = 5.8 Hz, 2H, NCH2), 6.08 (d, J = 16.1 Hz, 1H, CH=CH), 6.96 (s, 1H), 7.36-7.43 (m, 3H, ArH), 7.46-7.48 (m, 2H, ArH), 7.73 (d, J = 15.4 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 353.28 [M + H]+.

(E)-1-(2-(2-(4-Methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (177): Yield 45%; 1H NMR (400 MHz, DMSO-d6) δ: 0.69 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.31 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.29 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 2.32 (s, 3H, CH3), 4.77 (brs, 2H, NCH2), 4.95 (brs, 2H, NCH2), 6.51 (d, J = 16.1 Hz, 1H, CH=CH), 7.21 (d, J = 8 Hz, 2H, ArH), 7.51 (d, J = 16.1 Hz, 1H, CH=CH), 7.48-7.50 (m, 2H, ArH), 7.72 (s, 1H), 8.20 (s, 1H); ESI-MS (m/z): 367.34 [M + H]+.

(E)-1-(2-(2-(4-Ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (178): Yield 61%; mp 198-200 oC; IR (film, cm-1): 3125, 3072, 2959, 2927, 2872, 1631, 1556, 1519, 1434, 1453, 1416, 1386, 1305, 1281, 1269, 1197, 1139, 1049, 966; 1H NMR (400 MHz, CDCl3) δ: 0.80 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.25 (t, J = 7.3 Hz, 3H, CH2CH3), 1.46 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.49 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 2.67 (q, J = 7.3 Hz, 2H, CH2CH3), 4.82 (t, J = 5.9 Hz, 2H, NCH2), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 6.04 (d, J = 15.4 Hz, 1H, CH=CH), 6.97 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H, ArH), 7.38 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.58, 15.27, 22.46, 27.31, 28.78, 46.05, 49.74, 108.47, 121.86, 127.80, 128.47, 132.31, 135.44, 138.03, 141.44, 146.80, 149.04, 151.31; ESI-MS (m/z): 381.26 [M + H]+.

(E)-1-(2-(5-Nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (179): Yield 40%; mp 210-211 oC; IR (film, cm-1): 3104, 2922, 2851, 1524, 1489, 1450, 1364, 1383, 1271, 1196, 1071, 1007, 967, 811; 1H NMR (400 MHz, CDCl3) δ: 0.79 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 0.95 (t, J= 7.3 Hz, 3H, CH2CH2CH3), 1.45 (sextet, J = 7.3


168

Hz, 2H, CH2CH2CH3), 1.65 (sextet, J = 8 Hz, 2H, CH2CH2CH3), 2.48 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 2.61 (t, J = 8 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.8 Hz, 2H, NCH2), 4.92 (t, J = 5.8 Hz, 2H, NCH2), 6.04 (d, J = 15.4 Hz, 1H, CH=CH), 6.98 (s, 1H), 7.21 (d, J = 8 Hz, 2H, ArH), 7.38 (d, J = 8 Hz, 2H, ArH), 7.72 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.59, 13.75, 22.48, 24.29, 27.32, 37.91, 46.06, 49.76, 108.41, 121.87, 127.74, 129.09, 132.31, 135.48, 141.52, 145.31, 149.07, 151.34; ESI-MS (m/z): 395.36 [M + H]+.

(E)-1-(2-(2-(4-iso-Propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (180): Yield 49%; mp 187-188 oC; IR (film, cm-1): 3128, 3081, 2958, 2924, 2871, 1628, 1516, 1452, 1432, 1416, 1385, 1305, 1268, 1196, 1047, 966, 819, 738; 1H NMR (400 MHz, CDCl3) δ: 0.80 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.26 (d, J = 6.6 Hz, 6H, CH(CH3)2), 1.45 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.49 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 2.93 (septet, J = 6.6 Hz, 1H, CH(CH3)2), 4.81 (t, J = 5.9 Hz, 2H, NCH2), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 6.04 (d, J = 15.4 Hz, 1H, CH=CH), 6.97 (s, 1H), 7.26 (d, J = 8 Hz, 2H, ArH), 7.39 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.59, 22.47, 23.73, 27.33, 34.06, 46.06, 49.75, 108.52, 121.86, 127.06, 127.83, 132.46, 135.45, 138.04, 141.45, 149.06, 151.33, 151.40; ESI-MS (m/z): 395.27 [M + H]+.

(E)-1-(2-(2-(4-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (181): Yield 52%; mp 201-202 oC; IR (film, cm-1): 3117, 2955, 2925, 2853, 1449, 1383, 1266, 1195, 1049, 969, 913, 822, 743; 1H NMR (400 MHz, CDCl3) δ: 0.79 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 0.93 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.36 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.45 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 1.57-1.64 (m, 2H), 2.48 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.63 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.9 Hz, 2H, NCH2), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 6.03 (d, J = 15.4 Hz, 1H,


169

CH=CH), 6.97 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H, ArH), 7.37 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 409.34 [M + H]+.

(E)-1-(2-(2-(4-tert-Butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (182): Yield 52%; mp 214-215 oC; IR (film, cm-1): 2959, 1458, 1377, 1263, 1183, 970, 820, 739; 1H NMR (400 MHz, CDCl3) δ: 0.80 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.33 (s, 9H, C(CH3)3), 1.45 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.49 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.1 Hz, 2H, NCH2), 4.92 (t, J = 5.1 Hz, 2H, NCH2), 6.04 (d, J = 15.4 Hz, 1H, CH=CH), 6.97 (s, 1H), 7.39-7.44 (m, 4H, ArH), 7.72 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 409.38 [M + H]+.

(E)-1-(2-(2-(4-Fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (183): Yield 41%; mp 203-204 oC; IR (film, cm-1): 3110, 2920, 2851, 1746, 1631, 1601, 1524, 1512, 1450, 1384, 1368, 1304, 1265, 1249, 1231, 1196, 1174, 1051, 967; 1H NMR (400 MHz, CDCl3) δ: 0.80 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.44-1.48 (m, 2H), 2.48 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (brs, 2H, NCH2), 4.92-4.93 (m, 2H, NCH2), 5.96 (d, J = 16.1 Hz, 1H, CH=CH), 6.91-6.96 (m, 2H, ArH), 7.10 (s, 1H), 7.40-7.47 (m, 2H, ArH), 7.68 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 371.30 [M + H]+.

(E)-1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (184): Yield 49%; mp 233-234 oC; IR (film, cm-1): 2926, 1523, 1487, 1449, 1431, 1382, 1364, 1269, 1195, 1171, 1053; 1H NMR (400 MHz, CDCl3) δ: 0.80 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.45 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.48 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.1 Hz, 2H, NCH2), 4.93 (t, J = 5.1 Hz, 2H, NCH2), 6.05 (d, J = 16.1 Hz, 1H, CH=CH), 6.94 (s, 1H), 7.32 (d, J = 8.0 Hz, 2H, ArH), 7.53 (d, J = 8.0 Hz, 2H, ArH), 7.64 (d, J = 15.4 Hz, 1H, CH=CH), 8.14 (s, 1H); ESI-MS (m/z): 431.22 [M + H]+, 433.18 [M + 2]+.


170

(E)-1-(2-(2-(4-Chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-propyl-1H-1,2,3-triazole (185): Yield 47%; mp 230-231 oC; IR (film, cm-1): 3103, 2917, 2848, 1449, 1437, 1383, 1364, 1271, 1195, 1171, 1093, 1053; 1H NMR (400 MHz, CDCl3) δ: 0.80 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.45 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.48 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.1 Hz, 2H, NCH2), 4.93 (t, J = 5.1 Hz, 2H, NCH2), 6.02 (d, J = 16.1 Hz, 1H, CH=CH), 6.94 (s, 1H), 7.38 (d, J = 5.1 Hz, 4H, ArH), 7.66 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 387.32 [M + H]+, 389.30 [M + 2]+.

(E)-4-Butyl-1-(2-(5-nitro-2-styryl-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (186): Yield 49%; mp 184-186 oC; IR (film, cm-1): 3107, 2928, 2858, 1523, 1450, 1430, 1383, 1260, 1197, 1048; 1H NMR (400 MHz, CDCl3) δ: 0.75 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.40 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.50 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.82 (t, J = 5.9 Hz, 2H, NCH2), 4.93 (t, J = 5.9 Hz, 2H, NCH2), 6.06 (d, J = 16.1 Hz, 1H, CH=CH), 6.95 (s, 1H), 7.36-7.42 (m, 3H, ArH), 7.45-7.47 (m, 2H, ArH), 7.73 (d, J = 16.1 Hz, 1H, CH=CH), 8.16 (s, 1H); ESI-MS (m/z): 367.30 [M + H]+.

(E)-4-Butyl-1-(2-(2-(4-methylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (187): Yield 47%; mp 214-215 oC; IR (film, cm-1): 2926, 2371, 1449, 1384, 1266, 1194, 1048, 970, 807; 1H NMR (400 MHz, CDCl3) δ: 0.76 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.40 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.37 (s, 3H, CH3), 2.50 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.81 (t, J = 5.8 Hz, 2H, NCH2), 4.92 (t, J = 5.8 Hz, 2H, NCH2), 6.02 (d, J = 16.1 Hz, 1H, CH=CH), 6.95 (s, 1H), 7.20 (d, J = 8 Hz, 2H, ArH), 7.35 (d, J = 8 Hz, 2H, ArH), 7.70 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 381.24 [M + H]+.

(E)-4-Butyl-1-(2-(2-(4-ethylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (188): Yield 57%; mp 209-210 oC; IR (film, cm-1): 2926, 2855, 1438, 1387, 1268, 1195, 969,


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821; 1H NMR (400 MHz, CDCl3) δ: 0.75 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.25 (t, J = 7.3 Hz, 3H, CH2CH3), 1.40 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.50 (t, J = 8 Hz, 2H, CH2CH2CH2CH3), 2.67 (q, J = 7.3 Hz, 2H, CH2CH3), 4.82 (t, J = 5.1 Hz, 2H, NCH2), 4.92 (t, J = 5.8 Hz, 2H, NCH2), 6.02 (d, J = 15.4 Hz, 1H, CH=CH), 6.95 (s, 1H), 7.23 (d, J = 8 Hz, 2H, ArH), 7.38 (d, J = 8 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 395.32 [M + H]+.

(E)-4-Butyl-1-(2-(5-nitro-2-(4-propylstyryl)-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (189): Yield 58%; mp 201-202 oC; IR (film, cm-1): 3117, 3067, 2956, 2927, 2859, 1521, 1448, 1431, 1381, 1266, 1193, 1140, 1048; 1H NMR (400 MHz, CDCl3) δ: 0.75 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 0.94 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.39 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.65 (sextet, J = 7.3 Hz, 2H, CH2CH2CH3), 2.50 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.60 (t, J = 7.3 Hz, 2H, CH2CH2CH3), 4.82 (t, J = 5.5 Hz, 2H, NCH2), 4.92 (t, J = 5.9 Hz, 2H, NCH2), 6.01 (d, J = 15.6 Hz, 1H, CH=CH), 6.95 (s, 1H), 7.21 (d, J = 7.8 Hz, 2H, ArH), 7.37 (d, J = 8.2 Hz, 2H, ArH), 7.71 (d, J = 15.6 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.62, 13.76, 22.11, 24.29, 25.03, 31.35, 37.92, 46.11, 49.78, 108.34, 121.81, 127.77, 129.09, 132.28, 135.49, 138.04, 141.48, 145.32, 149.26, 151.36; ESI-MS (m/z): 409.30 [M + H]+.

(E)-4-Butyl-1-(2-(2-(4-iso-propylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (190): Yield 60%; mp 198-199 oC; IR (film, cm-1): 3120, 2958, 2923, 2854, 1625, 1515, 1433, 1417, 1385, 1305, 1268, 1193, 1175, 1141, 1049, 969, 926, 897, 820, 739; 1H NMR (400 MHz, CDCl3) δ: 0.73 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.17 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.24 (d, J = 6.8 Hz, 6H, CH(CH3)2), 1.38 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.49 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.91 (septet, J =


172

6.8 Hz, 1H, CH(CH3)2), 4.80 (t, J = 5.5 Hz, 2H, NCH2), 4.90 (t, J = 5.9 Hz, 2H, NCH2), 5.99 (d, J = 15.6 Hz, 1H, CH=CH), 6.94 (s, 1H), 7.24 (d, J = 7.8 Hz, 2H, ArH), 7.37 (d, J = 8.2 Hz, 2H, ArH), 7.70 (d, J = 15.6 Hz, 1H, CH=CH), 8.13 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.61, 22.11, 23.73, 25.02, 31.35, 34.06, 46.11, 49.77, 108.38, 121.81, 127.06, 127.86, 132.39, 135.47, 138.03, 141.41, 149.24, 151.40; ESI-MS (m/z): 409.30 [M + H]+.

(E)-4-Butyl-1-(2-(2-(4-butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (191): Yield 59%; mp 203-204 oC; IR (KBr, cm-1): 3131, 2957, 2928, 2857, 1624, 1514, 1447, 1432, 1381, 1305, 1264, 1231, 1192, 1170, 1048, 971, 820; 1H NMR (400 MHz, CDCl3) δ: 0.75 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 0.93 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.16-1.25 (m, 4H), 1.31-1.43 (m, 4H), 2.50 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.63 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.81 (t, J = 5.9 Hz, 2H, NCH2), 4.91 (t, J = 5.9 Hz, 2H, NCH2), 6.02 (d, J = 15.4 Hz, 1H, CH=CH), 6.95 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H, ArH), 7.37 (d, J = 8.0 Hz, 2H, ArH), 7.71 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.62, 13.91, 22.11, 22.30, 25.03, 31.35, 33.33, 35.56, 46.11, 49.77, 108.32, 121.81, 127.78, 129.04, 132.23, 135.49, 138.03, 141.48, 145.56, 149.25, 151.36; ESI-MS (m/z): 423.32 [M + H]+.

(E)-4-Butyl-1-(2-(2-(4-tert-butylstyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (192): Yield 34%; mp 166-167 oC; IR (film, cm-1): 3123, 2958, 2925, 2855, 1628, 1517, 1457, 1431, 1381, 1279, 1265, 1215, 1190; 1H NMR (400 MHz, CDCl3) δ: 0.74 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.33 (s, 9H, C(CH3)3), 1.40 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.51 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.82 (t, J = 5.8 Hz, 2H, NCH2), 4.92 (t, J = 5.1 Hz, 2H, NCH2), 6.01 (d, J = 15.4 Hz, 1H, CH=CH), 6.95 (s, 1H), 7.41 (dd, J = 8.8, 4.4 Hz, 4H, ArH), 7.72 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 423.30 [M + H]+.


173

(E)-4-Butyl-1-(2-(2-(4-fluorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (193): Yield 35%; mp 189-190 oC; 1H NMR (400 MHz, CDCl3) δ: 0.76 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.35-1.44 (m, 2H, CH2CH2CH2CH3), 2.50 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.82 (t, J = 5.8 Hz, 2H, NCH2), 4.89-4.94 (m, 2H, NCH2), 6.93 (d, J = 15.4 Hz, 1H, CH=CH), 6.94 (s, 1H), 7.07-7.12 (m, 2H, ArH), 7.41 (d, J = 8 Hz, 1H, ArH), 7.43-7.47 (m, 1H, ArH), 7.68 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 385.22 [M + H]+.

(E)-1-(2-(2-(4-Bromostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-butyl-1H-1,2,3-triazole (194): Yield 69%; mp 219-220 oC; IR (film, cm-1): 2918, 1914, 1519, 1488, 1450, 1384, 1271, 1196, 1174, 1074, 1048, 1008, 967, 812, 740; 1H NMR (400 MHz, CDCl3) δ: 0.76 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.38 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.50 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.82 (t, J = 5.1 Hz, 2H, NCH2), 4.93 (t, J = 5.1 Hz, 2H, NCH2), 6.02 (d, J = 16.1 Hz, 1H, CH=CH), 6.93 (s, 1H), 7.32 (d, J = 8.0 Hz, 2H, ArH), 7.53 (d, J = 8.0 Hz, 2H, ArH), 7.64 (d, J = 16.1 Hz, 1H, CH=CH), 8.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.65, 22.09, 25.01, 31.39, 46.22, 49.81, 110.11, 121.96, 124.27, 129.12, 132.19, 133.68, 135.31, 138.02, 139.77, 149.28, 150.69; ESI-MS (m/z): 445.20 [M + H]+, 447.18 [M + 2]+.

(E)-4-Butyl-1-(2-(2-(4-chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazole (195): Yield 40%; mp 214-215 oC; IR (film, cm-1): 2923, 2852, 2365, 2345, 1443, 1381, 1266, 1190, 821; 1H NMR (400 MHz, CDCl3) δ: 0.74 (t, J = 7.3 Hz, 3H, CH2CH2CH2CH3), 1.19 (sextet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 1.40 (pentet, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 2.51 (t, J = 7.3 Hz, 2H, CH2CH2CH2CH3), 4.82 (t, J = 5.8 Hz, 2H, NCH2), 4.92 (t, J = 5.8 Hz, 2H, NCH2), 6.02 (d, J = 15.4 Hz, 1H, CH=CH), 6.95 (s,


174

1H), 7.41 (dd, J = 8.8 Hz, 3.7 Hz, 4H, ArH), 7.72 (d, J = 15.4 Hz, 1H, CH=CH), 8.15 (s, 1H); ESI-MS (m/z): 401.22 [M + H]+, 403.24 [M + 2]+.

Synthesis of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanamine (196)84: To a stirred solution of 1-(2-azidoethyl)-2-methyl-5-nitro-1H-imidazole (64; 1.0 g, 5.10 mmol) in dry THF (15 mL) a solution of PPh3 (2.0 g, 7.65 mmol) in dry THF (10 mL) was added dropwise at 20 oC and stirred for 3 h (scheme 2.6). To this conc. HCl (15 mL) was added and the mixture was heated under reflux for 5 h. After completion of the reaction the solvent was removed under reduced pressure. The residue obtained was partitioned between CHCl3 and water. The aqueous layer was collected and basified with NaOH solution and extracted with CHCl3. The chloroform layer was dried over Na2SO4 and then solvent removed to get 2-(2-methyl-5-nitro-lH-imidazolyl)ethylamine (196) as a viscous brown liquid.

Typical procedure for the synthesis of 3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-2-phenylthiazolidin-4-one (197) and related compounds (198-203)85: To a solution of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanamine (196; 200 mg, 1.17 mmol) in dry THF (10 mL), benzaldehyde (135.8 mg, 1.29 mmol) was added at 0 oC and the reaction mixture was stirred for 5 min at this temperature. Then, thioglycolic acid (3 equiv) was added to it and after 5 min DCC (266.5 mg, 1.29 mmol) was added to the reaction mixture at 0 °C. The reaction mixture was stirred for an additional 1 h at room temperature. The dicyclohexylurea formed was filtered and filtrate was concentrated to dryness under reduced pressure and the residue was taken-up in ethyl acetate. The ethyl acetate layer was washed with 5% citric acid solution, brine, 5% sodium bicarbonate solution and finally with brine. The organic layer was dried over sodium sulfate and evaporated to dryness at reduced pressure. The crude product thus obtained was purified by column chromatography on silica gel using ethyl acetate-hexane as eluent to obtain


175

compound 197. Yield 21%; IR (film, cm-1): 2925, 1678, 1528, 1465, 1429, 1385, 1363, 1262, 1189, 1147; 1H NMR (400 MHz, CDCl3) δ: 2.50 (s, 3H, CH3), 3.21-3.28 (m, 1H, COCH2S), 3.68-3.75(m, 2H, NCH2), 3.83 (dd, J = 16.1, 1.5 Hz, 1H, COCH2S), 4.29-4.44 (m, 2H, NCH2), 5.38 (d, J = 1.5 Hz, 1H, CHPh), 7.24-7.25 (m, 1H, ArH), 7.35-7.38 (m, 4H, ArH), 7.88 (s, 1H); ESI-MS (m/z): 333.15 [M + H]+.

3-(2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl)-2-p-tolylthiazolidin-4-one (198): Yield 25%; IR (film, cm-1): 2923, 2853, 1688, 1464, 1364, 1262, 1189, 1076; 1H NMR (400 MHz, CDCl3) δ: 2.35 (s, 3H, CH3), 2.56 (s, 3H, CH3), 3.27-3.34 (m, 1H, COCH2S), 3.65-3.72 (m, 2H, NCH2), 3.81 (dd, J = 16.0, 1.8 Hz, 1H, COCH2S), 4.36-4.43 (m, 2H, NCH2), 5.37 (d, J = 1.4 Hz, 1H, CHPh), 7.12-7.18 (m, 4H, ArH), 7.88 (s, 1H); ESI-MS (m/z): 347.28 [M + H]+.

2-(4-Ethylphenyl)-3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)thiazolidin-4-one (199): Yield 27%; 1H NMR (400 MHz, CDCl3) δ: 1.22 (t, J = 7.3 Hz, 3H, CH2CH3), 2.53 (s, 3H, CH3), 2.64 (q, J = 7.3 Hz, 2H, CH2CH3), 3.28 (d, J = 12.0 Hz, 1H, COCH2S), 3.68 (d, J = 15.4 Hz, 2H), 3.80 (d, J = 15.4 Hz, 1H, COCH2S), 4.38 (s, 2H), 5.36 (s, 1H, CHPh), 7.16 (dd, J = 6.7 Hz, 8.0 Hz, 4H, ArH), 7.87 (s, 1H); ESI-MS (m/z): 361.23 [M + H]+.

2-(2-Bromophenyl)-3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)thiazolidin-4-one (200): Yield 30%; 1H NMR (400 MHz, CDCl3) δ: 2.54 (s, 3H, CH3), 3.25 (brs, 1H, COCH2S), 3.66-3.70 (m, 2H, NCH2), 3.81 (dd, J = 16.1, 1.5 Hz, 1H, COCH2S), 4.39 (s, 2H, NCH2), 5.41 (s, 1H, CHPh), 6.98 (d, J = 8.8 Hz, 1H, ArH), 7.02-7.08 (m, 2H, ArH), 7.32-7.37 (m, 1H, ArH), 7.92 (s, 1H); ESI-MS (m/z): 411.09 [M + H]+, 413.04 [M + 2]+.

2-(4-Bromophenyl)-3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)thiazolidin-4-one (201): Yield 24%; 1H NMR (400 MHz, CDCl3) δ: 2.51 (s, 3H, CH3), 3.18-3.25 (m, 1H,


176

COCH2S), 3.68-3.76 (m, 2H, NCH2), 3.82 (dd, J = 16.1, 1.5 Hz, 1H, COCH2S), 4.32-4.41 (m, 2H, NCH2), 5.37 (s, 1H, CHPh), 7.14 (d, J = 8.8 Hz, 2H, ArH), 7.50 (d, J = 8.8 Hz, 2H, ArH), 7.90 (s, 1H); ESI-MS (m/z): 411.10 [M + H]+, 413.12 [M + 2]+.

2-(4-Chlorophenyl)-3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)thiazolidin-4-one (202): Yield 22%; IR (film, cm-1): 2928, 1683, 1528, 1465, 1429, 1405, 1386, 1363, 1262, 1189, 1089, 1013; 1H NMR (400 MHz, CDCl3) δ: 2.48 (s, 3H, CH3), 3.15-3.23 (m, 1H, SCH2CO), 3.65-3.73 (m, 2H), 3.79 (dd, J = 15.6, 1.8 Hz, 1H, SCH2CO), 4.27-4.41 (m, 2H), 5.35 (d, J = 1.4 Hz, 1H, CHPh), 7.18 (d, J = 8.7 Hz, 2H, ArH), 7.32 (d, J = 8.7 Hz, 2H, ArH), 7.87 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 13.87, 32.31, 42.66, 42.78, 63.64, 128.56, 129.45, 133.17, 135.54, 136.84, 138.13, 150.68, 171.85; ESI-MS (m/z): 367.13 [M + H]+, 369.13 [M + 2]+.

2-(4-Fluorophenyl)-3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)thiazolidin-4-one (203): Yield 35%; IR (film, cm-1): 2924, 1681, 1528, 1509, 1465, 1429, 1406, 1363, 1262, 1224, 1189, 1157; 1H NMR (400 MHz, CDCl3) δ: 2.51 (s, 3H, CH3), 3.18-3.25 (m, 1H, COCH2S), 3.67-3.74 (m, 2H, NCH2), 3.82 (dd, J = 16.1, 1.5 Hz, 1H, COCH2S), 4.28-4.44 (m, 2H, NCH2), 5.39 (s, 1H, CHPh), 7.05-7.09 (m,2H, ArH), 7.25-7.28 (m, 2H, ArH), 7.90 (s, 1H); ESI-MS (m/z): 351.20 [M + H]+.


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