SYNTHESIS OF (2E,2'E)-1,1'-(4,6-BIS((1-BENZYL-1H-1,2,3-TRIAZOL-4- YL)METHOXY)-1,3-PHENYLENE)BIS(3-ARYLPROP-2-EN-1-ONE)S

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1 SYTHESIS F (2E,2'E)-1,1'-(4,6-BIS((1-BEZYL-1H-1,2,3-TRIAZL-4- YL)METHXY)-1,3-PHEYLEE)BIS(3-ARYLPRP-2-E-1-E)S Introduction: Bis-heterocyclic compounds are gaining increased interest in the recent past as the dimeric analogues have proven to be having better and potential biological activity than the corresponding monomer 1-3. Bis-heterocyclic compounds also show biological activities such as antimicrobial 4, antifungal 5, anti-inflammatory 6, antiviral 7, anti-hiv 8. n the other hand 1,2,3- Triazoles are an important class of heterocycles due to their wide range of applications as synthetic intermediates and in pharmaceuticals. Several 1,2,3-triazoles have been reported to exhibit anti-hiv 9, anticancer 10, antioxidant 11. 1,2,3-triazole moiety is also a part of number of drugs such as β-lactum antibiotic of Tazobactam, Carboxyamidotriazole (CAI) and Cefatrizine 12. Chalcones are widely distributed in nature and are known to have multipronged activity, they exhibit wide spectrum of biological activities, such as antibacterial, antifungal 13, antioxidant 14 and antitumor 15 activities. A number of chalcone derivatives, have also been found to inhibit several important enzymes in cellular systems, protein tyrosine kinase 16 and aldose reductase 17. Previous approaches: 1) T. Biet and. Avarvari 18 have reported the synthesis of 4,4'-(4',5'-Dimethyl-[2,2'-bi(1,3- dithiolylidene)]-4,5-diyl)bis(1-benzyl-1h-1,2,3-triazole) (3.2) by reacting 4,5-diethynyl-4',5'- dimethyl-2,2'-bi(1,3-dithiolylidene) (3.1) with benzylazide in the presence of Cp*RuCl(PPh 3 ) 2 in dry THF. Scheme-3.1: Synthesis of 4,4'-(4',5'-Dimethyl-[2,2'-bi(1,3-dithiolylidene)]-4,5-diyl)bis(1-benzyl- 1H-1,2,3-triazole) (3.2) 71

2 S S H S Benzylazide S S S Cp*RuCl(PPh 3 ) 2, S S THF,65 C (3.1) H (3.2) Bn Bn 2) L. Li et al., 19 have synthesized substituted Bis-1,2,3-triazoles (3.5) by 1,3-dipolar cycloaddition of alkylalkyne (3.3), alkylazide (3.4) in the presence of CuBr were added into ethanol solution of aet under dry air atmosphere at 0 C. Scheme-3.2: Synthesis of substituted Bis-1,2,3-triazoles (3.5) R + R 1 3 CuBr, Air (3.3) (3.4) aet,0 o C R R R 1 R 1 (3.5) 3) M. L. Ferreira et al., 20 have synthesized 2,3,4,5-Tetra--acetyl-1,6-dideoxy-1,6-bis-(4- substituted-1h-1,2,3-triazol-1-yl)-d-mannitols (3.7) by reacting (2R,3R,4R,5R)-1,6- diazidohexane-2,3,4,5-tetrayl tetraacetate (3.6) with alkyl alkyne in dichloromethane:water (1:1), CuS 4.5H 2 and sodium ascorbate. Scheme-3.3: Synthesis of 2,3,4,5-Tetra--acetyl-1,6-dideoxy-1,6-bis-(4-substituted-1H-1,2,3- triazol-1-yl)-d-mannitols (3.7) Ac Ac 3 Ac Ac 3 alkylalkyne CH 2 Cl 2 :H 2 CuS 4.5H 2 a ascorbate R Ac Ac Ac (3.6) (3.7) Ac R 72

3 4) Peng Wu et al., 21 have reported the synthesis of 1-Chloro-,-bis((1-alkyl-1H-1,2,3-triazol-4- yl)methyl)methanamines (3.9) by reacting -(chloromethyl)--(prop-2-yn-1-yl)prop-2-yn-1- amine (3.8) with alkylazide in t-butylalcohol:water (1:1) in the presence of CuS 4.5H 2 and sodium ascorbate. 73

4 Scheme-3.4: Synthesis of 1-Chloro-,-bis((1-alkyl-1H-1,2,3-triazol-4-yl)methyl)methanamines (3.9) R R 3 CuS 4.5H 2, aasc. R H 2 / t-buh (1:1) Cl (3.8) (3.9) Cl 5) J. Gonzalez et al., 22 have synthesized 3,3'-Dibenzyl-5,5'-diphenyl-3H,3'H-4,4'-bi(1,2,3- triazole) (3.12) by 1,3-dipolar cycloaddition of phenylacetylene (3.10) with benzylazide (3.11) in the presence of CuI in methanol and sodium hydroxide. Scheme-3.5: Synthesis of 3,3'-Dibenzyl-5,5'-diphenyl-3H,3'H-4,4'-bi(1,2,3-triazole) (3.12) + 3 (3.10) (3.11) CuI, MeH ah, rt. (3.12) 74

5 SECTI-A: SYTHESIS F (2E,2'E)-1,1'-(4,6-BIS((1-BEZYL-1H-1,2,3-TRIAZL-4- YL)METHXY)-1,3-PHEYLEE)BIS(3-ARYLPRP-2-E-1-E)S FRM BIS- CHALCES (Route-A) Present work: Literature survey revealed that the bis-heterocyclic compounds are found to exhibit various biological activities. Therefore we have taken up the synthesis of (2E,2'E)-1,1'-(4,6- Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-arylprop-2-en-1-one)s with a view to study their ease of formation and also to evaluate their biological activity. All these compounds were synthesized under both conventional heating and microwave irradiation methods. The reaction time and yields are compared in both the methods. Further, the increasing importance of microwave irradiation as a source of thermal energy in organic reactions and the use of microwave oven in this regard is well established in Microwave induced rganic Reaction Enhancement (MRE). It could be named as e-chemistry in view of its simplicity, easy, effectiveness, economical and eco-friendly nature. It is viewed already as an important component of Green Chemistry. Therefore, in the present investigation, it was proposed to use both conventional and microwave methods, at different levels. Microwave-assisted organic synthesis (MAS) offers new possibilities for the development of any chemical reaction that is thermally possible. Ar Ar (3.13 a-e) 75

6 Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s from bis-chalcone (route-a) involves five steps. 1) Synthesis of Benzyl azide 2) Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone 3) Synthesis of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s. 4) Synthesis of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2-en-1- one)s. 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s. 1) Synthesis of Benzyl azide (3.20) (already discussed in chapter-ii, section-a) 2) Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16) under conventional heating and microwave irradiation Conventional heating method: 4,6-Diacetyl resorcinol (3.16) is the key starting materials for the synthesis of title compounds was prepared in excellent yield by condensing resorcinol (3.14) with acetic anhydride (3.15) in the presence of anhydrous ZnCl 2. Microwave irradiation method: 4,6-Diacetyl resorcinol (3.16) was also prepared by microwave irradiation of a mixture of resorcinol (3.14) and acetic anhydride (3.15) in the presence of anhydrous ZnCl 2. Scheme-3.6: Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16). H H H 3 C H ZnCl + 2 H 3 C / MWI (3.14) (3.15) (3.16) H 76

7 3) Synthesis of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s under conventional heating and microwave irradiation methods. Conventional heating method: A mixture of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16), aromatic aldehydes (3.17 a-e) in alcoholic potassium hydroxide were stirred for 8-10 hr to afford (2E,2'E)-1,1'-(4,6- Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.18 a-e). Microwave irradiation method: A mixture of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16), aromatic aldehydes (3.17 a-e) in alcoholic potassium hydroxide were subjected to microwave irradiation at 320 watts for 5-7 min to afford (2E,2'E)-1,1'-(4,6-dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.18 a-e). Scheme-3.7: Synthesis of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3- arylprop-2-en-1-one)s (3.18 a-e). H H H H + KH, EtH Ar-CH / MWI Ar Ar (3.16) (3.17 a-e) (3.18 a-e) a b c d e Ar CH 3 H 3 C CH 3 Cl S 4) Synthesis of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2-en- 1-one)s (3.19 a-e) under conventional heating and microwave irradiation methods. 77

8 Conventional heating method: A mixture of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.18 a-e) and propargyl bromide, K 2 C 3 in acetone were refluxed for 8-10 hr to afford 1,1'-(4,6- bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanones (3.19 a-e). Microwave Irradiation method: A mixture of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.18 a-e), propargyl bromide were adsorbed on potassium carbonate and subjected to microwave irradiation at 180 watts for 5-6 min. to afford 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3- phenylene)diethanones (3.19 a-e). Scheme-3.8: Synthesis of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3- arylprop-2-en-1-one)s (3.19 a-e) Ar H H Br Ar K 2 C 3, acetone / DMF Ar / MWI (3.18 a-e) (3.19 a-e) Ar a b c d e Ar CH 3 H 3 C CH 3 Cl S 78

9 Table-1: Physical data of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3- arylprop-2-en-1-one)s (3.19 a-e). S. M. P. Compound o ( C) (2E,2'E)-1,1'-(4,6- Bis(prop-2-yn-1-yloxy)- 1 1,3-phenylene)bis(3-(ptolyl)prop-2-en-1-one) 124 (3.19 a) (2E,2'E)-1,1'-(4,6- Bis(prop-2-yn-1-yloxy)- 2 1,3-phenylene)bis(3-(3-156 methoxyphenyl)prop-2- en-1-one) (3.19 b) (2E,2'E)-1,1'-(4,6- Bis(prop-2-yn-1-yloxy)- 3 1,3-phenylene)bis(3-(4-116 methoxyphenyl)prop-2- en-1-one) (3.19 c) (2E,2'E)-1,1'-(4,6- Bis(prop-2-yn-1-yloxy)- 4 1,3-phenylene)bis(3-(2-128 chlorophenyl)prop-2-en- 1-one) (3.19 d) (2E,2'E)-1,1'-(4,6- Bis(prop-2-yn-1-yloxy)- 5 1,3-phenylene)bis(3-133 (thiophen-2-yl)prop-2-en- 1-one) (3.19 e) M.F. (M.Wt.) C 32 H 26 4 (474) C 32 H 26 6 (506) C 32 H 26 6 (506) C 30 H 22 Cl 2 4 (514) C 26 H 18 4 S 2 (458) Reaction time Yield (%) Conventional MWI (hr) Conventional MWI (min)

10 As a representative case the spectral analysis of (3.19 c) is discussed. The IR spectrum (KBr, cm -1, Fig-3.1) of (3.19 c) showed characteristic carbonyl peak at H-MR spectrum (CDCl 3, 400MHz, Fig-3.2) of (3.19 c) exhibited a singlet at δ 2.61 integrating for two protons was assigned to acetylene CH and another singlet δ 4.85 was integrating for four protons was assigned to -CH 2 protons, which indicates the formation of bis-propargylated compounds. A peak at δ 3.81 integrating for six protons was assigned to -CH 3. A multiplet in the aromatic region at δ integrating for five protons was assigned to anisyl and C 5 -H protons. Three doublets at δ , δ and δ integrating for two, four and two protons were assigned to Hα-olefinic, anisyl and Hβ-olefinic protons respectively. A singlet at δ 8.15 integrating for one proton was assigned to C 2 -H proton. In the mass spectrum (Fig-3.3) of (3.19 c) showed m/z = 507 [M+H] + (100 %). 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-e) under conventional heating and microwave irradiation methods. Conventional method using CuS 4.5H 2 & Sodium ascorbate: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2- en-1-one)s (3.19 a-e), benzyl azide (3.20), CuS 4. 5H 2 and sodium ascorbate in t-buh: H 2 (2:1, v/v) was stirred at room temperature for hr to give compound (2E,2'E)-1,1'-(4,6- bis((1-benzyl-1h-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a- e). Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2- en-1-one)s (3.19 a-e), benzyl azide (3.20), CuS 4.5H 2 and sodium ascorbate in t-buh: H 2 (2:1, v/v) was subjected to microwave irradiation at 160 watts for 8-9 min to afford 80

11 corresponding (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis (3-arylprop-2-en-1-one)s (3.13 a-e). Conventional method using CuI: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2- en-1-one)s (3.19 a-e), benzyl azide (3.20), CuI, triethylamine in DMF was stirred at room temperature for hr to give (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)- 1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-e). Microwave irradiation method using CuI: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2- en-1-one)s (3.19 a-e), benzyl azide (3.20), CuI, triethylamine in DMF was subjected to microwave irradiation at 160 watts for 7-9 min to afford corresponding (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-e). Scheme-3.9: Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-e). Ar 3 i) CuS 4.5H 2 Sodiumascorbate + t-buh : H 2 (2:1) Ar (or) Ar ii) CuI, DMF, Et 3 (3.19 a-e) (3.20) R T / MWI (313 a-e) Ar a b c d e Ar CH 3 H 3 C CH 3 Cl S 81

12 Table-2: Physical data of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)- 1,3-phenylene)bis(3-arylprop-2-en-1-one)s from bis-chalcone (3.13 a-e). Reaction time Yield (%) S. o Compound M. P. ( C) M.F. (M.Wt.) Conventional (hr) CuS 4. 5H 2 CuI MWI (min) Conventional CuS 4.5H 2 CuI CuS 4. 5H 2 CuI MWI CuS 4. 5H 2 CuI (2E,2'E)-1,1'-(4,6-Bis((1-1 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-(p-tolyl)prop- 146 C 46 H (740) en-1-one) (3.13 a) (2E,2'E)-1,1'-(4,6-Bis((1- benzyl-1h-1,2,3-triazol-4-2 yl)methoxy)-1,3- phenylene)bis(3-(3-167 C 46 H (772) methoxyphenyl)prop-2-en-1- one) (3.13 b) (2E,2'E)-1,1'-(4,6-Bis((1- benzyl-1h-1,2,3-triazol-4-3 yl)methoxy)-1,3- phenylene)bis(3-(4-171 C 46 H (772) methoxyphenyl)prop-2-en-1- one) (3.13 c) (2E,2'E)-1,1'-(4,6-Bis((1- benzyl-1h-1,2,3-triazol-4-4 yl)methoxy)-1,3- phenylene)bis(3-(2-188 C 44 H 34 Cl (780) chlorophenyl)prop-2-en-1-one) (3.13 d) (2E,2'E)-1,1'-(4,6-Bis((1-5 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-(thiophen C 40 H S 2 (724) yl)prop-2-en-1-one) (3.13 e) 82

13 All the compounds were characterized by their elemental analysis, IR, 1 H & 13 C MR and mass spectral data. As a representative case the spectral analysis of (3.13 c) is discussed. The IR spectrum (KBr, cm -1, Fig-3.4) of (3.13 c) showed characteristic carbonyl peak at 1648 and C= peak 1597 respectively. 1 H-MR spectrum (CDCl 3, 400 MHz, Fig-3.5) of (3.13 c) exhibited a singlet at δ 5.35 and 5.37 ppm were integrating for eight protons was assigned to -CH 2 and -CH 2 methylene protons respectively, which indicates the formation of bis-1,2,3-triazole. Two singlets in the aromatic region at δ 6.98 and δ 8.09 integrating for one proton each were assigned to C 5 -H and C 2 -H protons respectively. A doublet at δ integrating for four protons was assigned to anisyl protons. Another doublet at δ integrating for two protons was assigned to β- olefinic protons with coupling constant (J = 15 Hz) it indicate the olefinic bond is Trans. A singlet at 3.85 integrating for six protons was assigned to methoxy protons. ther signals in the aromatic region between δ integrating for remaining 18 protons were assigned to the aromatic ring protons. 13 C-MR (CDCl 3, 100 MHz, Fig-3.6) spectrum of (3.13 c) showed characteristic peaks at: δ (C=), (C-), (C-), 143.3, 142.7, 134.2, 130.1, 129.1, 128.7, 128.0, 124.6, 123.2, 122.9, 114.4, 98.2, 63 (CH 2 ), 55.4 (CH 3 ) and 54.2 (CH 2 ). In the mass spectrum (Fig-3.7) of (3.13 c) showed m/z = 773 [M+H] + (35 %). 83

14 SECTI-B: SYTHESIS F (2E,2'E)-1,1'-(4,6-BIS((1-BEZYL-1H-1,2,3-TRIAZL-4- YL)METHXY)-1,3-PHEYLEE)BIS(3-ARYLPRP-2-E-1-E)S FRM BIS- TRIAZLE (Route-B) Present work: In the previous section (Section-A of in this chapter) we have reported the synthesis of title compounds by using Claisen-Schmidt condensations followed by Click reactions (route-a). The route-a, suffers from longer reaction times, tedious workup and purification. Therefore alternative method for the synthesis of title compounds is imperative. The title compounds can also be synthesized by using Click reaction followed by Claisen-Schmidt condensations (route- B). Therefore we have takenup the synthesis of title compounds by route-b. Ar Ar (3.13 a-l) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s from bis-triazole (3.21 a-l) (Route-B) involves four steps. 1) Synthesis of Benzyl azide 2) Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone 3) Synthesis of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone. 4) Synthesis of 1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)diethanone 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s. 1) Synthesis of Benzyl azide (3.20) (already discussed in chapter-ii, section-a) 84

15 2) Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16) (already discussed in chapter-iii, section-a) 3) Synthesis of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21) under conventional heating and microwave irradiation methods. Conventional heating method: A mixture of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16) and propargyl bromide, K 2 C 3 in acetone were refluxed for 8 hr to afford 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3- phenylene)diethanone (3.21). Microwave Irradiation method: A mixture of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16), propargyl bromide were adsorbed on potassium carbonate and subjected to microwave irradiation at 180 watts for 6 min. to afford 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21). Scheme-3.10: Synthesis of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21). H H Br K 2 C 3, acetone / DMF / MWI (3.16) (3.21) Spectral analysis of 1,1 -(4,6-Bis(prop-2ynyloxy)-1,3-phenylene)diethanone (3.21) is discussed below. In IR spectrum (KBr, cm -1, Fig-3.8) of (3.21) the characteristic absorptions observed at 3304 ( C H), 2127 (C C) and 1674 (>C=). In the 1 H-MR spectrum (300 MHz, CDCl 3, Fig. 3.9) of (3.21) exhibited a singlet at δ 2.60 integrating for two protons was assigned to C-H group, which indicate formation of propargylation and singlet another singlet at δ 2.61 integrating for six protons was assigned to methyl group. In the aromatic region of the spectrum two singlets observed at δ 8.3 and 6.78 integrating for one proton each were assigned to H-2 and H-4 respectively. The spectrum also exhibited a singlet at δ 4.78 integrating for four protons were 85

16 assigned to two methylene protons. In the 13 C-MR spectrum (75 MHz, CDCl 3, Fig-3.10) of (3.21) the signals appeared at 196.7, 160.8, 134.4, 121.9, 97.9, 56.5 and In the Mass spectrum (Fig-3.11) of (3.21) molecular ion observed at m/z =270 (30%). 4) Synthesis of 1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)diethanone (3.22) under conventional heating and microwave irradiation methods. Conventional conditions using CuS 4.5H 2 & Sodium ascorbate method: A mixture of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21), benzyl azide (3.20), CuS 4.5H 2 and sodium ascorbate in t-buh:h 2 (2:1, v/v) was stirred at room temperature for 24 hr to give compound 1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)- 1,3-phenylene)diethanone (3.22). Microwave irradiation using CuS 4.5H 2 & Sodium ascorbate method: A mixture of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21), benzyl azide (3.20), CuS 4.5H 2 and sodium ascorbate in t-buh:h 2 (2:1, v/v) was subjected to microwave irradiation to afford corresponding 1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4- yl)methoxy)-1,3-phenylene)diethanone (3.22). Conventional conditions using CuI method: A mixture of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21), benzyl azide (3.20), CuI, triethylamine in DMF was stirred at room temperature for 24 hr to give 1,1'- (4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)diethanone (3.22). Microwave irradiation using CuI method: A mixture of 1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21), benzyl azide (3.20), CuI, triethylamine in DMF was subjected to microwave irradiation to afford corresponding 1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)diethanone (3.22). 86

17 Scheme-3.11: Synthesis of 1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)diethanone (3.22). + 3 i) CuS 4.5H 2 Sodiumascorbate t-buh : H 2 (2:1) (or) (3.21) (3.20) ii) CuI, DMF, Et 3 R T / MWI (3.22) Structures of the products were characterized by spectral analysis. As a representative case the spectral analysis of (3.22) was characterized by its spectral data, In IR spectrum (KBr, cm -1, Fig-3.12) of (3.22) the characteristic peak observed at 1581 (C=) and disappearance of C C peak confirms the formation of triazole rings. In the 1 H-MR spectrum (300 MHz, CDCl 3, Fig-3.13) of (3.22) the protons of the newly formed triazole rings appeared at δ 8.42 as singlet. The protons of two phenyl groups and H-3 appeared between δ as multiplet, integrating for 11 protons. The two singlets at 5.4 and 5.62 integrating for four protons each were assigned to two -CH 2 and -CH 2 respectively. At δ 8.02 a singlet integrating for one proton was assigned to H-6 proton. A singlet in aliphatic region at δ 2.45 integrating for six protons was assigned to methyl group. In the 13 C-MR spectrum (75 MHz, CDCl 3, Fig-3.14) of (3.22) peaks appeared as follows: δ 62.5 (-CH 2 ), 54.3(-CH 2 ), 196.9, 161.8, 134.5, 134.2, 129.1, 128.9, 128.0, 121.4, 98.2 and In the MS (Fig-3.15) of compound (3.22) peak observed at m/z 537 [M+H] + (100%). 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-l) under conventional heating and microwave irradiation methods. Conventional heating method: A mixture of 1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)diethanone (3.22), aromatic aldehydes (3.17 a-l) in alcoholic potassium hydroxide 87

18 were stirred for 8-10 hr to afford (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)- 1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-l). Microwave irradiation method: A mixture of 1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)diethanone (3.22), aromatic aldehydes (3.17 a-l) in alcoholic potassium hydroxide were subjected to microwave irradiation at 320 watts for 5-7 min to afford (2E,2'E)-1,1'-(4,6- bis((1-benzyl-1h-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a- l). Scheme-3.7: Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-l). Ar-CH KH, EtH / MWI Ar Ar (3.22) (3.17 a-l) (3.13 a-l) a b c d e f Ar CH 3 Cl S H 3 C CH 3 g h i j k l CH 3 Ar Cl CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 88

19 Table-3: Physical data of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)- 1,3-phenylene)bis(3-arylprop-2-en-1-one)s from bis-triazole (3.13 a-l) Reaction time Yield (%) S. o. Compound M.P. ( C) M.F. (M.Wt.) Conv. (hr) MWI (min) Conv. MWI (2E,2'E)-1,1'-(4,6-Bis((1-1 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-(p-tolyl)prop- 146 C 46 H (740) en-1-one) (3.13 a) (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-3-2 yl)methoxy)-1,3- phenylene)bis(3-(3-167 C 46 H (772) methoxyphenyl)prop-2-en-1- one) (3.13 b) (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4-3 yl)methoxy)-1,3- phenylene)bis(3-(4-171 C 46 H (772) methoxyphenyl)prop-2-en-1- one) (3.13 c) (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4-4 yl)methoxy)-1,3- phenylene)bis(3-(2-188 C 44H 34 Cl (780) chlorophenyl)prop-2-en-1- one) (3.13 d) 89

20 (2E,2'E)-1,1'-(4,6-bis((1-5 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-(thiophen C 40 H S 2 (724) yl)prop-2-en-1-one) (3.13 e) (2E,2'E)-1,1'-(4,6-bis((1-6 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-phenylprop- 176 C 44 H (712) en-1-one) (3.13 f) (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4-7 yl)methoxy)-1,3- phenylene)bis(3-(4-193 C 44H 34 Cl (780) chlorophenyl)prop-2-en-1- one) (3.13 g) (2E,2'E)-1,1'-(4,6-bis((1-8 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-(furan C 40 H (692) yl)prop-2-en-1-one) (3.13 h) (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4-9 yl)methoxy)-1,3- phenylene)bis(3-(2,4-136 C 48 H (832) dimethoxyphenyl)prop-2-en-1- one) (3.13 i) 10 (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3-129 C 50 H (892)

21 phenylene)bis(3-(2,4,6- trimethoxyphenyl)prop-2-en- 1-one) (3.13 j) (2E,2'E)-1,1'-(4,6-bis((1- benzyl-1h-1,2,3-triazol-4-11 yl)methoxy)-1,3- phenylene)bis(3-(4-163 C 50 H (796) isopropylphenyl)prop-2-en-1- one) (3.13 k) (2E,2'E)-1,1'-(4,6-bis((1-12 benzyl-1h-1,2,3-triazol-4- yl)methoxy)-1,3- phenylene)bis(3-(naphthalen- 156 C 52 H (812) yl)prop-2-en-1-one) (3.13 l) 91

22 All the compounds were characterized by their elemental analysis, IR, 1 H & 13 C MR and mass spectral data. As a representative case the spectral analysis of (3.13 f) is discussed. In IR (KBr, cm -1, Fig-3.16) spectrum of (3.13 f) showed characteristic peaks at 1652 and 1609, were assigend groups C= and C= respectively. 1 H-MR spectrum (CDCl 3, 400 MHz, Fig-3.17) of (3.13 f) exhibited a singlet at δ 5.34 and 5.37 were integrating for eight protons was assigned to -CH 2 and -CH 2 methylene protons respectively. Two singlets in the aromatic region at δ 7.01 and δ 8.17 integrating for one proton each were assigned to C 5 -H and C 2 -H protons respectively. A doublet at δ (J=16 Hz) integrating for two protons was assigned to β-olefinic protons it indicates the formation of Trans α,β-unsaturated carbonyl group. ther signals in the aromatic region between δ integrating for 24 protons were assigned to the aromatic ring and α- olefinic protons. 13 C-MR (CDCl 3, 100 MHz, Fig-3.18) spectrum of (3.13 f) showed characteristic peaks at: δ (C=), (C-), 143.0, 142.5, 134.9, 134.6, 134.1, 130.2, 129.1, 128.9, 128.7, 128.4, 128.0, 126.8, 123.2, 122.6, 98.1, 63.0 (-CH 2 ) and 54.2 (-CH 2 ). In the mass spectrum (Fig-3.19) of (3.13 f) showed m/z = 713 [M+H] + (100 %). 92

23 Conclusion: In Conclusion, we have successfully synthesized a new series of (2E,2'E)-1,1'-(4,6-Bis((1- benzyl-1h-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-arylprop-2-en-1-one)s in two possible synthetic routes (route-a & B). As per our observation route-b (Section-B) resulted higher yields, lesser reaction times and it is much easier to isolate & purify the products compared with route-a (Section-A). Route-B requires lesser number of precursors to synthesize the title compounds than route-a. Therefore reaction times are less and more economic. Moreover we synthesized all the compounds under conventional and microwave irradiation conditions. The microwave methodology proved to be an easier facile and environmentally benign synthesis in which the reaction time is reduced with better yields. 93

24 Experimental Section-A: Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s from bis-chalcones (route-a) involves five steps. 1) Synthesis of Benzyl azide 2) Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone 3) Synthesis of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s. 4) Synthesis of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2-en-1- one)s. 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s. 1) Synthesis of Benzyl azide (3.20) (already discussed in chapter-ii, section-a) 2) Synthesis of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16) under conventional heating and microwave irradiation methods. Conventional heating method: Resorcinol (3.14) (0.22 gm, 2 mmol) was added to a mixture of freshly fused and powdered zinc chloride (0.544 gm, 4 mmol) and acetic anhydride (3.15) (0.41 gm, 4 mmol) with stirring and the mixture was gently heated on a flame at 138 C for 15 min. The resulting red viscous mass was cooled to room temperature and stirred with dil. HCl (1:1 v/v, 80 ml) to give 1,1'-(4,6-dihydroxy-1,3-phenylene)diethanone (3.16) as orange red crystals. It was filtered, dried and recrystallized from methanol as white needles. Yield: 0.3 gm (78%), M.P. 180 o C (lit. M.P C) 23. Microwave irradiation method: A mixture of resorcinol (3.14) (0.11 gm, 1 mmol), powdered anhydrous zinc chloride (0.272 gm, 2 mmol) and acetic anhydride (3.15) (0.204 gm, 2 mmol) was taken into quartz tube and 94

25 inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation at 160 watts for 3 min with an every 30 sec intervals. The resulting red viscous mass was cooled to room temperature and stirred with dil. HCl (1:1 v/v, 80 ml) to give 1,1'-(4,6-dihydroxy-1,3- phenylene)diethanone (3.16) as orange red crystals. It was filtered, dried and recrystallized from methanol as white needles. Yield: 1.75 gm (90%), M.P. 180 C (lit. M.P C) 23 3) Synthesis of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-arylprop-2-en-1-one)s (3.18 a-e). Synthesis of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-(4-methoxyphenyl) prop-2-en-1-one) (3.18 c) under conventional heating and microwave irradiation methods. Conventional heating method: To an alcoholic solution of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16) (0.194 gm, 1 mmol), 4-methoxy benzaldehyde (3.17 c) (0.14 gm, 1 mmol) and KH (0.224 gm, 4 mmol) was taken in to a round bottomed flask and stirred at room temperature for 8 hr. After completion of the reaction as indicated by the TLC, the reaction mixture was neutralized with dil. HCl. The crude product obtained was filtered, dried and recrystallized from chloroform to afford (2E,2'E)-1,1'-(4,6-dihydroxy-1,3-phenylene)bis(3-(4-methoxyphenyl)prop-2-en-1-one) (3.18 c) as yellow crystals. Yield: gm, 85% Microwave Irradiation method: A mixture of 1,1'-(4,6-Dihydroxy-1,3-phenylene)diethanone (3.16) (0.194 gm, 1 mmol), 4- methoxy benzaldehyde (3.17 c) (0.140 gm, 1 mmol) and KH (0.224 gm, 4 mmol) in ethanol (10 ml) was taken into quartz tube and inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation for 5 min at 160 watts with 30 sec time interval. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was 95

26 neutralized with dil. HCl, solid obtained was filtered, washed with water, dried and recrystallized from chloroform to yield pure (2E,2'E)-1,1'-(4,6-dihydroxy-1,3-phenylene)bis(3-(4- methoxyphenyl)prop-2-en-1-one) (3.18 c) as yellow crystals. Yield: gm, 90% Employing the similar procedure as mentioned for (3.18 c), the remaining compounds (3.18 a, b, d & e) and compared with literature melting points. 4) Synthesis of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-arylprop-2-en- 1-one)s (3.19 a-e). (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4-methoxyphenyl) prop-2-en-1-one) (3.19 c) under conventional heating and microwave irradiation methods. Conventional heating method: A mixture of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-(4-methoxyphenyl)prop- 2-en-1-one) (3.18 c) (0.43 gm, 1 mmol) and propargyl bromide (0.29 gm, 2.5 mmol), K 2 C 3 (0.5 gm, 4 mmol) in acetone (20 ml) was taken in a round bottomed flask and refluxed for 8 hrs. Progress of the reaction was monitored by TLC. After completion of the reaction, acetone was distilled under vacuum and it was diluted with cold water and the precipitate formed was filtered, washed with water and crystallized from methanol as white powder of (2E,2'E)-1,1'-(4,6- Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4-methoxyphenyl)prop-2-en-1-one) (3.19 c). Microwave Irradiation method: A mixture of (2E,2'E)-1,1'-(4,6-Dihydroxy-1,3-phenylene)bis(3-(4-methoxyphenyl)prop- 2-en-1-one) (3.18 c) (0.43 gm, 1 mmol), propargyl bromide (0.29 gm, 2.5 mmol) and potassium carbonate (0.5 gm, 4 mmol) in DMF (5 ml) was taken into quartz tube and inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation at 180 watts for 6 min. with an interval of 30 sec. Progress of the reaction was monitored by TLC. After completion of the reaction it was diluted with cold water and the precipitate formed was filtered, washed with 96

27 water and crystallized from methanol as white powder (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)- 1,3-phenylene)bis(3-(4-methoxyphenyl)prop-2-en-1-one) (3.19 c). Employing the similar procedure as mentioned for (3.19 c), the remaining compounds (3.19 a, b, d & e) were prepared. a) Synthesis of (2E,2'E)-1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(p-tolyl)prop-2- en-1-one) (3.19 a). Conventional heating method: Yield: 80% Microwave irradiation method: Yield: 91% IR (KBr): v 2090 (C C), 1652 (C=), 1609 (C=C), 1166 (C-) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.12 (s, 1H, ArH), (d, 2H, H β ), (d, 4H, ArH), (d, 2H, H α ), (d, 4H, ArH), 6.84 (s, 1H, ArH), 4.88 (s, 4H, 2 X -CH 2 -), 2.61 (s, 2H, CH), 2.38 (s, 6H, Ar-CH 3 ); MS: m/z = 475 [M+H] +. b) Synthesis of (2E,2'E)-1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(3- methoxyphenyl)prop-2-en-1-one) (3.19 b). Conventional heating method: Yield: 82% Microwave irradiation method: Yield: 92% 97

28 IR (KBr): v 2095 (C C), 1643 (C=), 1599 (C=C), 1162 (C-) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.14 (s, 1H, ArH), (d, 2H, H β ), (d, 2H, H α ), (m, 6H, ArH), (d, 2H, ArH), 6.85 (s, 1H, ArH), 4.86 (s, 4H, 2 X -CH 2 ), 3.84 (s, 6H, 2 X - CH 3 ), 2.63 (s, 2H, CH); MS: m/z = 507 [M+H] +. c) Synthesis of (2E,2'E)-1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4- methoxyphenyl)prop-2-en-1-one) (3.19 c). Conventional heating method: Yield: 83% Microwave irradiation method: Yield: 92% IR (KBr): v 2094 (C C), 1652 (C=), 1599 (C=C), 1162 (C-) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.15 (s, 1H, ArH), (d, 2H, H β ), (d, 4H, ArH), (d, 2H, H α ), (m, 5H, ArH), 4.85 (s, 4H, 2 X -CH 2 ), 3.81 (s, 6H, 2 X -CH 3 ), 2.61 (s, 2H, CH); MS: m/z = 507 [M+H] +. d) Synthesis of (2E,2'E)-1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(2- chlorophenyl)prop-2-en-1-one) (3.19 d). Conventional heating method: Yield: 81% Microwave irradiation method: Yield: 90% IR (KBr): v 2092 (C C), 1648 (C=), 1602 (C=C), 1161 (C-) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.17 (s, 1H, ArH), (d, 2H, H β ), (d, 2H, ArH), (m, 8H, ArH), 6.79 (s, 1H, ArH), 4.91 (s, 4H, 2 X -CH 2 -), 2.62 (s, 2H, CH); MS: m/z = 515 [M+H] +. 98

29 e) Synthesis of (2E,2'E)-1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(thiophen-2- yl)prop-2-en-1-one) (3.19 e). Conventional heating method: Yield: 82% Microwave irradiation method: Yield: 93% IR (KBr): v 2097 (C C), 1644 (C=), 1599 (C=C), 1159 (C-) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.13 (s, 1H, ArH), (d, 2H, H β ), (d, 2H, ArH), (d, 2H, ArH), (d, 2H, H α ), (m, 2H, ArH), 6.82 (s, 1H, ArH), 4.89 (s, 4H, 2 X -CH 2 - ), 2.63 (s, 2H, CH); MS: m/z = 459 [M+H] +. phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-e) 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3- (4-methoxyphenyl)prop-2-en-1-one) (3.13 c) under conventional heating and microwave irradiation methods. Conventional method using CuS 4.5H 2 & Sodium ascorbate: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4- methoxyphenyl)prop-2-en-1-one) (3.19 c) (0.51 gm, 1 mmol), benzyl azide (3.20) (0.27 gm, 2 mmol), CuS 4.5H 2 (0.024 gm, 2 mmol) and sodium ascorbate (0.04 gm, 2 mmol) in 20ml of t- BuH:H 2 (2:1, v/v) was taken in a round bottomed flask. The reaction mixture was stirred at room temperature for 23 hrs. Progress of the reaction was monitored by TLC. After completion of the reaction, the solid was filtered, dried and purified by column chromatography using pet ether:ethylacetate (9:1, v/v) to yield pure (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4- yl)methoxy)-1,3-phenylene)bis(3-(4-methoxyphenyl)prop-2-en-1-one) (3.13 c). 99

30 Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4- methoxyphenyl)prop-2-en-1-one) (3.19 c) (0.51 gm, 1 mmol), benzyl azide (3.20) (0.27 gm, 2 mmol), CuS 4.5H 2 (0.024 gm, 2 mmol) and sodium ascorbate (0.04 gm, 2 mmol) in 10 ml of DMF:H 2 (1:7) was taken into quartz tube and inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation at 320 watts for 8.5 min with an 30 sec intervals. The completion of the reaction was monitored by TLC. After completion of the reaction the solid separated was filtered, dried and purified by column chromatography using pet ether: ethylacetate (9:1, v/v) to yield pure (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-(4-methoxyphenyl)prop-2-en-1-one) (3.13 c). Conventional method using CuI: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4- methoxyphenyl)prop-2-en-1-one) (3.19 c) (0.506 gm, 1 mmol), benzyl azide (3.20) (0.266 gm, 2 mmol), CuI (0.042 gm, 2 mmol), triethylamine (0.2gm, 2 mmol) in DMF (10 ml) was taken in a round bottomed flask and stirred at room temperature for 22 hr. Progress of the reaction was monitored by TLC. After completion of the reaction, the solid was filtered, dried and purified by column chromatography using pet ether:ethylacetate (9:1, v/v) to yield pure (2E,2'E)-1,1'-(4,6- bis((1-benzyl-1h-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-(4-methoxyphenyl)prop-2-en- 1-one) (3.13 c). Microwave irradiation method using CuI: A mixture of (2E,2'E)-1,1'-(4,6-Bis(prop-2-yn-1-yloxy)-1,3-phenylene)bis(3-(4- methoxyphenyl)prop-2-en-1-one) (3.19 c) (0.51 gm, 1 mmol), benzyl azide (3.20) (0.266 gm, 2 mmol), CuI (0.042 gm, 2 mmol), triethylamine (0.2 gm, 2 mmol) in DMF (5 ml) was taken into quartz tube and inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation at 320 watts for 7 min with 30 sec intervals Progress of the reaction was monitored by TLC. After completion of the reaction, the solid was filtered, dried and purified by column chromatography using pet ether:ethylacetate (9:1, v/v) to yield pure (2E,2'E)-1,1'-(4,6-100

31 bis((1-benzyl-1h-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)bis(3-(4-methoxyphenyl)prop-2-en- 1-one) (3.13 c). Employing the similar procedure as mentioned for (3.13 c), the remaining compounds (3.13 a, b, d & e) were prepared. a) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-(p-tolyl)prop-2-en-1-one) (3.13 a) Conventional method using CuS 4.5H 2 & Sodium ascorbate: Yield: 65% Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: Yield: 70% Conventional method using CuI: Yield: 75% Microwave irradiation method using CuI: Yield: 85% IR (KBr): v 1647 (C=), 1598 (C=), 1261 (Ar-), 1157 (-C) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.13 (s, 1H, ArH), (m, 4H, β-olefinic proton & ArH), (m, 16H, ArH), (d, 4H, ArH & α-olefinic proton), 7.00 (s, 1H, ArH ), 5.37 (s, 4H, -CH 2 ), 5.35 (s, 4H, -CH 2 ), 2.38 (s, 6H, CH 3 ); 13 C-MR (CDCl 3, 100 MHz): δ 190 (C=), (C-), 142.8, 140.8, 135.3, 134.4, 134.1, 132.2, 129.6, 129.1, 128.8, 128.4, 128.0, 125.8, 123.2, 122.8, 98.2, 63.0 (-CH 2 ), 54.2 (-CH 2 ) and 21.5 (CH 3 ); MS: m/z = 741 [M+H] + 100%; Anal. Calcd for C 46 H : C, 74.58, H, 5.44,, Found: C, 74.52, H, 5.40,,

32 b) Synthesis of (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-(3-methoxyphenyl)prop-2-en-1-one) (3.13 c). Conventional method using CuS 4.5H 2 & Sodium ascorbate: Yield: 66% Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: Yield: 72% Conventional method using CuI: Yield: 76% Microwave irradiation method using CuI: Yield: 86% IR (KBr): v 1651 (C=), 1604 (C=), 1259 (Ar-), 1162 (-C) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.14 (s, 1H, ArH), (d, J=15Hz, 2H, β-olefinic proton), (m, 12H, ArH), (m, 11H, ArH & α-olefinic proton), 5.37 (s, 4H, -CH 2 ), 5.35 (s, 4H, -CH 2 ), 3.83 (s, 6H, CH 3 ); 13 C-MR (CDCl 3, 100 MHz): δ (C=), (C-), (C-), 142.5, 136.4, 134.5, 134.2, 129.9, 129.0, 128.8, 128.1, 127.4, 127.0, 123.3, 122.8, 121.1, 116.3, 113.1, 98.1, 62.9 (-CH 2 ), 55.4 (-CH 3 ) and 54.2 (-CH 2 ); MS: m/z = 773 [M+H] + 100%; Anal. Calcd for C 46 H : C, 71.49, H, 5.22,, Found: C, 71.43, H, 5.25,, c) Synthesis of (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-(4-methoxyphenyl)prop-2-en-1-one) (3.13 c) Conventional method using CuS 4.5H 2 & Sodium ascorbate: Yield: 65% 102

33 Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: Yield: 71% Conventional method using CuI: Yield: 75% Microwave irradiation method using CuI: Yield: 84% IR (KBr): v 1648 (C=), 1597 (C=), 1255 (Ar-), 1159 (-C) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.09 (s, 1H, ArH), (d, J=15Hz, 2H, β-olefinic proton), (d, 4H, ArH), (m, 10H, ArH), (m, 4H, ArH & α-olefinic proton), 6.98 (s,1h, ArH), (d, 4H, ArH); 5.37 (s, 4H, -CH 2 ), 5.35 (s, 4H, CH 2 ), 3.85 (s, 6H, -CH 3 ); 13 C-MR (CDCl 3, 100 MHz): δ (C=), (C-), (C-), 143.3, 142.7, 134.2, 130.1, 129.1, 128.7, 128.0, 124.6, 123.2, 122.9, 114.4, 98.2, 63 (CH 2 ), 55.4 (-CH 3 ) and 54.2 (-CH 2 ); MS: m/z = 773 [M+H] + 35%; Anal. Calcd for C 46 H : C, 71.49, H, 5.22,, Found: C, 71.42, H, 5.26,, d) Synthesis of (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-(2-chlorophenyl)prop-2-en-1-one) (3.13 d) Conventional method using CuS 4.5H 2 & Sodium ascorbate: Yield: 64% Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: Yield: 71% Conventional method using CuI: Yield: 74% 103

34 Microwave irradiation method using CuI: Yield: 83% IR (KBr): v 1651 (C=); 1604 (C=); 1272 (Ar-); 1165 (-C) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.19 (s, 1H, ArH), ( d, J=16Hz, 2H, β-olefinic proton), (m, 4H, ArH), (m, 14H, ArH), (m, 4H, ArH & α-olefinic proton), 7.04 (s, 1H, ArH), 5.40 (s, 4H, -CH 2 ), 5.37 (s, 4H, -CH 2 ); 13 C-MR (CDCl 3, 100 MHz): δ (C=), (C-), 141.2, 136.1, 134.8, 134.1, 133.8, 130.1, 129.5, 129.1, 128.9, 128.0, 127.0, 123.2, 122.4, 98.1, 62.8 (-CH 2 ) and 54.3 (-CH 2 ); MS: m/z = 781 [M+H] + 100%; Anal. Calcd for C 44 H 34 Cl : C, 67.61, H, 4.38,, Found: C, 67.56, H, 4.32,, e) Synthesis of (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-(thiophen-2-yl)prop-2-en-1-one) (3.13 e) Conventional method using CuS 4.5H 2 & Sodium ascorbate: Yield: 66% Microwave irradiation method using CuS 4.5H 2 & Sodium ascorbate: Yield: 72% Conventional method using CuI: Yield: 75% Microwave irradiation method using CuI: Yield: 86% IR (KBr): v 1645 (C=), 1597 (C=), 1265 (Ar-), 1158 (-C) cm -1 ; 1 H-MR (CDCl 3, 400 MHz): δ 8.12 (s, 1H, ArH), (d, J=16Hz, 2H, β-olefinic proton), 7.59 (s, 2H, ArH), (m, 16H, ArH & α-olefinic proton), (m, 2H, ArH), 7.05 (s, 1H, ArH), 5.42 (s, 104

35 4H, -CH 2 ), 5.38 (s, 4H, -CH 2 ); 13 C-MR (CDCl 3, 100 MHz): (C=), (C-), 143.2, 140.5, 135.2, 134.5, 134.2, 131.6, 129.1, 128.8, 128.4, 128.3, 128.0, 125.7, 123.2, 122.6, 98.1, 63.0 (-CH 2 ) and 54.2 (-CH 2 ); MS: m/z = 725 [M+H] + 100%; Anal. Calcd for C 40 H S 2 : C, 66.28, H, 4.45,, 11.59, S, Found: C, 66.21, H, 4.49,, 11.55, S, Section-B: Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s involves five steps 1) Synthesis of Benzyl azide 2) Synthesis of 4,6-Diacetyl resorcinol 3) Synthesis of 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone 4) Synthesis of 1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene)diethanone 5) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s 1) Synthesis of Benzylazide (3.20) (already discussed in chapter-ii, section-a) 2) Synthesis of 4,6-Diacetyl resorcinol (3.16) (already discussed in chapter-iii, section-a) 3) Synthesis of 1,1 -(4,6-Bis(prop-2ynyloxy)-1,3-phenylene)diethanone (3.21) under conventional heating and microwave irradiation method Conventional heating method: 4,6-Diacetyl resorcinol (3.16) (1 gm, 5 mmol) was dissolved in acetone (20 ml), propargylbromide (1.3 gm, 12 mmol) and K 2 C 3 (1.5 gm) was taken into a round bottom flask and refluxed for 8 hr. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure and added 30 ml ice cold water, then extracted with EtAc and dried over anhydrous a 2 S 4. The solvent was evaporated under reduced pressure, the crude purified by column chromatography using hexane:etac (4:1) as eluent to give 1,1 -(4,6-Bis(prop-2ynyloxy)-1,3-phenylene)diethanone (3.21). Yield: 1.18 gm (88%), M.P. 112 o C 105

36 Microwave irradiation method: A mixture of 4,6-Diacetyl resorcinol (3.16) (1 gm, 5 mmol), propargyl bromide (1.3 gm, 12 mol), potassium carbonate (1.5 gm) in 5ml DMF was taken into quartz tube and inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation at 160 watts for 6 min with an 30 sec intervals. The progress of the reaction was monitored by TLC. After completion of the reaction, added 30 ml ice cold water, extracted with EtAc and dried over anhydrous a 2 S 4. Crude was purified by column chromatography using hexane:etac (4:1) as eluent to give 1,1 -(4,6-Bis(prop-2ynyloxy)-1,3-phenylene)diethanone (3.21). Yield: 1.25 gm (92%), M.P. 112 o C IR (KBr); 3304, 2169, 2127, 1674, 1592, 1359, 1233, 1199, 1011 cm -1 ; 1 H-MR (CDCl 3, 300 MHz): 8.30 (s, 1H, H-4), 6.78 (s, 1H, H-7), 4.88 (s, 4H, CH 2 ), 2.60 (s, 6H, CH 3 ), 2.61 (s, 2H, C-H ); 13 C-MR (CDCl 3,75 MHz): δ 196.7, 160.8, 134.4, 121.9, 97.9, 56.5 and 31.5; MS m/z: ) Synthesis of 1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3-phenylene) diethanone (3.22) under conventional and microwave irradiation method Conventional method using Copper (II) sulphate & Sodium ascorbate: A mixture of 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21) (0.27 gm, 1 mmol), benzyl azide (3.20) (0.27 gm, 2 mmol), CuS 4.5H 2 (0.024 gm, 2 mmol) and sodium ascorbate (0.04 gm, 2 mmol) in t-buh:h 2 (2:1,v/v) (5 ml) was taken in to a round bottomed flask and stirred at room temperature for 24 hr. Progress of the reaction monitored by TLC, after completion of the reaction, the resulting mixture was poured in to ice cold water (20 ml) and extracted with EtAc (30 ml), washed twice with saturated solution of H 4 Cl, twice with brine and dried over a 2 S 4. The organic layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluted with hexane:etac (2:1, v/v) to give compound (3.22). Yield: 0.9 gm (95%), M.P o C 106

37 Microwave irradiation method using Copper (II) sulphate & Sodium ascorbate: A mixture of 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21) (0.5 gm, 1 mmol), benzyl azide (3.20) (0.27 gm, 2 mmol), CuS 4.5H 2 (0.024 gm, 2 mmol) and sodium ascorbate (0.04 gm, 2 mmol) in t-buh: H 2 (2:1,v/v) (5 ml) was taken into quartz tube and inserted into a Teflon vial with screw capped and then it was subjected to microwave irradiation at 320 watts for 8 min. Progress of the reaction monitored by TLC, after completion of the reaction, the resulting mixture was poured in to ice cold water (20 ml) and extracted with EtAc (30 ml), washed twice with saturated solution of H 4 Cl, twice with brine and dried over a 2 S 4. The organic layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluted with hexane:etac (2:1) to give compound (3.22). Yield: 0.9 gm (95%), M.P o C Conventional method using Copper (I) iodide: A mixture of 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21) (0.5 gm, 1 mmol), benzyl azide (3.20) (0.27 gm, 2 mmol), triethylamine (0.026 gm, 2.5 mmol) and CuI (0.02 gm, 0.1 mmol) in DMF (5 ml) was stirred under room temperature for 24 hr. After completion of the reaction (monitored by TLC), the resulting mixture was poured in to ice cold water (20 ml), extracted with 30 ml EtAc, washed twice with saturated solution of H 4 Cl, twice with brine and dried over a 2 S 4. The organic layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluted with hexane:etac (2:1) to give compound (3.22). Yield: 0.9 gm (95%), M.P o C Microwave irradiation method using CuI: A mixture of 1,1'-(4,6-bis(prop-2-yn-1-yloxy)-1,3-phenylene)diethanone (3.21) (0.5 gm, 1 mmol), benzyl azide (3.20) (0.27 gm, 2 mmol), triethylamine (0.026 gm, 2.5 mmol) and CuI (0.02 gm, 0.1 mmol) in DMF (5 ml) was taken into quartz tube and inserted into a Teflon vial 107

38 with screw capped and then it was subjected to microwave irradiation at 320 watts for 6 min. Progress of the reaction was monitored by TLC. After completion of the reaction, the resulting mixture was poured in to ice cold water (20 ml), extracted with 30 ml EtAc, washed twice with saturated solution of H 4 Cl, twice with brine and dried over a 2 S 4. The organic layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluted with hexane:etac (2:1) to give compound (3.22). Yield: 0.9 gm (95%), M.P o C IR (KBr): 1664, 1581, 1496, 1434, 1356, 1287, 1190, 1052 and 992 cm -1 ; 1 H-MR (CDCl 3, 300 MHz): δ 8.42 (s, 2H, triazole protons), (m, 11H, Ar-H, H 3 ), 5.62 (s, 4H, - CH 2 -), 5.4 (s, 4H, -CH 2 ), 8.02 (s, 1H, H-6), 2.45 (6H, s, 2 X CH 3 ); 13 C-MR (CDCl 3, 75 MHz): δ 196.9, 161.8, 134.5, 134.2, 129.1, 128.9, 128.0, 121.4, 98.2, 62.5 and 31.5; MS (m/z)= 537 [M+H] + ; Anal.Calcd for C 30 H : C, 67.15; H, 5.26;, Found: C, 67.17; H, 5.24;, ) Synthesis of (2E,2'E)-1,1'-(4,6-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-arylprop-2-en-1-one)s (3.13 a-l ) Synthesis of (2E,2'E)-1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)bis(3-phenylprop-2-en-1-one) (3.13 f) under conventional and microwave irradiation method. Conventional stirring method: To a mixture of 1,1'-(4,6-bis((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-1,3- phenylene)diethanone (3.22) (0.54 gm, 1 mmol) and benzaldehyde (3.17 f) (0.212 gm, 2 mmol) in EtH (20 ml), pellets of KH (1 gm) was refluxed for 8 hr. The progress of the reaction was monitored by TLC. After completion of reaction, it was poured into crushed ice, carefully neutralized with 3 HCl and extracted with EtAc (15 ml). The organic layer was concentrated 108