Lalit D. Khillare, Umesh R. Pratap, Manisha R. Bhosle, Sambhajit. Dhumal

Supplementary File

For

Syntheses of biodynamic heterocycles: Baker’s yeast assisted cyclocondensations of organic nucleophiles and phenacyl chlorides

Lalit D. Khillare, Umesh R. Pratap, Manisha R. Bhosle, SambhajiT. Dhumal,

Mahendra B. Bhalerao, Ramrao A. Mane*

Department of Chemistry, Dr.BabasahebAmbedkarMarathwada University, Aurangabad (MS) 431 004, India,

E-mail:

Experimental

The chemicals used were of laboratory grade. Melting points of all synthesised compounds were determined in open capillary tubes and are uncorrected. 1H NMR spectra were recorded on a Bruker DRX-400 MHz NMR spectrometer and 13C NMR spectra were recorded on a Bruker DRX-75 NMR in CDCl3/DMSO-d6 using tetramethylsilane (TMS) as internal standard, and chemical shifts are in δppm. Direct analyses in real time (DART) mass spectra were recorded on a Vokudelna ES+2000. Reaction progress of each compound was checked by thin-layer chromatography (TLC) using silica gel, 60F254 aluminium sheets as adsorbent, with visualisation accomplished by iodine/ ultraviolet light. Baker’s yeast was purchased from local market.

General procedure for the synthesis of 5-phenyl-1,3,4-thiadiazol-2-amine[1](2c)

A mixture of benzoic acid (60 mmol), thiosemicarbazide (78 mmol) and POCl3 (80 mL) was heated at 1000C for 8 h. The progress of the reaction was checked by TLC. After 8h of heating reaction mixture was poured oncrushed ice, and then basified using an aqueous solution ofsodium hydroxide topH 8–9 at cool condition. The precipitate was collected by filtration andpurified by crystallisation method. The orange solid was obtained from dry ethanol. Yield 82%, M. P. 221-2230C;

General procedure for the synthesis of 4-amino-5-phenyl-4H-1, 2, 4-triazole-3-thiol[2](2e)

A mixtureof potassium hydroxide (40 mmol), methanol (100mL) and benzohydrazide (40mmol) was treated with carbon disulphide (50 mmol). This mixture was diluted with 150 mL of methanol and stirred for 6 h at room temperature. Then dry ether (200 mL) was added to the reaction mass and the precipitated solid was filtered, washed with ether, and vacuum dried. Theobtained salt potassium hydrazine (20 mmol), hydrazine hydrate (40 mmol) and 2mL of water were refluxed understirring for 2h. The colour of the reaction mixture was found to be changed i.e. white to green and homogenous solution was formed. The progress of the reaction was checked by TLC.Cool down reaction mix and add 100mLof coldwater and acidified with conc. HClto pH 5–6.The white precipitate formedwas filtered, washed with cold water and crystallized from dry ethanol.Yield 80%, M. P. 194-1960C.

General experimental procedure for synthesis of 4-substitutedphenylthiazol-2-amines (3a-f):

A mixture of substituted phenacyl chlorides (1a-f) (6 mmol), thiourea (2a) (6 mmol) and dry baker’s yeast (2g) in acetonitrile (25-30 mL) was stirred at room temperature for the specified time. The progress of the reaction was monitored by TLC using ethyl acetate: hexane (2:8) as an eluent. After the specified reaction time the reaction content was filtered through the bed of Celite to remove the yeast. Acetonitrile was removed from the filtrate by vacuum distillation. Cold water (100 mL) was added to the crude residue, and the reaction mass was neutralised by adding aqueous NaOH to make the solution alkaline (pH 8). The resulting precipitate was then filtered on Buchner funnel and washed with cold water. It was then purified by crystallization using medium dry ethanol (Scheme 1) (3a-f).

General experimental procedure for synthesis of 4-(substitutedphenyl)-2-phenylthiazoles(4a-f):

A mixture of substituted phenacyl chlorides (1a-f) (6 mmol), thiobenzamide (2b) (6 mmol) and dry baker’s yeast (2g) in acetonitrile (25-30 mL) was stirred at room temperature for the specified time. The progress of the reaction was monitored by TLC using ethyl acetate: hexane (2:8) as an eluent. After the specified reaction time the reaction content was filtered through the bed of Celite to remove the yeast. Acetonitrile was removed from the filtrate by vacuum distillation.Cold water (100 mL) was added to the crude residue.The resulting mass was neutralised and then the solid obtained was filtered and washed with cold water. It was further purified by crystallization using dry ethanol (Scheme 1) (4a-f).

General experimental procedure for synthesis of 6-(4-substitutedphenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazoles(5a-f):

A mixture of substituted phenacyl chlorides (6 mmol)(1a-f), 5-phenyl-1,3,4-thiadiazol-2-amine (2c) (6 mmol) and dry baker’s yeast (2g) in acetonitrile (25-30 mL) was stirred at room temperature for the specified time. The progress of the reaction was monitored by TLC using ethyl acetate: hexane (5:5) as an eluent. After the specified reaction time the reaction content was filtered through the bed of Celite to remove the yeast. Acetonitrile was removed from the filtrate by vacuum distillation. Cold water (100 mL) was added to the crude residue.The resulting mass was neutralised and then the solid obtained was filtered and washed with cold water. It was further purified by crystallization using dry ethanol (Scheme 1) (5a-f).

General experimental procedure for synthesis of 2-(4-substitutedphenyl)quinoxalines(6a-f):

A mixture of substituted phenacyl chlorides (1a-f) (6 mmol), o-phenylenediamine (2d) (6 mmol) and dry baker’s yeast (2g) in acetonitrile (25-30 mL) was stirred at room temperature for the specified time. The progress of the reaction was monitored by TLC using ethyl acetate: hexane (5:5) as an eluent. After the specified reaction time the reaction content was filtered through the bed of Celite to remove the yeast. Acetonitrile was removed from the filtrate by vacuum distillation. Cold water (100 mL) was added to the crude residue.The resulting mass was neutralised and then the solid obtained was filtered and washed with cold water. It was further purified by crystallization using dry ethanol (Scheme 1) (6a-f).

General experimental procedure for synthesis of 6-(substitutedphenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines (7a-f):

A mixture of substituted phenacyl chlorides (1a-f) (6 mmol), 4-amino-5-aryl-4H-1,2,4-triazole-3-thiol (2e) (6 mmol) and dry baker’s yeast (2g) in acetonitrile (25-30 mL) was stirred at room temperature for the specified time. The progress of the reaction was monitored by TLC using ethyl acetate: hexane (5:5) as an eluent. After the specified reaction time the reaction content was filtered through the bed of Celite to remove the yeast. Acetonitrile was removed from the filtrate by vacuum distillation. Cold water (100 mL) was added to the crude residue.The resulting mass was neutralised and then the solid obtained was filtered and washed with cold water. It was further purified by crystallization using dry ethanol (Scheme 1) (7a-f).

General experimental procedure for synthesis of 2-(4-substitutedphenyl)H-imidazo[1,2-a]pyridines (8a-f):

A mixture of substituted phenacyl chlorides (1a-f) (6 mmol), pyridin-2-amine (2f) (6 mmol) and dry baker’s yeast (2g) in acetonitrile (25-30 mL) was stirred at room temperature for the specified time. The progress of the reaction was monitored by TLC using ethyl acetate: hexane (5:5) as an eluent. After the specified reaction time the reaction content was filtered through the bed of Celite to remove the yeast. Acetonitrile was removed from the filtrate by vacuum distillation. Cold water (100 mL) was added to the crude residue.The resulting mass was neutralised and then the solid obtained was filtered and washed with cold water. It was further purified by crystallization using dry ethanol (Scheme 1) (8a-f).

EcoScale of synthesised compounds (3a-f, 4a-f,5a-f,6a-f,7a-f,8a-f) (Table 1)

A= Yield (100 – %yield)/2

B= Price of reaction components

C= Safety

D= Technical setup

E= Temperature/time

F= Workup and purification

EcoScale = 100 - sum of individual penalties

Table 1: The penalty points to calculate the EcoScale

aBased on the hazard warning symbols. bDropping funnel, syringe pump, ga pressure regulator, etc. cMicrowave irradiation, ultrasoundor photochemical activation, etc. dscCO2, high pressurehydrogenation equipment, etc. eIf applicable, the process includesdrying of solvent with desiccant and filtration of desiccant.

E- Factor:

Plausible reaction mechanism of cyclocondensation

References:

[1] K. B. Zheng, J. He, J. Zhang , Chinese Chemical Letters19, 1281 (2008).

[2] J. Khalafy, M. Mohammadlou, M. Mahmoody, F. Salami, A. P. Marjani, Tetrahedron Letters56, 1528 (2015).

[3] Koen Van Aken, Lucjan Strekowski, Luc Patiny, Beilstein Journal of Organic Chemistry 1 (2006)

[4]Roger A. SheldonGreen Chem.9, 1273 (2007).

Characterization data of synthesised compounds

5-phenyl-1, 3, 4-thiadiazol-2-amine (2c):

1H NMR (300 MHz, DMSO-d6): δ7.40-7.48(m, 5H, Ar-H); 7.73 (s, 2H, NH2),13C NMR (75 MHz, DMSO-d6):δ 126.2, 128.0, 128.8, 134.5, 156.9, 168.6;ESI-MS [M+H+]: m/z =178.1 for molecular formula C8H7N3S.

4-amino-5-phenyl-4H-1, 2, 4-triazole-3-thiol (2e):

1H NMR (300 MHz, DMSO-d6): δ5.78 (s, 2H, NH2), 7.52-8.03(m, 5H, Ar-H); 13.92 (s, 1H, SH), 13C NMR (75 MHz, DMSO-d6): δ126.2, 128.0, 128.8, 134.5, 161.6, 175.1; ESI-MS [M+H+]: m/z =193.0 for molecular formula C8H8N4S.

4-phenylthiazol-2-amine (3a):

1H NMR(300 MHz, CDCl3):δ 5.29-5.34(s,2H, NH2), 6.70(s,1H,Thiazole);7.28-7.77(m,5H,Ar-H), 13C NMR(75 MHz, CDCl3): δ102.9, 126.2, 128.0, 128.8, 134.5, 151.1, 167.7; ESI-MS [M+H+]: m/z =177.1for molecular formula C9H8N2S.

4-(4-methoxyphenyl)thiazol-2-amine (3b):

1H NMR(300 MHz, CDCl3): δ3.73 (s, 3H, OCH3),5.29-5.34(s,2H, NH2), 6.71(s,1H,Thiazole);7.28-7.75(m,4H,Ar-H), 13C NMR(75 MHz, CDCl3): δ102.9, 126.2, 128.0, 128.8, 134.5, 151.1, 167.7; ESI-MS [M+H+]: m/z =207.1for molecular formula C10H10N2OS.

4-p-tolylthiazol-2-amine (3c):

1H NMR(300 MHz, CDCl3):δ 2.38(s, 3H, CH3), 5.29-5.34(s,2H, NH2), 6.68(s,1H,Thiazole); 7.28-7.75(m,4H,Ar-H), 13C NMR(75 MHz, CDCl3): δ25.0, 102.9, 126.2, 128.0, 128.8, 134.5, 151.1, 167.7; ESI-MS [M+H+]: m/z = 177.1formolecular formula C9H8N2S.

4-(4-fluorophenyl)thiazol-2-amine (3d) :

1H NMR(300 MHz, CDCl3): δ5.27-5.30(s, 2H, NH2), 6.65(s,1H,Thiazole); 7.28-7.56(m,4H,Ar-H), 13C NMR(75 MHz, CDCl3):δ 102.0, 116.1, 128.0, 128.8, 134.5, 161.1, 167.3; ESI-MS [M+H+]: m/z = 195.0for molecular formula C9H7FN2S.

4-(4-chlorophenyl)thiazol-2-amine (3e):

1H NMR(300 MHz, CDCl3): δ5.29-5.34(s, 2H, NH2), 6.70(s,1H,Thiazole); 7.28-7.70(m,4H,Ar-H), 13C NMR(75 MHz, CDCl3):δ 102.2, 128.0, 128.8,130.1 134.5, 151.1, 167.7; ESI-MS [M+H+]: m/z = 211.1for molecular formula C9H7ClN2S.

4-(4-bromophenyl)thiazol-2-amine (3f):

1H NMR(300 MHz, CDCl3): δ5.29-5.34(s, 2H, NH2), 6.70(s,1H,Thiazole); 7.28-7.49(m,4H,Ar-H), 13C NMR(75 MHz, CDCl3): δ102.2, 123.0,128.8, 130.1, 151.1, 167.7; ESI-MS [M+H+]: m/z = 256.1for molecular formulaC9H7BrN2S.

2, 4-diphenylthiazole (5a):

1H-NMR (300 MHz, CDCl3): δ7.39-7.48 (m, 5H, Ar-H), 7.91-8.03 (m, 5H, Ar-H); 13C NMR (75 MHz, CDCl3):δ112.7, 126.5, 126.6, 128.2, 128.8, 128.9, 130.0, 133.8, 134.5, 156.3, 167.9; ESI-MS [M+H+]: m/z =238.1 for molecular formula C15H11NS.

4-(4-methoxyphenyl)-2-phenylthiazole (5b):

1H NMR (300 MHz, CDCl3): δ2.43(s, 3H, OCH3)7.11-7.24 (m, 4H, Ar-H), 7.29-7.98 (m, 4H, Ar-H); 13C NMR (75 MHz, CDCl3):δ55.3, 110.9, 114.1, 126.6, 127.5, 127.7, 128.9, 129.9, 133.8, 156.1, 159.6, 167.7; ESI-MS [M+H+]: m/z =268.0 for molecular formula C16H13NOS.

2-phenyl-4-p-tolylthiazole (5c):

1H NMR (300 MHz, CDCl3): δ 2.43(s, 3H, CH3)7.11-7.24 (m, 4H, Ar-H), 7.29-7.98 (m, 4H, Ar-H); 13C NMR (75 MHz, CDCl3):δ55.3, 110.9, 114.1, 126.6, 127.5, 127.7, 128.9, 129.9, 133.8, 156.1, 159.6, 167.7; ESI-MS [M+H+]: m/z =268.0 for molecular formula C16H13NOS.

4-(4-fluorophenyl)-2-phenylthiazole (5d):

1H NMR (300 MHz, CDCl3): δ 7.37-7.45 (m, 4H, Ar-H), 7.88-8.01 (m, 5H, Ar-H); 13C NMR (75 MHz, CDCl3):δ 113.0, 123.1, 126.7, 127.8, 129.0, 129.1, 130.3, 133.1, 151.1, 155.2, 168.3; ESI-MS [M+H+]: m/z = 256.2for molecular formula C15H10FNS.

4-(4-chlorophenyl)-2-phenylthiazole (5e):

1H NMR (300 MHz, CDCl3): δ 7.37-7.48 (m, 4H,Ar-H), 7.89-8.05 (m, 5H, Ar-H); 13C NMR (75MHz, CDCl3):δ113.0, 126.7, 127.8, 129.0,129.1, 130.3, 133.1, 133.7, 134.1, 155.2, 168.3; ESI-MS [M+H+]: m/z = 272.2for molecular formula C15H10ClNS.

4-(4-bromophenyl)-2-phenylthiazole (5f):

1H NMR (300 MHz, CDCl3): δ 7.37-7.48 (m, 4H, Ar-H), 7.88-8.05 (m, 5H, Ar-H); 13C NMR (75 MHz, CDCl3):δppm113.0, 123.1, 126.7, 127.8, 129.0, 129.1, 130.3, 133.1, 133.7, 155.2, 168.3; ESI-MS [M+H+]: m/z = 315.2for molecular formula C15H10BrNS.

2,6-diphenylimidazo[2,1-b][1,3,4]thiadiazole(5a):

1H NMR (300 MHz, CDCl3):δ7.14–7.58 (m, 10H, Ar-H), 8.01 (s,1H);13C NMR (75 MHz, CDCl3):δppm122.1, 126.5, 126.9, 129.1, 129.4, 130.1, 131.9, 132.5, 133.4, 140.2, 143.9; ESI-MS [M+H+]: m/z = 278.9 for molecular formula C16H11N3S.

6-(4-methoxyphenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazole(5b):

1H NMR (300 MHz, CDCl3):δ3.63 (s, 3H, OCH3), 6.94–7.42 (m, 9H, Ar-H), 8.02 (s, 1H);13C NMR (75 MHz, CDCl3):δ55.9, 114.7, 122.1, 126.5, 126.9, 129.1, 129.4, 130.1, 131.9, 132.5, 140.2, 143.9; ESI-MS [M+H+]: m/z = 308.1 for molecular formula C17H13N3OS.

2-phenyl-6-p-tolylimidazo[2,1-b][1,3,4]thiadiazole (5c):

1H NMR (300 MHz, CDCl3):δ1.27 (s, 3H, CH3), 7.25–7.57 (m, 9H, Ar-H), 7.99(s, 1H);13C NMR (75 MHz, CDCl3):δ 24.3, 122.1, 126.5, 126.9, 129.1, 129.4, 130.1, 131.9, 132.5, 133.4, 138.2, 140.2, 143.9; ESI-MS [M+H+]: m/z = 292.2 for molecular formula C17H13N3S.

6-(4-fluorophenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazole (5d) :

1H NMR (300 MHz, CDCl3):δ7.34–7.65 (m, 9H, Ar-H), 8.01 (s, 1H);13C NMR (75 MHz, CDCl3):δ 122.1, 126.5, 126.9, 129.1, 129.4, 130.1, 131.9, 132.5, 133.4, 140.2, 143.9, 151.9; ESI-MS [M+H+]: m/z = 296.1 for molecular formula C16H10FN3S.

6-(4-chlorophenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazole (5e) :

1H NMR (300 MHz, CDCl3):δ7.37-7.92 (m, 9H, Ar-H), 8.04(s,1H); 13C NMR (75 MHz, CDCl3):δ122.1, 126.5, 126.9, 129.1, 129.4, 130.1, 131.9, 132.5, 133.4, 140.2, 143.9;ESI-MS [M+H+]: m/z = 312.1 for molecular formula C16H10ClN3S.

6-(4-bromophenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazole (5f) :

1H NMR (300 MHz, CDCl3):δ7.34–7.67 (m, 9H, Ar-H), 8.01 (s, 1H);13C NMR (75 MHz, CDCl3):δ122.1, 126.5, 126.9, 129.1, 129.4, 130.1, 131.9, 132.5, 133.4, 140.2, 143.9, ESI-MS [M+H+]: m/z = 357.2 for molecular formula C16H10BrN3S.

2-phenylquinoxaline (6a):

1H NMR (300 MHz, CDCl3):δ7.53-8.21 (m, 9H), 9.33 (s, 1H);13C NMR (75 MHz, CDCl3):δ 127.2, 127.5, 129.1, 129.5, 129.6, 130.2, 130.3, 136.8, 141.6, 142.3, 143.3, 151.9; ESI-MS [M+H+]: m/z = 207.1 for molecular formula C14H10N2.

2-(4-methoxyphenyl)quinoxaline (6b):

1H NMR (300 MHz, CDCl3):δ 3.87(s, 3H, OCH3), 7.04-8.18 (m, 8H), 9.28 (s, 1H);13C NMR (75 MHz, CDCl3):δ 55.4, 114.6,128.9, 129.0, 129.0, 129.3, 129.4, 130.1, 141.2, 142.3, 143.0, 151.4, 161.4; ESI-MS [M+H+]: m/z = 237.0 for molecular formula C15H12N2O.

2-p-tolylquinoxaline (6c):

1H NMR (300 MHz, CDCl3):δ2.48(s, 3H, CH3), 7.28-8.18 (m, 8H), 9.28 (s, 1H);13C NMR (75 MHz, CDCl3):δ21.4, 127.4, 129.1, 129.3, 129.9, 130.2, 134.0, 140.5, 141.4, 141.4, 142.3, 143.3, 151.8; ESI-MS [M+H+]: m/z = 221.1 for molecular formula C15H12N2.

2-(4-fluorophenyl)quinoxaline (6d):

1H NMR (300 MHz, CDCl3):δ7.28-8.19 (m, 8H), 9.28 (s, 1H);13C NMR (75 MHz, CDCl3):δ 124.9, 128.9, 129.1, 129.6, 129.7, 130.4, 132.3, 135.6, 141.6, 142.6, 142.6, 142.2, 142.7, 150.5, 161.9; ESI-MS [M+H+]: m/z = 225.2 for molecular formula C14H9FN2.

2-(4-chlorophenyl)quinoxaline (6e):

1H NMR (300 MHz, CDCl3): δ7.28-8.18 (m, 8H), 9.31 (s, 1H);13C NMR (75 MHz, CDCl3): δ 128.7, 129.1, 130.5, 135.2, 136.6, 141.6, 142.2, 142.9, 150.6; ESI-MS [M+H+]: m/z = 241.1 for molecular formula C14H9ClN2.

2-(4-bromophenyl)quinoxaline (6f):

1H NMR (300 MHz, CDCl3):δ7.68-8.15 (m, 8H), 9.290 (s, 1H);13C NMR (75 MHz, CDCl3):δ 124.9, 128.9, 129.1, 129.6, 129.7, 130.4, 132.3, 135.6, 141.6, 142.6, 142.6, 142.2, 142.7, 150.5; ESI-MS [M+H+]: m/z = 286.1 for molecular formula C14H9BrN2.

3,6-diphenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (7a):

1H-NMR (300 MHz, CDCl3):δ3.90 (s, 2H, CH2),7.49-8.01(m, 10H, Ar-H),13C NMR (75 MHz, CDCl3):δ 30.9, 127.1, 127.8, 129.2, 130.0, 132.2, 133.4, 139.3, 152.1, 153.3;ESI-MS [M+H+]: m/z = 293.2 for molecular formula C16H12N4S.

6-(4-methoxyphenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine(7b):

1H-NMR (300 MHz, CDCl3):δ 3.90 (s, 2H, CH2),7.49-8.09(m, 9H, Ar-H); 13C NMR (75 MHz, CDCl3):δ30.9, 55.1, 127.1, 127.8, 129.2, 130.0, 132.2, 133.4, 139.3, 152.1, 153.3;ESI-MS [M+H+]: m/z = 223.1 for molecular formula C17H14N4OS.

3-phenyl-6-p-tolyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine(7c):

1H-NMR (300 MHz, CDCl3):δ 3.90 (s, 2H, CH2),7.49-8.09(m, 9H, Ar-H);13C NMR (75 MHz, CDCl3):δ21.3, 30.9, 127.1, 127.8, 129.2, 130.0, 132.2, 133.4, 139.3, 141.9, 152.1, 153.3;ESI-MS [M+H+]: m/z = 307.1 for molecular formula C17H14N4S.

6-(4-fluorophenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine(7d) :

1H-NMR (300 MHz, CDCl3):δ3.90 (s, 2H, CH2),7.49-8.09(m, 9H, Ar-H); 13C NMR (75 MHz, CDCl3):δ30.9, 127.1, 127.8, 129.2, 130.0, 132.2, 133.4, 139.3, 152.1, 153.3;ESI-MS [M+H+]: m/z = 311.0 for molecular formula C16H11FN4S.

6-(4-chlorophenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (7e) :

1H-NMR (300 MHz, CDCl3):δ3.90 (s, 2H, CH2),7.49-8.09(m, 9H, Ar-H),13C NMR (75 MHz, CDCl3):δ 30.9, 127.1, 127.8, 129.2, 130.0, 132.2, 133.4, 139.3, 152.1, 153.3;ESI-MS [M+H+]: m/z = 327.0 for molecular formula C16H11ClN4S.

6-(4-bromophenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (7f):

1H-NMR (300 MHz, CDCl3):δ 3.90 (s, 2H, CH2),7.49-8.09(m, 9H, Ar-H);13C NMR (75 MHz, CDCl3):δ 30.9, 127.1, 127.8, 129.2, 130.0, 132.2, 133.4, 139.3, 152.1, 153.3;ESI-MS [M+H+]: m/z = 372.2 for molecular formula C16H11BrN4S.

3-phenylH-imidazo[1,2-a]pyridine(8a):

1H-NMR (300 MHz, CDCl3): δ 6.72-6.78 (m, 1H), 7.12-7.17 (m, 1H),7.29-7.35 (t, 1H),7.40-7.46 (m, 2H), 7.60-7.64(d,1H), 7.84(s,1H),7.93-7.97(m,2H), 8.06-8.09 (d, 1H); 13C NMR (75 MHz, CDCl3):δ108.3,112.5,117.7,124.8,125.7,126.2,127.0,128.1,128.9,133.9,145.8,145.9; ESI-MS [M+H+]: m/z = 195.3 for molecular formula C13H10N2.

2-(4-methoxyphenyl)H-imidazo[1,2-a]pyridine (8b):

1H-NMR (300 MHz, CDCl3): δ3.87 (s, 3 H), 6.74–6.78 (m, 1 H), 6.97–6.99 (d, 2 H), 7.14–7.17 (t, 1 H), 7.61 (d, 1 H), 7.78 (s, 1 H), 7.89 (d, 2 H), 8.1 (d, 1 H);13C NMR (75 MHz, CDCl3):δ108.3, 112.5, 117.7, 124.8, 125.7, 126.2, 127.0, 128.1, 128.9, 133.9, 145.8, 145.9; ESI-MS [M+H+]: m/z =225.1 for molecular formula C14H12N2O.

2-p-tolylH-imidazo[1,2-a]pyridine(8c) :

1H NMR (300 MHz, CDCl3): δ 2.39 (s, 3H), 6.75-6.78 (m, 1H), 7.14−7.17 (m, 1H), 7.26-7.33 (t, 1H), 7.40-7.46 (m, 2H), 7.60-7.64 (d, 1H), 7.83 (s, 1H), 7.84 (s, 1H), 8.06-8.10 (d, 1H);13C NMR (75 MHz, CDCl3): δ 21.2, 108.8, 112.3, 117.3, 124.5, 125.5, 125.9, 129.4, 130.8, 137.7, 142.6, 145.8; ESI-MS [M+H+]::m/z = 209.2for molecular formula C14H12N2.

2-(4-fluorophenyl)H-imidazo[1,2-a]pyridine(8d):

1H NMR (300 MHz, CDCl3): δ6.78–6.81 (t, 1 H), 7.11–7.18(m, 3 H), 7.62–7.64 (d, 1 H), 7.82 (s, 1 H), 7.91–7.95 (m, 2 H), 8.12 (d, 1 H); 13C NMR (75 MHz, CDCl3): δ108.9, 111.5, 116.5, 124.5, 126.2, 127.8, 131.2, 132.6, 143.6, 144.7, 159.4;ESI-MS [M+H+]::m/z = 213.1[M+H+]for molecular formula C13H9FN2.

2-(4-chlorophenyl)H-imidazo[1,2-a]pyridine(8e) :

1H NMR (300 MHz, CDCl3): δ 6.78–6.81 (t, 1 H), 7.18–7.21 (m, 1 H), 7.39–7.42 (m, 2 H), 7.61–7.64 (d, 1 H), 7.84 (s, 1 H), 7.88–7.90 (m, 2 H), 8.12 (d, 1 H);13C NMR (75 MHz, CDCl3): δ106.9, 111.5, 116.5, 123.8, 124.5, 126.2, 127.8, 131.2, 132.6, 143.6, 144.7; ESI-MS [M+H+]:: m/z = 229.2 [M+H+]for molecular formula C13H9ClN2.

2-(4-bromophenyl)H-imidazo[1,2-a]pyridine(8f) :

1H NMR (300 MHz, CDCl3): δ 6.78–6.82 (t, 1H), 7.18–7.21 (m, 1 H), 7.55–7.57 (m, 2 H), 7.62–7.64 (d, 1 H), 7.81 (s, 1 H), 7.83–7.85 (m, 2 H), 8.11 (d, 1 H); 13C NMR (75 MHz, CDCl3): δ107.2, 111.6, 116.5, 120.8, 123.9, 124,5, 126.5, 130.8, 131.7, 143.6, 144.7; ESI-MS [M+H+]:: m/z =273.2 [M+H+]for molecular formula C13H9BrN2.

[Scan Copies of Mass, 1H NMR and 13C NMR spectra]

Mass spectra of 5-phenyl-1,3,4-thiadiazol-2-amine (2c)

H1 NMR spectra of 5-phenyl-1,3,4-thiadiazol-2-amine (2c)

Mass spectra of 4-amino-5-phenyl-4H-1,2, 4-triazole-3-thiol (2e)

H1 NMR spectra of 4-amino-5-phenyl-4H-1,2, 4-triazole-3-thiol (2e)

Mass spectra of 4-phenylthiazol-2-amine (3a)

H1MR spectra of 4-phenylthiazol-2-amine (3a)

13C NMR spectra of 4-phenylthiazol-2-amine (3a)

Mass spectra of 4-(4-chlorophenyl)-2-phenylthiazole (5e)

H1 NMR spectra of 4-(4-chlorophenyl)-2-phenylthiazole (5e)

13C NMR spectra of 4-(4-chlorophenyl)-2-phenylthiazole (5e)

Mass spectra of 2,6-diphenylimidazo[2,1-b][1,3,4]thiadiazole(5a)

H1 NMR spectra of 2-phenylquinoxaline (6a)

Mass spectra of 6-(4-chlorophenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (7e)

H1 NMR spectra of 6-(4-chlorophenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (7e)

Mass NMR spectra of 3-phenylH-imidazo[1,2-a]pyridine (8a)

H1 NMR spectra of 3-phenylH-imidazo[1,2-a]pyridine (8a)

13C NMR spectra of 3-phenylH-imidazo[1,2-a]pyridine (8a)

1