S1

SUPPORTING INFORMATION

Mechanochemical Solid-State Synthesis of 2-Aminothiazoles, Quinoxalines and Bezoylbenzofurans from Ketones by One-Pot Sequential Acid- and Base-Mediated

Reactions

Honnappa Nagarajaiah,* Abhaya K. Mishra, and Jarugu Narasimha Moorthy*

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, INDIA

E-mail: moorthy@iitk.ac.in

Contents

1. Spectral data of products S3-S4 2. References S5 3. 1H NMR spectrum of 2-amino-4-(p-bromophenyl)thiazole (2a) in CDCl3

S6 4. 1H NMR spectrum of 2-phenylamino-4-(p-bromophenyl)thiazole (2b) in CDCl3

S7 5. 1H NMR spectrum of 2-(p-bromophenyl)amino-4-(p-bromophenyl)thiazole (2c) in

CDCl3 S8

6. 1H NMR spectrum of 2-(p-chlorophenyl)amino-4-(p-bromophenyl)thiazole (2d) in CDCl3

S9

7. 1H NMR spectrum of 2-(p-tolyl)amino-4-(p-bromophenyl)thiazole (2e) in CDCl3 S10 8. 1H NMR spectrum of 2-(2,5-dimethylphenyl)amino-4-(p-bromophenyl)thiazole (2f) in

CDCl3 S11

9. 13C NMR spectrum of 2-(2,5-dimethylphenyl)amino-4-(p-bromophenyl)thiazole (2f) in CDCl3

S12

10. 1H NMR spectrum of 2-(2-benzylidenehydrazinyl)-4-(p-bromophenyl)thiazole (2g) in CDCl3

S13

11. 1H NMR spectrum of 2-(2-(p-bromobenzylidene)hydrazinyl)-4-(p-bromophenyl)thiazole (2h) in CDCl3

S14

12. 1H NMR spectrum of 4-(p-bromophenyl)-2-(2-(p-methoxybenzylidene)hydrazinyl) thiazole (2i) in CDCl3

S15

13. 1H NMR spectrum of 2-amino-4,5-diphenylthiazole (2j) in CDCl3 S16

14. 1H NMR spectrum of 2-(p-chlorophenyl)amino-4,5-diphenylthiazole (2k) in CDCl3 S17

15. 13C NMR spectrum of 2-(p-chlorophenyl)amino-4,5-diphenylthiazole (2k) in CDCl3 S18

16. 1H NMR spectrum of 4,5-diphenyl-2-(p-tolyl)aminothiazole (2l) in CDCl3 S19

17. 13C NMR spectrum of 4,5-diphenyl-2-(p-tolyl)aminothiazole (2l) in CDCl3 S20

18. 1H NMR spectrum of 2-(2,5-dimethylphenyl)amino-4,5-diphenylthiazole (2m) in CDCl3 S21

19. 13C NMR spectrum of 2-(2,5-dimethylphenyl)amino-4,5-diphenylthiazole (2m) in CDCl3

S22

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2016

S2

20. 1H NMR spectrum of 2-amino-8H-indeno[1,2-d]thiazole (4a) in CDCl3 S23 21. 1H NMR spectrum of 2-phenylamino-8H-indeno[1,2-d]thiazole (4b) in CDCl3

S24 22. 1H NMR spectrum of 2-(p-bromophenyl)amino-8H-indeno[1,2-d]thiazole (4c) in CDCl3 S25 23. 13C NMR spectrum of 2-(p-bromophenyl)amino-8H-indeno[1,2-d]thiazole (4c) in CDCl3 S26 24. 1H NMR spectrum of 2-(p-chlorophenyl)amino-8H-indeno[1,2-d]thiazole (4d) in CDCl3 S27 25. 13C NMR spectrum of 2-(p-chlorophenyl)amino-8H-indeno[1,2-d]thiazole (4d) in CDCl3

S28 26. 1H NMR spectrum of 2-(p-tolyl)amino-8H-indeno[1,2-d]thiazole (4e) in CDCl3 S29 27. 13C NMR spectrum of 2-(p-tolyl)amino-8H-indeno[1,2-d]thiazole (4e) in CDCl3

S30 28. 1H NMR spectrum of 2-(2,5-dimethylphenyl)amino-8H-indeno[1,2-d]thiazole (4f) in

CDCl3 S31

29. 13C NMR spectrum of 2-(2,5-dimethylphenyl)amino-8H-indeno[1,2-d]thiazole (4f) in CDCl3

S32

30. 1H NMR spectrum of 2-(p-bromophenyl)quinoxaline (5a) in CDCl3 S33 31. 1H NMR spectrum of 2-(p-bromophenyl)-6/7-methylquinoxaline (5b+5b') in CDCl3

S34 32. 1H NMR spectrum of 11H-indeno[2,1-b]quinoxaline (6a) in CDCl3 S35 33. 1H NMR spectrum of 7/8-methyl-11H-indeno[2,1-b]quinoxaline (6b+6b') in CDCl3

S36 34. 13C NMR spectrum of 7/8-methyl-11H-indeno[2,1-b]quinoxaline (6b+6b') in CDCl3

S37 35. 1H NMR spectrum of 2-benzofuranyl-(p-bromophenyl)methanone (7a) in CDCl3

S38 36. 1H NMR spectrum of (p-bromophenyl)(5,7-dibromo-2-benzofuranyl)methanone (7b) in

CDCl3 S39

S3

Spectral Data of Products

2-Amino-4-(p-bromophenyl)thiazole (2a).1 Pale yellow solid; Rf 0.40 (25 % EtOAc/petroleum ether); mp

170–172 °C; 1H NMR (400 MHz, CDCl3) δ 5.01 (brs, 2H), 6.73 (s, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.64 (d,

J = 8.2 Hz, 2H).

2-Phenylamino-4-(p-bromophenyl)thiazole (2b).2 Pale yellow solid; Rf 0.50 (5% EtOAc/petroleum ether);

mp 132–134 °C; 1H NMR (400 MHz, CDCl3) δ 6.83 (s, 1H), 7.07–7.11 (m, 1H), 7.35–7.40 (m, 4H), 7.51

(d, J = 8.6 Hz, 2H), 7.72 (d, J = 8.6 Hz, 2H).

2-(p-Bromophenyl)amino-4-(p-bromophenyl)thiazole (2c).3 Pale yellow solid; Rf 0.65 (5%

EtOAc/petroleum ether); mp 158–160 °C; 1H NMR (400 MHz, CDCl3) δ 6.85 (s, 1H), 7.32 (d, J = 8.9 Hz,

2H), 7.39 (brs, 1H), 7.46 (d, 8.9 Hz, 2H), 7.52 (d, J = 8.7 Hz, 2H), 7.71(d, J = 8.7 Hz, 2H).

2-(p-Chlorophenyl)amino-4-(p-bromophenyl)thiazole (2d).2 White solid; Rf 0.65 (5% EtOAc/petroleum

ether); mp 160–162 °C; 1H NMR (400 MHz, CDCl3) δ 6.84 (s, 1H), 7.31 (d, J = 8.9 Hz, 2H), 7.37 (d, 8.9

Hz, 2H), 7.41 (brs, 1H), 7.52 (d, J = 8.7 Hz, 2H), 7.71(d, J = 8.7 Hz, 2H).

2-(p-Tolyl)amino-4-(p-bromophenyl)thiazole (2e).2 Colorless solid; Rf 0.68 (5% EtOAc/petroleum ether);

mp 160–162 °C; 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 6.78 (s, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.25

(d, J = 8.4 Hz, 2H), 7.39 (brs, 1H), 7.50 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H).

2-(2-Benzylidenehydrazinyl)-4-(p-bromophenyl)thiazole (2g).4 Pale brown solid; Rf 0.40 (10%

EtOAc/petroleum ether); mp 216–218 °C; 1H NMR (400 MHz, CDCl3) δ 6.88 (s, 1H), 7.34–7.38 (m, 3H),

7.40–7.42 (m, 3H), 7.52 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H).

2-(2-(p-Bromobenzylidene)hydrazinyl)-4-(p-bromophenyl)thiazole (2h).5 Pale brown solid; Rf 0.30 (10%

EtOAc/petroleum ether); mp 200–202 °C; 1H NMR (400 MHz, CDCl3) δ 6.87 (s, 1H), 7.27 (d, J = 8.7 Hz,

2H), 7.36 (s, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H).

4-(p-Bromophenyl)-2-(2-(p-methoxybenzylidene)hydrazinyl)thiazole (2i).5 Pale brown solid; Rf 0.50 (10%

EtOAc/petroleum ether); mp 198–200 °C; 1H NMR (400 MHz, CDCl3) δ 3.84 (s, 3H), 6.86 (s, 1H), 6.88

(d, J = 8.7 Hz, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.45 (s, 1H), 7.51 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 8.5 Hz,

2H).

2-Amino-4,5-diphenylthiazole (2j).6 Colorless crystalline; Rf 0.50 (25% EtOAc/petroleum ether); mp 176–

178 °C; 1H NMR (400 MHz, CDCl3) δ 5.10 (s, 2H), 7.21–7.29 (m, 8H), 7.44–7.47 (m, 2H).

2-Amino-8H-indeno[1,2-d]thiazole (4a).7 Pale brown solid; Rf 0.20 (10% EtOAc/petroleum ether); mp

192–194 °C; 1H NMR (400 MHz, CDCl3) δ 3.70 (s, 2H), 5.06 (brs, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.33 (t, J

= 7.5 Hz, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H).

S4

2-Phenylamino-8H-indeno[1,2-d]thiazole (4b).8 Off-white solid; Rf 0.42 (5% EtOAc/petroleum ether);

mp 172–174 °C; 1H NMR (400 MHz, CDCl3) δ 3.76 (s, 2H), 7.13–7.16 (m, 1H), 7.22–7.26 (m, 1H),

7.34–7.43 (m, 5H), 7.48 (d, J = 7.3 Hz, 1H), 7.66 (d, J = 7.3 Hz, 1H).

2-(p-Bromophenyl)quinoxaline (5a).9 Pale orange yellow solid; Rf 0.50 (10% EtOAc/petroleum ether);

mp 122–124 °C; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 2H), 7.74–7.83 (m, 2H), 8.09 (d, J =

8.2 Hz, 2H), 8.11–8.16 (m, 2H), 9.30 (s, 1H).

2-(p-Bromophenyl)-6/7-methylquinoxaline (5b+5b').10 Pale yellow solid; Rf 0.50 (10% EtOAc/petroleum

ether); isomers ratio (ca. 1:1); mp 136–138 °C; 1H NMR (400 MHz, CDCl3) δ 2.62 (s, 3H), 7.58–7.64 (m,

1H), 7.68–7.70 (m, 2H), 7.89 (s, 1H), 7.92 (s, 1H), 7.99–8.08 (m, 3H), 9.23 (s, 0.5H), 9.25 (s, 0.5H). (It

should be noted that the spectral data are for an inseparable mixture with only the signal at δ ca. 9.2 split

up as two signals. For each of these signals, the integration is accounted for 0.5 proton.)

11H-indeno[2,1-b]quinoxaline (6a).11 Pale yellow solid; Rf 0.35 (10% EtOAc/petroleum ether); mp 148–

150 °C; 1H NMR (400 MHz, CDCl3) δ 4.15 (s, 2H), 7.52–7.57 (m, 2H), 7.65–7.67 (m, 1H), 7.70–7.77

(m, 2H), 8.10 (d, J = 9.6 Hz, 1H), 8.17 (d, J = 7.2 Hz, 1H), 8.26 (d, J = 7.2 Hz, 1H).

2-Benzofuranyl-(p-bromophenyl)methanone (7a).12 White solid; Rf 0.75 (5% EtOAc/petroleum ether); mp

170–172 °C; 1H NMR (400 MHz, CDCl3) δ 7.35 (t, J = 7.3 Hz, 1H), 7.52 (t, J = 7.2 Hz, 1H), 7.55 (s,

1H), 7.64 (d, J = 8.1 Hz, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.74 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 8.5 Hz, 2H).

(p-Bromophenyl)(5,7-dibromo-2-benzofuranyl)methanone (7b).13 White solid; Rf 0.80 (5%

EtOAc/petroleum ether); mp 198–200 °C; 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.71 (d, J = 8.6

Hz, 2H), 7.79 (d, J = 1.6 Hz, 1H), 7.82 (d, J = 1.7 Hz, 1H), 8.03 (d, J = 8.6 Hz, 2H).

S5

References

[1] Y-P. Zhu, J-J. Yuan, Q. Zhao, M. Lian, Q-H. Gao, M-C. Liu, Y. Yang and A-X. Wu, Tetrahedron,

2012, 68, 173.

[2] K. S. Jain, J. B. Bariwal, M. K. Kathiravan, V. K. Raskar, G. S. Wankhede, N. A. Londhe and S. N.

Dighe, Green Sustainable Chem., 2011, 1, 36.

[3] R. Gupta, D. Sharma and S. Singh, Phosphorus Sulfur Silicon Relat. Elem., 2010, 185, 1321.

[4] S. K. Bharti and S. K. Singh, Med. Chem. Res., 2014, 23, 1004.

[5] L. Lohrey, T. N. Uehara, S. Tani, J. Yamaguchi, H-U. Humpf and K. Itami, Eur. J. Org. Chem.,

2014, 3387.

[6] A. Kamal, M. Balakrishna, V. L. Nayak, T. B. Shaik, S. Faazil and V. D. Nimbart,

ChemMedChem., 2014, 9, 2766.

[7] A. Goblyos, S. N. Santiago, D. Pietra, T. Mulder-Krieger, J. F. D. Kunzel, J. Brussee and A. P.

IJzerman, Bioorg. Med. Chem., 2005, 13, 2079.

[8] C. M. Thompson, J. L. Poole, J. L. Cross, I. Akritopoulou-Zanze and S. W. Djuric, Molecules,

2011, 16, 9161.

[9] P. Ghosh and A. Mandal, Green Chem. Lett. Rev., 2013, 6, 45.

[10] F. Pan, T-M. Chen, J-J Cao, J-P Zou and W. Zhang, Tetrahedron Lett., 2012, 53, 2508.

[11] F. Lassagne, F. Chevallier and F. Mongin, Synth. Commun., 2014, 44, 141.

[12] Y. Shang, C. Wang, X. He, K. Ju, M. Zhang, S. Yu and J. Wu, Tetrahedron, 2010, 66, 9629.

[13] M. L. N. Rao, D. K. Awasthi and D. Banerjee, Tetrahedron Lett., 2007, 48, 431.

S6

Figure S1. 1H NMR spectrum of 2-amino-4-(p-bromophenyl)thiazole in CDCl3.

2a S

NNH2

Br

S7

Figure S2. 1H NMR spectrum of 2-phenylamino-4-(p-bromophenyl)thiazole in CDCl3.

S

NNH

Br

2b

S8

Figure S3. 1H NMR spectrum of 2-(p-bromophenyl)amino-4-(p-bromophenyl)thiazole in CDCl3.

2c S

N

Br

NH

Br

S9

Figure S4. 1H NMR spectrum of 2-(p-chlorophenyl)amino-4-(p-bromophenyl)thiazole in CDCl3.

2d

S

N

Br

NH

Cl

S10

Figure S5. 1H NMR spectrum of 2-(p-tolyl)amino-4-(p-bromophenyl)thiazole in CDCl3.

2e

S

N

Br

NH

CH3

S11

Figure S6. 1H NMR spectrum of 2-(2,5-dimethylphenyl)amino-4-(p-bromophenyl)thiazole in CDCl3.

2f

S

N

Br

NH CH3

H3C

S12

Figure S7. 13C NMR spectrum of 2-(2,5-dimethylphenyl)amino-4-(p-bromophenyl)thiazole in CDCl3.

2f

S

N

Br

NH CH3

H3C

S13

Figure S8. 1H NMR spectrum of 2-(2-benzylidenehydrazinyl)-4-(p-bromophenyl)thiazole in CDCl3.

S

N

Br

NH

N

2g

S14

Figure S9. 1H NMR spectrum of 2-(2-(p-bromobenzylidene)hydrazinyl)-4-(p-bromophenyl)thiazole in

CDCl3.

2h

S

N

Br

NH

N

Br

S15

Figure S10. 1H NMR spectrum of 4-(p-bromophenyl)-2-(2-(p-methoxybenzylidene)hydrazinyl) thiazole in CDCl3.

2i

S

N

Br

NH

N

OCH3

S16

Figure S11. 1H NMR spectrum of 2-amino-4,5-diphenylthiazole in CDCl3.

S

NNH2

2j

S17

Figure S12. 1H NMR spectrum of 2-(p-chlorophenyl)amino-4,5-diphenylthiazole in CDCl3.

S

NNH

Cl

2k

S18

Figure S13. 13C NMR spectrum of 2-(p-chlorophenyl)amino-4,5-diphenylthiazole in CDCl3.

S

NNH

Cl

2k

S19

Figure S14. 1H NMR spectrum of 4,5-diphenyl-2-(p-tolyl)aminothiazole in CDCl3.

S

NNH

CH3

2l

S20

Figure S15. 13C NMR spectrum of 4,5-diphenyl-2-(p-tolyl)aminothiazole in CDCl3.

S

NNH

CH3

2l

S21

Figure S16. 1H NMR spectrum of 2-(2,5-dimethylphenyl)amino-4,5-diphenylthiazole in CDCl3.

S

NNH

H3C

CH3

2m

S22

Figure S17. 13C NMR spectrum of 2-(2,5-dimethylphenyl)amino-4,5-diphenylthiazole in CDCl3.

S

NNH

H3C

CH3

2m

S23

Figure S18. 1H NMR spectrum of 2-amino-8H-indeno[1,2-d]thiazole in CDCl3.

4a

S

N NH2

S24

Figure S19. 1H NMR spectrum of 2-phenylamino-8H-indeno[1,2-d]thiazole in CDCl3.

4b

S

N HN

S25

Figure S20. 1H NMR spectrum of 2-(p-bromophenyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4c

S

N HN

Br

S26

Figure S21. 13C NMR spectrum of 2-(p-bromophenyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4c

S

N HN

Br

S27

Figure S22. 1H NMR spectrum of 2-(p-chlorophenyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4d

S

N HN

Cl

S28

Figure S23. 13C NMR spectrum of 2-(p-chlorophenyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4d

S

N HN

Cl

S29

Figure S24. 1H NMR spectrum of 2-(p-tolyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4e

S

N HN

CH3

S30

Figure S25. 13C NMR spectrum of 2-(p-tolyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4e

S

N HN

CH3

S31

Figure S26. 1H NMR spectrum of 2-(2,5-dimethylphenyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4f

S

N HN

CH3

H3C

S32

Figure S27. 13C NMR spectrum of 2-(2,5-dimethylphenyl)amino-8H-indeno[1,2-d]thiazole in CDCl3.

4f

S

N HN

CH3

H3C

S33

Figure S28. 1H NMR spectrum of 2-(p-bromophenyl)quinoxaline in CDCl3.

5a

N

N

Br

S34

Figure S29. 1H NMR spectrum of 2-(p-bromophenyl)-6/7-methylquinoxaline in CDCl3.

5b + 5b' (ca.1:1)

N

N

Br

CH3

N

N

Br

CH3

S35

Figure S30. 1H NMR spectrum of 11H-indeno[2,1-b]quinoxaline in CDCl3.

6a

N

N

S36

Figure S31. 1H NMR spectrum of 7/8-methyl-11H-indeno[2,1-b]quinoxaline in CDCl3.

6b + 6b’ (50:50)

N

N

CH3

N

N CH3

S37

Figure S32. 13C NMR spectrum of 7/8-methyl-11H-indeno[2,1-b]quinoxaline in CDCl3.

N

N

CH3

N

N CH3

6b + 6b’ (50:50)

S38

Figure S33. 1H NMR spectrum of 2-benzofuranyl-(p-bromophenyl)methanone in CDCl3.

7a

O

O

Br

S39

Figure S34. 1H NMR spectrum of (p-bromophenyl)(5,7-dibromo-2-benzofuranyl)methanone in CDCl3.

7b

O

O

Br

Br

Br