Solid-State Synthesis of β-Enamino Ketones from Solid 1,3-Dicarbonyl Compounds and Ammonium Salts or Amines

Abstract

A facile amination of solid 1,3-dicarbonyl compounds with ammonium salts or amines in solid state has been achieved by mechanochemical grinding in the presence of KHSO₄ and SiO₂. Most of the reactions proceed smoothly at room temperature under solid-state conditions and give their corresponding β-imino derivatives in high yields. The method has the advantage of simple manipulation and mild conditions.

enamination - 1,3-dicarbonyl compounds - solid state - mechanochemistry

References and Notes

1a Tomioka K. Ando K. Takemasa Y. Koga K. J. Am. Chem. Soc.  1984,  106:  2718 

1b Georg IG. Kant J. Tetrahedron Lett.  1988,  29:  403 

1c Lubell WD. Kitamura M. Noyori R. Tetrahedron: Asymmetry  1991,  2:  543 

1d Bartoli G. Cimarelli C. Marcantoni E. Palmieri G. Petrini M. J. Org. Chem.  1994,  59:  5328 

2a Bartoli G. Bosco M. Cimarelli C. Dalpozzo R. Guercio G. Palmieri G. J. Chem. Soc., Perkin Trans. 1  1993,  2081 

2b Bartoli G. Bosco M. Cimarelli C. Dalpozzo R. Palmieri G. J. Chem. Soc., Perkin Trans. 1  1992,  2095 

2c Bartoli G. Bosco M. Cimarelli C. Dalpozzo R. Munno GD. Guercio G. Palmier G. J. Org. Chem.  1992,  57:  6020 

3a Alberola A. Calvo LA. Ortega AG. Ruiz MCS. Yustos P. J. Org. Chem.  1999,  64:  9493 

3b Chaaban I. Greenhill JV. Akhtar P. J. Chem. Soc., Perkin Trans. 1  1979,  1593 

3c Augusti R. Kascheres C. J. Org. Chem.  1993,  58:  7079 

3d Eberlin MN. Kascheres C. J. Org. Chem.  1988,  53:  2084 

3e Al-Omran F. El-Khair AA.
J. Heterocycl. Chem.  2005,  45:  307 

3f Müller A. Maier A. Neumann R. Maas G. Eur. J. Org. Chem.  1998,  1177 

3g Bejan E. Aït-Haddou H. Daran JC. Balavoine GGA. Eur. J. Org. Chem.  1998,  2907 

4 Eddington ND. Cox DS. Khurana M. Salama NN. Stables JP. Harrison SJ. Negussie A. Taylor RS. Tran UQ. Moore JA. Barrow JC. Scott KR. Eur. J. Med. Chem.  2003,  49 

5 Azzaro M. Geribaldi S. Videau B. Synthesis  1981,  880 

6 Dannhardt G. Bauer A. Nowe U. J. Prakt. Chem.  1998,  340:  256 

7 Boger DL. Ishizaki T. Wysocki JR. Munk SA. Kitos PA. Suntornwat O. J. Am. Chem. Soc.  1989,  111:  6461 

8a Baraladi PG. Simoni D. Manfredini S. Synthesis  1983,  902 

8b Martin DF. Janusonis GA. Martin BB. J. Am. Chem. Soc.  1961,  83:  73 

8c Ferraz HMC. Oliceira EO. Payret-Arrua ME. Brandt CA. J. Org. Chem.  1995,  60:  7357 

8d Kloek JA. Leschinsky KL.
J. Org. Chem.  1978,  43:  1460 

8e Soloshonok VA. Kukhar V. Tetrahedron  1996,  52:  6953 

8f Leflemme N. Dallemange P. Rault S. Synthesis  2002,  1740 

9a Zhu G. Chen Z. Zhang X. J. Org. Chem.  1999,  64:  6907 

9b Garaldi PG. Simoni D. Manfredini S. Synthesis  1983,  902 

9c Marchalin S. Kuthan J. Collect. Czech. Chem. Commun.  1983,  48:  3112 

9d Marchalin S. Kuthan J. Collect. Czech. Chem. Commun.  1984,  49:  1395 

10 Rodríguez H. Reyes O. Suarez M. Garay HE. Pérez R. Cruz LJ. Verdecia Y. Martín N. Seoane C. Tetrahedron Lett.  2002,  43:  439 

11a Saeed AAH. J. Chem. Eng. Data  1984,  29:  358 

11b Hauser CR. Reynolds GA. J. Am. Chem. Soc.  1948,  70:  2402 

11c Coffey S. Thomson JK. Wilson FJ.
J. Chem. Soc.  1936,  856 

12 Martin DF. Janusonis GA. Martin BB. J. Am. Chem. Soc.  1961,  83:  73 

13a Hickmot PW. Sheppard G. J. Chem. Soc., Perkin Trans. 1  1972,  1038 

13b Bieräugel H. Akkerman JM. Lapierre Armande JC. Pandit UK. Recl. Trav. Chim. Pays-Bas  1976,  95:  266 

13c Gravel D. Labelle M. Can. J. Chem.  1985,  63:  1874 

13d Yapi AD. Mustofa M. Valentin A. Chavignon O. Teulade JC. Mallie M. Chapat J.-P. Blache Y. Chem. Pharm. Bull.  2000,  48:  1886 

14a Naringrekar VH. Stella VJ. J. Pharm. Sci.  1990,  79:  138 

14b Brown RJ. Carver FWS. Hollingsworth BL. J. Org. Chem.  1967,  32:  2624 

14c Brandt CA. Da Silva ACMP. Pancote CG. Brito CL. Da Silveira MAB. Synthesis  2004,  1557 

15 Das B. Venkateswarlu K. Majhi A. Reddy RM. Reddy NK. Rao KY. Ravikumar K. Sridhar B. J. Mol. Catal. A: Chem.  2006,  246:  276 

16 Cartaya-Marin CP. Henderson DG. Soeder RW. Synth. Commun.  1997,  27:  4275 

17a Rechsteimer B. Texier-Boullet F. Hamelin J. Tetrahedron Lett.  1993,  34:  5071 

17b Braibante HTS. Braibante MEF. Rosso GB. Oriques DA. J. Braz. Chem. Soc.  2003,  14:  994 

18 Valduga CJ. Squizani A. Braibante HS. Braibante MEF. Synthesis  1998,  1019 

19 Stefane B. Polanc S. Synlett  2004,  698 

20 Texier-Bouliet F. Synthesis  1985,  679 

21 Gao Y.-H. Zhang Q.-H. Xu J.-X. Synth. Commun.  2004,  34:  909 

22 Bartoli G. Bosco M. Locatelli M. Marcantoni E. Melchiorre P. Sambri L. Synlett  2004,  239 

23 Khodaei MM. Khosropour AR. Kookhazadeh M. Synlett  2004,  1980 

24 Arcadi A. Bianchi G. Di Giuseppe S. Marinelli F. Green Chem.  2003,  5:  64 

25 Dalpozzo R. Nino AD. Nardi M. Russo B. Procopio A. Synthesis  2006,  1127 

26 Silva FC. De Souza MCBV. Ferreira VF. Sabino SJ. Antunes OAC. Catal. Commun.  2004,  5:  151 

27 Stefani HA. Costa IM. de O. Silva D. Synthesis  2000,  1526 

28 Khosropour AR. Khodaei MM. Kookhazadeh M. Tetrahedron Lett.  2004,  45:  1725 

29 Khodaei MM. Khosropour AR. Kookhazadeh M. Can. J. Chem.  2005,  83:  209 

30 Zhang Z.-H. Yin L. Wang Y.-M. Adv. Synth. Catal.  2006,  348:  184 

31 Kaupp G. Schmeyers J. Boy J. Chemosphere  2001,  43:  55 

32

General Procedure for the Preparation of β-Enamino Ketones
A mixture of the solid 1,3-dicarbonyl compound (5 mmol), amine (or ammonium, 5 mmol), and KHSO₄/SiO₂ (0.136 g, weight ratio 1:1) was ground in a mortar at r.t. for the appropriate time. After completion of the reaction as indicated by TLC, the reaction mixture was extracted with CH₂Cl₂ (2 × 10 mL). The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to give a product with high purity. The solid product could be further purified by recrystallization in PE (Table  [²] , entries 1-15) or in EtOH (Table  [³] , entries 1-12).
3-Amino-1-phenylbut-2-en-1-one (2a)
Mp 138-140 ˚C; lit. [³³a] 144-145 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.06 (s, 3 H), 5.21 (br, 1 H, NH), 5.74 (s, 1 H), 7.39-7.45 (m, 3 H), 7.87-7.89 (m, 2 H), 10.22 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 22.92, 92.34, 127.10, 128.22, 130.83, 140.20, 162.91, 189.54.
3-Amino-1-(4-methoxyphenyl)but-2-en-1-one (2b) [³³b]
Mp 106-108 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.04 (s, 3 H), 3.85 (s, 3 H), 5.11 (br, 1 H,NH), 5.70 (s, 1 H), 6.89-6.92 (m, 2 H), 7.85-7.88 (m, 2 H), 10.13 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 22.95, 55.36, 91.88, 113.43, 129.03, 132.90, 161.89, 162.14, 188.65.
3-Amino-1-(4-fluorophenyl)but-2-en-1-one (2c) [³³b]
Mp 106-108 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.06 (s, 3 H), 5.21 (br, 1 H, NH), 5.67 (s, 1 H), 7.06-7.09 (m, 2 H), 7.87-7.90 (m, 2 H), 10.19 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃) δ = 22.95 91.99, 115.14 (d, J = 20 Hz), 129.39 (d, J = 9 Hz), 136.40, 136.42 163.30 (d, J = 56 Hz), 165.52, 188.08. Ethyl 2-Amino-4-oxo-4-phenylbut-2-enoate (2d)
Mp 49-51 ˚C; lit. [³³c] 50-51 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 1.41 (t, 3 H, J = 7 Hz), 4.38 (q, 2 H, J = 7 Hz), 6.04 (br, 1 H, NH), 6.67 (s, 1 H), 7.46-7.54 (m, 3 H), 7.96-9.98 (m, 2 H), 9.49 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.13, 62.70, 93.26, 127.45, 128.44, 131.29, 139.28, 147.49, 163.88, 191.80.
3-Aminocyclohex-2-enone (2e)
Mp 128-130 ˚C; lit. [³³d] 133 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 1.97 (m, 2H), 2.29 (t, 2H, J = 6 Hz), 2.35 (t, 2H, J = 6 Hz), 4.67 (br, 2H, NH), 5.26 (s, 1H). ^¹³C NMR (125 MHz, D₂O) δ = 23.89, 30.60, 36.94, 99.56, 177.00, 203.01.
3-Amino-5,5-dimethylcyclohex-2-enone (2f)
Mp 164-166 ˚C; lit. [³³d] 165-167 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 1.08 (s, 6 H), 2.16 (s, 2 H), 2.20 (s, 2 H), 4.71 (br, 2 H, NH), 5.25 (s, 1 H). ^¹³C NMR (125 MHz, D₂O) δ = 28.35, 32.88, 42.65, 49.86, 99.27, 163.46, 197.31.
3-Amino-1,3-diphenylprop-2-en-1-one (2g) [³³e]
Mp 78-79 ˚C. ^¹H NMR (500 MHz, CDCl₃) δ = 5.46 (br, 1 H, NH), 6.16 (s, 1 H), 7.42-7.53 (m, 6 H), 7.64-7.65 (m, 2 H), 7.94-7.96 (m, 2 H), 10.43 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃) δ = 91.93, 126.36, 127.24, 128.32, 129.06, 130.74, 131.06, 137.63, 140.36, 162.88, 190.26.
3-Amino-1-(thiophen-2-yl)but-2-en-1-one (2h)
Mp 168-170 ˚C; lit. [³³b] 168-170 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.03 (s, 3 H), 5.31 (br, 1 H,NH), 5.60 (s, 1 H), 7.05-7.56 (m, 3 H), 9.91 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 22.73, 92.00, 127.73, 127.87, 130.21, 146.99, 162.82, 182.21.
3-(4-Methoxyphenylamino)-1-phenylbut-2-en-1-one (3a) [³³f]
Mp 100-102 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.07 (s, 3 H), 3.82 (s, 3 H), 5.86 (s, 1 H), 6.89-6.91 (m, 2 H), 7.10-7.12 (m, 2 H), 7.41-7.46 (m, 3 H), 7.90-7.92 (m, 2 H), 12.92 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.27, 55.52, 93.59, 114.37, 126.64, 127.05, 128.28, 130.80, 131.46, 140.16, 157.89, 163.21, 188.47.
3-(4-Chlorophenylamino)-1-phenylbut-2-en-1-one (3b)
Mp 126-128 ˚C; lit. [³³g] 128-129 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.12 (s, 3 H), 5.91 (s, 1 H), 7.09-7.15 (m, 2 H), 7.31-7.34 (m, 2 H), 7.41-7.48 (m, 3 H), 7.90-7.92 (m, 2 H), 13.07 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.30, 94.63, 125.80, 127.01, 128.26, 129.23, 131.02, 131.15, 137.20, 139.71, 161.63, 188.88.
3-(4-Nitrophenylamino)-1-phenylbut-2-en-1-one (3c) [³³h]
Mp 140-142 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.33 (s,
3 H), 6.04 (s, 1 H), 7.25-7.28 (m, 2 H), 7.44-7.47 (m, 2 H), 7.50-7.52 (m, 1 H), 7.88-7.93 (m, 2 H), 8.21-8.25 (m, 2 H), 13.41 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.18, 97.54, 122.26, 125.22, 127.30, 128.50, 131.73, 139.20, 144.13, 145.18, 159.16, 189.99.
1-Phenyl-3-( p -tolylamino)but-2-en-1-one (3d) [³³i]
Mp 114-116 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.10 (s,
3 H), 2.35 (s, 3 H), 5.87 (s, 1 H), 7.05-7.07 (m, 2 H), 7.15-7.25 (m, 2 H), 7.40-7.46 (m, 3 H), 7.90-7.93 (m, 2 H), 13.03 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.38, 20.97, 93.92, 124.85, 127.06, 128.27, 129.76, 130.82, 135.72, 136.02, 140.14, 162.60, 188.48.
1-(4-Methoxyphenyl)-3-(4-methoxyphenylamino)but-2-en-1-one (3e) [³³j]
Mp 142-143 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.05 (s, 3 H), 3.82 (s, 3 H), 3.86 (s, 3 H), 5.82 (s, 1 H), 6.88-6.94 (m, 4 H), 7.09-7.11 (m, 2 H), 7.89-7.91 (m, 2 H), 12.85 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.26, 55.36, 55.49, 93.05, 113.47, 114.31, 126.57, 128.90, 131.67, 132.81, 157.74, 161.87, 162.41, 187.62. 1-(4-Fluorophenyl)-3-(4-methoxyphenylamino)but-2-en-1-one (3f)
Mp 116-118 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.06 (s, 3 H), 3.82 (s, 3 H), 5.80 (s, 1 H), 6.89-6.91 (m, 2 H), 7.07-7.11 (m, 4 H), 7.90-7.93 (m, 2 H), 12.87 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.25, 55.49, 93.15, 114.37, 115.16 (d, J = 21 Hz), 126.63, 129.24 (d, J = 9 Hz), 131.35, 136.36 (d, J = 4 Hz), 157.94, 163.38 (d, J = 22 Hz), 165.47, 186.94. IR (KBr): 3440, 1599, 1543, 1515, 1496, 1462, 1436, 1328, 1251, 1198, 1105, 1031, 855, 779, 520 cm^-¹. MS (EI): m/z (%) = 286 (18), 285 (100) [M⁺], 284 (70), 270 (18), 190 (11), 162 (36), 147 (22), 123 (71), 108 (9), 95 (27). Anal. Calcd for C₁₇H₁₆FNO₂: C, 71.56; H, 5.65; N, 4.91. Found: C, 71.51; H, 5.60; N, 4.87.
Ethyl 2-(4-Nitrophenylamino)-4-oxo-4-phenylbut-2-enoate (3g)
Mp 98-99 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 1.22 (t, 3 H, J = 7 Hz), 4.28 (q, 2 H, J = 7 Hz), 6.67 (s, 1 H), 7.04-7.05 (m, 2 H), 7.47-7.51 (m, 2 H), 7.57-7.60 (m, 1 H), 7.97-7.99 (m, 2 H), 8.19-8.21 (m, 2 H), 11.95 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 13.83, 62.79, 101.02, 120.30, 125.09, 127.77, 128.76, 132.95, 138.10, 143.72, 145.72, 146.95, 163.64, 191.94. IR (KBr): 3441, 2981, 1373, 1619, 1585, 1510, 1337, 1281, 1226, 1163, 1108, 1051, 1016, 831, 853, 750, 591, 552, 493 cm^-¹. MS (EI): m/z (%) = 341 (5), 340 (33) [M⁺], 339 (31), 294 (14), 268 (18), 267 (84), 236 (26), 221 (15), 105 (100), 77 (42). Anal. Calcd for C₁₈H₁₆N₂O_5: C, 63.52; H, 4.74; N, 8.23. Found: C, 63.50; H, 4.67; N, 8.14.
3-(4-Nitrophenylamino)cyclohex-2-enone (3h) [³³k]
Mp 176-178 ˚C.^¹H NMR (500 MHz, CDCl₃): δ = 2.07-2.11 (m, 2 H), 2.42 (t, 2 H, J = 7 Hz), 2.56 (t, 2 H, J = 6 Hz), 5.85 (s, 1 H), 6.83 (br, 1 H, NH), 7.26-7.29 (m, 2 H), 8.19-8.21 (m, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.65, 29.82, 36.55, 103.13, 121.31, 125.32, 143.35, 144.94, 159.90, 198.94.
3-(4-Methoxyphenylamino)-5,5-dimethylcyclohex-2-enone (3i)
Mp 186-188 ˚C; lit. [³³l] 186-188 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 1.05 (s, 6 H), 2.15 (s, 2 H), 2.32 (s, 2 H), 3.78 (s, 3 H), 5.34 (s, 1 H), 6.82 (dd, 2 H, J = 2, 7 Hz), 7.04 (dd, 2 H, J = 2, 7 Hz), 7.28 (s, 1 H).^¹³C NMR (125 MHz, CDCl₃): δ = 28.27, 32.76, 43.02, 50.36, 55.46, 96.96, 114.37, 126.07, 131.14, 157.46, 162.87, 197.61.
3-(2,5-Dichlorophenylamino)-5,5-dimethylcyclohex-2-enone (3j)
Mp 182-184 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 1.14 (s, 6 H), 2.26 (s, 2 H), 2.39 (s, 2 H), 5.61 (s, 1 H), 6.12 (br, 1 H), 7.07-7.42 (m, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 28.28, 32.89, 43.74, 50.34, 100.78, 124.56, 125.27, 125.96, 130.79, 133.30, 136.28, 158.05, 198.18. IR (KBr) 3442, 3225, 2953, 2873, 1597, 1537, 1464, 1402, 1364, 1269, 1092, 1048, 925, 893, 827, 743, 519 cm^-¹. MS (EI): m/z (%) = 285 (42), 283 (50), 268 (20), 266 (20), 227 (36), 192 (100), 164 (28). Anal. Calcd for C₁₄H₁₅Cl₂NO: C, 59.17; H, 5.32; N, 4.93. Found: C, 59.09; H, 5.28; N, 4.90.
1,3-Diphenyl-3-( p -tolylamino)prop-2-en-1-one (3k) [³³m]
Mp 120-122 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.23 (s, 3 H), 6.05 (s, 1 H), 6.68-7.95 (m, 14 H), 12.90 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.79, 96.57, 123.21, 127.22, 128.33, 128.38, 128.49, 129.31, 129.55, 131.17, 133.86, 135.94, 136.80, 139.98, 161.74, 189.43.
3-(4-Chlorophenylamino)-1-(thiophen-2-yl)but-2-en-1-one (3l)
Mp 80-82 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 2.11 (s, 3 H), 5.78 (s, 1 H), 7.06-7.61 (m, 7 H), 12.71 (br, 1 H, NH). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.31, 94.51, 125.74, 127.89, 128.14, 129.34, 130.66, 131.21, 137.24, 146.56, 161.33, 181.88. IR (KBr): 3441, 3095, 1623, 1562, 1481, 1418, 1373, 1381, 1229, 1093, 1031, 824, 834, 766, 722, 502
cm^-¹. MS (EI): m/z (%) = 279 (25), 278 (39), 277 (67), 276 (84), 244 (87), 111 (100), 83 (8). Anal. Calcd for C₁₄H₁₂ClNOS: C, 60.54; H, 4.35; N, 5.04. Found: C, 60.50; H, 4.31; N, 5.01.

33a Baraldi PG. Synthesis  1983,  902 

33b Singh B. Lesher GY. J. Heterocycl. Chem.  1990,  27:  2085 

33c Baraldi PG. Tetrahedron  1987,  43:  235 

33d Wang G.-W. Green Chem.  2006,  8:  1080 

33e Sviridov SI. Tetrahedron  2007,  63:  12195 

33f Simunek P. Tetrahedron  2005,  61:  8130 

33g Boatman S. J. Org. Chem.  1966,  31:  1785 

33h Tan SF. Ang KP. Jayachandran H. J. Chem. Soc., Perkin Trans. 2  1983,  1011 

33i Khodaei MM. Khosropour AR. Kookhazadeh M. Can. J. Chem.  2005,  83:  209 

33j Lyubchanskaya VM. Mukhanova TI. Panisheva EK. Alekseeva LM. Granik VG. Khim. Farm. Zh.  1995,  29:  40 ; Chem. Abstr. 1995, 124, 145843

33k Zhuo J.-C. Magn. Reson. Chem.  1997,  355:  311 

33l Vovk MB. Russ. J. Org. Chem.  2007,  43:  256 

33m Bannikova YN. Khalturina VV. Sedegova EA. Maslivets AN. Russ. J. Org. Chem.  2007,  43:  154