Abstract
Primary thioamides are prepared in excellent yield from the corresponding nitrile by treatment with ammonium sulfide in methanol, at room temperature for electron-deficient aromatic nitriles or under microwave irradiation at 80 °C or 130 °C in 15-30 minutes for other aromatic and aliphatic nitriles. This procedure avoids the use of gaseous H2 S under high pressure, proceeds in the absence of base and provides thioamides usually without the need for chromatographic purification.
Key words
thioamides - nitriles - microwaves
References
1a Takahata H.
Yamazaki T.
Heterocycles
1988,
27:
1953
1b Hurd RN.
Delamater GT.
Chem. Rev.
1961,
61:
45
2 Brillon D.
Sulfur Rep.
1992,
12:
297
3 Cava MP.
Levinson MI.
Tetrahedron
1985,
41:
5061
4 Hartke K.
Gerber H.-D.
J. Prakt. Chem.
1996,
338:
763
5 Charette AB.
Grenon M.
J. Org. Chem.
2003,
68:
5792
6 Walter W.
Bode KD.
Angew. Chem., Int. Ed. Engl.
1996,
5:
447
7 Fairfull AES.
Lowe JL.
Peak DA.
J. Chem. Soc.
1952,
742
8a Kindler K.
Liebigs Ann. Chem.
1923,
431:
187
8b Wang C.-H.
Hwang F.-Y.
Horng J.-M.
Chen C.-T.
Heterocycles
1979,
12:
1191
9 Gabriel S.
Heymann P.
Ber. Dtsch. Chem. Ges.
1890,
23:
157
10 Erlenmeyer H.
Degen K.
Helv. Chim. Acta
1946,
29:
1080
11 Albert A.
Ber. Dtsch. Chem. Ges.
1915,
48:
470
12 Taylor EC.
Zoltewicz JA.
J. Am. Chem. Soc.
1960,
82:
2656
13 Liboska R.
Zyka D.
Bobek M.
Synthesis
2002,
1649
14 Brillon D.
Synth. Commun.
1992,
22:
1397
15 Shiao MJ.
Lai LL.
Ku WS.
Lin PY.
Hwu JR.
J. Org. Chem.
1993,
58:
4742
16a Gabriel C.
Gabriel S.
Grant EH.
Halstead BSJ.
Mingos DMP.
Chem. Soc. Rev.
1998,
27:
213
16b Kuhnert N.
Angew. Chem. Int. Ed.
2002,
41:
1863
16c Lidström P.
Tierney J.
Wathey B.
Westman J.
Tetrahedron
2001,
57:
9225
16d Loupy A.
Petit A.
Hamelin J.
Texier-Boullet F.
Jacquault P.
Mathé D.
Synthesis
1998,
1213
16e Galema SA.
Chem. Soc. Rev.
1997,
26:
233
16f Caddick S.
Tetrahedron
1995,
51:
10403
16g Strauss CR.
Trainor RW.
Aust. J. Chem.
1995,
48:
1665
16h Loupy A.
Wiley VCH;
Weinheim:
2002.
17 Zbruyev OI.
Stiasni N.
Kappe CO.
J. Comb. Chem.
2003,
5:
145
18 Varma RS.
Kumar D.
Org. Lett.
1999,
1:
697
19 Bagley MC.
Dale JW.
Jenkins RL.
Bower J.
Chem. Commun.
2004,
102
20 Bagley MC.
Dale JW.
Xiong X.
Bower J.
Org. Lett.
2003,
5:
4421
21
General Procedure for Reaction of Nitriles 1 and Ammonium Sulfide at Room Temperature (Method A). A solution of nitrile 1 (0.5 mmol, 1 equiv) and (NH4 )2 S (0.5 mmol, 1 equiv; 50 wt.% in H2 O) in MeOH (5 mL) was stirred at r.t. for 18 h, evaporated in vacuo and partitioned between EtOAc (10 mL) and H2 O (10 mL). The aqueous layer was further extracted with EtOAc (2 × 5 mL) and the organic extracts were combined, washed with brine (10 mL), dried (Na2 SO4 ) and evaporated in vacuo to give thioamide 2 .
22
General Procedure for Microwave-Assisted Reaction of Nitriles 1 and Ammonium Sulfide (Method B). A solution of nitrile 1 (0.5 mmol, 1 equiv) and (NH4 )2 S (0.5 mmol, 1 equiv; 50 wt.% in H2 O) in MeOH (5 mL) was irradiated for 15 min in a self-tunable CEM microwave Discover synthesizer at 80 °C (initial power 100 W) and then cooled using a flow of compressed air, evaporated in vacuo and partitioned between EtOAc and H2 O. The aqueous layer was further extracted with EtOAc (2 × 5 mL) and the organic extracts were combined, washed with brine (10 mL), dried (Na2 SO4 ) and evaporated in vacuo to give thioamide 2 .
23 Feiring AE.
J. Org. Chem.
1976,
41:
148
24 Walter W.
Curts J.
Chem. Ber.
1960,
93:
1511
25 Inami K.
Shiba T.
Bull Chem. Soc. Jpn.
1985,
58:
352
26 The nitriles depicted in Figure
[1
27 The reaction of 2-cyanopyridine(1a ) with ammonium sulfide according to method A has been conducted on a larger scale (10 mmol) to give thioamide 2a without any reduction in yield.
28 With a volatile aliphatic nitrile, such as 1c , evaporation in vacuo after an aqueous work-up removed unreacted starting material. For reactions that were not quantitative, purification by column chromatography on silica was usually required. For experiments that gave >98% yield (Table
[2
