Ammonium Phosphorodithioate: A Mild, Easily Handled, Efficient, and Air-Stable Reagent for the Conversion of Amides into Thioamides

Abstract

A simple, efficient, and new method has been developed for the synthesis of thioamides from amides. As described below, the reaction of a variety of aromatic and aliphatic amides in the presence of ammonium phosphorodithioate as an efficient reagent proceeded effectively to afford the corresponding thioamides in high yields. This method is easy, rapid, and high-yielding for the synthesis of thioamides from amides using an easily handled reagent.

thioamides - amides - phosphorodithioates - thionation

References and Notes

1a Oare DA. Sanner MA. Heathcock CH. J. Org. Chem.  1990,  55:  132 

1b Heathcock CH. Davidson SK. Mills SG. Sanner MA. J. Org. Chem.  1992,  57:  2531 

1c Magnus P. Mendoza JS. Stamford A. Ladlow M. Willis P. J. Am. Chem. Chem. Soc.  1992,  114:  10232 

1d Kim G. Chu-Moyer MY. Danshefsky SJ. Schulte GK. J. Am. Chem. Soc.  1993,  115:  30 

1e Takahata H. Banba Y. Mozumi M. Yamazaki T. Heterocycles  1986,  24:  947 

1f Takahata H. Yamazaki T. Heterocycles  1988,  27:  1953 

1g Hurd RN. Delmater GT. Chem. Rev.  1961,  61:  45 

1h Roth HJ. Kleemann A. Drug Synthesis, In Pharmaceutical Chemistry   Vol. 1:  Wiley; New York: 1988. 

1i Hoeg-Jensen T. Phosphorus, Sulfur Silicon Relat. Elem.  1996,  108:  1 

2 Sherman DB. Spatola AF. Wire WS. Burks TF. Nguyen TM.-D. Schiller PW. Biochem. Biophys. Res. Commun.  1982,  162:  1126 

3 Albert A. Knecht H. Andersen E. Hungerford V. Schreier MH. Papageorgiou C. Bioorg. Med. Chem.  1988,  8:  2203 

4 Jeschke P. Harder A. Etzel W. dau W. Thielking G. Bonse G. Linuma K. Pest Manag. Sci.  2001,  57:  1000 

5 Cynamon MH. Gimi R. Gyenes F. Sharpe CA. Bergmann KE. Han HJ. Gregor LB. Rapolu R. Luciano G. Welch T. J. Med. Chem.  1995,  38:  3902 

6 Renau TE. Ludwig MS. Drach JC. Townsend LB. Bioorg. Med. Chem. Lett.  1992,  2:  1755 

7 Mehanna AS. Belani JD. Kelley CJ. Pallansc LA. Med. Chem.  2007,  3:  513 

8 Suzyki Y. Yazaki R. Kumagai N. Shibasaki M. Angew. Chem. Int. Ed.  2009,  48:  5026 

9a Kindler K. Justus Liebigs Ann. Chem.  1923,  431:  187 

9b Zbruyev OI. Stiasni N. Kapper CO. J. Comb. Chem.  2003,  5:  145 

9c Wang C.-H. Hwang F.-Y. Horng J.-M. Chen C.-T. Heterocycles  1979,  12:  1191 

9d Albert A. Ber. Dtsch. Chem. Ges.  1915,  48:  470 

9e Taylor EC. Zoltewicz JA. J. Am. Chem. Soc.  1960,  82:  2656 

9f Liboska R. Zyka D. Bobek M. Synthesis  2002,  1649 

9g Benner SA. Tetrahedron Lett.  1981,  22:  1851 

9h Benner SA. Tetrahedron Lett.  1981,  22:  1855 

9i Shiao MJ. Lai LL. Ku WS. Lin PY. Hwu JR. J. Org. Chem.  1993,  58:  4772 

9j Brillon D. Synth. Commun.  1992,  22:  1397 

10 Okamoto K. Yamamoto T. Kanbara T. Synlett  2007,  2687 

For selected articles, see:

11a Ozturk T. Ertas E. Mert O. Chem. Rev.  2007,  107:  5210 

11b Varma RS. Kumar D. Org. Lett.  1999,  1:  697 

11c Curphey TJ. J. Org. Chem.  2002,  67:  6461 

12 Charette AB. Gernon M. J. Org. Chem.  2003,  68:  5792 

13 Pathak U. Pandey LK. Tank R. J. Org. Chem.  2008,  78:  2890 

14 Borthakur N. Goswami A. Tetrahedron Lett.  1995,  36:  6745 

15 Cho D. Ahn J. De Castro KA. Ahn H. Rhee H. Tetrahedron  2010,  66:  5583 

16a Kaboudin B. Norouzi H. Synthesis  2004,  2035 

16b Kaboudin B. Elhamifar D. Synthesis  2006,  224 

16c Kaboudin B. Elhamifar D. Farjadian F. Org. Prep. Proced. Int.  2006,  38:  412 

17

The amide (5 mmol) was added to a mixture of O,O-diethyl ammonium phosphorodithioate salt (10 mmol, 2.03 g)^¹6a and toluene (5 mL), and the reaction mixture was stirred for 4-10 h at reflux. After stirring for a known period (Table  [²] ), the mixture was evaporated under reduced pressure. The resulting mixture was subjected to column chromatography on silica gel with EtOAc-n-hexane (1:9), and evaporation of the solvent under reduced pressure gave pure products in 70-91% yields. All products gave satisfactory spectral data in accord with the assigned structures and literature reports.^{9-¹6,¹8-²²}
Thiobenzamide (2a)
^¹H NMR (400 MHz, CDCl₃): δ = 7.29 (br, 1 H, NH₂), 7.43 (t, 2 H, J = 8.0 Hz), 7.54 (t, 1 H, J = 8.0 Hz), 7.89 (d, 2 H, J = 8.0 Hz), 7.90 (br, 1 H, NH₂). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 126.9, 128.5, 132.1, 139.2, 202.2.
2-Chlorothiobenzamide (2b)
^¹H NMR (400 MHz, CDCl₃): δ = 7.35 (br, 1 H, NH₂), 7.28-7.48 (m, 3 H), 7.62 (d, 1 H, J = 8.0 Hz), 8.45 (br, 1 H, NH₂). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 127.1, 128.2, 130.1, 130.2, 131.0, 140.4, 201.5.
3-Chlorothiobenzamide (2c)
^¹H NMR (400 MHz, CDCl₃): δ = 7.29 (br, 1 H, NH₂), 7.37 (t, 1 H, J = 8.0 Hz), 7.50 (d, 1 H, J = 8.0 Hz), 7.72 (d, 1 H, J = 8.0 Hz), 7.88 (s, 1 H), 7.92 (br, 1 H, NH₂). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 124.8, 127.3, 131.9, 134.6, 140.8, 201.1.
N -Phenylthiobenzamide (2d)
^¹H NMR (400 MHz, CDCl₃): δ = 7.23-7.90 (m, 10 H), 9.03 (br, 1 H, NH). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 123.6, 126.7, 127.0, 128.7, 129.1, 131.3, 138.9, 143.3, 198.3.
N -(2-Ethylphenyl)thiobenzamide (2e)
^¹H NMR (400 MHz, CDCl₃): δ = 1.29 (t, 3 H, J = 7.6 Hz), 2.71 (q, 2 H, J = 7.6 Hz), 7.23-7.45 (m, 3 H), 7.47 (t, 2 H, J = 7.6 Hz), 7.57 (t, 2 H, J = 7.2 Hz), 7.93 (d, 2 H, J = 7.2 Hz), 8.87 (br, 1 H, NH). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 14.4, 24.5, 126.8, 127.4, 128.5, 128.7, 129.2, 131.5, 137.0, 139.8, 142.2, 200.0.
N -(4-Methoxyphenyl)thiobenzamide (2f)
^¹H NMR (400 MHz, CDCl₃): δ = 3.88 (s, 3 H), 7.01 (d, 2 H, J = 7.2 Hz), 7.45 (t, 2 H, J = 7.6 Hz), 7.53 (t, 1 H, J = 7.2 Hz), 7.66 (d, 2 H, J = 7.2 Hz), 7.89 (d, 2 H, J = 7.2 Hz), 8.97 (br, 1 H, NH). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 55.5, 114.2, 125.6, 126.7, 128.7, 129.2, 131.3, 131.9, 143.0, 158.2, 198.2.
N -(4-Bromophenyl)thiobenzamide (2g)
^¹H NMR (400 MHz, CDCl₃): δ = 7.40-7.65 (m, 5 H), 7.74 (d, 2 H, J = 7.2 Hz), 7.87 (d, 2 H, J = 7.2 Hz), 8.98 (br, 1 H, NH). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 119.9, 125.1, 128.8, 129.2, 131.5, 132.2, 137.9, 198.0.
N -Cyclohexylthiobenzamide (2h)
^¹H NMR (400 MHz, CDCl₃): δ = 1.19-1.60 (m, 5 H), 1.62-1.85 (m, 3 H), 2.17-2.25 (m, 2 H), 4.48-4.61 (m, 1 H), 7.36 (t, 2 H, J = 7.6 Hz), 7.44 (t, 1 H, J = 7.2 Hz), 7.54 (br, 1 H, NH), 7.70 (d, 2 H, J = 7.2 Hz). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 24.7, 25.5, 31.6, 55.0, 126.7, 128.4, 130.9, 142.3, 197.6.
2-Chloro- N -cyclohexylthiobenzamide (2i)
^¹H NMR (400 MHz, CDCl₃): δ = 1.19-1.60 (m, 5 H), 1.62-1.85 (m, 3 H), 2.17-2.25 (m, 2 H), 4.48-4.62 (m, 1 H), 7.27-7.40 (m, 3 H, NH), 7.50-7.40 (m, 1 H), 7.57-7.62 (m, 1 H). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 24.6, 25.5, 31.3, 54.8, 127.0, 128.3, 129.9, 130.1, 130.3, 142.2, 195.5.
N,N- Dimethylthiobenzamide (2j)
^¹H NMR (400 MHz, CDCl₃): δ = 3.03 (s, 3 H), 3.47 (s, 3 H), 7.15-7.29 (m, 5 H). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 43.2, 44.2, 125.7, 128.3, 128.5, 143.3, 200.7.
4-Methyl- N , N- dimethylthiobenzamide (2k)
^¹H NMR (400 MHz, CDCl₃): δ = 2.34 (s, 3 H), 3.16 (s, 3 H), 3.57 (s, 3 H), 7.13 (d, 2 H, J = 8.0 Hz), 7.20 (d, 2 H, J = 8.0 Hz). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 21.3, 43.4, 44.3, 125.9, 128.9, 138.7, 140.6, 201.4.
4-Chloro- N , N- dimethylthiobenzamide (2l)
CAS No. 15563-46. ^¹H NMR (400 MHz, CDCl₃): δ = 3.19 (s, 3 H), 3.60 (s, 3 H), 7.26 (d, 2 H, J = 8.4 Hz), 7.34 (d, 2 H, J = 8.4 Hz). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 43.3, 44.2, 127.3, 128.6, 134.6, 141.6, 199.8.
3-Methyl- N , N- dimethylthiobenzamide (2m)
^¹H NMR (400 MHz, CDCl₃): δ = 2.34 (s, 3 H), 3.14 (s, 3 H), 3.57 (s, 3 H), 7.05 (d, 1 H, J = 7.6 Hz), 7.12 (d, 2 H, J = 6.0 Hz), 7.22 (d, 1 H, J = 8.0 Hz). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 21.4, 43.2, 44.2, 122.6, 126.3, 128.2, 129.3, 138.1, 143.4, 201.4.
Thioacetamide (2n)
CAS No. 62-55-5. ^¹H NMR (400 MHz, CDCl₃): δ = 3.34 (s, 3 H), 8.90-9.20 (br, 2 H, NH₂). ^¹³C NMR (100.65 MHz, CDCl₃): δ = 31.0, 206.1.

18 Habibi M. Habibi MH. Tangestaninejad S. Fallah-Shojaie A. Mohammadpoor-Baltork I. Tayyari SF. Emtiazi G. Hamidimotlagh R. J. Coord. Chem.  2005,  58:  955 

19 Alliger G. Smith GEP. Carr EL. Stevens HP.
J. Org. Chem.  1949,  14:  962 

20 Rauf MK. Bolte M. Badshah A. Acta Crystallogr., Sect. E: Struct. Rep. Online  2009,  65:  01265 

21 Hori T. Otani Y. Kawahata M. Yamaguchi K. Ohwada T. J. Org. Chem.  2008,  73:  9102 

22 Scheibye S. Pedersen BS. Lawesson S.-O. Bull. Soc. Chim. Belg.  1978,  78:  229 

23 Bagley MC. Chapaneri K. Glover C. Merritt EA. Synlett  2004,  2615