Synthetic, mechanistic, and structural studies related to 1,2,4-dithiazolidine-3,5-dione

Journal of Organic Chemistry

Volumn 61, Issue 19, 1996, Pages 6639-6645

  Chen, Lin ^a   Thompson, Tracy R ^a,c   Hammer, Robert P ^a,b   Barany, George ^a  

^a University of Minnesota   (United States)

^b LOUISIANA STATE UNIVERSITY   (United States)

^c EDGEWOOD COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000476738     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo960723u     Document Type: Article

References (54)

1. (a) Xu, Q.; Musier-Forsyth, K.; Hammer, R. P.; Barany, G. In Peptides: Chemistry, Structure & Biology. Proceedings of the 14th American Peptide Symposium; Kaumaya, P. T. P.; Hodges, R. S. Eds.; Mayflower Scientific: Kingswinford, England, 1996; pp 123-124.
2. (b) Xu, Q.; Musier-Forsyth, K.; Hammer, R. P.; Barany, G. Nucleic Acids Res. 1996, 24, 1602-1607.
3. (a) Review: Zumach, G.; Kühle, E. Angew Chem., Int. Ed. Engl. 1970, 9, 54-63.
4. (b) Dahms, G.; Haas, A.; Klug, W. Chem. Ber. 1971, 104, 2732-2742.
5. 3N (1 equiv) to give 2, mp 56-57 °C (iPrOH); 30% yield for conversion 2 to 1, mp 142-144 °C (toluene).
6. 3) δ 157.3, 60.9, 14.4].
7. Compound 1 is also claimed in two patents, but as stated in a review (ref 3a), the methods that are general for N-R-1,2,4-dithiazolidine-3,5-diones (R = alkyl, aryl) fail for the special case R = H. The patents referred to describe the following. (a) R'O(C=S)NHR + Cl(C=O)SCl: Zumach, G.; Weiss, W.; Kühle, E., Belgian Patent 682,-991, June 23, 1966; British Patent 1,136,737, June 21, 1966; Chem. Abstr. 1969, 70, 77951p. (b) H(C=O)NHR + 2 Cl(C=O)SCl: Zumach, G.; Weiss, W.; Kühle, E., Farbenfabriken Bayer AG. Belgian Patent 682,820, June 20, 1966; Chem. Abstr. 1968, 68, 105203a. For a comprehensive description of this and the related patent literature, see ref 3a and the following: (d) Kühle, E. The Chemistry of the Sulfenic Acids; Georg Thieme: Stuttgart, Germany, 1973.
8. Compound 1 is also claimed in two patents, but as stated in a review (ref 3a), the methods that are general for N-R-1,2,4-dithiazolidine-3,5-diones (R = alkyl, aryl) fail for the special case R = H. The patents referred to describe the following. (a) R'O(C=S)NHR + Cl(C=O)SCl: Zumach, G.; Weiss, W.; Kühle, E., Belgian Patent 682,-991, June 23, 1966; British Patent 1,136,737, June 21, 1966; Chem. Abstr. 1969, 70, 77951p. (b) H(C=O)NHR + 2 Cl(C=O)SCl: Zumach, G.; Weiss, W.; Kühle, E., Farbenfabriken Bayer AG. Belgian Patent 682,820, June 20, 1966; Chem. Abstr. 1968, 68, 105203a. For a comprehensive description of this and the related patent literature, see ref 3a and the following: (d) Kühle, E. The Chemistry of the Sulfenic Acids; Georg Thieme: Stuttgart, Germany, 1973.
9. Compound 1 is also claimed in two patents, but as stated in a review (ref 3a), the methods that are general for N-R-1,2,4-dithiazolidine-3,5-diones (R = alkyl, aryl) fail for the special case R = H. The patents referred to describe the following. (a) R'O(C=S)NHR + Cl(C=O)SCl: Zumach, G.; Weiss, W.; Kühle, E., Belgian Patent 682,-991, June 23, 1966; British Patent 1,136,737, June 21, 1966; Chem. Abstr. 1969, 70, 77951p. (b) H(C=O)NHR + 2 Cl(C=O)SCl: Zumach, G.; Weiss, W.; Kühle, E., Farbenfabriken Bayer AG. Belgian Patent 682,820, June 20, 1966; Chem. Abstr. 1968, 68, 105203a. For a comprehensive description of this and the related patent literature, see ref 3a and the following: (d) Kühle, E. The Chemistry of the Sulfenic Acids; Georg Thieme: Stuttgart, Germany, 1973.
10. 2N-R′ corresponding to amino acids and peptides] are described in the following: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1977, 99, 7363-7365. (b) Słomczyńska, U.; Barany, G. J. Heterocycl. Chem. 1984, 21, 241-246. (c) Barany, G.; Słomczyńska, U.; Mott, A. W. Abstracts of Papers, 187th National Meeting of the American Chemical Society, St. Louis, MO, April 8-13, 1984; American Chemical Society: Washington, DC, 1984; ORG 32. (d) Zalipsky; S.; Albericio, F.; Słomczyńska, U.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 740-783. (e) Hammer, R. P.; Barany, G. Abstracts of Papers, 195th National Meeting of the American Chemical Society, Toronto, Canada, June 5-10, 1988; American Chemical Society: Washington, DC, 1988; ORG 137.
11. 2N-R′ corresponding to amino acids and peptides] are described in the following: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1977, 99, 7363-7365. (b) Słomczyńska, U.; Barany, G. J. Heterocycl. Chem. 1984, 21, 241-246. (c) Barany, G.; Słomczyńska, U.; Mott, A. W. Abstracts of Papers, 187th National Meeting of the American Chemical Society, St. Louis, MO, April 8-13, 1984; American Chemical Society: Washington, DC, 1984; ORG 32. (d) Zalipsky; S.; Albericio, F.; Słomczyńska, U.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 740-783. (e) Hammer, R. P.; Barany, G. Abstracts of Papers, 195th National Meeting of the American Chemical Society, Toronto, Canada, June 5-10, 1988; American Chemical Society: Washington, DC, 1988; ORG 137.
12. 2N-R′ corresponding to amino acids and peptides] are described in the following: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1977, 99, 7363-7365. (b) Słomczyńska, U.; Barany, G. J. Heterocycl. Chem. 1984, 21, 241-246. (c) Barany, G.; Słomczyńska, U.; Mott, A. W. Abstracts of Papers, 187th National Meeting of the American Chemical Society, St. Louis, MO, April 8-13, 1984; American Chemical Society: Washington, DC, 1984; ORG 32. (d) Zalipsky; S.; Albericio, F.; Słomczyńska, U.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 740-783. (e) Hammer, R. P.; Barany, G. Abstracts of Papers, 195th National Meeting of the American Chemical Society, Toronto, Canada, June 5-10, 1988; American Chemical Society: Washington, DC, 1988; ORG 137.
13. 2N-R′ corresponding to amino acids and peptides] are described in the following: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1977, 99, 7363-7365. (b) Słomczyńska, U.; Barany, G. J. Heterocycl. Chem. 1984, 21, 241-246. (c) Barany, G.; Słomczyńska, U.; Mott, A. W. Abstracts of Papers, 187th National Meeting of the American Chemical Society, St. Louis, MO, April 8-13, 1984; American Chemical Society: Washington, DC, 1984; ORG 32. (d) Zalipsky; S.; Albericio, F.; Słomczyńska, U.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 740-783. (e) Hammer, R. P.; Barany, G. Abstracts of Papers, 195th National Meeting of the American Chemical Society, Toronto, Canada, June 5-10, 1988; American Chemical Society: Washington, DC, 1988; ORG 137.
14. 2N-R′ corresponding to amino acids and peptides] are described in the following: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1977, 99, 7363-7365. (b) Słomczyńska, U.; Barany, G. J. Heterocycl. Chem. 1984, 21, 241-246. (c) Barany, G.; Słomczyńska, U.; Mott, A. W. Abstracts of Papers, 187th National Meeting of the American Chemical Society, St. Louis, MO, April 8-13, 1984; American Chemical Society: Washington, DC, 1984; ORG 32. (d) Zalipsky; S.; Albericio, F.; Słomczyńska, U.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 740-783. (e) Hammer, R. P.; Barany, G. Abstracts of Papers, 195th National Meeting of the American Chemical Society, Toronto, Canada, June 5-10, 1988; American Chemical Society: Washington, DC, 1988; ORG 137.
15. The dithiasuccinoyl (Dts) amino protecting group, removable by thiolysis and other reductive methods, was described first in ref 5a and has been applied in numerous other papers from our laboratories, e.g.: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1980, 102, 3084-3095. (b) Barany, G.; Albericio, F. J. Am. Chem. Soc. 1985,107, 4936-4942. (c) Albericio, F.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 177-205. (d) Hammer, R. P.; Albericio, F.; Gera, L.; Barany, G. Int. J. Pept. Protein Res. 1991, 36, 31-45. (e) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Barany, G. J. Am. Chem. Soc. 1996, 118, 3148-3155 and references cited in all of these papers.
16. The dithiasuccinoyl (Dts) amino protecting group, removable by thiolysis and other reductive methods, was described first in ref 5a and has been applied in numerous other papers from our laboratories, e.g.: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1980, 102, 3084-3095. (b) Barany, G.; Albericio, F. J. Am. Chem. Soc. 1985,107, 4936-4942. (c) Albericio, F.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 177-205. (d) Hammer, R. P.; Albericio, F.; Gera, L.; Barany, G. Int. J. Pept. Protein Res. 1991, 36, 31-45. (e) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Barany, G. J. Am. Chem. Soc. 1996, 118, 3148-3155 and references cited in all of these papers.
17. The dithiasuccinoyl (Dts) amino protecting group, removable by thiolysis and other reductive methods, was described first in ref 5a and has been applied in numerous other papers from our laboratories, e.g.: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1980, 102, 3084-3095. (b) Barany, G.; Albericio, F. J. Am. Chem. Soc. 1985,107, 4936-4942. (c) Albericio, F.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 177-205. (d) Hammer, R. P.; Albericio, F.; Gera, L.; Barany, G. Int. J. Pept. Protein Res. 1991, 36, 31-45. (e) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Barany, G. J. Am. Chem. Soc. 1996, 118, 3148-3155 and references cited in all of these papers.
18. The dithiasuccinoyl (Dts) amino protecting group, removable by thiolysis and other reductive methods, was described first in ref 5a and has been applied in numerous other papers from our laboratories, e.g.: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1980, 102, 3084-3095. (b) Barany, G.; Albericio, F. J. Am. Chem. Soc. 1985,107, 4936-4942. (c) Albericio, F.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 177-205. (d) Hammer, R. P.; Albericio, F.; Gera, L.; Barany, G. Int. J. Pept. Protein Res. 1991, 36, 31-45. (e) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Barany, G. J. Am. Chem. Soc. 1996, 118, 3148-3155 and references cited in all of these papers.
19. The dithiasuccinoyl (Dts) amino protecting group, removable by thiolysis and other reductive methods, was described first in ref 5a and has been applied in numerous other papers from our laboratories, e.g.: (a) Barany, G.; Merrifield, R. B. J. Am. Chem. Soc. 1980, 102, 3084-3095. (b) Barany, G.; Albericio, F. J. Am. Chem. Soc. 1985,107, 4936-4942. (c) Albericio, F.; Barany, G. Int. J. Pept. Protein Res. 1987, 30, 177-205. (d) Hammer, R. P.; Albericio, F.; Gera, L.; Barany, G. Int. J. Pept. Protein Res. 1991, 36, 31-45. (e) Jensen, K. J.; Hansen, P. R.; Venugopal, D.; Barany, G. J. Am. Chem. Soc. 1996, 118, 3148-3155 and references cited in all of these papers.
20. For a review of Gabriel synthesis of amines (alkylation of phthalimide salts, followed by dephthaloylation), see: Gibson, M. S.; Bradshaw, R. W. Angew. Chem., Int. Ed. Engl. 1968, 7, 919-930.
21. Compound 2 also has attractive properties for efficient sulfurization (see ref 2b and Scheme 4 of the present paper) and in Gabriellike syntheses: Chen, L.; Hammer, R. P.; Barany, G., work in progress.
22. Compound 3 has been described previously: (a) Holmberg, B. Chem. Zentralbl. 1930, 1925-1926. (b) Kresze, G.; Horn, A.; Philippson, R.; Trede, A. Chem. Ber. 1965, 98, 3401-3409. The paper by Kresze and co-workers includes some interesting mechanistic experiments, including crossover studies.
23. Compound 3 has been described previously: (a) Holmberg, B. Chem. Zentralbl. 1930, 1925-1926. (b) Kresze, G.; Horn, A.; Philippson, R.; Trede, A. Chem. Ber. 1965, 98, 3401-3409. The paper by Kresze and co-workers includes some interesting mechanistic experiments, including crossover studies.
24. (a) Blankenhorn, E. J. Prakt. Chem. 1877, 16, 358-384.
25. (b) Wheeler, H. L.; Barnes, B. Am. Chem. J. 1899, 22, 141-151.
26. (c) Davies, W.; MacLauren, J. A. J. Chem. Soc. 1951, 1434-1438.
27. (d) Goerdeler, J.; Schulze, A. Chem. Ber. 1982, 115, 1252-1255.
28. (a) Weiss, W. German Patent 1,224,720, Nov 11, 1966; Chem. Abstr. 1966, 65, 12112h.
29. (b) Barany, G.; Schroll, A. L.; Mott, A. W.; Halsrud, D. A. J. Org. Chem. 1983, 48, 4750-4761.
30. Cyanic acid (bp 23.5 °C) readily trimerizes to cyanuric acid (2,4,6-trihydroxy-1,3,5-triazine), a material with limited or negligible solubility in organic solvents that decomposes prior to melting. Review: Smolin, E. M.; Rapoport, L. In The Chemistry of Heterocyclic Compounds; Weissberger, A. Ed.; Wiley Interscience: New York, 1959; Vol. 13, pp 17-48. Some of the reactions described in this work gave a byproduct, which, on the basis of solubility properties and mass spectrometry, is assigned as cyanuric acid.
31. 3) is the solvent, the major product appears to be 11 (Scheme 2), which decomposes upon workup back to starting material 4.
32. Data taken from the following: Reichardt, C. Solvents and Solvent Effects in Organic Chemistry; VCH Verlagsgesellschaft: Weinheim, 1988; pp 408-410.
33. 3, the results are not strictly comparable to our observations on the reactions of 4 and 5). Physical and spectral properties of 6 are also reported herein.
34. Literature routes to 7, and some mechanistic proposals, are described in ref 9b and the following: (a) Walter, W. Justus Liebigs Ann. Chem. 1960, 833, 49-55.
35. (b) El-Wassimy, M. T. M.; Jorgensen, K. A.; Lawesson, S.-O. Tetrahedron 1983, 39, 1729-1734.
36. (c) Hu, N. K.; Aso, Y.; Otsubo, T.; Ogura, F. Chem. Lett. 1986, 603-606.
37. 3CN produced only the corresponding nitriles, RC≡N.
38. I.e., for R ≠ H, the reaction of R'O(C=S)NHR + Cl(C=O)SCl (compare to refs 3a and 4a) gives rise to low levels of carbamoylsulfenyl chlorides ClS(C=O)NHR, which cyclodimerize with loss of HCl + 1/2S to provide the heterocycle drawn below; see ref 5b for detailed mechanistic studies including crossover experiments. equation presented
39. As an example where 5 acts merely as an oxidant, in ref 3a, Zumach and Kühle report that Cl(C=O)SCl (5) reacts with thiophenol (PhSH) to give diphenyl disulfide (PhSSPh) plus COS and HCl. A more complicated further example is given in ref 5c.
40. The reactions of thiocarbamates with sulfenyl chlorides to provide formimidoyldisulfanes were described first by Harris: Harris, J. F., Jr. J. Am. Chem. Soc. 1960, 82, 155-158. They are supported by ample examples and mechanistic studies from Kühle (refs 3 and 4) and us (ref 5 and herein). See text for experimental evidence supporting the structure of intermediate 8 and studies of its further transformations.
41. 2, to thiocarbamates or thioamides. For examples, see: (a) McGowan, G. J. Chem. Soc. 1886, 190-196. (b) Barrett, A. G. M.; Barton, D. H. R.; Colle, R. J. Chem. Soc., Perkin Trans 1 1980, 665-671.
42. 2, to thiocarbamates or thioamides. For examples, see: (a) McGowan, G. J. Chem. Soc. 1886, 190-196. (b) Barrett, A. G. M.; Barton, D. H. R.; Colle, R. J. Chem. Soc., Perkin Trans 1 1980, 665-671.
43. An analogue of 11 with ethoxy groups replaced by phenyl groups has been isolated and subsequently converted to a thiadiazole by oxidation, see ref 9b.
44. 2O). The δ = 4.92 ppm for the methylene protons of the Et group indicates a strongly electropositive center and is also consistent with an ammonium form [in contrast, bis(formimidoyl)disulfane 10 has δ = 4.29 ppm for the methylene protons of the Et group].
45. The authors have deposited atomic coordinates for the structures of compounds 1 and 2 with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, on request, from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
46. Barany, G. Cryst. Struct. Commun. 1982, 11, 913-928 and references cited therein. This work provides a relevant discussion of planarities, bond lengths, bond angles, and dihedral angles in a number of five-membered heterocyclic disulfides.
47. (a) The reference spectral positions for isocyanurate 14 were established on a reasonably pure crystalline sample, mp 75-88 °C, which was obtained from the residue of a redistillation of the contents of an old bottle of ethyl isocyanate (EtN=C=O).
48. 3) δ 172.9, 64.1, 14.1]. (c) Literature mp's: 95 °C for 14; 30 °C for the cyanurate isomer; see: Dictionary of Organic Compounds, 5th ed.; Chapman & Hall: New York, 1982; C-10334 and T-02371, pp 131 and 5388.
49. 3) δ 172.9, 64.1, 14.1]. (c) Literature mp's: 95 °C for 14; 30 °C for the cyanurate isomer; see: Dictionary of Organic Compounds, 5th ed.; Chapman & Hall: New York, 1982; C-10334 and T-02371, pp 131 and 5388.
50. For relatively complicated routes to EtOC≡N, see: (a) Jensen, K. A.; Holm, A. Acta Chem. Scand. 1964, 18, 826-828. (b) Martin, D.; Mucke, W. Chem. Ber. 1965, 98, 2059-2062. For alkyl cyanate chemistry, see: (c) Jensen, K. A.; Due, M.; Holm, A.; Wentrup, C. Acta Chem. Scand. 1966, 20, 2091-2106.
51. For relatively complicated routes to EtOC≡N, see: (a) Jensen, K. A.; Holm, A. Acta Chem. Scand. 1964, 18, 826-828. (b) Martin, D.; Mucke, W. Chem. Ber. 1965, 98, 2059-2062. For alkyl cyanate chemistry, see: (c) Jensen, K. A.; Due, M.; Holm, A.; Wentrup, C. Acta Chem. Scand. 1966, 20, 2091-2106.
52. For relatively complicated routes to EtOC≡N, see: (a) Jensen, K. A.; Holm, A. Acta Chem. Scand. 1964, 18, 826-828. (b) Martin, D.; Mucke, W. Chem. Ber. 1965, 98, 2059-2062. For alkyl cyanate chemistry, see: (c) Jensen, K. A.; Due, M.; Holm, A.; Wentrup, C. Acta Chem. Scand. 1966, 20, 2091-2106.
53. On a 20 mmol scale, crude 2 from the reaction of 4 and 5 was treated as described in the text with concentrated aqueous HCl. Surprisingly, relatively little 1 was isolated (∼15% based on 4), and the main product (∼40% of the crude product) was cyanuric acid (compare to ref 12).
54. The Merck Index, 11th ed.; Budavari, S., Ed.; Merck & Co.: Rahway, NJ 1989; No. 4721, p 759.