· 2,4-Bis(methylthio)-1,3,2,4-dithiadiphosphetane 2,4-Disulfide
· (MW 284.38)
(reagent for the conversion of carboxylic acids into dithioesters and carbonyl groups into thiocarbonyl groups)
Alternate Name: Davy's reagent.
Physical Data: mp 125-136 °C.
Solubility: sol hot aromatic hydrocarbons, chlorobenzene.
Form Supplied in: pale yellow, evil-smelling crystals.
Analysis of Reagent Purity: 1H NMR spectrum: d = 2.86 (d, J = 20 Hz, CH3).
Preparative Method: reaction of P4S10 with methanethiol or methanol.1
Purification: washing with cyclohexane.
Handling, Storage, and Precautions: should be stored in the cold with exclusion of moisture. It is very toxic and must be handled under a hood or in glove-boxes due to its intolerable odor and the hazardous methanethiol which is easily liberated with moisture.
2,4-Bis(methylthio)-1,3,2,4-dithiadiphosphetane 2,4-disulfide as well as the analogous ethylthio, isopropylthio, and benzylthio derivatives have been introduced as reagents for syntheses by Davy and Metzner. These compounds (Davy's reagent, DR) can be used in the same way as Lawesson's reagent, LR (see 2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-Disulfide), for the thionation of carbonyl groups. DR is, however, considerably more reactive and in many cases more selective than LR. Furthermore, it exhibits the unique ability to transform carboxylic acids into dithiocarboxylic esters in one step. Similar dithiadiphosphetane disulfides with arylthio substituents have been designed in order to achieve an even improved effectiveness in thionation reactions and also to produce a more conveniently handled
reagent compared with the obnoxious DR. The so-called Japanese reagent (JR), 2,4-bis(phenylthio)-1,3,2,4-dithiadiphosphetane 2,4-disulfide,3 has recently found considerable synthetic application.
Transformation of Carboxylic Acids into Dithiocarboxylic Esters.2,4
Dithioesters bearing functional groups such as C=C double bonds,2 halogen,2,5 nitro,6 or phenoxy groups2 are obtained with yields of up to 68% on reaction of aliphatic (eq 1)2b or aromatic (eq 2)5b carboxylic acids with DR in boiling chlorobenzene. Acid chlorides can also be used as starting material.2b,4 Isolation and handling of pure DR can be avoided by using a one-pot procedure (eq 3),7 which consists of first reacting methanol or ethanol with P4S10 followed by addition of the carboxylic acid and further P4S10. The above mentioned JR enables one to prepare phenyl dithiocarboxylates in extremely short reaction times (eq 4).3
Thionation of Carbonyl Compounds.
Diaryl thioketones8 and 2,4-bis(diphenylmethylene)cyclobutane-1,3-dithione9 were obtained on reaction of the corresponding ketones with DR. On the other hand, JR was utilized to thionate selectively the carbonyl group of benzil monophenylimine.10 If carboxylic esters or lactones are reacted with DR, dithiocarboxylic esters4 or dithiolactones4,8 are formed, i.e. the carbonyl group is thionated and the alkoxy group is substituted by an alkylthio group. Bis(5-methyl-2-thienyl) disulfide is produced in this way from a butenolide (eq 5).4
A systematic study on the thionation reactions of primary, secondary, and tertiary amides and lactams with DR compared with LR and 2,4-bis(4-phenoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, the so-called Belleau's reagent (BR),11 has been performed.12 Generally, good yields are obtained with whichever reagent is used, but each reagent may exhibit advantages in a special case. DR has been mainly utilized for the preparation of simple thioamides (eq 6).8
JR has found application in endothiopeptide synthesis.3,13,14 One carbonyl group of a cyclohexapeptide is selectively thionated with JR (eq 7).15 The cyclic thiopeptide exhibits enhanced effectiveness as an inhibitor of triosephosphate isomerase (TIM). This results from the pronounced alteration of the backbone conformation which is due to different hydrogen bridges. Belleau's reagent, BR, can be used similarly to JR to prepare thiooligopeptides selectively16,17 or thiono esters of the carbohydrate series (eq 8).18
- 1. Davy, H. Sulfur Lett. 1985, 3, 39.
- 2. (a) Davy, H. CC 1982, 457. (b) Davy, H.; Metzner, P. JCR(S) 1985, 272; JCR(M) 1985, 2701.
- 3. Yokoyama, M.; Hasegawa, Y.; Hatanaka, H.; Kawazoe, Y.; Imamoto, T. S 1984, 827.
- 4. Yousif, N. M.; Pedersen, U.; Yde, B.; Lawesson, S.-O. T 1984, 40, 2663.
- 5. (a) Böge, A.; Voss, J. CB 1990, 123, 1733. (b) Gade, T.; Streek, M.; Voss, J. CB 1992, 125, 127.
- 6. Wollny, B.; Voss, J. PS 1992, 71, 231.
- 7. Davy, H.; Metzner, P. CI(L) 1985, 824.
- 8. Pedersen, U.; Yde, B.; Yousif, N. M.; Lawesson, S.-O. Sulfur Lett. 1983, 1, 167.
- 9. Strehlow, T.; Voss, J.; Spohnholz, R.; Adiwidjaja, G. CB 1991, 124, 1397.
- 10. Hafez, T. S. PS 1992, 66, 87.
- 11. Lajoie, G.; Lépine, F.; Maziak, L.; Belleau, E. TL 1983, 24, 3815.
- 12. Yde, B.; Yousif, N. M.; Pedersen, U.; Thomsen, I.; Lawesson, S.-O. T 1984, 40, 2047.
- 13. Guziec, F. S., Jr.; Wasmund, L. M. JCR(S) 1989, 155; JCR(M) 1989, 1301.
- 14. Shalaby, A. M.; Shabana, R.; Salem, E. M. S.; Osman, S. A. M. Egypt. J. Chem. 1988, 31, 697 (CA 1992, 117, 131 540h).
- 15. Kessler, H.; Matter, H.; Geyer, A.; Diehl, H.-J.; Köck, M.; Kurz, G.; Opperdoes, F. R.; Callens, M.; Wierenga, R. K. AG(E) 1992, 31, 328.
- 16. Sauvé, G.; Rao, V. S.; Lajoie, G.; Belleau, B. CJC 1985, 63, 3089.
- 17. Campbell, M. M.; Ross, B. C.; Semple, G. TL 1989, 30, 1997.
- 18. Barrett, A. G. M.; Lee, A. C. JOC 1992, 57, 2818.
Universität Hamburg, Germany
Copyright © 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.