Dithiadiphosphetane disulfides

Fewer routes are known for the preparation of dithiophosphonic acids. Nevertheless sodium dithiophosphophonates have been prepared in high yields from reaction of dithiadiphosphetane disulfides with a sodium alkoxide or aryloxide in the corresponding alcohol solution (Equation 25).40,41... 

Diathiadiphosphetane disulfides are probably the most studied and the most thermally and hydrolytically stable of all the phosphorus-chalcogen heterocycles. They contain a central four membered P2S2 ring and can be prepared from heating phosphorus pentasulfide with aromatic compounds. The most well-known of these is Lawesson s reagent (43), which is made from anisole and phosphorus pentasulfide,92 and is used extensively in organic synthesis procedures (see Section 5.4.1). Other dithiadiphosphetane disulfides of note are 44 and 45, formed from the reaction of phosphorus pentasulfide with ferrocene or 1 -bromonaphthalene respectively.93... 

In contrast to 43-45 the non-aromatic dithiadiphosphetane disulfides are much more difficult to prepare, requiring the use of high temperatures and hydrogen sulfide (Equation 70).94... 

General. Several reviews on 2,4-bis(4-methoxyphenyl)-l,3, 2,4-dithiadiphosphetane disulfide, Lawesson s Reagent (LR), have appeared since 1992, which deal with its chemical properties and reactions and, in particular, its use in synthetic chemistry. The most valuable and comprehensive one was authored by Jesberger et al. Li et al. have written a Chinese review article on new applications of LR in organic s)fntheses. A modification of LR which carries tert-butyl substituents (13) has been described by Foreman. Compound 13 is better soluble in organic solvents and thus more reactive than LR. Reports on the use of LR in syntheses of thioaldehydes and thioketones have appeared. 

A diversity of thiolactams has been prepared from the corresponding lactams by use of LR or of the modified reagent (13). Monobactam analogs, e.g., the weakly antibacterial -thiolactam (93), have been prepared by thionation of suitably protected optically active /3-lactams with LR or Davy s reagent (2,4-bis (methylthio)-l,3,2,4-dithiadiphosphetane disulfide), deprotection and subsequent introduction of the side chain. Very recently, an efficient solid-phase synthesis of 1,3,4-trisubstituted /3-thiolactams has been described. The y-thiolactam (94) has been prepared as an intermediate for the synthesis of analogs of the acetylcholinesterase inhibitor huperzine B. Transformation of the quinoline alkaloid cytisine into its thio analog (95) enhanced its biological activity. ... 

In this case 2,4-bis(4-phenoxyphenyl)-l,3,2,4-dithiadiphosphetane disulfide was used instead of, LR Ohno, M. Itoh, M. Ohashi, T. Eguchi, S., Synthesis 1993, 793. 

Feldman, K. S. Schildknegt, K., J. Org. Chem. 1994, 59, 1129. A corresponding thionoester O-ethyl 2,2-dichloro-3-methylcyclopro-panethioate has been obtained by using 2,4-diphenyl-l,3,2,4-dithiadiphosphetane disulfide (Yokoyama, M. Hasegawa, Y Hatanaka, H. Kawazoe, Y Imamoto, X, Synthesis 1984, 827) instead ofLR. 

LR, 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)-l,3,2,4-dithiadiphosphetane 2,4-disulfide, has recently found considerable synthetic application. 

Bis-(4-methoxyphenyl)-[l,3,2,4]dithiadiphosphetane 2,4-disulfide, transforms the carbonyl groups of ketones, amides and esters into the corresponding thiocarbonyl compounds. Cf. Knorr thiophene synthesis. 

Thiopyrimidines can be prepared by thiolysis of halopyrimidines or by thiation of pyrimidinones with phosphorus pentasulfide or Lawesson s reagent (2,4-bis-/i-methoxyphenyl-l,3,2,4-dithiadiphosphetane-2,4-disulfide) <2003JOC9971>. The dithiation of uracil and thiamine has also been performed with the assistance of microwave irradiation using phosphorus pentasulfide absorbed on silica gel <2001SC2231>. 

The addition of H2S to an aldehyde or ketone can result in a variety of products. The most usual product is the trithiane 9.m a-Hydroxy thiols (6) can be prepared from polychloro and polyfluoro aldehydes and ketones.110 Apparently 6 are stable only when prepared from these compounds, and not even for all of them. Thioketones2 (7) can be prepared from certain ketones, such as diaryl ketones, by treatment with H2S and an acid catalyst, usually HCI. They are often unstable and tend to trimerize (to 9) or to react with air. Thioaldehydes111 are even less stable and simple ones112 apparently have never been isolated, though f-BuCHS has been prepared in solution, where it exists for several hours at 20°C.111 A high-yield synthesis of thioketones involves treatment of acyclic114 ketones with 2,4-bis(4-methoxyphenyl)- ,3,2,4-dithiadiphosphetane-2,4-disulfide 10 (known as Lawesson s... 

The first reported l,3,2X -thiazaphosphetidine ring system 588 was obtained by cycloaddition of isocyanates to l,2X -azaphospholes. They are in equilibrium with 2,4,lX -diazaphosphetidine-3-thiones. Two other 1,3,2-thiazaphosphetidines (e.g., 589) have been obtained by treatment of Af-nitrosoamines with 2,4-bisO -methoxyphenyl)-l,3,2,4-dithiadiphosphetane-2,4-disulfide. The addition of carbon disulfide to phosphinimes to give a phosphine sulfide and an isocyanate may involve a cyclic intermediate. ... 

In the last decade the methods of converting carbonyl to the corresponding thiocarbonyl compounds have been substantially improved. " Therefore, thioxo- as well as dithio-carboxylic esters are accessible from esters, thiol esters and even carboxylic acids by reacting them with phosphorus pentasul-fide or 1,3,2,4-dithiadiphosphetane 2,4-disulfides such as Lawesson s or Davy s reagent (equation 4 cf. Chapter 4.1, this volume). 

Syntheses and properties of phosphorus-sulfur compounds on the basis of 1,3,2,4-dithiadiphosphetane 2,4-disulfides 02ZOB1442. 

The best preparative method for mercaptopyrimidines varies from position to position from thioureas and their equivalents. Thiones in any of the electrophilic positions are prepared by thiolysis of halo-pyrimidines, or commonly by thiation of pyrimidinones using phosphorus pentasulfide or, more recently, the superior Lawesson reagent 2,4-bis-/ -methoxyphenyl-l,3,2,4-dithiadiphosphetane 2,4-disulfide. Thiolysis in the 5-position requires a metal sulfide and a 5-bromide under vigorous conditions. Alternatively, pyrimidines substituted with strongly electron-donating substituents may be sulfonated, for example, by chlorosulfonic acid, in the 5-position with subsequent reduction to thiol. 

Pyrazine- and quinoxalinethiones have been synthesized by treatment of halogeno compounds with sodium or potassium hydrogen sulfide, sodium polysulfide, phosphorus pentasulfide, or thiourea . Pyrazinethiones are directly prepared by treating 2(177)-pyrazinones with Lawesson s reagent (2,4-bis(4-methoxyphenyl)-l,3,2,4-dithiadiphosphetane 2,4-disulfide) <83H(20)797>. They are also obtained by treatment of (4-methoxybenzylthio)pyrazines with mer-cury(II) acetate and successive reduction <93JCS(P1)15>. 

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