Thioacids

Dimethy1aminocarbodithioic acid (dimethyldithiocarbamic acid) (C H NS2) Dipropylaminocarbodithioic acid (dipropyldithiocarbamic acid) 

Pentamethyleneaminocarbodithioic acid (piperidine-N-dithiocarboxylic 57Ja,73SSC acid) 

Hexamethyleneaminocarbodithioic acid Morpholine-N-carbodithioic acid (C H 0NS2) 

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The thiazole ring can be obtained directly by other methods, but they have limited application. An example is the synthesis of Cook and Heilbron using a-aminonitriles or a-aminoamides and carbon disulfide (or thioacid derivatives) as reactants of type II. 

Thioacids (191) react with ia -thiocyanatoacetophenone to produce 2-mercapto-4-phenylthiazole (192) (Scheme 99). With tbioacetic acid 192 is obtained directly while with thiobenzoic acid, an acyclic intermediate (193) has been isolated that is cyclized by heating with dilute acid (Scheme 100) (143). 

Replacement of Oxygen by Other Chalcogens. Acids derived from oxoacids by replacement of oxygen by sulfur are called thioacids, and the number of replacements are given by prefixes di-, tri-, and so on. The affixes seleno- and telluro- are used analogously. 

Diaryl derivatives of the 1,3-oxathiolylium system (29) are prepared by acid-catalyzed cyclization of the /3-keto thioesters (28) which are readily prepared from thioacid salts (27)... 

Thioacids have a most disagreeable odour and slowly decompose in air. Their boiling points are lower than those of the coiTcsponding oxygen counterparts and they are less soluble in water, but soluble in most organic solvents. An important dithioacid is dithiocarbonic acid (HO—CS2H). Whilst the free acid is unknown, many derivatives have been prepared such as potassium xanthate giving a yellow precipitate of copper xanthate with copper salts ... 

Cleavage with thioacids IRCOSH) results in the formation of amides, R 2NC(0)R. The concept was extended to the formation of ureas, thioureas, and thioamides. ... 

Numerous peroxoacid or thioacid derivatives of Se and Te have been reported but these add little to the discussion of the reaction chemistry or the stmcture types already... 

Phenyl-l,2,3,4-thiatriazole was prepared in this laboratory in 1952 and shown by its infrared spectrum not to be an azide. However, this observation was made in conjunction with rather extensive studies of thioacids and their derivatives and was not published until 1961, when sixteen 5-aryl- and 5-heterocyclyl-l,2,3,4-thiatriazoles were described. Independently, 5-phenyl-1,2,3,4-thiatriazole was also obtained by Bacchetti and Alemagna, Kirmse, and Smith and Kenny and shown by its infrared spectrum not to be an azide. The last two groups of investigators also prepared some other 5-sub-stituted-l,2,3,4-thiatriazoles. Finally, Scottcommented on the anomalous infrared spectra of thiocarbamoyl azides and concluded that they were actually thiatriazoles. 

Reaction of etio acid 67 with N,N-dimethylthioformamidoyl chloride probably gives initially the mixed anhydride 71 this is not isolated but undergoes O to S carbonyl migration to the anhydride 72. Saponification then leads to the thioacid 73. Reaction of the sodium salt of the acid witli bromochloromethane affords cloticasone propionate (74). The corresponding reaction with hioniofluoromethane leads to fluticasone propionate (75) [16]. 

Finally, non-racemic phosphorothioic and phosphonothioic acids 98 were obtained via a PTE-catalysed stereoselective hydrolysis of the prochiral substrates 97 (Equation 48). ° The absolute configurations of the thioacids 98 depended on whether native PTE or its mutants were used. 

The first reductive kinetic resolution of racemic sulphoxides was reported by Balenovic and Bregant. They found that L-cysteine reacted with racemic sulphoxides to produce a mixture of L-cystine, sulphide and non-reduced optically active starting sulphoxide (equation 147). Mikojajczyk and Para reported that the reaction of optically active phosphonothioic acid 268 with racemic sulphoxides used in a 1 2 ratio gave the non-reduced optically active sulphoxides, however, with a low optical purity (equation 148). It is interesting to note that a clear relationship was found between the chirality of the reducing P-thioacid 268 and the recovered sulphoxide. Partial asymmetric reduction of racemic sulphoxides also occurs when a complex of LiAlH with chiral alcohols , as well as a mixture of formamidine sulphinic acid with chiral amines, are used as chiral reducing systems. ... 

Fig. 7.9 Oxidative acylation of thioacids. The second reaction step is fast, the third slow (Liu and Orgel, 1997)...

Dipeptide Amino thioester DCC Peptide thioacid 93 20060L823... 

Dithiophosphoric acids, (RO)2PS2H, have been used for the thionation of carbonyl groups in certain aldehydes, ketones, amides, esters, thio-carboxylates and other organics.163 The mechanism for this reaction proceeds via a reversible nucleophilic attack of the thioacid on the carbonyl compound, which can then rearrange by way of a four-membered PSCO cyclic intermediate into the desired C=S containing molecule and thiophosphoric acid (Equation 81).163... 

Interest in the organotin derivatives of the acids and thioacids of phosphorus arises from their potential biological action and the wide variety of structures that have been identified by X-ray diffraction. These structures are often particularly complex when the compounds are derived from the partially hydrolyzed mono- or diorganotin compounds, and words such as cubes, drums, crowns, butterflies, clusters, oxygen-capped clusters, and extended clusters have been use to describe them. References to the early work are given in Ref 351, and a recent review is available.352... 

The data in the tables can generally be interpreted satisfactorily without invoking such orientation effects. This is not to say that they do not exist at all, but simply that they must be relatively small. The major difficulty in identifying any small effect is the elimination of all other possibilities. Storm and Koshland (1972ab) have made the best attempt to do this in their discussion of the relative rates of lactonization of the series of hydroxy and thioacids B.2.1-9 and C.2.1-5, but these rates were found to parallel the equilibrium constants for the lactonization, and it seems probable that the dominant effect controlling reactivity in these systems—and not corrected for—is the relief of ground-state strain discussed above. 

Simple alkyl or aryl thioesters are commonly assayed as substrates of hydrolases, witness the hydrolysis of phenyl thioesters by horse serum carbox-ylesterase [150], For most substrates investigated, e.g., phenyl thioacetate, phenyl thiopropionate, and phenyl thiobutyrate (7.66, R = Me, Et, and Bu, respectively), kcat values were found, which were a few times larger than those of corresponding nitrophenyl esters, whereas the affinities were lower by approximately one order of magnitude. Methyl and phenyl esters of various linear thioacids were also found to be good substrates of mammalian liver carboxylesterases and serum cholinesterases [151]. 

Snatzke and co-workers (25) have also reported a general correlation for the a-proton of a series of a-substituted propionamides in PEA. Several other correlations have been made for carboxylic and phosphorus thioacids these are separately discussed in the next section. 

Domling et al. made react (3-amino butyric thioacid, 89, the isobutyraldehyde 64, and 86 into the product 90, which simultaneously contains a 13-lactam group and a thiazole system. 

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