Phosphorus, thiol derivatives

Organophosphate pesticides are synthetic and are usually esters, amides, or thiol derivatives of phosphoric, phosphonic, phosphorothioic, or phosphonothioic acids. Over 100 organo phosphorus compounds, representing a variety of chemical, physical, and biological properties, are currently on the market (Table 23.1). 

The thiol derivatives of arsenic can be prepared by similar methods to those used for phosphorus " Various mixed derivatives such as BuPhAsSPr can be prepared from BuPhAsI and PrSNa in absolute ethanoP . Displacement of an OEt group may occur in PhAsCl(OEt), but this reaction may involve rearrangement of an unstable intermediate PhAs(OEt)SBui . ... 

The )V-(2,2-diethoxycarbonyl)vinyl derivative of cephalosporin C (34) was reacted with thiols in water at pH 6.5 at 60°C for 5-6 hr, or in boiling methylene chloride for 50 min, or in the absence of a solvent at 140°C for 15 min to give the mercapto derivatives (1584) (82EUP45717). When the mercapto derivatives (1584) first were reacted with dimethylaniline and dichlorodimethylsilane at 30°C for 10 min, the mixtures were then cooled to -10°C, and phosphorus pentachloride was added, followed by stirring at -5°C for 40 min, the 7-aminoceph-3-ene-4-carboxylic acid derivatives (1585) were obtained after work-up. 

The possibility of orbital reorganization in ion-radicals should be taken into account. Thus, organic derivatives of three-valence phosphorus exist in the sp hybrid state and an electron is removed from one of these orbitals. The cation-radical formed can retain the initial orbital configuration, but can also convert into the sp d hybrid state. In the latter case, one additional orbital of the phosphorus atom becomes accessible for the reactant attack. If Y—H bond in the reactant is weak, the reaction R3P+ -f YH proceeds with the participation of an sp frontal orbital according to the radical mechanism. Thiols are typical reactants with the weak Y—H bonds. If anions (A ) react with RjP, the vacant sp d orbital of the phosphorus appears to be a target. Scheme 3.14 illustrates the orbital pictures and the reaction directions. 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, allenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphorus oxychloride [10025-87-3], POCl3 (11). Because sulfonic acids are generally not converted direcdy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphorus pentachloride [10026-13-8] and phosphorus pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl halides (12,13). The conversion may also be accomplished by continuous electrolysis of thiols or disulfides in the presence of aqueous HQ [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfuric acid [7789-21-1], or by reaction of the sulfonic acid or sulfonate with fluorosulfuric acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl halide, can be achieved under oxidative halogenation conditions (15). 

The only alkyl group reported as reductively removed is the di-phenylmethyl substituent from N3 in compound 165.153 Deoxygenation of N-oxides can be done thermally (heating in toluene with oxygen transfer to solvent) for compounds of type 166,44 or more commonly by use of phosphorus derivatives, as described for compounds 32, 33,45 166,44 and 167.61 Halogens can be reductively removed from [l,2,3]triazolo-[4,5-6]pyridines 160,146 168,220 and 169,142 and from pentachloro derivative 164, giving dichloro compound 170.208 Removal of thiol groups by reduction... 

The stable tautomer of indole-2-thiol is the thione, thiooxindole, and this compound and simple derivatives are conveniently prepared from the corresponding oxindoles by reaction with phosphorus pentasulfide (69CPB550). Like the pyrrole analogs, these compounds are quite oxygen sensitive. Spande has reviewed other aspects of the synthesis of sulfur-substituted indoles, including methods for the synthesis of compounds with carbocyclic sulfur substituents (79HC(25-3)199). 

The use of hypervalent iodine reagents for heteroatom-heteroatom bond forming reactions is well established in the context of classical oxidation chemistry [1-11]. For example, oxidations of anilines to azobenzenes, thiols to disulfides, and sulfides to sulfoxides with aryl-A3-iodanes were documented decades ago [1-5]. During the last ten years, particular attention has also been given to oxidative transformations of compounds derived from heavier elements, including the interception of reaction intermediates or initially formed products with external nucleophiles. A second important development is the utilization of sulfonyliminoiodanes, ArI = NS02R, for heteroatom-nitrogen bond formation, especially for imidations of sulfur, selenium, phosphorus and arsenic com-... 

Chlorobenz[d]isothiazole-l, 1-dioxide ( pseudosaccharin chloride ) (6)3,24.25, lee, 25i, 26i, 262 displays the reactivity of a cyclic imidoyl chloride263 resembling very much carboxylic acid halides. In previous sections preparation of 3, 4, 5, 13, 68, 86, 89 from 6 has been mentioned. Derivatives of 6 substituted in the phenyl ring have been described.250 Interestingly, Meadow observed231 that crude 6 and material that contained phosphorus pentachloride reacted with thiols more readily than the pure compound. In the reaction of 6 with aromatic sulfonamides, aluminum chloride had been added for activation.252... 

Substrates usefully employed in Mannich reactions are, in general, XH compounds having nucleophilic properties, with X being equal to C, N, or other heteroatoms (Fig. 4). In particular, CH compounds are suitably activated saturated and unsaturated derivatives, and NH substrates may be amines, amides, hetcrocyclcs, etc. Out of OH sub-stratcs, alcohols are mainly able to give stable Mannich products. Sulfur- and phosphorus-containing substrates are XH derivatives having the H atom bonded to the hetcroatom in the lower oxidation state, i.e., thiols, sulfinic acids, and, respectively, phosphine and phosphorous acid derivatives. As and Se compounds have also been successfully used. All these substrates are listed in more detail in Sec. D of this chapter. 

The reaction of (1) with hypochlorous acid leads to chlorination at the 5- and 6-positions.30 Oxidative chlorination with phosphorus pentachloride gives the 2,9-dichloro-[l], as well as the 2,3,8,9-tetrachloro-[l]31 Chlorinated-[l] may be converted sequentially through the thiol-[l] to the sulfonato-[l] 32 Several trihalomethyl derivatives, particularly fluorinated phenanthrolines, have also been prepared 33-37... 

The facility with which the phosphorus-carbon bond in acylphosphonic derivatives is cleaved by the action of the more basic nucleophiles has already been commented upon. Those nucleophiles include alkoxides and amines, but it may be noted that thiols undergo normal addition to the carbonyl group. With regard to the latter, diethyl acetylphosphonate yields the monothioacetals 256 the derivatives may not be stable thermally but their decomposition occurs with cleavage of the phosphorus-carbon bond Reactions between the same substrate and simple carboxamides in the presence of an acid catalyst under dry conditions furnish the acylated enamides 257 ". ... 

By reacting 3-thiol-5-phenyl-4-pyrrolyl-1,3,4-triazole (160) with chloroacetic acid or phenacyl bromide, the 3-carboxymethylthio- (161) and 3-phenacylthiotriazole (162) were obtained, and underwent intramolecular cyclization reactions via electrophilic substitutions. The cyclization of the former in boiling ppa produced thiadiazepinone (163) (38% yield), while the latter was cyclized to the phenyl derivative (164) (50% yield), 3,9-diphenyl-l,2,4-triazolo[3,4-t]pyrazolo[l,2-d]-l,3,4-thiadiazepine, by heating with phosphorus oxychloride (Scheme 28) <82G345>. 

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