Aldehydes reaction with dithiols

Thioacetals and -ketals. A1C13 is an effective catalyst for the condensation of aldehydes and ketones with thiols or dithiols. The reaction of thiols with carbonyl groups with an a-proton results in low yields but the reaction with dithiols proceeds in high yield.8... 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

The acyl anion (R-C=0) is not stable as such, but when an aldehyde is converted into a 1,3-dithiane by reaction with propane-1,3-dithiol and then treated with base, it forms an acyl anion equivalent, and hence is susceptible to attack by electrophilic reagents (see Section 5.9). Two extensive compilations of formyl and acyl anion synthons together with references to their reactions... 

Thioacetals. Aldehydes, ketones, or acetals, both cyclic and acyclic, can be converted into thioacetals by reaction with a thiol or dithiol and MgBr2 (2.1 equiv.) in ether at 25°. The difference in reactivity between acetals and ketones permits selective conversion of acetals into thioacetals without acetalization of a ketone. 

Alkyl groups in dithioles (3a, b) possess acidic protons and condense with aldehydes to form 5-vinyldithioles (109). This type of reactivity has been widely used in the preparation of some l,6,6aA4-trithiapentalenes (5) or precursors (7iAHC(i3)i6i) by reaction with carbon disulfide (Scheme 17). 

The alkylation of different polymeric reagents 268 (prepared from the corresponding odorless 1,3-dithiols and aldehydes) has been performed by successive deprotonation with n-BuLi and reaction with alkyl bromides and iodides. Final oxidation with periodic acid or with mercury(II) perchlorate gave the corresponding ketones (Scheme 73)452. 

The formation of thioacetals from aldehydes and ketones involves the reaction with a thiol such as ethane-1,2-dithiol in the presence of a Lewis acid catalyst such as boron trifluoride eiherate. These derivatives have been described earlier. 

Carotenoid and supracarotenoid TTFs became available in a general synthesis involving the dimerization of co-(l,3-dithiol-2-ylidene) polyenals 820 by reaction with Lawesson s reagent. The aldehydes 820 were prepared by reaction of unsaturated dialdehydes 819 with 818 and triphenylphosphine (Scheme 124) <2003HCA2589>. 

Alkyl groups on l,2-dithiole-3-thiones react fairly readily with carbonyl groups to form 5-vinyl-1,2-dithioles <87EUP256929, 92JAP(K)04I 17377). For example, 5-methyl-l,2-dithiole-3-thione (102) reacts with aldehydes or acetals to form 5-vinyl-l,2-dithiole-3-thiones (103) <82AHC(3I)63,92SUL227). Carbanion formation, reaction with carbon disulfide, and further elaboration converts the dithiole-... 

Of course, derivatization methods can also be used for the identification of organic acids. For example, volatile fatty acids in urine and plant protein hydrolysates were esterified with phenyldiazomethane and the resulting benzyl esters were separated by glass capillary GC [254]. Janos et al. [255] described a method for the analysis of dimedone derivatives of formaldehyde and other aliphatic aldehydes on capillary columns. Phenolic amines, 3-methoxycatecholamines, indoleamines and related amines can be determined as their N,0-ethyloxycarbonyl derivatives [256]. The reaction of dithiols and certain monothiols with phenylarsine oxide was used for derivatization prior to GC [257]. Destructive GC methods for the identification of microorganisms were described in refs. 258-261. 

Dihydro-l,3-dithiepins (218) have usually been obtained from (Z)-l,4-dichloro-2-butene (214) via the isothiouronium salt (215) (Scheme 36). For the preparation of the 2-unsubstituted 4,7-dihydro-l,3-dithiepin, the isothiouronium salt can be reacted directly with dibromomethane and potassium hydroxide in methanol <76TL1251,780PP133), but isolation of the dithiol (217) and acid-catalyzed reaction with an aldehyde or ketone in a second step is preferred for the preparation of 2-substituted 4,7-dihydro-1,3-dithiepins <93JCS(P2)87l>. 

These polymers form from reactions of dithiols with aldehydes or ketones ... 

Dithioacetals, 1,3-dithianes or 13-dithiolanes are prepared by reaction of the corresponding carbonyl compound in the presence of an acid catalyst (cone. HQ, Lewis acids such as Znh, BFs EtaO, TMS-Cl, etc.) with a thiol or dithiol. Silica gel treated with thionyl chloride was found to be an effective as well as selective catalyst for thioacetalization of aldehydes. Thioacetalization can also be achieved using a (polystyryl)diphenylphosphine-4odine complex as a catalyst Conversion of aldehydes or acetals into 1,3-dithianes is achieved with the aid of organotin thioalkoxides and organotin triflates or with 2,2-di-methyl-2-sila-l,3-dithiane. Direct conversion of carboxylic acids to 1,3-dithianes can be carried out by reaction with 1,3,2-dithiabomenane-dimethyl sulfide and tin(II) chloride or 1,3,2-dithiaborolene with trichloromethyllithium followed by basic hydrolysis. 

An alternate route not involving 2-lithio-l,3,5-trithianes for the preparation of 2-substituted-l,3,5-trithianes recently has been reported . This method involves reaction of an aldehyde 77 with the dithiol 78 to yield the 2-substituted trithiane 79. 

C=0. It is therefore susceptible to nucleophilic attack at carbon. Methods have been developed by which this polarization is effectively reversed so that the carbon atom itself becomes the nucleophilic centre. Such an inversion is known as umpolung. An example is provided by the 1,3-dithiane system. An aldehyde may be converted into a cyclic dithioacetal by reaction with propane-1,3-dithiol in the presence of an acid. The two adjacent electronegative sulphur atoms make the C—H bond of this acetal rather acidic. Treatment with butyllithium therefore affords a lithio derivative in which the carbon atom is susceptible to electrophilic attack. The 1,3-dithiane system is reconverted into a carbonyl group by acid hydrolysis in the presence of mercury(II) ions, which complex with the dithiol. The RCO group in the original aldehyde is thus equivalent to R—C=0 (Fig. 3.10). 

Another example of polymer-supported A1 based Lewis acid is cross-linked polystyrene-supported aluminum triflate (79). Cross-linked polystyrene-supported AICI3 (72) was easily converted into (79) by treatment with triflic acid. This catalyst was applied to dithioacetalization of carbonyl compounds and transdithioacetal-ization of acetals (Scheme 19.19) [44]. From benzaldehyde the corresponding dithioacetal (84) was obtained in the presence of the polymeric catalyst (79) in 98% yield in 30 minutes. The same product was also obtained from the dimethyl acetal (85) in 94% yield. Chemoselectivity of the polymeric catalyst was also demonstrated in Scheme 19.19. Aldehydes reacted faster in the presence of ketone (34) to give the dithioacetals with (79). Aliphatic ketone (89) exclusively reacted with dithiol (81) in the presence of aromatic ketone (34). These chemoselectivities were higher than those obtained from the reactions using nonsupported Al(OTf)3. 

Cyclic thioacetals are formed by the reaction of dithiols with aldehydes and ketones (Section 17-8). The hydrogens on the carbon positioned between the two sulfur atoms in thioacetals are acidic enough (pKi, — 31) to be removed by suitably strong bases, such as alkyllithiums. The negative charge in the conjugate base is stabilized inductively by the highly polarizable sulfur atoms. 

Dithioacetals of reducing sugars are obtained by reaction with a dithiol, such as ethane dithiol, and zinc chloride [37] (reaction 4.38). The acetylated dithioacetal can be desulfurized by cartalytic reduction using Raney nickel to reduce the carbonyl group to a hydrocarbon [38] (reaction 4.38). The 1,1-dithioacetal can be used to reversibly protect the aldehyde group, since it can be readily removed by acid hydrolysis. 

The catalysed alkylation of l//,4//-pyrazol-5-ones is solvent dependent. In benzene, bis-alkylation occurs at the 4-position whereas, in a carbon disulphide benzene mixture, O-alkylation is observed, although the major product (4, Scheme 5.22) results from nucleophilic attack by the pyrazolone on the carbon disulphide, followed by alkylation of the dithiolate dianion [92]. The catalysed reaction of 2-thiono-3-aryl-thiazolidin-4-ones with alkylating agents under soliddiquid two-phase conditions results in alkylation at the 5-position (60-80%) [93]. The aldol condensation of the thiazolidinones with aryl aldehydes is also catalysed by quaternary ammonium salts. 

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