Dithiols aldehydes

Keywords monothiol, dithiol, aldehyde, Cdl2, microwave irradiation, dithioace-talization, dithioacetal, 1,3-dithiolane... 

The cycloaddition of alkynes with the tributylphosphine-carbondisulfide adduct 131 results in the in situ formation of the ylides 132 which react with aldehydes to give the novel 2-arylidene or 2-alkylidene-l,3-dithioles 133 (Scheme 36) [132]. Concerning ylides C-substituted by sulfur we can also mention a publication on the behavior of various keto-stabilized ylides towards acyclic and cyclic a s-disulfides allowing the synthesis of substituted thiazoles, thiols, and dithiols [133]. 

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. 

Converting furfuraldehyde into its 1,3-dithian-2-y] derivative by reacting it with propane-1,3-dithiol could also be the basis of a route to furoin. Once deprotonated. this forms an acyl anion equivalent that could be reacted with a second equivalent of the aldehyde and then protonated and deprotected to yield furoin ... 

We have suggested a mechanism of formation of these compounds that involves a dithiol intermediate which interacts with ammonia giving the corresponding amino derivative, followed by a nucleophilic attack of the amino group upon another molecule of an aldehyde, the formation of a precursor intermediate, and heterocyclization with an elimination of a molecule of water. 

Protection and deprotection of the dithiol The formaldehyde dithioace-tal (129) could be prepared by reacting the dithiol with diiodomethane and pyridine, but not with paraformaldehyde. Other thioacetals could be prepared by the standard procedure (aldehyde, BF3 etherate). Interestingly, both cis and trans dithiols gave the thioacetal, thereby enabling the complete conversion of mixtures of cis and trans dithiols to the pure cis derivative. Several mechanistic explanations are possible for the epimeri-zation at C-6 in the thioacetalization of the trans dithiol, but detailed analysis has not been done. 

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. 

Resin-bound diols, amino alcohols, and dithiols, which reversibly form cyclic acetals with aldehydes and ketones, have been successfully used as linkers for carbonyl compounds (Entries 5-11, Table 3.40). Acetal formation on insoluble supports can be achieved by azeotropic removal of water (C6H6, TsOH, reflux [720]), whereas dithio-acetals can be prepared by acid-catalysis alone (BF3 OEt2 or TMSC1 CHCI3,0 °C, 2 h [721]). /V-Acylaminals such as R-CFI(OMe)NFI-CO-Pol have been prepared by treatment of resin-bound amides H2NCO-Pol with aldehydes in the presence of HC(OMe)3 and TFA [722],... 

Keywords ketone, aldehyde, ethane-1,2-dithiol, neutral alumina surface, dithio-acetal, 1,3-dithiolane... 

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... 

The reaction of aldehydes or ketones with ethane-1,2-dithiol or propane-1,3-dithiol to form 1,3-dithiolanes or 1,3-dithianes is an important reaction, as these compounds under suitable conditions are acyl anion equivalents (see Section 5.9, p. 626). These cyclic dithioacetals have been less used as protective groups, though when required are formed in high yield in the presence of boron trifluoride-etherate.138... 

Thioacetals, arising from the reaction of an aldehyde or ketone with either two moles of a thiol or one mole of a 1,2- or 1,3-dithiol, are useful both as a means of protection of a carbonyl group (Section 5.8.8, p. 625) and as important intermediates in organic synthesis. 

In particular, 1,3-dithiane prepared from dimethoxymethane (methylal) and pro pane-1,3-dithiol in the presence of boron trifluoride-etherate,237 and 2-alkyl-1,3-dithianes prepared similarly from aldehydes,2383 are important acyl anion equivalents. These and other uses are discussed in Sections 5.7.5, p. 596, and 6.6.1, p. 909. A wide-ranging review of the reversal of polarity of the carbonyl group through the formation of these sulphur-containing reagents has emphasised their value in organic synthesis.2388... 

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... 

An efficient double conjugate addition of ethane and propane dithiols in the presence of sodium methoxide to propargylic carbonyl compounds (127) has been developed. The corresponding amino-substituted propargylic aldehydes afforded piperidine derivatives.182... 

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. 

Using the same reactor, a premixed solution of aldehyde or ketone and dithiol (1.0 M, 1 1) in anhydrous MeCN was passed through the Amberlyst-15 126 containing packed bed. The reaction products were again collected in MeCN and analyzed every 10 min by GC-MS. Once optimized, the reactions were conducted for 1 h, to produce the required quantity of each 1,3-dithiane or 1,3-dithiolane, the reaction products were then concentrated in vacuo and analyzed by 1H NMR spectroscopy (Tables 16 and 17) (Wiles et al., 2007b). 

The anion derived from the 1,3-dithiole 367 reacts with thioxanthone to give the 9-(l,3-dithiol-2-ylidene)thiox-anthene derivative which is a 7t-electron donor system. The introduction of a benzaldehyde unit at the 4-position of the dithiole ring was achieved by iodination and a Pd-mediated cross-coupling with 4-formylbenzeneboronic acid. The aldehyde group allowed attachment to C(,o via a 1,3-dipolar cycloaddition of an azomethine ylide (Scheme 87) <2005JMC1232>. 

Dimethylthioformamide reacts at a methylene group in the 3- or 5-position of a 1,2-dithiolium cation. This reaction may be performed in acetic anhydride. The resulting Vilsmeier salt (32), treated with aqueous sodium hydroxide, gives an a-(l,2-dithiol-3-ylidene) aldehyde.49... 

UV spectra of a-(l,2-dithiol-3-ylidene)aldehydes or ketones [l-oxa-6,6a>S,IV-dithiapentalenes (111), X = 0] have been less systematically studied than those of 111 (X = S). Some of these data are given in Table VI. 

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). 

Dithiins (151) are made by reaction of aldehydes with 1,3-dithiols. Treatment of these with suitable electrophilic oxidizing agents, e.g. Br2, forms 1,2-dithiolylium ions (4) by ring contraction (Scheme 27) (66AHC(7)39). The synthesis may be applied to ben-zodithiolylium ions as well. A synthesis of the dithiole antibiotic holomycin (Section 4.31.4) from a 1,3-dithiin is related in concept (77JOC2891). 

Alkoxy compounds of type (163) can serve as generators of carbenes. Thus, treatment of the methoxy derivative (163) with trichloroacetic acid in benzene produces a carbene which in the presence of aromatic aldehydes, forms the dithiole derivatives (75) (80MI43200). 

Another entry to 1,3-benzodithiolylium salts (275) involves acid-catalyzed condensation of benzene-1,2-dithiols (273) with aldehydes followed by oxidation of the intermediates (274) using oxidizing reagents. This reaction also works with dialdehydes (80AHC(27)15l). 

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