Ketones with thiols

Thioketals are readily prepared by reaction of saturated 3-ketones with thiols or dithiols in the presence of boron trifluoride or hydrogen chloride catalysts. Selective protection of the 3-ketone in the presence of a 6-ketone is possible by carrying out the reaction in diluted medium. Similarly, 3-ketones react selectively with monothiols " " or with bulky dithiols in the presence of 6-, 7-, 11- and 12-ketones. 

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... 

Scheme4.82. Reactions of 2,3-epoxycarboxylic acid derivatives and epoxy ketones with thiols [349, 359, 362—364].

Dithianes, thioacetals and -ketals, enol thiol ethers. This clay is a useful catalyst for reactions of ketones with thiols. The condensations are usually conducted in refluxing toluene with a Dean-Stark trap for water.1... 

The reaction of aldehydes or ketones with thiols, usually with a Lewis acid catalyst, leads to dithioacetals or dithioketals. The most common catalyst used is probably boron trifluoride etherate (BF3 OEt2). Similarly reactions that use 1,2-ethanedithiol or 1,3-propanedithiolleadto 1,3-dithiolanes, such as 18 or l,3-dithianes. " Dithioa-cetals can also be prepared from aldehydes or ketones by treatment with thiols in the presence of TiCU, SiCU, LiBp4, AKOTfls, with a disulfide RSSR (R = alkyl or aryl), or with methylthiotrimethylsilane (MeSSiMe3). " ... 

Potassium carbonate. Solid potassium hydroxide is very rapid and efficient. Its use is limited almost entirely to the initial drying of organic bases. Alternatively, sometimes the base is shaken first with a concentrated solution of potassium hydroxide to remove most of the water present. Unsuitable for acids, aldehydes, ketones, phenols, thiols, amides and esters. Also used for drying gaseous amines and ammonia. 

Thioketals are readily prepared by treating the corresponding ketone with ethanedithiol and propane-1,3-dithiol. The 12-ketone fails to react with monothiols such as ethanethiol or thiophenol or with the bulkier 1-phenylethane-1,2-dithiol or tetralin-2,3-di thiol. The A Ei2-ketone... 

Aldehydes and ketones react with thiols to yield thioacetals just as they react with alcohols to yield acetals. Predict the product of the following reaction, and propose a mechanism ... 

Aldehydes and ketones have been converted to sulfides by treatment with thiols and pyridine-borane, RCOR -I- R"SH —+ RR CHSR", in a reductive alkylation reaction, analogous to 16-6. 

The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane, provides 9,ll-ethano-13,15-isoxazolinoprostanoids, PGH analogs, with alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (461). Chemical transformations of 9,11-ethano-13,15-isoxazolinoprostanoids furnish prostanoids with bifunctional fragments of P-hydroxyketone and a-aminoalcohol in the oo-chain. The reaction of P-hydroxy ketones with methanesulfonyl chloride gives rise to prostanoids with an enone component in the oo-chain. 9,ll-Ethano-16-thiaprostanoids have been prepared, for the first time, by nucleophilic addition of thiols to the polarized double bond in the oo-chain. The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane provides 9,ll-ethano-13,15-isoxazolinoprostanoids with an alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (462). 

With thiol in the presence of Et3N in CDC13, allenyl ketones give /3,y-unsaturated enones. However, in the absence of Et3N, the same reaction affords a,/3-unsaturated enones [193]. 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

The addition of thiols to a,j3-unsaturated ketones with [bmim][PF ] in water was investigated. It was found that product could be obtained in up to 95% yield in 10 min (Scheme 77) [199]. 

The study (05ZOR89) showed that thenoines actively react with thiols in acidic media at room temperature to give /1-keto sulfides 250 in good yields. On alkaline hydrolysis, the latter compounds are readily cleaved to ketones 251, which are valuable intermediates for subsequent syntheses. In 06MI2, they were involved in a Fischer reaction and indole- bridged dithienylethenes 252 and 253 were obtained. Hence, a convenient procedure was developed for the transformation of readily available acyloins into photochromic indole-bridged dithienylethenes (Scheme 71). 

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... 

A wide range of linker groups are currently used with SynPhase crowns. They accommodate formation of the following functional groups upon cleavage carboxylic acids, primary and secondary amides, sulfonamides, alcohols, phenols, amines, anilines, anilides, hydroxymates, aldehydes, ketones, and thiols. 

Singlet excited state acid dissociation constants pK can be smaller or greater than the ground state constant pK by as much as 8 units. Phenols, thiols and aromatic amines are stronger acids upon excitation, whereas carboxylic acids, aldehydes and ketones with lowest >(71, ) states become much more basic. Triplet state constants pKr are closer to those for the ground state. Forster s cycle may be used to determine A pK =pK —pK) from fluorescence measurements if proton transfer occurs within the lifetime of the excited molecule. 

Halomethyl ketones and acids are known to react with thiols and imidazoles. TPCK reacts far more rapidly with chymotrypsin than it does with normal histidine-containing peptides because of its high reactivity as an affinity label. This can be seen in Table 9.2 for an analogous chloromethyl ketone. In addition to this important diagnostic feature, the irreversible inhibition of chymotrypsin by TPCK has four other characteristic features 1,4... 

The reactions of vinyl sulfones with various nucleophiles are usually stereoselective. Substituted vinyl sulfones are less reactive toward nucleophiles than the analogous vinyl ketones or esters 10 and are quite inert toward thiols. Peptide vinyl sulfones do not react with thiols such as glutathione under enzyme assay conditions. The reaction of thiols with aryl vinyl sulfones has been reported, however, it is performed in the presence of base. 11 ... 

A tandem 1,4-addition-Meerwein-Ponndorf-Verley (MPV) reduction allows the reduction of a, /i-unsaturated ketones with excellent ee and in good yield using a camphor-based thiol as reductant.274 The 1,4-addition is reversible and the high ee stems from the subsequent 1,7-hydride shift the overall process is thus one of dynamic kinetic resolution. A crossover experiment demonstrated that the shift is intramolecular. Subsequent reductive desulfurization yielded fiilly saturated compounds in an impressive overall asymmetric reductive technique with apparently wide general applicability. 

Nafion-H exhibits lower activity. In the acetylation of alcohols,673 in the transformation of aldehydes and ketones with trimethyl orthoformate to the corresponding dimethylacetals,674 and in the formation of acylals,675 longer reaction times (several hours) are required to achieve high yields at room temperature. Furthermore, the formation of ethylenedithioacetals in benzene674 and the direct transformation of acetals to thioacetals with ethane-1,2-thiol in dichloromethane676 can only be performed at reflux temperature. 

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. 

Sulfides. Aldehydes and ketones react with thiols in TFA in the presence of HI I, /pyridine to form sulfides (equation I).1... 

A better strategy for monoalkylation of primary aliphatic amines is their condensation with aldehydes or ketones followed by reduction of the resulting imine. Alternatively, primary amines can be converted into sulfonamides, which can be readily N-alkylated and then hydrolyzed (less readily) with strong acids [21-23] or cleaved with thiols (Scheme 6.32). 

The reactions of hydrogen peroxide with vanadate have been of interest for many years. Much of the early work was concerned with the function of peroxovanadates as oxygen transfer agents. Alkenes and similar compounds such as allyl alcohols can be hydroxylated or epoxidized. Even alkanes can be hydroxylated, whereas alcohols can be oxidized to aldehydes or ketones and thiols oxidized to sulphones or sulphoxides. Aromatic molecules, including benzene, can be hydroxylated. The rich chemistry associated with the peroxovanadates has, therefore, led to extensive studies of their reaction chemistry. To this end, x-ray diffraction studies have successfully provided details of a number of peroxovanadate structures. 

Bismuth(m) nitrate catalyzes Michael addition of a,/Yunsaturated ketones with amines, thiols, and carbamates, although the promoting role of Bi(N03)3 is not fully understood (Equation (91)).100 The Biginelli cyclocondensation of a mixture of (3-keto esters, aldehydes, and urea is mediated by BiCl3, affording 3,4-dihydropyrimidin-2(lH)-ones (Equation (92)).149 Bi(OCOCF3)3 is an efficient catalyst for the regio- and chemoselective synthesis of /3-enaminones in water.150... 

In general, thioacetals can be made in a similar way to normal (oxygen-based) acetals-by treatment of an aldehyde or a ketone with a thiol and an acid catalyst—though a Lewis acid such as BF3 is usually needed rather than a pro tic acid. The most easily made, most stable toward hydrolysis, and most reactive towards alkylation are cyclic thioacetals derived from 1,3-propanedithiol, known as dithianes. 

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