Thiols addition products

Since all of the thiol addition products were unknown compounds, except for racemic 3-phenylthiocyclohexanone, it became necessary to devise a method far determining the absolute configuration without resorting to Bijvoet s method (53) for each new compound (see Table 4). This was accomplished by preparing the thioacetal of the adamantanedione, a model 3-thiosubstituted cyclohexanone of known absolute configuration (54) (eq. [10]). 

The kinetics of the addition of IV-acetyl-L-cysteine, N-acetylcysteamine, and N2-acetyl-L-lysine (NAL) to / -methoxycinnamate, / -methoxycinnamide, anthranilate, and crotonyl or sorboyl thiol ester have been studied, and the thiol addition products identified. The reaction rates increased at higher pH and the crotyl thiol ester was found to be 7.9 times more reactive than a sorboyl thiol ester toward IV-acetyl-L-cysteine addition. These unsaturated thiol esters may serve as a means of covalently binding UVA and UVB sunscreens to the outer layer of skin to provide long-lasting protection.128... 

The nature of such reactions has been checked for MnOa, FeaOg, C02O3, by carrying out the oxidation in the presence of an alkene. Formation of large amounts of thiol addition products to the double bond suggests intermediacy of thiyl radicals. 

The structure of the aminochrome-thiol addition product (122) has recently been investigated in depth [249] and proved to be identical with that originally proposed by Mattok and Heacock [239, 240], It was shown that... 

The semicarbazone (134) was too water-soluble to isolate readily, but it was possible to isolate other derivatives of the aminochrome-thiol addition products of this type one such compound was the p-nitrophenylhydrazone of the addition product between adrenochrome and )S-mercaptopropionic acid which was readily obtained in pure crystalline form. The structure of this compound (135) was established by consideration of the microanalytical data and spectroscopic (u.v. visible, i.r. and n.m.r) properties. A total of five derivatives of this type have been prepared and fully identified (see Table 63) [249]. 

Table 6.3 some aminochrome-thiol addition product phenylhydrazine derivatives... 

The thiol addition product was detectable spectrophotometrically and the intermediate with R = CH2CH2OH was isolated and its structure proved by and C-NMR. The intermediate could then be converted to the dihydro compound showing that the addition must have occurred at position C-4a and not N-5. This work thus provides evidence for the existence of a thiol addition intermediate involving the C(4a)—N(5) bond in nonenzymatic reductions of flavins and analogues by thiols. 

The main by-products of this synthesis type are sulfides and the isomer resulting from the Markownikoff addition to the alkene. For example, in the synthesis of 1-butanethiol (eq. 4), 5-thianonane, C H SC H, and 2-butanethiol are produced as by-products. The 2-butanethiol has uses as a herbicide intermediate and a gas odorant blend component and is further processed. The 5-thianonane is incinerated or reprocessed for fuel value. Sulfides account for up to 10% of the thiols produced. Another 2—5% is the Markownikoff addition product. 

Dehydrocoelenterazine (D) forms an addition product (E) when treated with acetone in the presence of benzylamine (Takahashi and Isobe, 1993). Thiol compounds, such as DTT (dithiothreitol) and glutathione, also add to D, forming an equilibrium mixture containing F (Takahashi and Isobe, 1994). These adducts are chemiluminescent. 

If vinylogous imidazole-A-carboxylates (route A) are treated with nucleophiles such as alkoxides or amines, the corresponding vinylogous carbonic esters or amides are obtained. While reaction of the vinylogous imidazole-TV-carboxylate with a thiol (route A) yields the addition product only, that of the corresponding imidazolium compound (route B) leads to the carbonic thioester in a substitution reaction [3]... 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

The 1,4-addition of selenophenols to cycloalkenones proceeds smoothly under the same conditions used in the thiophenol addition (see Section V) (eq. [18]). Although the e.e. of the products is 40 to 65%, compared with the 60 to 80% achieved in the thiol addition reaction, the solid adducts are readily purified to enantiomeric purity by crystallization (63). 

Although the mechanism of this reaction has not been studied as thoroughly as that of the thiol addition reaction, there appears to be considerable similarity in the main features of the reaction. Thus, although the transition state may well differ in a number of details, the transition state shown earlier (Figure 10) appears to predict the correct configuration for the products of the selenophenol addition as well as of the thiophenol addition to cyclohexenones. 

A bicyclic urea (123) was an unexpected product of the reaction between pyrrolidine and the phenyl ester of 2-cyano-l,4,5,6-tetrahydro-l-pyridinecarboxylic acid (124 R = Ph) the corresponding methyl ester (124 R = Me) reacted, as expected, to give the product of Michael addition (125). ° The better leaving ability of phenoxide vs methoxide presumably tilted the reaction towards the substitution rather than the addition product, although thiols (e.g. PhSH) underwent only the addition reaction. 

Where it is possible to distinguish the products, thiol additions show stereospecificity. The products of addition of hydrogen sulfide, thio-phenol, and thiolacetic acid to 1-chlorocyclohexene are to be 75%, 94%, and 66% cis-l, 2-disubstituted cyclohexane, respectively.88 The addition of thiolacetic acid is less stereopecific than the other thiols. The stereospecificity apparently depends upon the ratio of addendum to 1-chlorocyclohexene, Phenylthiyl radical addition to 1-methylcyclo-... 

Generally, the vinyl heterocycles polymerize under the influence of a radical initiator, but, under such conditions, thiols react with 1-vinylpyrroles to give the expected addition products (77KGS1636). 

The thiylation of conjugated dienes and allenes proceeds as expected. Thus, the acid-catalyzed reaction of thiols with 1,3-dienes affords the 1,4-addition product,552 whereas the nucleophilic addition to allene provides the product arising from sulfur attack at the central carbon (equations 303 and 304).553... 

Chen and co-workers later reported the successful asymmetric 1,4-addition of aryl thiols to a,/ -unsaturated cyclic enones and imides using Takemoto s elegantly simple catalyst (3) [43]. This bifunctional amine-thiourea catalyst gives optimal reactivity and reproducibility when used at 10 mol% loading in the presence of freshly dried 4 A molecular sieves (MS). This combination afforded the expected addition products in high yields (90-99%) and moderate to good enantioselectiv-ities (55-85% ee) for a variety of cyclic and acyclic Michael acceptors (Table 6.2). 

Treatment of TiCl4 with 2 equivalents of thiol at ambient temperature gives yellow addition products of the type ds-TiCl4(HSR)2, while the reaction with potassium salts in the THF affords molecular T SR),44 complexes with a distorted tetrahedral TiS4 core. When R = Me3Q,H4, the Ti—S bonds are considerably shorter than... 

There have been two published reports on the syntheses of stable 1,2,4-triazolyl carbenes. Thermal decomposition in vacuo of 5-methoxytriazoline 208 provided in quantitative yield l,2,4-triazol-5-ylidene 209, a stable carbene in the absence of oxygen and moisture <0381292>. This nucleophilic carbene 209 could react with a variety of alcohols, thiols, amines, oxygen, sulfur, selenium, isocyanantes, and metal carbonyls to form a myriad of addition products. Reactions of 1,2,4-triazolyl perchlorate salts 210 with base afforded stable nucleophilic 1,2,4-triazol-5-ylidenes 211, which could react with acetonitrile and elemental sulfur and selenium to yield addition products <03JOC5762>. 

To further investigate the scope and utility of the reaction, Plourde [17] carried out thiol addition to supported aminocychtol 122, formed by reaction of aminocychtol 121 with Wang resin carbonate 120 (Scheme 26). Treatment of 122 with benzyl thiol and AIBN followed by cleavage from support gave the product sulfide 123 in good yield and purity. 

Alternatively, the addition of thiols or thiocarboxylic acids to alkenes can be carried out under base catalysis. For example, the reaction of racemic 4-/m-butoxy-2-cyclopentenone with (—)-10-mercaptoisoborneol occurs in the presence of a catalytic amount of A, M, A 1, /V -tetrameth vl-ethylenediamine. The addition product was, however, a 1 1 mixture of the corresponding diastereomeric sulfides 65. 

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