Substitution thiols

Another entry into the anti ulcer sweepstakes is etinfidine (50). It is synthesized by displacement of halide from 4-chloromethyl-5-methylimidazole (4 ) with substituted thiol The latter is itself made from thiourea analogue by an addition-elimination reaction with cysteamine 52. °... 

The boron enolates of a-substituted thiol esters also give excellent facial selectivity.135 CH(CH3)2 (CHg"/ -CH2)2BCI... 

One of the most common strategies for the preparation of thiophenes involves the intramolecular condensation of a-thioglycolates (and related a-substituted thiols) onto adjacent carbonyls. One prominent example involved the synthesis of naturally occurring... 

Many examples of the synthesis of tetrahydropyrans are based on the cyclization of 1,5-diols and related compounds which can provide an electrophilic site for ring closure . Thus, pentane-1,5-diols can be quantitatively cyclized to the pyran in the presence of BuSnCl3 <1988G483> or via an intramolecular Mitsunobu condensation with cyanomethylenetributylphosphorane <1996TL2463>. Tetrahydrothiopyrans are prepared similarly by cyclizations of suitably substituted thiols . 

The synthesis of thiiranes starting from y substituted thioles and oxiranes can be achieved as follows. 

In addition to end-on attachment, there is also side-on attachment of rod-like molecules onto GNPs. Through laterally substituted thiol, the rod-like nematic LC molecule 10 containing a lateral alkyl thiol was linked to GNPs together with some other /2-alkane thiols forming a mixed monolayer (Scheme 4.3), which had two components in nearly equal proportions (ca. 1 1) on GNP surface (Fig. 4.6). Both the hexane- and dodecanethiol coated hybrids GNPs exhibited nematic LC behavior which displayed typical marbled or Schlieren textures (Fig. 4.7) [55]. 

Generally, the reaction works well for electron-deficient anilines. A modified approach using in situ prepared chlorosulfonium salts is preferred for more electron-rich anilines. Substituted thiol derivatives can be used to produce 3-oxindoles, which can be further reduced to 3-indole derivatives that are not available via the Gassman indole synthesis. The reaction is equally useful for the preparation of isatin derivatives vide infra). Historically, the Gassman oxindole synthesis has found applications in the preparation of heterocycles with medical or insecticidal properties. The reaction also has potential applications for the synthesis of oxindole containing natural products. ... 

The observation of a large kinetic isotope effect indicates that isotopically substituted thiol hydrogen participates directly in a vibrational mode, whose frequency changes on going to the transition state, i.e. that S—H bond cleavage is an integral part of the transition state. The fact that a value for of 2-80 was obtained for the addition of benzene-... 

The synthesis of thiiranes starts either from P-substituted thiols or from oxiranes and I q I can be achieved as follows. I---- ... 

Thiols themselves are sometimes prepared by nucleophilic substitution using the conju gate base of H2S... 

Thioesters undergo the same kinds of reactions as esters and by similar mechanisms Nucleophilic acyl substitution of a thioester gives a thiol along with the product of acyl transfer For example... 

Bivalent Sulfur. The prefix thio, placed before an affix that denotes the oxygen-containing group or an oxygen atom, implies the replacement of that oxygen by sulfur. Thus the suffix -thiol denotes — SH, -thione denotes —(C)=S and implies the presence of an =S at a nonterminal carbon atom, -thioic acid denotes [(C)=S]OH [(C)=0]SH (that is, the O-substituted acid and the 5-substi-... 

Salts of thiols (170) or of sulfinic acids (171) react like the alkoxides, giving 4-alkylthio- or 4-alkylsulfono-substituted butyrates. Alkali cyanides give 4-cyanobutyrates (172), hydroxylamine gives a hydroxamic acid (173), and hydra2ine a hydra2ide (174). 

Table 3 gives the corresponding physical properties of some commercially important substituted pyridines having halogen, carboxyHc acid, ester, carboxamide, nitrile, carbiaol, aminomethyl, amino, thiol, and hydroxyl substituents. 

Thiols can be prepared by a variety of methods. The most-utilised of these synthetic methods for tertiary and secondary thiols is acid-catalysed synthesis for normal and secondary thiols, the most-utilised methods are free-radical-initiated, alcohol substitution, or halide substitution for mercaptoalcohols, the most-utilised method is oxhane addition and for mercaptoacids and mercaptonitnles, the most-utilised methods are Michael-type additions. 

Alcohol Substitution. In the early period of normal thiol production, the normal alcohols were utilized as feedstocks. The use of a strong acid catalyst results in the formation of a significant amount of secondary thiol, along with other isomers resulting from skeletal isomerization of the starting material. This process has largely been replaced by uv-initiation because of the higher relative cost of alcohol vs alkene feedstock. 

Methanethiol (eq. 6) and cyclohexanethiol (eq. 7) are the only commercially important thiols prepared using alcohol substitution. In most cases, when the alcohol is utilized, less control over the substitution patterns is obtained. Only one isomer is obtainable in the case of methanol and cyclohexanol. 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Ethyleneamines are used in certain petroleum refining operations as well. Eor example, an EDA solution of sodium 2-aminoethoxide is used to extract thiols from straight-mn petroleum distillates (314) a combination of substituted phenol and AEP are used as an antioxidant to control fouling during processing of a hydrocarbon (315) AEP is used to separate alkenes from thermally cracked petroleum products (316) and TEPA is used to separate carbon disulfide from a pyrolysis fraction from ethylene production (317). EDA and DETA are used in the preparation and reprocessing of certain... 

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