Methanethiolate nucleophile

The addition of nucleophiles to double and triple bond systems is often a convenient way of effecting an intramolecular ring closure. Addition to cyano groups has received considerable attention, as in addition to ring formation it provides a convenient method for the introduction of an amino group. Reaction of methyl Af-cyanodithiocarbimidate with Af-methylaminoacetonitrile resulted in displacement of methanethiol and formation of (314). Sodium ethoxide treatment in DMF converted (314) into a 4-amino-5-cyanoimidazole... 

Electrostatic potential maps of (a) formaldehyde (CH20) and (b) methanethiol (CH3SH) are shown. Is the formaldehyde carbon atom likely to be electrophilic or nucleophilic What about the methanethiol sulfur atom Explain. 

Sulfonium salt 103a also underwent ring-opening reactions with nucleophiles, such as NaBH4, sodium azide, and sodium methanethiolate, to afford trithiocins 107 (see Equation (30) and Table 18) <1996BCJ2349> and <1998BCJ1187>. 

By far most of the reports on addition reactions of hetero-nucleophiles to activated dienes deal with sulfur-nucleophiles17,48,80,120-137, in particular in the synthesis of 7/3-sulfur-substituted steroids which, like their carbon-substituted counterparts (Section n.A), are of interest because of their ability to inhibit the biosynthesis of estrogens80,129-137. Early investigations17,120-122 concentrated on simple acyclic Michael acceptors like methyl sorbate and 2,4-pentadienenitrile. Bravo and coworkers120 observed the formation of a 3 1 mixture of the 1,6- and 1,4-adduct in the reaction of methyl sorbate with methanethiol in basic medium (equation 39). In contrast to this, 2,4-pentadienenitrile adds various thiols regioselectively at C-5, i.e. in a 1,6-fashion (equation 40)17,121,122, and the same is true for reactions of this substrate with hydrogen sulfide (equation 41), sodium bisulfite and ethyl thioglycolate17. 

The conjugate addition of a thiol, methanethiol, to the a,(5-unsaturated aldehyde acrolein may be used in the synthesis of the amino acid methionine. Under basic conditions, the nucleophile will be the thiolate anion, and 1,4-addition leads to the thia-aldehyde. Methionine may then be obtained via... 

The key step in this synthesis is an intramolecular nucleophilic attack on the electron-rich indole nucleus by the carbocation derived from the p-keto sulfoxide in the presence of acid. Finally, the intermediate tetrahydrocarbazole aromatizes by elimination of methanethiol under the conditions of the reaction to produce the hydroxycarbazole (511) (Scheme 5.12). 

In the presence of a catalytic amount of methanethiolate-bridged diruthenium complex (la abbreviated as met-DIRUX), reactions of propargylic alcohols (2) with a variety of heteroatom-centered nucleophiles such as alcohols, thiols, amines, amides, and diphenylphosphine oxide gave the corresponding propargylic substituted... 

Examples of nucleophilic attack at the saturated 2-carbon of dihydro-l,4-thiazines, which may be assisted by the neighboring sulfur atom, are shown below. The nucleophiles include water, which was used in the acid-catalyzed hydrolysis of the ketal in 236 (Equation 21) <1982S424>, methanol in the conversion of 214 into a monothioacetal (Equation 22) <1982JHC131>, ethanol and dimethylaniline, which both reacted with 237 (Scheme 29) <1982TL4963>, and triethyl phosphite that was used to convert 238 into the phosphonate 239 required for Wadsworth-Emmons reaction (Equation 23) <2004BML1477>. Compound 240 reacted with both methanol and methanethiol (Equation 24) <1990JME1898>. 

Nucleophilic displacement of other functionalities Displacement of bromide by thiolacetate was one of the earliest successful methods for the introduction of a sulfur substituent on the piperazinedione ring (68BBR402). It was subsequently found that treatment of 3,6-dibromo-l,4-dimethylpiperazine-2,5-dione (115) with methanolic methanethiolate... 

Loss of methanethiol from 132 following nucleophilic attack by a ring nitrogen atom under basic conditions, or thermally, afforded the s-triazolo[4,3-6]-s-triazole (133).135 In a recently reported reaction,136 methylation of the thioamide group in 134 resulted in cyclodeamination to give the quaternary salt 135 with loss of 2,6-dichloroaniline, rather than loss of methanethiol as in 132 - 133. 

Chlorinated 2H- pyrimido[l, 2-6 ]pyridazin-2-ones are known to undergo a variety of nucleophilic displacement reactions. Displacement of the chlorine atom in both the 4- and 7-positions of these compounds with methylamine and sodium methanethiolate is facile. Displacement of the chlorine atom in the 3-position does not occur. Therefore, 3,4,7-trichloro-2//-pyrimido[l,2-6]pyridazin-2-one (34) reacts with methanethiol in sodium methoxide to give 3-chloro-4,7-bis(methylthio)-2//-pyrimido[l,2-6]pyridazin-2-one (70) (71JOC3506). 

Two mechanisms (i.e. direct hydrolysis and alternatively a path via an unstable acyl phosphate intermediate) are involved in the hydrolysis in phosphate buffer of N-arylsulfonyl / -lactams such as (130).107 The acyl phosphate intermediate can be trapped with hydrazine. The alkaline hydrolysis of some torsionally distorted lactams, i.e. the bridged benz[rfe]isoquinolin-l-ones (131), in 70% (v/v) DMSO-water has been compared under the same conditions with the hydrolysis of AvA-dimethyl-1 -naphthamide (132). The relative rates of reaction and activation parameters indicate the effect of torsional distortion.108 The reaction of the tricyclic azetidinones (133) with trifluoroacetic acid gives the bicyclic thioesters (135). The mechanism may involve acid-catalysed elimination of methanethiol to give an azetinone intermediate (134) which, after nucleophilic attack of the thiol, is converted into (135).109... 

It is reported that an industrial explosion was initiated by charging potassium hydroxide in place of potassium carbonate to the chloro-nitro compound in the sulfoxide [1], Dry potassium carbonate is a useful base for nucleophilic displacement of chlorine in such systems, reaction being controlled by addition of the nucleophile. The carbonate is not soluble in DMSO and possesses no significant nucleophilic activity itself. Hydroxides have, to create phenoxide salts as the first product. These are better nucleophiles than their progenitor, and also base-destabilised nitro compounds. Result heat and probable loss of control. As it nears its boiling point DMSO also becomes susceptible to exothermic breakdown, initially to methanethiol and formaldehyde. Methanethiolate is an even better nucleophile than a phenoxide and also a fairly proficient reducer of nitro-groups, while formaldehyde condenses with phenols under base catalysis in a reaction which has itself caused many an industrial runaway and explosion. There is thus a choice of routes to disaster. Industrial scale nucleophilic substitution on chloro-nitroaromatics has previously demonstrated considerable hazard in presence of water or hydroxide, even in solvents not themselves prone to exothermic decomposition [2],... 

V-Bromosuccinimide (NBS) is a reagent used to substitute benzylic and allylic hydrogens with bromine. The benzylic bromide undergoes SN2 substitution with the nucleophile, methanethiolate. As in part (e), the alkyl halide is more reactive toward substitution than the aryl halide. 

Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

The 1-oxide function appears to play a major role in the cleavage of the tetrahydrothiopyran ring in the 2-(3-pyridinyl)tetrahydrothiopyran 1-oxide derivative 397, promoting nucleophilic attack by the methanethiol anion at the tricoordinate S atom (Equation 104) <1996JOC8701>. 

In Figure 4.14, we learned about the Chugaev elimination in connection with the synthesis of alkenes. The second (primary) product of this reaction is the dithiocarbonic acid 5-methyl ester (A). It equilibrates with the zwitterion B, which decomposes into carbon oxysulfide (a heterocumulene) and methanethiol (a heteroatom nucleophile). 

A characteristic of organic sulfur compounds, especially volatile (low molecular mass) thiols, is their disagreeable odors. For example, 3-methyl-1-butanethiol and 2-butene-1-thiol are ingredients of a skunk s perfume, and methanethiol or ethanethiol is usually added, in small amounts, to natural gas, which is odorless by itself, so that leaks can be readily detected. The chemical properties of thiols and sulfides differ from those of alcohols and ethers in that thiols are somewhat stronger acids than alcohols and the sulfur atoms of these compounds are considerably more nucleophilic than the oxygen of their analogs. They are excellent nucleophiles in substitution reactions. 

The thiourea (180) rapidly cyclizes with diethoxymethyl acetate to the thione (181) from which derivatives can be made via nucleophilic displacement of methanethiol e.g. 182 Scheme 57) (74JHC991). 

Nucleophilic displacement of halogen by thiophenol occurs in 1-substituted 2-halogenobenzimidazoles and in l,3-diakyl-2-chlorobenzimidazolium tetrafluoroborates. The reactions of 4-haloimidazolium salts with sulfide or methanethiolate ions are accompanied by some replacement of halogen, but reduction and ring cleavage to give N- methyl-thioamides can also take place. 

The structural and stereochemical requisites for the base-catalysed C4, C -bis-jS-lactam to fused bis-y-lactam rearrangement have been studied and a pathway involving opening of the 2-azetidinone (see Scheme 119) has been proposed for the transformation. Acid-catalysed elimination of methanethiol to yield an azetinone intermediate (464) which, by nucleophilic addition of the eliminated agent, is converted into the isomeric thioesters (465) has been proposed to account for the formation of these bicyclic thioesters on reaction of tricyclic azetidinone (463) with trifluoroacetic acid. A new base-catalysed rearrangement of iV-substituted 4,4-dimethyl-1,2-thiazet-... 

Roper spearheaded the research on coordinated thioaldehydes. In 1977 he established the nucleophilicity of the ligand in an osmium complex (441) which can easily be alkylated at the sulfur atom to give 442. Acidification, however, yields first a methanethiolate complex (443) and eventually liberates methanethiol (263). 

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