Nucleophilic Attack on Carbon

91COS(6)65,93PAC1319,94AG(E)599 . New reactions as well as new examples of older reactions will be presented in this section. 

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Lithium aluminum hydride normally reacts with thiiranes via nucleophilic attack on carbon, but where that process is hindered sulfur is attacked to give the alkene, usually in good yield, and lithium sulfide (70JPR421). 

Nucleophilic attack on carbon in thiirane and thiirene dioxides. . ... 

A. Nucleophilic Attack on Carbon. —(/) Activated Olefins. A study of triarylphosphine-catalysed dimerization of acrylonitrile to 2-methylene-glutaronitrile (26) and 1,4-dicyano-l-butene (27) has established a balance between phosphine nucleophilicity and protolytic strength of the solvent. The reaction of methyl vinyl ketone with triphenylphosphine in triethyl-silanol gave only 3-methylene-2,6-heptadienone (28). 

A study of debrominations of vtc-dibromides promoted by diaryl tellurides and din-hexyl telluride has established several key features of the elimination process the highly stereoselective reactions of e/7f/tro-dibromides are much more rapid than for fhreo-dibromides, to form trans- and cw-alkenes, respectively the reaction is accelerated in a more polar solvent, and by electron-donating substituents on the diaryl telluride or carbocation stabilizing substituents on the carbons bearing bromine. Alternative mechanistic interpretations of the reaction, which is of first-order dependence on both telluride and vtc-dibromide, have been considered. These have included involvement of TeAr2 in nucleophilic attack on carbon (with displacement of Br and formation of a telluronium intermediate), nucleophilic attack on bromine (concerted E2- k debromination) and abstraction of Br+ from an intermediate carbocation. These alternatives have been discounted in favour of a bromonium ion model (Scheme 9) in which the role of TeArs is to abstract Br+ in competition with reversal of the preequilibrium bromonium ion formation. The insensitivity of reaction rate to added LiBr suggests that the bromonium ion is tightly paired with Br. ... 

The Zn OH (A), the enzyme is essentially present in this form at the physiological pH, is a relatively good nucleophile and poised for nucleophilic attack on carbon dioxide. Structural studies indicated... 

When an ion participates in a nucleophilic attack on carbon, it must slough off some of the solvent molecules that stabilize it in solution. Otherwise, the ion cannot get close enough to the carbon, to which it will become attached, to begin forming a bond. Sloughing off solvent molecules will be less favorable for a small ion than a large ion. Consequently, we expect Cle to be less reactive than I . 

The enzyme urease catalyzes the hydrolysis of urea to form carbamate ion (equation 32). At pH 7.0 and 38 °C, the urease-catalyzed hydrolysis of urea is at least 1014 times as fast as the spontaneous hydrolysis of urea. Jack bean urease is a nickel(II) metalloenzyme502 with each of its six identical subunits containing one active site and two metal ions, and at least one of these nickel ions is implicated in the hydrolysis. It has been suggested503 that all substrates for urease (urea, N-hydroxyurea, 7V-methylurea, semicarbazide formamide and acetamide) are activated towards nucleophilic attack on carbon as a result of O-coordination to the active nickel(II) site as in (155). Nickel(II) ions have been found504 to promote the ethanolysis and hydrolysis of N-(2-pyridylmethyl)urea (Scheme 39) and this system is considered to be a useful model for the enzyme. 

Important reactions of CS2 involve nucleophilic attacks on carbon by the ions SH and OR and by primary or secondary amines, which lead, respectively, to thiocarbonates, xanthates, and dithiocarbamates, for example,... 

Addition of anionic nucleophiles to alkenes and to heteronuclear double bond systems (C=0, C=S) also lies within the scope of this Section. Chloride and cyanide ions are effieient initiators of the polymerization and copolymerization of acrylonitrile in dipolar non-HBD solvents, as reported by Parker [6], Even some 1,3-dipolar cycloaddition reactions leading to heterocyclic compounds are often better carried out in dipolar non-HBD solvents in order to increase rates and yields [311], The rate of alkaline hydrolysis of ethyl and 4-nitrophenyl acetate in dimethyl sulfoxide/water mixtures increases with increasing dimethyl sulfoxide concentration due to the increased activity of the hydroxide ion. This is presumably caused by its reduced solvation in the dipolar non-HBD solvent [312, 313]. Dimethyl sulfoxide greatly accelerates the formation of oximes from carbonyl compounds and hydroxylamine, as shown for substituted 9-oxofluorenes [314]. Nucleophilic attack on carbon disulfide by cyanide ion is possible only in A,A-dimethylformamide [315]. The fluoride ion, dissolved as tetraalkylammo-nium fluoride in dipolar difluoromethane, even reacts with carbon dioxide to yield the fluorocarbonate ion, F-C02 [840]. 

As seen, addition of excess strong donor ligand may induce a nucleophilic attack on carbon instead of simple displacement of a ligand. 

The pyrimidine moiety of purines is 7t-electron deficient, whereas the imidazole ring is a Jt-electron excessive system. The direction of the dipole moment is altered by the introduction of substituents, by protoiiation, tautomerization or base pairing. The 7t-excessive character of the imidazole moiety of various purines makes it suitable for anion formation upon treatment with sodium hydride, potassium hydroxide, potassium carbonate or other reagents which are used during electrophilic reactions, such as alkylation or glycosylation. The nucleophilic attack on carbons occurs in the order C8 > C6 > C2. A number of purine syntheses use the displacement of existing substituents. 

As shown in Scheme 21, aliphatic primary amines may react in three ways with 5-aryl-3-methylthio-l,2-dithiolium ions. ° The products are 49, a 5-aryl-l,2-dithiole-3-thione, by sulfur demethylation 50, a methyl 3-alkylamino-3-aryldithioacrylate, by nucleophilic attack on carbon 5 and/or 51, a 2-alkyl-5-arylisothiazoline-3-thione, by nucleophilic attack on carbon 3. 

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