Hydrides nucleophilic substitution reactions

This is not strictly correct, in that hydride, from say sodium hydride, never acts as a nucleophile, but because of its small size and high charge density it always acts as a base. Nevertheless, there are a number of complex metal hydrides such as lithium aluminium hydride (LiAlHj LAH) and sodium borohydride (NaBH4) that deliver hydride in such a manner that it appears to act as a nucleophile. We have already met these reagents under nucleophilic substitution reactions (see Section 6.3.5). Hydride is also a very poor leaving group, so hydride reduction reactions are also irreversible (see Section 7.1.2). 

The carbonyl group at G-4 of the 3-aryl-4-benzoylazetidin-2-one is reduced with sodium borohydride to the corresponding hydroxyl group <2003T5259>. Treatment of azetidin-2-one 372 with sodium hydride gave a fused tricyclic azetidin-2-one 373 (Equation 140) as a result of an intramolecular nucleophilic substitution reaction of the alkoxide with an aromatic group at the C-3 position. 

These nucleophilic substitution reactions are much more facile when better leaving groups (e.g. halide ions instead of hydride ions) are employed. 

The net result is that Nu replaces Z—a nucleophilic substitution reaction. This reaction is often called nucleophilic acyl substitution to distinguish it from the nucleophilic substitution reactions at sp hybridized carbons discussed in Chapter 7. Nucleophilic substitution with two different nucleophiles—hydride (H ) and carbanions (R )— is discussed in Chapter 20. Other nucleophiles are examined in Chapter 22. 

Silicon compounds with coordination number larger than four are the object of many studies first with respect to their application as catalysts in organic and inorganic syntheses and second as starting materials for the preparation of a broad variety of organosilicon compounds [1]. Additionally, hypervalent silicon hydride compounds can successfully be used as model compounds to study, for instance, the mechanism of nucleophilic substitution reactions, which is of great interest since the silicon atom is able to easily extend its coordination number [1]. Moreover, hypervalent silanes are suitable as starting materials for the synthesis and stabilization of low-valent silanediyl transition metal complexes [2-5]. 

The formation of the sultone (160) probably involves addition of the complex across the alkene double bond, a 1,2-hydride shift and an intramolecular nucleophilic substitution reaction. The sultone (161) is formed by addition of sulfur trioxide to give the unstable p-sultone which rearranges to the more stable y-isomer (161). Another useful route to sultones is by metallation of alkanesulfonate esters for example, butane-1,3-dimethylsulfonate (162), prepared from butanel,3-diol, yields the 8-sultone, namely 6-methyl-l,2-oxathiin-2,2-dioxide (163) (Scheme 67). 

Alkylation of Azide Ion and Reduction A much better method for preparing a primary amine from an alkyl halide is first to convert the alkyl halide to an alkyl azide (R — N3) by a nucleophilic substitution reaction, then reduce the azide to a primary amine with lithium aluminum hydride. 

There has been a study of nucleophilic substitution reactions in the benzene analogue l,2-dihydro-l,2-azaborine. With oxygen nucleophiles, an associative mechanism is likely involving intermediates (2) followed by dehydrogenation, while with carbon nucleophiles, the likely path involves deprotonation followed by nucleophilic addition to give a dianion (3) and then hydride loss. Also involving boron chemistry, the reaction of tri(pentafluorophenyl)boron with diarylphosphinyl-substituted acetylenes has been shown to result in the formation of 1,1-carboborafion products such as (4). 

In addition to the usual substitution reactions directly on the nitrogen atom of the amino or amido group, there are (as noted earlier, e.g.. Table 7.7) substitution reactions with other nucleophiles that can be converted to the amino (or substituted amino) group. These include incorporation of the azido function (produced by, e.g., a nucleophilic substitution reaction of azide anion [Ns"] on an alkyl halide) and its subsequent reduction (with lithium aluminum hydride, LiALH,) (Equation 10.60) or triphenylphosphine [( 5115)3 ] (Equation 10.61) to the corresponding amine, as well as a similar displacement reaction with isocyanate (0=C=N ) (Equation... 

In Summary Pyridine undergoes slow electrophilic aromatic substitution preferentially at C3. Nucleophilic substitution reactions occur more readily to expel hydride or another leaving group from either C2 or C4. 

The higjily water-soluble dienophiles 2.4f and2.4g have been synthesised as outlined in Scheme 2.5. Both compounds were prepared from p-(bromomethyl)benzaldehyde (2.8) which was synthesised by reducing p-(bromomethyl)benzonitrile (2.7) with diisobutyl aluminium hydride following a literature procedure2.4f was obtained in two steps by conversion of 2.8 to the corresponding sodium sulfonate (2.9), followed by an aldol reaction with 2-acetylpyridine. In the preparation of 2.4g the sequence of steps had to be reversed Here, the aldol condensation of 2.8 with 2-acetylpyridine was followed by nucleophilic substitution of the bromide of 2.10 by trimethylamine. Attempts to prepare 2.4f from 2.10 by treatment with sodium sulfite failed, due to decomposition of 2.10 under the conditions required for the substitution by sulfite anion. 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

Another example of a nucleophilic acyl substitution reaction, this one a substitution by hydride inn to effect partial reduction of a thioester to an aldehyde, occurs in the biosynthesis of mevaldehyde, an intermediate in terpenoid... 

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