Imides, reaction with alkyl halides

Chiral oxazolidinone auxiliaries derived from D-xylose were applied by Koell et al. [156]. The oxazolidinones were acylated with various acid halides furnishing imides, which are substrates for a-alkylation reactions. For example, the butyric acid derivative 213 was deprotonated with LDA to give the (Z)-configured enolate 214, which was reacted with methyl iodide (Scheme 10.71). The methylated product 215 was formed in a moderate yield of 45% and a diastereomeric ratio of 7 1. The approach of the electrophile occurred from the less hindered /-face of the enolate... 

Symmetrical disulfides (73) may be prepared by reaction of alkyl halides with disodium disulfide (Scheme 43). The product is contaminated with triand polysulfides owing to the presence of impurities in the disodium disulfide however, lower members of the series of dialkyl disulfides may be purified by fractional distillation. Disulfides can also be obtained from thiols by mild oxidation, e.g. by treatment with iodine or dimethyl sulfoxide (DMSO) (Scheme 44). In the reaction with iodine, the hydriodic acid formed must be removed, otherwise the disulfide is largely reduced back to the thiol by hydriodic acid which is a powerful reducing agent. Pure unsymmetrical disulfides are more difficult to prepare owing to their tendency to undergo disproportionation they can, however, be synthesised from thiols by treatment with imides (see p. 59) or sulfenyl halides (51) (Scheme 45). 

Ionic liquids (IL) can be used as solvents for nucleophilic substitution reactions of alkyl halides or tosylates with NaN3. ° The authors studied three ionic liquids (84 and 85), [bmim][PF6], [bmim][N(Tf)2]> [hpyr][N(Tf)2] (where bmim = l-butyl-3-methyl-imidazo-lium, hpyr = 1-hexylpyridinium, PFg = hexafluorophosphate, N(Tf)2 = bis(trifluoromethy lsulfonyl)imide). It was observed that nucleofugacity scales for this reaction are similar to those reported for the same process in cyclohexane. It was also observed that elimination reaction does not compete with substitution even in cases with sterically hindered substrates such as the triflate ester of diacetone-D-glucose 81. The nucleophilic displacement on n-octyl mesylate (86) with potassium azide in a biphase system of supercritical carbon dioxide (SCCO2) and water, in the presence of catalyst Bu4PBr is also an adequate medium for the synthesis of the corresponding azide 87 ° (Scheme 3.11). 

JV-Alkylation of sulphodi-imides can be effected by trialkyloxonium salts, or by conversion into iV-alkali-metal salts and reaction with alkyl halides. Reactions of sulphur difluoride di-imides afforded nitrogen analogues of sulphuric acid, e.g. (129). Photoelectron spectra and molecular properties of... 

Phthalimide. C<,H4 (CO), NH, is an imide of commercial and industrial importance, forming a number of interesting derivatives. With alcoholic potash, phthalimide forms a potassium derivative. C(,H4 (COb -NK. which, when reacted with ethyl iodide (or other alkyl halides), yields eihylphthalimidc. C(,H4 (COi N - C2Hj Ihe latter product, when hydrolyzed wilh an acid or alkali, further yields ethylamine. Such reaction chains are useful in ihe preparation of certain primary amines and their derivatives. 

The enantioselective complexation technique can also be applied as one step in the reaction sequence, providing chiral substrates for the next step. We will now discuss the example of Gabriel synthesis between potassium phthalimide 41 and alkyl bromide 42, which leads to optically active amines (Scheme 1) [51], Instead of the complicated preparation of chiral alkyl bromides (halides), imides (43), which are reaction intermediates, have been resolved. Upon treatment with hydrazine and KOH, these gave optically active amines. The chiral host (S,S)-(-)-6 or the chiral biaryl host (,S>(-j-40 was used for the effective resolution of the intermediates 43. Racemic mixtures 43a-d were resolved by complex formation with the host (S,S)-(-)-6 in a mixture of diethyl ether and light petroleum. 

An acid—base reaction forms a nucleophilic anion that can react with an unhindered alkyl halide— that is, CH3X or RCH2X—in an 5 2 reaction to form a substitution product. This alkylated imide is then hydrolyzed with aqueous base to give a 1° amine and a dicarboxylate. This reaction is similar to the hydrolysis of amides to afford carboxylate anions and amines, as discussed in Section 22.13. The overall result of this two-step sequence is nucleophilic substitution of X by NH2, so the Gabriel synthesis can be used to prepare 1° amines only. 

Alkyl phenyl telluriums react with AT-chloro-A-sodio-4-methylbenzenesulfonamide in refluxing THF to yield terminal olefins from prim, alkyl groups and a mixture of 1 -alkenes and 2-alkenes from sec. alkyl groups. Diorgano tellurium imides were postulated as intermediates. Considering the synthesis of the alkyl phenyl tellurium from an alkyl halide and benzenetellurolate, the overall reaction is the conversion of an alkyl halide to an olefin. Starting with lithiomethyl phenyl tellurium and an alkyl halide, the resulting olefin will have one carbon atom more than the alkyl halide. ... 

For synthetic purposes cyclized radicals are preferentially trapped by chlorine [16], bromine [60], or iodine atom donors [54] to provide y9-functionalized tetrahy-drofurans, for instance halides 35-37 (Scheme 9), which serve as building blocks for subsequent ionic or free-radical reactions. This radical version of the classical halogen cyclization (Bartlett reaction [61]) is particularly useful if functionalized tetrahydrofurans can be obtained from terminal alkyl- or aryl-substituted alkenols. If these compounds are reacted for example with iodine or with A -bromosuccin-imide, tetrahydropyrans are formed from ionic cyclofunctionalizations [62], If, however, the corresponding alkenols are converted into a thiohydroxamic acid... 

Amides are unreactive compounds but do react with water and alcohols if the reaction mixture is heated in the presence of an acid. Nitriles are harder to hydrolyze than amides. The Gabriel synthesis, which converts alkyl halides into primary amines, involves the hydrolysis of an imide. 

Barbierreactions. In nitrile solvents, the condensation of alkyl halides with carbonyl compounds gives alcohols. The reaction between esters and iodoalkanes proceeds only in the presence of Nil. With an iron(IIl) salt as a catalyst, cyclic A-iodoalkyl imides form polycyclic enamides via carbinol lactams. ... 

The most commonly used ADA modules contain the pyrimidine-2,4-dione nucleus. Not surprisingly, N-alkylation of thymine or uracil with an alkyl halide provides a simple, one-step method of functionalizing this module. Other ADA units include simple imides (e.g., 10), heterocycle 13, which was used by Kelly in a bisubstrate reaction template [17], and the anthyridinone or anthyridan units in 15 and 18, respectively. The latter modules are synthesized by double Friedlander condensation of 2,6-diaminopyridine-3,5-dicarboxal-... 

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