Gabriel synthesis alternative

An alternative to Gabriel synthesis is based on the alkylation of tnfluoro-acetamide [770, 777[ or Al-benzyl triflamide [772] in place of the classical phtalimide (equations 96 and 97). 

An alternative to the Gabriel synthesis, in which alkyl halides can be converted to primary amines in good yields, involves treatment of the halide with the strong base guanidine followed by alkaline hydrolysis. There are several alternative... 

An alternative reagent equivalent for the amide anion synthon is the potassium salt of phthalimide which can only react with one molecular proportion of alkyl halide. The resulting JV-alkylphthalimide is then cleaved to the primary amine (the Gabriel synthesis). The preliminary preparation of potassium phthalimide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75% ethanol) may be avoided in some cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The cleavage of the JV-substituted phthalimide is best effected by reaction with hydrazine hydrate and then heating the reaction mixture with hydrochloric acid. The insoluble phthalylhydrazide is filtered off, leaving the amine hydrochloride in solution from which the amine may be liberated and isolated in the appropriate manner. 

A milder alternative to the classical Gabriel synthesis, which allows the appendage of a protected primary amine to a secondary alkyl group, exploits the Mit-sunobu inversion2 as illustrated in Scheme 8.15.27 The method can also be adapted to the synthesis of -protected hydroxylamines [Scheme 8,16)22... 

Identify the lettered intermediates in the following reaction scheme. This is an alternative method to synthesize amino acids, based on the Gabriel synthesis of 1 ° amines (Section 25.7A). 

The most convenient method of making a-aminoaldehydes is by reduction of a-amino acid esters using sodium amalgam [5, 6] by what has come to be known as the Akabori method. Alternatively, an a-halogenocarbonyl compound can be converted via the Gabriel synthesis into the aminocarbonyl... 

The sequence provides a useful alternative to the Gabriel synthesis particularly for preparation of amines containing nitrile, ester, or amide groups, which are hydrolyzed to a carboxylic acid group when the phthaloyl group is removed. 

Zwierzak and co-workers have reported on the use of a phosphoramidate as an alternative to the phthalimide in the Gabriel synthesis.22 "0 However, several drawbacks to their method led to revisions in the original method. In particular, the use of toxic benzene as a solvent, deprotection by gaseous HC1 in benzene, and low yields were discouraging. The modified procedure reaction involves nucleophilic amination by diethyl yV-sodio-./V-(r-butoxycarbonyl)phosphoramidate 37 with tetrabutylammonium bromide as a catalyst in acetonitrile. Carrying out the reactions in tetrahydrofuran led... 

Tris(dimethylamino)phosphine added to a soln. of N-benzylthiophthalimide in benzene whereupon an exothermic reaction ensues N-benzylphthalimide. Y 87%. - This method provides an alternative to the Gabriel synthesis of prim, amines. F. e. s. D. N. Harpp and B. A. Orwig, Tetrah. Let. 1970, 2691. 

Primary alkylamines are also available from alkenes in a simple two-step phosphoramidomercuration-demercuration sequence, and from halides via iV-carbalkoxyphosphoromonoamidates in an alternative to the Gabriel synthesis. The synthesis of N-labelled primary alkylamines has also been described. ... 

Aminobutanoic acid, commonly known as y-aminobutyric acid or GABA, is a neurotransmitter. Explain why it cannot be synthesized by a Gabriel synthesis using 4-chlorobutanoic acid. What alternate chlorinated acid derivative might be used. 

Another alternative for preparing a primary amine from an alkyl halide is the Gabriel amine synthesis, which uses a phthalimide alkylation. An imide (—CONHCO—) is similar to a /3-keto ester in that the acidic N-H hydrogen is flanked by two carbonyl groups. Thus, imides are deprotonated by such bases as KOH, and the resultant anions are readily alkylated in a reaction similar to the acetoacetic ester synthesis (Section 22.7). Basic hydrolysis of the N-alkylated imide then yields a primary amine product. The imide hydrolysis step is analogous to the hydrolysis of an amide (Section 21.7). 

An alternative to the azide synthesis is the Gabriel amine synthesis, which uses a phthalimide alkylation for preparing a primary amine from an alkyl halide. Imides (-CONHCO-) are similar to ethyl acetoacetate in that... 

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