Gabriel synthesis, modified

The modified procedure involves refluxing the N-substituted phthaUmide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydtazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has been employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

Ethyleneimine was fkst piepaied commeicially in 1938 from 2-chloioethylaniine and NaOH by a modified Gabriel synthesis (21). 

Onaka demonstrated the utility of a modified Fisher method in the one-step synthesis of oxazole alkaloid Halfordinol (16) in higher overall yield than previously reported by Robinson-Gabriel synthesis. ... 

Methyl r-butyl iminodicarboxylate (91) and di-r-butyl iminodicarboxylate (93) have been used in a modified Gabriel synthesis. Thus, the potassium salt of (91) reacted with alkyl halides to give the corresponding A/-alkylated products (92) in 59-95% yields (in DMF or DMSO, 20-60 C) except for alkylating reagents susceptible to base-catalyzed side reactions. Under basic conditions, (92) gave N-t-butoxycarbonylamines, whereas, with trifluoroacetic acid, iV-methoxycarbonylamines were obtained (Scheme 40). ... 

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... 

Modified Gabriel synthesis. Methanolic 4 N KOH added at 80-90° to a soln. of phthalimide in dimethylformamide while methanol distills off, cooled to room temp., a-bromopropiophenone in dimethylformamide added to the precipitated K-phthalimide, and stirred 30 min. at 50° a-phthalimidopropiophenone. Y 85%. F. e. and procedure s. H. K. Muller and G. Rieck, J. pr. 9, 30 (1959). 

Han, Y., Hu, H. A convenient synthesis of primary amines using sodium diformylamide as a modified Gabriel reagent. Synthesis 1990, 122-124. 

The modified Gabriel reagent (168) has been shown to have considerable potential for the synthesis of iV-Boc-a-amino-acids, by condensation with a-bromo-esters followed by hydrolysis and decarboxylation (Scheme 38) yields are high throughout.A new route to a-amino-acids is by aminoalkylation of olefins by open-chain adducts of glyoxylic acid and amides, carbamates, and ureas. ... 

Synthesis.—Alcohols can be induced to act as electrophiles in a modified Gabriel amine synthesis alkoxyphosphonium salts efficiently alkylate phthalimide and other imides (Scheme 119) with almost complete inversion... 

Gabriel Rokicki is a chemistry professor at the Faculty of Chemistry, Warsaw University of Technology, Poland, where he received all his academic education (MSc in 1971, PhD in 1989, and tenure professor in 2002). His current scientific activities include synthesis, stmcture, and properties of polymer materials, such as aliphatic polycarbonates, polyurethanes, epoxy resins, and biodegradable polymers. He has devoted a special interest to the use of functional polymers in obtaining specialty ceramic materials as well as to polymer recycling. Earlier major interests included the utilization of carbon dioxide and cyclic carbonates in the synthesis of condensation polymers. Another topic of interest was polymeric ion-sensors based on modified calixarenes. He is the author and coauthor of 160 scientific papers and holds more than 50 patents in the above-mentioned areas. At the Faculty of Chemistry of Warsaw University of Technology, he conducts lectures on polymer chemistry and technology. 

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