Gabriel reaction

A related aziridine synthesis is the Gabriel reaction (a.k.a. Gabriel-Cromwell reaction), which involves an intramolecular Sn2 reaction of a P-amino halide. However, the reaction has become so common that the name Gabriel is not tightly related to the transformation. 

The stereochemical control of the Gabriel reaction by chiral catalysts can be further enhanced in the synthesis of optically active a-amino acids when optically pure (-)-bornyl a-bromo esters are used (Table 12.8) [4]. 

Phenacylamine hydrochloride has been prepared by (1) the hydrolysis of the quaternary salt obtained from phenacyl bromide and hexamethylenetetramine (the Delepine reaction),6-11 (2) the hydrolysis of N-phenacylphthalimide (the Gabriel reaction),12-14... 

In the Gabriel reaction, cydizatjon to the thnee-membered aziri- < dine u strongly favored over the four-mew b red saetidiue, since treatment of (XII) with sodium hydroxide gives (XIII) and not (XIV).19 ... 

Most side-chain halobenzo [6 (thiophenes react normally with diethyl sodiomalonate 439,447,490,500,535 and its O-alkyl derivatives,499,536 but elimination may predominate in the case of a secondary halo compound.499 Halomethylbenzo [6]thiophenes react normally with potassium phthalimide in the Gabriel reaction (Section VI,H, 2). Where dehydrohalogenation is possible, alcoholic potassium hydroxide gives the corresponding olefin in good yield.469... 

In practice the most common method is the one based upon obtaining a,(3-dihalogen derivatives of unsaturated ketones with their subsequent interaction with ammonia or primary amines, known as the Gabriel reaction (Scheme 1.1). 

Besides o,/ -dibromopropan-l-ones, there are references related to using o,/ -dichloro [26], o-chloro [19] and a-iodo derivatives [27] in the Gabriel reaction. Bicyclic aziridines 16 were obtained by the treatment of ce-iodocyclohexene 14 with benzylamines 15 in the presence of cesium carbonate in xylene [27] (Scheme 1.4). 

At the time of the original [2.2.2] synthesis the compounds 1 and 3 were not commercially available. They had to be prepared from a common starting material, the triethylene glycol, which was transformed by oxidation to the diacid 1 or by bromi-nation followed by Gabriel reaction to the diamine 3.2... 

Gabriel reaction, 679 Gattermann-Koch reaction, 280 Gattermann reaction, 94, 280 Glycerides, preparation, 481, 482 Glycidamides, preparation, 570 Glycidic acids, decarboxylation, 295 pyrolysis, 348... 

Bacon, R. G. R., Karim, A. Copper-catalyzed substitution of aryl halides by potassium phthalimide an extension of the Gabriel reaction. J. 

Sato, M., Ebine, S., Akabori, S. Condensation of halobenzenes and haloferrocenes with phthalimide in the presence of copper(l) oxide a simplified Gabriel reaction. Synthesis 1981,472 73. 

Kubo, A., Kubota, H., Takahashi, M., Nunami, K.-i. Dynamic kinetic resolution utilizing 2-oxoimidazolidine-4-carboxylate as a chiral auxiliary stereoselective synthesis of a-amino acids by Gabriel reaction. Tetrahedron Lett. 1996, 37, 4957-4960. 

Phthalimides are relatively stable under both acidic and basic conditions but are easily cleaved by nucleophiles. Its cleavage is often accomplished using hydrazine according to the Ing-Manske procedure of the Gabriel reaction. 

Gabriel reaction. Review.1 The Gabriel reaction is ordinarily not applicable to aryl halides however, under catalysis with cuprous bromide or iodide and in boiling DMA (dimethylacetamide) as solvent, aryl bromides or iodides (but not chlorides) react with potassium phthalimide to give phthalimido compounds in >5-95% yield.2... 

The formation of aminals via the Gabriel reaction can arise on changing the solvent from toluene to dimethylformamide, in the presence of sodium salts of N-heterocycles.31 In this unique example, 63 could be prepared in useful quantities in a more practical technique than with previous methods which required high heat and/or pressure conditions.32 - The required phthalimide derivatives 62 was also formed but in low yields. 

Esters of (A -formylaminomethyl)phosphonic acid (159), important as precursors to the corresponding esters of (isocyanomethyl)phosphonic acid (160) [themselves useful in further syntheses of (aminoalkyl)phosphonic acids (Section IV.D.l)], have been made through the variation of the Michaelis-Arbuzov reaction which employs quaternary ammonium salts, e.g. 158 . The very few examples of this modification include its combination with the Gabriel reaction in a preparation of (phthalimidomethyl)phosphonic diesters ... 

The following sequence (equation 6) constitutes a convenient alternative to the conversion of alkyl halides into alkylamines by the Gabriel reaction with potassium phthaUmide. In this one-pot procedure, an alkyl bromide RBr (R = Bu, -Bu, 2-pentyl, 2-octyl, PhCH2CH2, HC=C, PhCH=CHCH2, cyclopentyl, cyclohexyl etc.) is treated with sodium azide in benzene in the presence of tetrabutylammonium bromide under phase-transfer conditions. Triethyl phosphite is then added and the resulting iminophosphorane is decomposed to the alkyl amine hydrochloride by adding benzene and hydrogen chloride. ... 

Several examples of this widely practiced name reaction have been applied in drug discovery abound. For example in a study describing the design and synthesis of inhibitors of hepatitis C virus (HCV) NS5B polymerase, thiazole intermediate was constructed via the Gabriel reaction, ... 

Other references related to the Gabriel reaction are cited in the Uterature. ... 

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