Gabriel

An important laboratory use involves the Gabriel synthesis of a-amino-acids. 

HCR and co-workers carried out a number of studies by employing 3D potential energy surfaces calculated by means of highly sophisticated ab initio approaches [88,91-101]. The results of these computations are in impressive agreement with the corresponding experimental findings. The discrepancies in the order of 100 wavenumbers, as in early ab initio studies [16,17], have been reduced in the HCR studies to only a few wavenumbers. In conclusion of their paper on the ( H ) system of NH2, Gabriel et al. state We believe... 

Benzylamine may be obtained by the Gabriel synthesis, which depends upon the use of potassium phthalimide. The latter upon heating with benzyl... 

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. 

Chapter IV. a-Chloromethylnaphthalene (IV,23) benzylamine (Gabriel synthesis) (IV,39) i r.N -dialkylanilines (from amines and trialkyl orthophosphates) (IV,42) a-naphthaldehyde (Sommelet reaction) (IV,120) a-phenyl-cinnamic acid (Perkin reaction using triethylamine) (IV,124) p-nitrostyrene (IV,129) p-bromonaphthalene and p naphthoic acid (from 2 naphthylamine-1 -sulphonic acid) (IV,62 and IV,164) diphenic acid (from phenanthrene) (IV,165). 

Gabriel synthesis Gattermaim aldehyde reaction Gattermann reaction Gattermann-Kocll reaction Gomberg-Hey reaction Grignard reaction... 

In 1890, Gabriel and Lauer (92) established that a-bromoamines react with CS2 to give 2-mercaptothiazolines (61). In the same laboratory, Hirsch (93) reacted /x-mercapto -methylthiazoline (61) with various alkyl iodides and obtained the corresponding S-alkyl derivatives. 

In 1896, Gabriel and Freiherr von Hirsch (96) condensed CSj with what they believed to be 1-aminopropylene (2-methylaziridine) and obtained isomeric 4- and S-methyl-Z-mercaptothiazoline (63 and 64). 

Probably first obtained by Hantzsch and Arapides (105) by condensation of a,/3-dichlorether with barium thiocyanate, and identified by its pyridine-like odor, thiazole was first prepared in 1889 by G. Popp (104) with a yield of 10% by the reduction in boiling ethanol of thiazol-2-yldiazonium sulfate resulting from the diazotization of 2-aminothiazole. prepared the year before by Traumann (103). The unique cyclization reaction affording directly the thiazole molecule was described in 1914 by Gabriel and Bachstez (106). They applied the method of cyclization, developed by Gabriel (107, 108), to the diethylacetal of 2-formylamino-ethanal and obtained thiazole with a yield of 62% - Thiazole was also formed in the course of a study on the ease of decarboxylation of the three possible monocarboxylic acids derived from it (109). On the other... 

This reaction was first described by Gabriel in 1910 (40), when he warmed an acylaminoketone (197a) with an equimolecular amount of phosphorus pentasulfide. The reaction (Scheme 103) is similar to the preparation of other five-membered oxygen- and sulfur-containing rings from 1,4-dicarbonyl compounds. 

The Gabriel s synthesis is also applicable when a polysubstituted thiazole is required (381, 550). Thus 2,4,5-trisubstituted thiazoles are obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at 100°C (550) or at higher temperature for heavier substituents (381). (Table 11-31). 

TABLE 11-31. THIAZOLES FROM -ACYLAMINOKETONES AND PHOSPHORUS PENTASULFIDE (Gabriel s synthesis)... 

The Gabriel s synthesis has been further extended to alkoxythiazoles. Thus 2-alkoxy (or aryloxymethyl) 5-methyl (or phenyl) thiazoles (200) were prepared by refluxing the corresponding acylaminoketone (199) in dry pr3ridine in the presence of P2S5 (Scheme 105) (409). 

A method that achieves the same end result as that desired by alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis Alkyl halides are converted to primary alkylamines without contam mation by secondary or tertiary amines The key reagent is the potassium salt of phthal imide prepared by the reaction... 

The Gabriel synthesis is based on work carried out by Siegmund Gabriel at the Uni versity of Berlin in the 1880s A detailed discussion of each step in the Gabriel synthesis of benzylamine can be found in the October 1975 Journal of Chemical Education (pp 670-671)... 

Aryl halides cannot be converted to arylammes by the Gabriel synthesis because they do not undergo nucleophilic substitution with N potassiophthalimide m the first step of the procedure... 

Among compounds other than simple alkyl halides a halo ketones and a halo esters have been employed as substrates m the Gabriel synthesis Alkyl p toluenesul fonate esters have also been used Because phthalimide can undergo only a single alkyl ation the formation of secondary and tertiary amines does not occur and the Gabriel synthesis is a valuable procedure for the laboratory preparation of primary amines... 

In Its overall design this procedure is similar to the Gabriel synthesis a nitrogen nude ophile IS used m a carbon-nitrogen bond forming operation and then converted to an ammo group m a subsequent transformation... 

Alkylation of phthalimide The Gabriel synthesis (Section 22 8) The potassium salt of phthalimide reacts with alkyl hal ides to give N alkylphthalimide deriva fives Hydrolysis or hydrazinolysis of this derivative yields a primary alkylamine... 

Isobutylamine and 2 phenylethylamine can be prepared by the Gabriel synthesis ten butyl amine N methylbenzylamine and aniline cannot... 

Gabriel synthesis (Section 22 8) Method for the synthesis of primary alkylamines in which a key step is the formation of a carbon-nitrogen bond by alkylation of the potassium salt of phthalimide... 

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