Gabriel-type synthesis

Phase-transfer catalysed N-alkylation of diphenylphosphinic amide (I) is totally unsuitable in the case of easily hydrolysable organic halides, especially those containing additional functional groups (i.e. carbonyl or carboalkoxyl) which decompose readily in strongly alkaline medium. To circumvent the difficulty connected with simultaneous mono- and dialkylation of (I) under anhydrous conditions, N-(t-butyloxycarbonyl) diethyl phosphoroamidate (X), a doubly-protected ammonia derivative, was devised as a useful and superior substitute of phthalimide in the Gabriel-type synthesis of amines. 

Slusarska, E., Zwierzak, A. Conversion of alcohols into primary amines, a new Mitsunobu version of Gabriel-type synthesis. Liebigs Ann. Chem. 1986, 402 05. 

In the last step the azide was warmed with /-butanol to effect Curtius rearrangement The reagent is used in a Gabriel-type synthesis of primary amines. Thus a suspension of sodium hydride in a solution of the diester in dimethylformamide was stirred at 60 for 6 hrs. to form the sodio derivative, a,a -dibromo-o-xylene was added,... 

Aniline allowed to react at -78° with trifluoromethanesulfonic acid anhydride and triethylamine in methylene diloride -> N-phenyltriflamide. Y 97%. - The protective group can be removed by reduction. F. e. and triflating agent, also Gabriel-type synthesis of prim, amines from halides via triflamides, s. J. B. Hendrickson and R. Bergeron, Tetrah. Let. 1973, 3839. 

Pteridine, 4-imino-1 -methyl-1,4-dihydro-basicity, 3, 270 Pteridine, 7-methoxy-synthesis, 3, 297 Pteridine, 2-methyl- H NMR, 3, 285 reactions, 3, 288 structure, 3, 266 Pteridine, 4-methyl-Gabriel s synthesis, 3, 309 H NMR, 3, 285 reactions, 3, 288 structure, 3, 266 Pteridine, 6-methyl-bromination, 3, 301 structure, 3, 266 synthesis, 3, 312 Pteridine, 7-methyl-aldol-type condensation, 3, 302 bromination, 3, 301 H NMR, 3, 285 structure, 3, 266 synthesis, 3, 312 Pteridine, 2-methylamino-solubility, 3, 271 Pteridine, 2-methyl-3,4-dihydro-striicture, 3, 279 Pteridine, 6-methyl-3,4-dihydro-structure, 3, 279... 

Synthesis from acylaminocarbonyl compounds and phosphorus pentasulfide and related condensations (Type C) Gabriel s synthesis... 

SAMPLE SOLUTION (a) The Gabriel synthesis is limited to preparation of amines of the type RCH2NH2, that is, primary alkylamines in which the amino group is bonded to a primary carbon. Butylamine may be prepared from butyl bromide by this method. 

The limitations of this approach can be seen in the reaction of a saturated solution of ammonia in 90% ethanol with ethyl bromide in a 16 1 molar ratio, under which conditions the yield of primary amine was 34.2% (at a 1 1 ratio the yield was 11.3%). Alkyl amines can be one type of substrate that does give reasonable yields of primary amine (provided a large excess of NH3 is used) are a-halo acids, which are converted to amino acids. A-Chloromethyl lactams also react with amines to give good yields to the A-aminomethyl lactam. Primary amines can be prepared from alkyl halides by 10-43, followed by reduction of the azide (19-32), or by the Gabriel synthesis (10-41). 

The original Gabriel-Colman pteridine synthesis7 used 6-methylpyrimidine-4,5-diamine and benzil to yield 4-methyl-6,7-diphenylpteridine (see Section 7.3.1.1.1.). This type of reaction generally gives good yields of the required pteridine, and is exemplified by the synthesis of 6,7-dimethylpteridine (l).49... 

Much like with total synthesis, the Gabriel-Heine aziridine isomerization has not found widespread application within the medicinal chemistry community, despite its ability to efficiently generate a variety of azoles. DeWald and coworkers at Parke-Davis used the Gabriel-Heine reaction in the preparation of potential antipsychotics. Compound 27 was rearranged upon exposure to sodium iodide in acetone to provide compounds of type 28 in moderate to good yield, which were evaluated as nondopamine-binding antipsychotics. 

In analogy to thiophene formation (cf. p. 96), thiazoles (mainly of the 2,5-disubstituted type) are obtained from (a-acylamino)ketones by sulfurization with P4S10 and subsequent cyclodehydration Gabriel synthesis) ... 

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