Amines from phthalimides

Amides are weakly nucleophilic and react only slowly with alkyl halides. The anions of amides are substantially more reactive. The classical Gabriel procedure for synthesis of amines from phthalimide is illustrative.58... 

Hydroxylamine hydrochloride-sodium alcohol Prim, amines from phthalimides under mild conditions Hydroxylaminolysis... 

Removal of protective groups under mild conditions Prim, amines from phthalimides Carboxylic acids from carboxylic acid esters... 

Simultaneous N-deacetylation, 0-debenzoylation, and formation of prim, amines from phthalimides s. 13, 39... 

The two-step procedure includes formation of a N-substituted phthalimide 3, and its subsequent cleavage to the primary amine 5. Phthalimide (which can be obtained from reaction of phthalic acid with ammonia) shows NH-acidity, since the negative charge of the phthalimide anion (the conjugated base) is stabilized... 

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). 

Protected primary allylic amines were generated from allylic carbonates and ammonia equivalents. Iridium-catalyzed allylic substitution has now been reported with sulfonamides [90, 91], imides [89, 91-93], and trifluoroacetamide [89] to form branched, protected, primary allylic amines (Table 5). When tested, yields and selectivities were highest from reactions catalyzed by complexes derived from L2. Reactions of potassium trifluoroacetamide and lithium di-tert-butyhminodi-carboxylate were conducted with catalysts derived from the simplified ligand L7. Reactions of nosylamide and trifluoroacetamide form singly-protected amine products. The other ammonia equivalents lead to the formation of doubly protected allylic amine products, but one protecting group can be removed selectively, except when the product is derived from phthalimide. 

A variant of Gabriel amine synthesis where hydrazine is used to release the amine from the corresponding phthalimide ... 

Further transamidation reactions are depicted in Scheme VI/6. In some respects, even the Gabriel synthesis, [15] [16] [17]3), a method for preparation of primary amines from N-substituted phthalimides by treatment with hydrazine,... 

The Gabriel synthesis consists of two steps and uses a nucleophile derived from phthalimide to synthesize 1° amines via nucleophilic substitution. The Gabriel synthesis begins with... 

Gabriel synthesis (Section 25.7A) A two-step method that converts an alkyl halide into a primary amine using a nucleophile derived from phthalimide. 

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... 

Gabriel synthesis Two-step preparation of primary amines from the corresponding alkyl halides using phthalimide as the nitrogen source. 182... 

Phthalimides. Alcohols are activated by (Me2N=CHCl) CF toward displacement with potassium phthalimide. By this method the synthesis of chiral amines from secondary alcohols (inversion of configuration) is accessible. 

Aminals, compounds having two amino groups bound to the same carbon atom, are represented in many medicinal agents having versatile therapeutic action, such as proteinase inhibitors and neurotensins. Antilla and coworkers developed an en antioselective synthesis of protected aminals from the amidation reaction of N Boc imines with a series of sulfonamides catalyzed by chiral phosphoric acids (Scheme 3.54a) [111]. In this novel enantioselective transformation, phosphoric acid 9 exhibited excellent catalytic activity and enantioselectivity in addition to N Boc aromatic imines. The enantioenriched aminal products were stable upon storage neither decomposition nor racemization was observed in solution over several days. The same research group reported the enantioselective amidation reaction of N Boc aromatic imines with phthalimide or its derivatives (Scheme 3.54b) [112]. 

The Gabriel synthesis involves the formation of primary amines from alkyl halides by using potassium phthalimide, thus preventing over-alkylation. 

It crystalhzes from ether in prisms, which melt at 228°. The imide is of interest on account of its use in the preparation of aliphatic amines. When phthalimide is treated in alcoholic solution with potassiuifi hydroxide, a metallic derivative of the imide is precipitated. This salt interacts with alkyl halides to... 

As discussed earlier in this chapter, ammonia is not always the best reagent to generate amines from halides. Amine surrogates such as azides or phthalimide usually give better yields in Si,f2-type reactions, although their... 

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