Gabriel synthesis of amines

The Gabriel synthesis of amines uses potassium phthalimide (prepared from the reaction of phthalimide with potassium hydroxide). The structure and preparation of potassium phthalimide is shown in Figure 13-13. The extensive conjugation (resonance) makes the ion very stable. An example of the Gabriel synthesis is in Figure 13-14. (The N2H4 reactant is hydrazine.) The Gabriel synthesis employs an 8, 2 mechanism, so it works best on primary alkyl halides and less well on secondary alkyl halides. It doesn t work on tertiary alkyl halides or aryl halides. 

The overall reaction involves replacing the halogen atom of the alkyl halide with an NH, unit. Another method is the Gabriel synthesis of amines. This involves treating phthalimide with KOH to abstract the N-H proton. The N-H proton of phthalimide is more acidic (pK9) than the N-H proton of an amide since the anion formed can be stabilised by resonance with both neighbouring carbonyl groups. The phthalimide ion can then be alkylated by treating it with an alkyl halide in nucleophilic substitution. 

One of the best methods of amino acid synthesis is a combination of the Gabriel synthesis of amines (Section 19-20) with the malonic ester synthesis of carboxylic acids (Section 22-16). The conventional malonic ester synthesis involves alkylation of diethyl malonate, followed by hydrolysis and decarboxylation to give an alkylated acetic acid. 

This method, a modification of the Gabriel synthesis of amines (Section 20.4A), uses potassium phthalimide and diethyl a-bromomalonate to prepare an imido malonic ester. The example shown is a synthesis of methionine ... 

Gabriel Synthesis of Amines. )V-Benzyltriflamide was originally introduced as a new nitrogen source for the Gabriel synthesis of amines. Based on its pKa of 6.8 in 67% DMF-water and a gas phase acidity of AGacid = 318.8, due to the powerful electron-withdrawing effect of the triflate function, it was reasoned that a weak base should be sufficient to induce the necessary A deprotonation. Typical conditions (eq 1) for W alkylation... 

Amides appear in such diverse compounds as penicillin V (a (3-lactam and an amide) and polypeptides (a-amino adds linked by amide bonds) and an imide, 1,2-benzenecarboxylic imide, is used in the Gabriel synthesis of amines. An imide is prepared in Experiment [24] and anhydrides are prepared in Experiments [25A] and [25B].The polyamide polymer, nylon, is prepared in Chapter 7, Sequence B. 

Gabriel synthesis of amines, 339 gas chromatographic collection glassware, 19, 21, 27... 

In Summary Racemic amino acids are made by the amination of 2-bromocarboxylic acids, applications of the Gabriel synthesis of amines, and the Strecker synthesis. The last method proceeds through an imine variation of the preparation of cyanohydrins, followed by hydrolysis. 

One of the best methods for synthesizing amino acids is based on the chemistry of malonate esters (Section 22.17) and a modification of the Gabriel synthesis of amines (Section 23.7). Diethyl acetamidomalonate has a nitrogen atom bonded to the a-carbon of the malonate ester. This nitrogen eventually becomes the nitrogen of the final amino acid product. 

Potassium phthalimide is a commercially available reagent, which is usually used in the Gabriel synthesis of amines (50). Halomethylsilanes interact with potassium phthalimide to form N-silylmethylphthalimides 32—48 (Scheme 24.4, Table 24.2)... 

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