Gabriel synthesis mechanism

The reaction with ammonia or amines, which undoubtedly proceeds by the SnAt mechanism, is catalyzed by copper and nickel salts, though these are normally used only with rather unreactive halides. This reaction, with phase-transfer catalysis, has been used to synthesize triarylamines. Copper ion catalysts (especially cuprous oxide or iodide) also permit the Gabriel synthesis (10-61) to be... 

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. 

Fig. 6.20. Mechanism of the second step of the Gabriel synthesis of primary alkyl amines.

Aminooxindols (11/153) are rearranged to 3-cinnolinols 11/154, if treated with equimolar amounts of /-butyl hypochlorite [106] [107] [108]. Compound 11/153 is known as Neber s lactam , and is formed from 11/154 with zinc and sulfuric acid. The mechanism preferred for the 11/153 —> 11/154 transformation involves nitrene formation [106]. - As already mentioned, the Gabriel synthesis (11/155 11/157) is a method for synthesis of primary amines. But the side product is the ring enlarged hydrazide, compare Chapter IV... 

The phthalimide anion is a strong nucleophile. It can react easily with primary alkyl halides to form substituted phthalimides. One advantage when working with substituted phthalimides is that when treated with hydrazine, primary amines are furnished through this alkylation protocol (Gabriel synthesis). For both synthetic pathways (a) and (b), suggest a suitable mechanism. 

The first step of this process occurs via an S 2 mechanism. Using this information, determine whether the Gabriel synthesis can be used to prepare the following amine. Explain your answer. 

Draw a mechanism for the last step of the Gabriel synthesis, performed under basic conditions. 

The Gabriel synthesis prepares 1° amines from alkyl halides. Since the reaction proceeds by an Sn2 mechanism, the halide must be CH3 or 1°, and X can t be bonded to an hybridized C. 

Show the mechanisms of each step in a Gabriel synthesis (See Model 3.). 

Write the mechanism of the last step in the Gabriel amine synthesis, the base-promoted hydrolysis of a phthalimi.de to yield an amine plus phthalale ion. 

Analogously to the precedent transition metal-catalyzed cycloisomerization of (Z)-pent-2-en-4-yn-l-ols like 113 into furan compounds (Scheme 8.45), Gabriele disclosed a general and a very convenient route leading to pyrroles 218 from nitrogen analogs of these reactive precursors (Scheme 8.81) [269]. Thus, di-, tri-, and tetra-substituted pyrroles 218 with different substitution patterns could be readily synthesized via the Cu(I)- or Cu(II)-catalyzed [270] cycloisomerization of (Z)-(2-en-4-ynyl)amines 217. The mechanism of this transformation is similar to that proposed for the transition metal-catalyzed synthesis of furans (Scheme 8.46). 

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