Nitrogen halides Subject

Bimolecular reactions of aniline with /V-acyloxy-/V-alkoxyamides are model Sn2 processes in which reactivity is dictated by a transition state that resembles normal Sn2 processes at carbon. Electronic influences of substituents support a non-synchronous process which has strong charge separation at the transition state and which is subject to steric effects around the reactive centre, at the nucleophile but not on the leaving group. The sp3 character of nitrogen and disconnection between the amino group and the amide carbonyl renders these reactions analogous to the displacement of halides in a-haloketones. 

Stepwise Selective Amine and Amide Alkylation (Fig. 14) 44 A first alkylation step is performed by suspending (78) in a 2 M solution of a suitable alkyl halide in DMF at 50° for 24-48 h. After thorough washing with DMF (3x), CH2C12 (3x), and THF (3x) intermediate (79) (usually formed with >85% purity) is subjected to the final alkylation. The reaction flask is sealed with a fresh rubber septum and flushed with nitrogen followed by cooling to 0°. In a separate flame-dried 25-ml round-bottom flask 12 equiv. (with respect to 79) of 5-phenylmethyl-2-oxazolidinone is added. To the reaction flask freshly distilled THF is added (the appropriate volume to provide a 0.2 M solution of the 5-phenylmethyl-2-oxazolidi-none). The resulting clear solution is then cooled to —78° and 1.6 M n-butyl... 

Oxazoles and benzoxazoles yield salts with acids, alkyl halides, methyl toluene-p-sulfonate, triethyloxonium fluoroborate, etc. Quaternization is subject to the well-known steric effect of bulky substituents 2-phenylbenzoxazole, for instance, does not react with ethyl iodide even at 240 °C. The weakly basic nature of oxazole (see Section 4.18.2.4) is reflected in the instability of its simple salts, such as hydrochlorides and picrates, which are readily hydrolyzed, even in air. 2-Aminooxazoles and 2-aminobenzoxazoles are alkylated at the ring nitrogen atom the anilinonaphthooxazole (124), on the other hand, reacts with methyl iodide to yield a mixture of methyl derivatives (equation 1). 

You have now seen how enols and enolates react with electrophiles based on hydrogen (deuterium), carbon, halogens, silicon, sulfur, and nitrogen. What remains to be seen is how new carbon-carbon bonds can be formed with alkyl halides and carbonyl compounds in their normal electrophilic mode. These reactions are the subject of Chapters 26-29. We must first look at the ways aromatic compounds react with electrophiles. You will see similarities with the behaviour of enols. 

The opening of activated cyclopropanes with nitrogen nucleophiles has been widely applied to the synthesis of pynolizidine and pyrroline alkaloids by Danishefsky this subject has been reviewed. A number of pyrroline annulations have been based on this principle, illustrated in equation (35a). > Similar opening can be accomplished with halides, cuprates, and sulfur or selenium nucleophiles. ... 

The silanes have been used as intermediates (e.g., R2M-TMS), in the conversion of metalloid halides R2MHal to their hydrides RjMH, which are then subjected to cyclization. They have also been used as leaving groups on heteroatoms such as nitrogen in their reactions with metalloid halides to give compounds such as the amides (107). 

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