Ammonium salts, alkyl with amides

When an alkyl aryl ketone is heated with yellow ammonium polysulphide solution at an elevated temperature, an aryl substituted aliphatic acid amide is foimed the product actually isolated is the amide of the ci-aryl carboxylic acid together with a smaller amount of the corresponding ammonium salt of the oarboxylio acid. Thus acetophenone affords phenylacetamide (50 per cent.) and ammonium phenylacetate (13 per cent.) ... 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondary, and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to control and often give mixtures of products, but tertiary amines are cleanly alkylated to give quaternary ammonium salts. Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide (Sections 21.4 and 21.5). Note that overacylation of the nitrogen does not occur because the amide product is much less nucleophilic and less reactive than the starting amine. 

Benzylic quaternary ammonium salts, when treated with alkali metal amides, undergo a rearrangement called the Sommelet-Hauser rearrangementSince the product is a benzylic tertiary amine, it can be further alkylated and the product again subjected to the rearrangement. This process can be continued around the ring until an ortho position is blocked. ... 

A thio-substituted, quaternary ammonium salt can be synthesized by the Michael addition of an alkyl thiol to acrylamide in the presence of benzyl trimethyl ammonium hydroxide as a catalyst [793-795]. The reaction leads to the crystallization of the adducts in essentially quantitative yield. Reduction of the amides by lithium aluminum hydride in tetrahydrofuran solution produces the desired amines, which are converted to desired halide by reaction of the methyl iodide with the amines. The inhibitor is useful in controlling corrosion such as that caused by CO2 and H2S. 

A C—N disconnection of a primary amine gives rise to the carbocation and amide anion synthons. It might be predicted therefore that treatment of an alkyl halide with ammonia (reagents equivalent to the above synthons) under pressure would constitute a suitable synthesis of a primary amine. In practice, however, the yield is poor since a mixture of all three classes of amines, together with some of the quaternary ammonium salt, is obtained, owing to more ready further alkylation of the sequentially formed products. 

A -Alkyl-A -(/3-keto)amides 1216 have been prepared using a traceless linker strategy starting from resin-bound benzylamines 1215. The ketoamides 1217 released from the resin react with an ammonium salt to afford 1,2,4-trisubstituted imidazoles 1218 in good yields and high purities (Scheme 297) <20000L323>. 

Sommelet-Hauser rearrangement The rearrangement of a benzyl quaternary ammonium salt, C6H5CH2N+R3X-, when treated with an alkali metal amide to give the orthomethylbenzyl tertiary amine, o-CH3C6H4CH2NR2. The tertiary amine may subsequently be alkylated, and the reaction... 

The enantioselective alkylation of A-protected a-amino esters has been studied with many chiral catalysts, including spirocyclic ammonium salt 10A, while (lOB) containing two binaphthyl components is an effective mediator for alkylation of protected glycine under phase-transfer conditions.p-f-Boc-amino acid derivatized with (-l-)-pseu-doephedrine enables enantioselective alkylation of the ensuing amides. - Note the enolate derived from 11 remains chiral, alkylation products are produced in high ee. ... 

Although the combined additive phosphonylation and esterification of an a,j5-unsatu-rated carboxylic acid by a trialkyl phosphite can thus easily, although not necessarily accurately, be envisaged, that of a similarly unsaturated ester, nitrile, or amide is perhaps not so readily apparent. Harvey showed that successful reaction between triethyl phosphite and such a substrate (Scheme 43) occurs in a protic medium. In this respect, the reactions proceed faster in methanol than in ethanol, but reactions are, in general, (including those of structurally analogous unsaturated ketones) much cleaner and faster when carried out in phenol, and also afford much higher yields in this solvent. It has also been shown that ammonium salts will also act as a proton source to allow completion of addition without alkylation. The later Russian workers used acetic acid with successful results ... 

However, treatment of 169 with the secondary amine, morpholine, did not result in the tertiary amide as expected, but yielded the ammonium salt 173 (Equation 35) <2003T1961>. Instead, the desired tertiary amide 174 was obtained in 75% yield by the alkylation of 171 (Equation 36) <2003T1961>. 

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