Acylation at nitrogen

Acylation of -ones and -diones appears to occur mainly at oxygen, but in the fused pyridazino[4,5-6]quinoline (312) the O-acyl derivative (313) was formed via an iV,0-diacyl derivative (72BSF1588). Reduced derivatives, however, are acylated at nitrogen. 

Acylations at nitrogen include N-acetylation using acetic anhydride (82H1595) and N-mesylation (84TL4223), as well as the N-carboxyalk-ylation of 81 and reaction of 82 with isocyanates or isothiocyanates to afford 83 (Scheme 2) (76JAP76-65757). Alkylations include methylation to yield N-methyl and N,N -dimethyl-l,2-diazocines (69JOC3237). An in-... 

Fortunately 81 is phenylalaninol—the alcohol from the amino acid phenylalanine. The workers decided to acylate at nitrogen first and so used chloracetyl chloride to make 77 which cyclised on treatment with base. 

Sulfonamides of type RS02NH2 or RS02NHR containing the S02NH moiety are weakly acidic and form water soluble sodium salts (see the Hinsberg separation of amines, p. 105). In such cases, removal of the acidic proton allows alkylation or acylation at nitrogen (Scheme 49). 

Alkylation and acylation at nitrogen in l-oxa-2,4-diazines, and the benzologs, has been discussed previously in summary, regioselective alkylation is possible at N-4 of 4/7-1-oxa-2,4-diazin-5(677)-ones, and acylation at N-2 of 2/7-benzo-l-oxa-2,4-diazines is slow <1996CHEC-II(6)651>. The N-2-alkylated l-oxa-2,4-diazines 68 and 69 have been produced as potential pesticides <2005W02005116032> the N-2-acylated fused-ring derivative 70 has been claimed as a reverse-turn peptidomimetic with potential anticancer activity <2002W02002096872>. 

As actually carried out, the chiral auxiliary was acylated at nitrogen with propanoyl chloride and the propanoyl group then deprotonated at its a carbon with lithium diiso-propylamide forming an enolate. 

Several examples can serve to illustrate the use of chiral auxiliaries. First, the chiral, heterocyclic, amino-add-derived lactam, (5)-4-(phenylmethyl)-2-oxazolidinone, is capable of conversion into an anion on treatment with butyllithium [CH3(CH2)2CH2Li]. Acylation at nitrogen with propanoyl chloride produces chiral propionamide. 

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