Acylaminomethylation

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

Dihydropyrido[2,3- /]pyrimidines have also been prepared from 3-acylaminomethyl-2-aminopyridines (53JA656). 

Bromination of the (acylaminomethyl)phosphonic esters (133) and subsequent dehydrobromination, leads to the (acyliminomethyl)phosphonate esters (134), precursors to a variety... 

Table 33 N-Cyclization of N-Acylaminomethyl Ether Derivatives of Allylic Alcohols (Equation 120)...

Studies on tethered derivatives of homoallylic alcohols are fewer in number. Iodocyclization of tri-chloroacetimidate derivatives of 4-penten-2-ol (21) gave cis- and franj-dihydrooxazines in an 80 20 ratio,234a 254b while cyclization of the /V-benzenesulfonylcarbamate derivatives (22) provided an 86 14 ratio of cyclic carbamates 253 Cyclization of the N-acylaminomethyl derivatives (23) with mercury(II) tri-fluoroacetate under conditions of kinetic control gave a 75 25 ratio of cis- and rrans-tetrahydrooxazine derivatives, but cyclization under conditions which allowed for equilibration of the organomercury intermediates produced a 6 94 ratio.238... 

Selenophene undergoes various electrophilic substitutions nitration, sulfonation, halogenation, mercuration, chloromethylation, aminomethylation, acylaminomethylation, acylation, formylation, and hydrogen exchange. 

The mercury-initiated cyclization of acylaminomethyl ether derivatives, obtained from acyclic allylic and homoallylic alcohols, proceeded in good yield to give either oxazolidines or 1,3-ox-azinanes. These heterocycles are readily hydrolyzed, hence, this method can be used to prepare amino alcohols starting from allylic and homoallylic alcohols. 

Reducing action. The reagent reductively cleaves N-acylaminomethyl and N-sulfonamido methyl compounds. Formic acid also can be used, but yields are lower. 

Good yields of pvrido[2,3-d] pyrimidines (37) were also obtained by the action of formamide on o-amino nitriles (36).16 Reduction of 2-amino-4,6-dimethyInicotinitriIc yields the 3-aminomcthyl compound (38). Acylation to the 3-acylaminomethyl derivative (39), followed by cyclization, by means of beat or phosphoryl chloride, yielded the diliydiopyrido[2,3-d]pyrimidin s (40).29... 

The amidomercuriation of )- or (Z)-allyl acylaminomethyl ethers (360) with mercury trifluoro-acetate, followed by reduction with sodium borohydride, leads to mixtures of oxazolidines (361) and 1,3-oxazines (362), the composition of the mixtures depending upon the reaction times (Scheme 98) <88TL3789>. 

Loss of an amine also occurs in acylaminomethylation of (acetylamino)-malonic ester, which proceeds, for example, in accord with the following reac-... 

Besonders elektronenarme Acylaminomethyl-Kationen (Amidomethyl-Kationen) reagie-ren in konz. Schwefelsaure mit 1,1-Dichlor-l-alkenen zu N-acylierten jS-Aminosauren (vgl. Tab. 75, S.437)918 919 ... 

Als Amid-Komponente haben sich Maleinimido-, Phthalimido- oder Trifluoracetamino-Gruppen beson-ders wirksam erwiesen. Die Erzeugung der Acylaminomethyl-Kationen gelingt nebcn der X-Abstraktion auch durch Umsetzung von Carbonsaure-amiden mit Formaldehyd in konz. Schwefelsaure. 

Acylaminomethyl-, o-acylaminobenzyl-, alkoxycarbonylaminomethy1-, and a-alkoxycarbonylaminobenzyl-alkylnitramines have been... 

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