A-Alkylamides

Physical Properties. Acetoacetic esters are high boiling Hquids with pleasant odors. Lower A/-aLkylamides are water-soluble Hquids acetoacetamide and acetoacetaryHdes are soHds. 4-Chloroacetoacetates are high boiling lachrymatory Hquids. Some physical properties are Hsted in Tables 3 and 4. 

Caibamates ate formed from an amine with a wide variety of reagents, of which the chloroformate is the most common amides are formed from the acid chloride. -Alkyl caibamates are cleaved by acid-catalyzed hydrolysis A/-alkylamides are cleaved by acidic or basic hydrolysis at teflux. conditions that cleave peptide bonds. 

Other methods for the synthesis of a-oxygenated A-alkylamides (or carbamates) include addition of oxygen nucleophiles to A-acyl (or A-alkoxycarbonyl) iminium ions, generated via either... 

Finally, another development is the use of A -alkylamides that selectively extract platinum from strong acid media, presumably by ion pair formation between the protonated amide and the chloroanions ... 

Addition of amides to a double bond in the presence of mercury(II) salts gave l-mercurio-2-ami-do derivatives 1. Reductive cleavage of the C—Hg bond with sodium borohydride and hydrolysis of the resulting A-alkylamides provided the corresponding primary amines 2. 

The best method for the preparation of A-alkylamide peptides employs 5-(4- [[(9//-fluoren-9-ylmethoxy)carbonyl](alkyl)amino]methyl -3,5-dimethoxyphenoxy)valeric acid [(R)-PAL handle, 29],f l which is derived from the PAL handle. The (R)PAL handle, when used in the same way as PAL, would transfer the alkylamine to the peptide. Similarly, the use of N-alkyl XALP 1 or A-alkyl Rink resinst °°l also gives rise to A-alkylamide peptides. The same conditions as those used to release peptides from PAL, Rink, and XAL apply for the A-alkyl analogues. The preparation of A/,A-dialkylamide peptides requires a backbone attachment strategy (see Section 4.3.1.2.5).f l... 

Activation of alkenes by amides and A-alkylamides has not been used as much as activation by ester groups. The amides are more difficult to reduce than the corresponding esters but have been reported to give the LHDs in 40-80% yields [2,4]. 

In contrast to the anion of diethyl phosphoramidate or trifluoromethanesulfonamide, which cannot be cleanly monoalkylated, - the anion of trifluoroacetamide (100) was monoalkylated by alkyl halides or alkyl methanesulfonate. The resulting A -alkylamides (101) were converted into primary amines by alkaline hydrolysis or reduction (NuBHa Scheme 42). Various primary amines were prepared from (100) with primary alkyl iodides or methanesulfonate, benzyl and allyl halides, a-bromocarbonyl compounds and 2,4-dinitrochlorobenzene. However, competitive elimination is a serious side reaction for less reactive primary alkyl chlorides and secondary halides or methanesulfonate. The synthesis of secondary amines from (100) has also been reported. ... 

A -Alkylamides form alkyl chlorides upon treatment with PClj or SOCh. Benzamides give better results than aliphatic amides (Scheme 13), with yields sometimes in the region of 80%. 

Famham, A.W., Sawicki, R.M. and White, J.C. (1986). The response of resistant houseflies to an unsynergised and synergised A-alkylamide. In Proceedings of the 5986 British Crop Protection Conference — Pests and Diseases 2, 645 649. 

Friedel-Crafts reactions. A-Alkylamides, ureas and sulfonamides serve as alkyl donors for benzene in the presence of AlCli. The selective formation of 2 -hydroxyphenylpyridinemethanols by the reaction of phenols with 2-pyridinealde-hyde is due to a metal template effect. 

The kind of complexity that can arise in these systems is well illustrated by the study of the oxidation of A-alkylamides [68,69], Double reactions occurring in the presence of metal ion catalysts are laid out in Scheme 1, the relative importance of each reaction depending on reaction conditions and on electron-directing and steric effects in the molecule. Overall kinetics are given for different reactions [68,69], but the complexity is such that detailed analysis is difficult or impossible. 

Analogously, TV-substituted derivatives, e.g., 2. are obtained by reducing A -alkylamides of mandelic acid2. 

Recent research into the Ritter reaction has concentrated on alternative means of generating the carbocation. Radiolytically formed carbocations have been reacted in the gas phase with aromatic and aliphatic cyanides yielding the corresponding nitrilium ions, which undergo condensation with water to yield A -alkylamides. 

The reaction of NO2 BF4 with A-alkylamides has been investigated [107,111] under different conditions, but nevertheless the results permit the conclusion that at a low temperature (-30 C), N-butylacetamide and ethyl n-butylcarbamate in acetonitrile are nitrated to the N-nitro derivatives [107] while at higher temperatures, (up to +10 C) nitrolysis takes place with formation of the corresponding carboxylic acid and alcohol as well as N2O [121]. The question as to which C—N bond is N-nitrated and cleaved in the reactions of A-alkyJamides with NO BFJ requires additional study. 

An asymmetric Favorskii rearrangement has been developed that yields optically active a-alkylamides from optically active a-chloroketones. The reaction is presumed to proceed through a chelated intermediate containing a six-membered ring. 

The long side chains of the acrylate ester group can apparently act as internal plasticizers. Substitution of a carboxyl group on the polymer chain increases brittleness. A more polar substituent, eg, an A/ -alkylamide group, is even less desirable. Copolymers of VDC with iV-alkylacrylamides are more brittle than the corresponding acrylates even when the side chains are long (85). Side-chain crystallization may be a contributing factor. 

The principle and typical conditions of SPE technology will be discussed by means of the alkoxylation of A -alkylamides in a nonaqueous solution, which is as an example that works nearly perfectly using simple graphite felt electrodes pressed onto the surface of a Nation 117 membrane [4]. 

A systematic investigation into structure-property relationship of novel long-chain A -alkylamide series 2 and O-alkyl ester series 3 arginine-based surfactants (Scheme 1) was carried out [25]. Compared to series 1, the new series 2 and 3 (Scheme 1) have two positively charged groups in the hydrophilic moiety, one in the primary amine and a second in the guanidine function. 

A convenient alternative to the Beckmann rearrangement is reported by Barton 1 Alkyl nitrones, readily available from the corresponding ketones, are smoothly transformed into A-alkylamides by treatment with toluene-/ -sulphonyl chloride, as shown in Scheme 36. Beckmann rearrangement of the oxime of (105) affords the isomeric lactam (106). This reaction is applicable also to saturated ketones. 

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