2-Aminoalcohols amides

D. Semeeia, M. Philippe (L Oreal). High-Yield Preparation of Ceramides by Conducting the Aminoalcohol Amidation in the Presence of Microwave Irradiation. Pur. Patent Application EP 884,305, 1998 PR Application 97/7,240, 11 Jun 1997) Chem. Abstr., 1999, 130, 52677y. 

Carbamates Isocyanates Hydroxynitriles Aminoalcohols Amides (Carboxamides)... 

Alkanenitriles (Linear-alkyl cyanides, 1-Cyanoalkanes) Alkanedinitriles Alkenenitriles Arylnitriles Benzonitrile Aminoethers Oxazole derivatives Oxazole Aminoalcohols Amides (Carboxamides)... 

Incorporation of extensive branching in the side chain similarly does not decrease pharmacologic activity. Reductive alkylation of aminoalcohol, 42, with isobutyraldehyde affords the amine, 43. Acylation of the amine with benzoyl chloride probably goes initially to the amide (44). The acid catalysis used in the reaction leads to an N to 0 acyl migration to afford iso-bucaine (45). ... 

Thioacylation of primary and secondary amines, including aminoacids and aminoalcohols, has been readily carried out from phosphonodithioacetate 28 (R = Et) and the resulting phosphorylated thio amides (thio carbamoyl-... 

Zinc borohydride, which is also a useful reagent,66 is prepared by reaction of ZnCl2 with NaBH4 in THF. Owing to the stronger Lewis acid character of Zn2+, Zn(BH4)2 is more reactive than NaBH4 toward esters and amides and reduces them to alcohols and amines, respectively.67 Zn(BH4)2 reduces carboxylic acids to primary alcohols.68 The reagent also smoothly reduces a-aminoacids to (3-aminoalcohols.69... 

The addition of ammonia to excess methyl acrylate (a linear monomer), followed by amidation with excess ethylenediamine afforded the resultant cascade molecule, and thus Tomalia [37] created the commercially available PAMAM starburst series of dendrimers (2, Fig. 2). Related core molecules such as ethylenediamine and aminoalcohols and other functionalizable groups such as thiol moieties were used to prepare similar dendrimers [38]. This methodology is applicable to most primary amines, resulting in a 1 —> 2 branching pattern. Recently, examples of related Si-, [39] P-, [40] and metallo systems [41], which follow this linear monomer protocol have been reported. 

Strong donor acceptor Water, glycol, glycerol, aminoalcohol, hydroxylamine, polyphenol, and amide... 

O-Benzyllactaldehyde dimethylhydrazone 230 allows a substrate control in the addition reaction of organomagnesium halides, leading almost exclusively to the 5yn-isomer 231 (equation 155) . The resulting hydrazide can be reduced on Raney Ni to the corresponding iyw-aminoalcohol 232. The stereoselective Grignard addition to a similar A-formyl hydrazone 233 proceeds with 92% diastereoselectivity (equation 156). The silylation of the amide nitrogen by TMSCl provides the pure iyw-adduct . 

The basic hydrolysis of imidate salt 118 takes a different course from that of imidate salt 112, yielding first only the amide rotamer 120B which is then slowly isomerized to the equilibrium mixture (ratio 3 1) of 120A and 120B. Treatment of the ester ammonium salt 119 under the same basic conditions gave directly the aminoalcohol 123. This result shows that the amino-ester 122 is not an intermediate in the basic hydrolysis of imidate 118. The formation of the amide rotamer 120B is therefore the result of the direct fragmentation of a tetrahedral intermediate whidh is formed from 118. 

Condensation of fumaric acid chloride monoethyl ester 147 with aminoalcohol 146, followed by intramolecular Michael addition of the isolated amide 148, afforded the l,4-benzoxazepine-3-acetate 149. The thermodynamically favored 3,5-tram-isomers were obtained (Scheme 21) <2002BMC385, 2002BMC401, 2002JME4571>. 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

An interesting version of the transesterification reactions was reported by Movassaghi et al., with the amidation of unactivated esters with amino alcohols (Scheme 9.27) [73]. The amidation was explained by carbene-alcohol interactions. A nucleophilic activation of the hydroxyl group of the aminoalcohol 90 by the catalyst 11 is followed by transesterification to the ester 91 which is in-situ-converted to the amide 92 through a N —> O acyl transfer. Various aliphatic and aromatic esters with different functionalities, as well as chiral aminoalcohols, are suitable for this reaction. 

Chemoselectivity in the AA process is also dependent on the pH [41] (see above) and the concentration [57] of the reaction mixture. Wuts and coworkers discovered that diol formation increased significantly from 4% to 45% when the concentration was increased from 0.014 to 0.050 g mL-1. Addition of acetamide (1 equivalent) at 0.05 g mL-1 improved the diol/aminoalcohol ratio to 5 95. Interestingly, other amides such as trifluoroacetamide and urea inhibited the reaction while the addition of methanesulfonamide led to large quantities of the diol (70%). 

Any kind of C-Mannich base has been actually allowed to react with a variety of amines, including aminoalcohols and amino acids. Cyclic amines, - including optically active derivatives, - and amides arc also employed as are a number of aromatic heterocycles. 

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