Amidation selectivity

The reagent in question is capable of reducing tertiary amides selectively to aldehydes. 

The extent of amide production varied erratically, depending on the nitrile and the biocatalyst. It was negligible in the hydrolysis of la, except when PfNLase was employed as the biocatalyst [3, 5]. The o-chloro substituent in lb caused NIT-104 and 107 to produce considerable amounts of amide. NIT-106, which acted selectively in the hydrolysis of la and lb, sluggishly mediated the hydrolysis of Ic into a nearly equimolar mixture of acid and amide. In conclusion, there is no best nitrilase with regard to acid/amide selectivity. 

In recent studies, using antidiuretic hormone-treated toad urinary bladder, Levine and Worthington [52] have been able to demonstrate experimentally the presence of co-transport of labeled methylurea and, to a lesser degree, acetamide and urea with unlabeled methylurea. They concluded that the demonstrations of co-transport is consistent with the presence of ADH-sensitive amide-selective channels rather than a mobile carrier. 

Table 3.16 CDI-Mediated Synthesis of Amides (Selected Examples) ...

Monosulfen- from (disulfen)-amides Selective and partial hydrolysis... 

Chi Z H, Chen X G, Holtz J S W and Asher S A 1998 UV resonance Raman-selective amide vibrational enhancement quantitative methodology for determining protein secondary structure Biochemistry 27 2854-64... 

The melting points of a few selected primary aromatic amides (together with those of the xanthylamides, where known) are collected in Table IV,191. A more detailed list will be found in the column headed Amides in Table IV,175 (Armnalic Carboxylic Acids). 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

The o-keto ester 513 is formed from a bulky secondary alcohol using tricy-clohexylphosphine or triarylphosphine, but the selectivity is low[367-369]. Alkenyl bromides are less reactive than aryl halides for double carbonyla-tion[367], a-Keto amides are obtained from aryl and alkenyl bromides, but a-keto esters are not obtained by their carbonylation in alcohol[370]. A mechanism for the double carbonylation was proposed[371,372],... 

Preparation of primary allylamines by the selective monoallylation of ammonia is not possible and they are prepared by indirect methods. The monoallylation of Li and Na amides of di-/-butoxycarbonyl (Boc) (305), followed by hydrolysis, affords a primary allylamine (306)[184],... 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

Whereas acid catalyzed hydrolysis of peptides cleaves amide bonds indiscriminately and eventually breaks all of them enzymatic hydrolysis is much more selective and is the method used to convert a peptide into smaller fragments... 

Hexamethylolmelamine can further condense in the presence of an acid catalyst ether linkages can also form (see Urea Eormaldehyde ). A wide variety of resins can be obtained by careful selection of pH, reaction temperature, reactant ratio, amino monomer, and extent of condensation. Eiquid coating resins are prepared by reacting methanol or butanol with the initial methylolated products. These can be used to produce hard, solvent-resistant coatings by heating with a variety of hydroxy, carboxyl, and amide functional polymers to produce a cross-linked film. 

Other fairly recent commercial products, poly(vinyl amine) and poly(vinyl amine vinyl alcohol), have addressed the need for primary amines and their selective reactivity. Prior efforts to synthesize poly(vinyl amine) have been limited because of the difficulty hydrolyzing the intermediate polymers. The current product is prepared from /V-ethenylformamide (20) formed from the reaction of acetaldehyde and formamide. The vinyl amide is polymerized with a free-radical initiator, then hydrolyzed (eq. 7). 

Synthetics. The lack of spice products to satisfy demand and the wide variation in price and availabihty have caused the manufacture of selected synthetics, chemically identical to the component in the natural spice, to replace the vital components of some spices. However, synthetic organic chemistry is not yet able to manufacture economically the many homologous piperine [94-62-2] components in black pepper or those capsaicin [404-86-4] amides in... 

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

Selected physical properties of various methacrylate esters, amides, and derivatives are given in Tables 1—4. Tables 3 and 4 describe more commercially available methacrylic acid derivatives. A2eotrope data for MMA are shown in Table 5 (8). The solubiUty of MMA in water at 25°C is 1.5%. Water solubiUty of longer alkyl methacrylates ranges from slight to insoluble. Some functionalized esters such as 2-dimethylaniinoethyl methacrylate are miscible and/or hydrolyze. The solubiUty of 2-hydroxypropyl methacrylate in water at 25°C is 13%. Vapor—Hquid equiUbrium (VLE) data have been pubHshed on methanol, methyl methacrylate, and methacrylic acid pairs (9), as have solubiUty data for this ternary system (10). VLE data are also available for methyl methacrylate, methacrylic acid, methyl a-hydroxyisobutyrate, methanol, and water, which are the critical components obtained in the commercially important acetone cyanohydrin route to methyl methacrylate (11). 

Ansamacrolides. Antibiotics ia the ansamacroHde family ate also referred to as ansamycias. They are benzenoid or naphthalenoid aromatic compounds ia which nonadjacent positions are bridged by an aliphatic chain to form a cycHc stmcture. One of the aliphatic—aromatic junctions is always an amide bond. Rifampin is a semisyntheticaHy derived member of this family and has clinical importance. It has selective antibacterial activity and inhibits RNA polymerase. 

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