Carbonyl groups, amino

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Both carbonyl groups of terephthaldehyde are reported to react with the exocyclic nitrogen of 2-aminothiazole yielding 1.4-phenylene bis(2-methyleneamino)thiazole. The same report describes the reactions of 2-amino-4-phenylthiazole with terephth aldehyde and salicylaldehyde as yielding 64 and 65, respectively (Scheme 45) (215), whose structures are based on ultraviolet and infrared spectra. 

The keto tautomer (211a) is involved in the high electrophilic reactivin-of the C-5 carbonyl group. Thus ring opening has been reported u ith various amino nucleophilic reagents. 

Amino groups rank rather low in seniority when the parent compound is identified for naming purposes Hydroxyl groups and carbonyl groups outrank ammo groups In these cases the ammo group is named as a substituent... 

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

Certain nucleophilic sp ies add to carbonyl groups to give tetrahedral intermediates that are unstable and break down to form a new double bond. An important group of such reactions are those with compounds containing primary amino groups. Scheme 8.2 lists some of the more familiar classes of such reactions. In general, these reactions are reversible, and mechanistic information can be obtained by study of either the forward or the reverse process. 

FIGURE 27.19 Proposed mechanism of hydrolysis of a peptide catalyzed by carboxypeptidase A. The peptide is bound at the active site by an ionic bond between its C-terminal amino acid and the positively charged side chain of arginine-145. Coordination of Zn to oxygen makes the carbon of the carbonyl group more positive and increases the rate of nucleophilic attack by water. 

In addition to illustrating the mechanics of translation. Figure 28.12 is important in that it shows the mechanism of peptide bond formation as a straightforward nucleophilic acyl substitution. Both methionine and alanine are attached to their respective tRNAs as esters. The amino group of alanine attacks the methionine carbonyl, displacing methionine from its tRNA and converting the carbonyl group of methionine from an ester to an anide function. 

Under basic conditions, the o-nitrotoluene (5) undergoes condensation with ethyl oxalate (2) to provide the a-ketoester 6. After hydrolysis of the ester functional group, the nitro moiety in 7 is then reduced to an amino function, which reacts with the carbonyl group to provide the cyclized intermediate 13. Aromatization of 13 by loss of water gives the indole-2-carboxylic acid (9). 

In an alternative reaction course, the primary amino group reacts with C-3, while the intermediate 134 undergoes cyclization either via nucleophilic attack by a Y function at the C-1 atom followed by elimination of HXR (also formed due to possible hydrolysis of the initial products and intermediates) or with involvement of one of the carbonyl groups (intermediates 132 and 136) (81UK1252 91UK103). 

In an alkaline medium the condensation of carbonyl and amino groups of the reactants seems to be more probable (pathway 1), although pathway 2, which is identical to the reactions of enaminoketones, is also possible. 

This four-atom replacement was observed in some reactions of uracil derivatives, containing at position 5 a substituent with the CCCN moiety. Treatment of the Z-isomer 5-(2-carbamoylvinyl)-l,3-dialkyluracil with ethanolic sodium ethoxide gave in good yield 3-ethoxycarbonylpyridin-6(lf/)-one (84%) together with 3-A-methylcarbamoyl)pyridin-6-(l7 )-one (10%) (85JOC1513) (Scheme 26). The reaction involves an initial attack of the terminal amino group of the side-chain on position 6 of the uracil molecule. C-6-N-1 bond fission and N-C bond formation yield the pyridin-6(l//)-one. A subsequent attack of the ethoxide ion on the carbonyl groups of the side-chain yields both pyridin-2-one derivatives (Scheme 26). Similar results were obtained with the -isomer. 

---