Ammonia, carbon atom reactions, amino

For a discussion of the formation of biomolecules in carbon atom reactions see P. B. Shevlin, D. W. McPherson, and P. MeUus, Tbe Reaction of Atomic Carbon with Ammonia. The Mechanism of Formation of Amino Acid Precursors, J. Am. Chem. Soc. 1983, 105, 488 and G. Flanagan, S. N. Ahmed and P. B. Shevlin, The Formation of Carbohydrates in the Reaction of Atomic Carbon with Water, J. Am. Chem. Soc. 1992, 114, 3892. 

Recent work on the mechanisms of the Walden inversion is reviewed, especially in its bearing on reactions involving substitution on the a-carbon atom of amino acids. Substitution of the halogen in o-bromo-acids by ammonia or amines is probably in most cases of the bimolecular nucleophilic type and is therefore accompanied by an inversion of configuration. But, in some cases, such as the bromo acids corresponding to valine and isoleucine, sterio factors reduce the rate of bimolecular substitution and amination occurs mainly by a unimolecular mechanism, with the result that configuration is retmned. 

N-Bromoamino acids form within seconds after mixing aqueous bromine and the amino acid in dilute aqueous solution (ref. 6), but are not stable end products of the reaction. Thus, Friedman and Morgulis (ref. 7) found that the oxidation of amino acids by hypobromite gives aldehydes and nitriles with one carbon atom less than the original amino acid, ammonia and CO2 (Scheme 1). The proportions of aldehyde and nitrile depend on the basicity of the medium, aldehyde formation being favoured by more basic conditions. 

Another catalytic application emanating from the Hieber base reaction was developed by Reppe and Vetter [108]. They showed that 1-propanol 126 could be generated by treatment of ethylene 125 with catalytic amounts of Fe(CO)5 78 under CO-pressure and basic reaction conditions (Scheme 33). Thereby, trimethylamine and V-alkylated amino acid derivatives mrned out to be optimal bases for this reaction. Like ethylene 125, propylene could be transferred mainly to 1-butanol diolefins like butadiene only reacted to monoalcohols. By employing these reaction conditions to olefins in the presence of ammonia, primary or secondary amines, mono-, di-, and trialkylamines were obtained whose alkyl chains were elongated with one carbon atom, compared to the olefins. 

In the Strecker synthesis an aldehyde is converted to an a-amino acid with one more carbon atom by a two-stage procedure in which an a-amino nitrile is an intermediate. The a-amino nitrile is formed by reaction of the aldehyde with ammonia or an ammonium salt and a source of cyanide ion. Hydrolysis of the nitrile group to a carboxylic acid function completes the synthesis. 

One of the nitrogen atoms of urea comes from ammonia, the other is transferred from the amino acid aspartate, while the carbon atom comes from C02. Ornithine, an amino acid that is not in the standard set of 20 amino acids and is not found in proteins, is the carrier of these nitrogen and carbon atoms. Five enzymatic reactions are involved in the urea cycle (Fig. 1), the first two of which take place in mitochondria, the other three in the cytosol ... 

The isomeric 3-alkylpurines, in contrast to the parent compounds, are highly reactive at the 2- and 6-carbon atoms. The susceptibility of the 2-carbon to nucleophilic attack is shown by the facility with which 6-oxo-3-methyl-2-methylmercaptopurine (28) is converted by ammonia into the 2-amino (29) and then with alkali into the 2-oxo (30) derivative.75 This reaction sequence explains why the action of aqueous ammonia on the 2-methylmercaptopurine (28) resulted in the isolation of 3-methylxanthine (30) rather than the required... 

Addition Reaction. The double bond of dehydroalanine and e-methyl dehydroalanine formed by the e-elimination reaction (Equation 6) is very reactive with nucleophiles in the solution. These may be added nucleophiles such as sulfite (44). sulfide (42), cysteine and other sulfhydryl compounds (20,47), amines such as a-N-acetyl lysine (47 ) or ammonia (48). Or the nucleophiles may be contributed by the side chains of amino acid residues, such as lysine, cysteine, histidine or tryptophan, in the protein undergoing reaction in alkaline solution. Some of these reactions are shown in Figure 1. Friedman (38) has postulated a number of additional compounds, including stereo-isomers for those shown in Figure 1, as well as those compounds formed from the reaction of B-methyldehydroalanine (from 6 elimination of threonine). He has also suggested a systematic nomenclature for these new amino acid derivatives (38). As pointed out by Friedman the stereochemistry can be complicated because of the number of asymmetric carbon atoms (two to three depending on derivative) possible. 

The reaction is closely similar to the Hofmann, Curtins, and Beckmann rearrangements. The over-all reaction consists of the conversion of RCOOR to RNH2, therefore where the carboxyl donor is the a-carboxyl group of an amino acid the resulting product would have two amino groups on the a-carbon atom. Consequently, ammonia is evolved and the corresponding aldehyde remains. On this basis the expected products from various esters are given in Fig. 10. 

Reaction with ninhydrin Ninhydrin is a strong oxidizing agent. When a solution of amino acid is boiled with ninhydrin, the amino acid is oxidatively deaminated to produce ammonia and a ketoacid. The keto acid is decarboxylated to produce an aldehyde with one carbon atom less than the parent amino acid. The net reaction is that ninhydrin oxidatively deaminates and decarboxylates a-amino acids to C02, NH3 and an aldehyde. The reduced ninhydrin then reacts with the liberated ammonia and another molecule of intact ninhydrin to produce a purple coloured compound known as Ruhemann s purple. 

Another type of chemical reaction that has been investigated is the addition of a nucleophile to a carbonyl center, illustrated for the addition of ammonia to a carbonyl group in Figure 18.10. Nucleophilic addition is an important feature of many biochemical reactions and appears to involve a tetrahedral intermediate. Burgi, Dunitz, and Eli Shelter studied molecules with both a carbonyl group and a tertiary amino group that were separated by varying numbers of carbon atoms. They measured,... 

From a theoretical point of view this is an extremely interesting reaction. The displacement of a hydroxyl group from a saturated carbon atom appears to be unknown in basic solution. The fact that amino-methane sulfonic acid can be isolated from the bisulfite addition product of formaldehyde on treatment with ammonia does not prove, of course, that a direct displacement, such as is indicated in XVI to XVII, actually occurred. Furthermore, it is quite clear that preliminary formation of an imine (XVIII) is not necessary for the reaction of aromatic amines with sodium bisulfite (steps XIX to XVIII to XVII, etc.). 1-Dimethyl-aminonaphthalene-4-sulfonic acid (XX) and l-aminonaphthalene-4-sulfonic acid (XIX) show similar reaction kinetics 16a when treated with sodium bisulfite, yet with the tertiary amine (XX) it is not possible to write an imino structure corresponding to XVIII. 

In this case, diethylenetriamine acts as a trinucleophile its interaction with amino enone 71 involves double nucleophilic addition at the /1-carbon, forming ammonia, and an attack at the carbonyl group, liberating water. The reaction takes place when the compound contains a polyfluoroalkyl substituent, not only enhancing the electrophilicity of the /1-carbon atom, but also stabilizing the imidazolidine ring. 

---