Deamination reaction

The treatment of amines with nitrous acid results in an initial rate-determining nitrosation which is followed by diazotisation and subsequent deamination. 

For secondary amines, the reaction stops at the nitrosamine stage, but with primary aromatic amines fast reaction effectively ceases at the diazonium ion. However, for primary aliphatic amines the unstable diazonium ions rapidly lose nitrogen and the resulting carbonium ion decomposes, often yielding olefins as the minor reaction products , e.g. (201). 

The multiplicity of the reaction products limits deamination as a useful synthetic method for the preparation of olefins but it is of great interest to compare the mode of reaction of the intermediate carbonium ion with those derived from solvolysis of alkyl halides and esters or acid-catalysed dehydration of alcohols. As nitrosation is the rate-determining step, evidence for carbonium-ion intermediates has to come from the nature and stereochemistry of the reaction products rather than from kinetic studies. 

A number of features in deamination have their counterparts in solvolytic El reactions. Transannular 1,5 and 1.6 shifts have been observed in deaminations of eight- to twelve-membered alicyclic amines, viz. 

All three conformations can give rise to I -butene and although this is not the major product it is formed in much greater abundance than from El reactions of 2-butyl halides or esters. Methyl rearrangement does not occur in this case as this would give rise to a less stable primary carbonium ion. A hydride shift is possible to give the same but essentially a new ion which subsequently breaks down, but this possibility can be excluded by the use of carbon-labelling experiments. 

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Figure 22 5 shows what happens when a typical primary alkylamine reacts with nitrous acid Because nitrogen free products result from the formation and decomposition of diazonium ions these reactions are often referred to as deamination reactions Alkyl... 

L/(mol-s) (39,40). QDI is also attacked by hydroxide ion (eq. 4) to produce a quinone monoimine (QMI), itself an oxidized developer derived from /)-aminopheno1. Such compounds can further react with coupler, albeit at a slower rate than QDI, to form a dye and were cited in the seminal patent as color developers (32). However, the dyes derived from this deaminated developer have different hues from the QDI dyes, and these hues are pH-dependent as a consequence of the phenoHc group contributed by the developer. Although the deamination reaction to produce QMI is fast, the rate constant is 10 to 10 L/(mol-s) (40—42), its effect is somewhat offset by the redox reaction of the QMI with the reduced developer, present in large excess, to regenerate the desired QDI. The primary net effect of the deamination reaction is to enlarge the resulting dye cloud (43). 

N- Aminoaziridines have been converted to alkenes by reaction with a variety of oxidizing agents (70JA1784). Usually, the deamination reaction is stereospecific. The oxidation of l-amino-2,3-diphenylaziridines with manganese dioxide, however, was not stereospecific. The trans compound gives entirely frans-stilbene, whereas the cfs-aziridine forms a mixture of 85% trans- and 15% c -aikene. cw-Stilbene is not isomerized to trans under the reaction conditions, and the results are explained in terms of an azamine intermediate which can isomerize through a tautomeric equilibrium. 

Thus, in contrast to an ionization process from a neutral substrate, which initially generates an intimate ion pair, deamination reactions generate a cation which does not have an anion closely associated with it. Furthermore, the leaving group, molecular nitrogen, is very stable so that little, if any, nutleophilic participation is needed for bond cleavage. The... 

Sodium borohydride has also been used to reduce aiyl diazonium salts in reductive deamination reactions. 

When a cyclic /3-amino alcohol—e.g. 1—is treated with nitrous acid, a deamination reaction can take place, to give a carbenium ion species 2, which in turn can undergo a rearrangement and subsequent loss of a proton to yield a ring-enlarged cyclic ketone 3. This reaction is called the Tiffeneau-Demjanov reactionit is of wider scope than the original Demjanov reaction ... 

Deamination reactions of (2-amino-l,l-dimethyl)ethyldiphenylphosphine oxide (57) result in the formation of three products, in each of which the diphenylphosphinyl group has migrated to the primary carbon of the starting material. These reactions are unusual examples of non-assisted migration of a phosphinyl group. 

Deamination, the hydrolytic loss of exocyclic amino groups on the DNA bases, is typically a very slow reaction. For example, deamination of cytosine residues in dnplex DNA occnrs with a half-life of about 30,000 years under physiological conditions, and the deamination of adenine residues is still more sluggish. " Alkylation at the N3-position of cytosine (Scheme 8.5) greatly increases the rate of deamination (ty2 = 406 h). Deamination of 3-methyl-2 -deoxycytidine proceeds 4000 times faster than the same reaction in the unalkylated nucleoside. Alkylation of the N3-position in cytosine residues also facilitates deglycosylation (Jy2 = 7700 h, lower pathway in Scheme 8.5), but the deamination reaction is 20 times faster and, therefore, predominates. ... 

The analogons deamination reaction is not observed in l-methyl-2 -deoxy-adenosine nncleosides. ° Rather, in the adenine series, the Dimroth rearrangement occnrs (Scheme 8.4). On the contrary, in styrene adducts of 2 -deoxyadenosine, the hydroxyl residue of the adduct undergoes intramolecular reaction with the base to initiate deamination (Scheme 8.6). ° ° Similarly, cytosine residues bearing styrene adducts at the N3-position undergo rapid deamination (nearly complete deamination is seen within 75h). °°... 

The scope of the deamination reaction was extended to the characterization of heparin segments containing 2-acetamido-2-deoxy-D-glucosyl residues by removing (by hydrazinolysis) the N-acetyl groups and cleaving with nitrous acid (at pH 4) the otherwise resistant segments.113,232... 

Two-step synthetic routes to poly(/i-aminoborazines) from /i-chloroborazines involve initial nucleophilic reaction of the /i-chloroborazine with appropriate linking reagents followed by a deamination reaction of the as-obtained /i-aminoborazine. The 5-tiichloroborazine undergoes nucleophilic attack by ammonia or amine derivatives on the boron atom linked to chlorine atoms. For the same reasons previously quoted a tertiary amine (e.g., Et3N) must be added to precipitate the corresponding hydrochloride. 

The deamination reaction destroys cytosine, the half-life of which is about 340 years at 298 K. 

Both enzymatic and whole cell-mediated transformation of sulfonamides has been described, usually with high removal efficiencies and relatively short treatments. Although different metabolites have been elucidated, no clear pathways have been defined however, the desulfonated metabolites have been widely identified (with LAC and fungal cells) along with the products of hydroxylation, formylation, and deamination reactions, and combinations of them. 

Figure 27.2 Treatment of cytosine bases with bisulfite results in a multi-step deamination reaction, ultimately leading to uracil formation.

In the first enzymatic step, phenylalanine ammonia lyase (PAL) converts phenylalanine to trans cinnamate, via a deamination reaction liberating ammonia. PAL can also convert tyrosine to p-coumarate, albeit at lower efficiency (MacDonald and D Cunha 2007). PAL functions as a tetramer of identical subunits, with two subunits combining to form one active site (Stafford 1990 MacDonald and D Cunha 2007). 

In contrast to other 2,5-anhydroaldoses (which exhibit mutarota-tion, possibly due to the formation of hemiacetals28), 2,5-anhydro-D-glucose does not show any mutarotation.27 The importance of this compound as a potentially useful precursor to C-nucleosides warrants a reinvestigation of the deamination reaction, and the definitive proof of the structure of the compound. The readily accessible 2,5-anhydro-D-mannose (11) does not possess the cis-disposed side-chains at C-2 and C-5 that would be required of a synthetic precursor to the naturally occurring C-nucleosides, with the exception of a-pyrazomycin (8). The possibility of an inversion of the orientation of the aldehyde group in 11 by equilibration under basic conditions could be considered. 

In the light of our present knowledge of the mechanism of these deamination reactions, it can be understood why deamination of either 2-amino-2-deoxy-D-mannonic acid, or the corresponding lactone, gives 2,5-anhydro-D-mannonic acid.39-42... 

There are virtually no drugs that are aldehydes but there are dietary aldehydes, and aldehydes are common metabolites of drugs including the aldehydes generated as intermediates in monoamine oxidase (MAO)-catalyzed deamination reactions, P450-catalyzed... 

Amino groups released by deamination reactions form ammonium ion (NH " ), which must not escape into the peripheral blood. An elevated concentration of ammonium ion in the blood, hyperammonemia, has toxic effects in the brain (cerebral edema, convulsions, coma, and death). Most tissues add excess nitrogen to the blood as glutamine. Muscle sends nitrogen to the liver as alanine and smaller quantities of other amino acids, in addition to glutamine. Figure I-17-1 summarizes the flow of nitrogen from tissues to either the liver or kidney for excretion. The reactions catalyzed by four major enzymes or classes of enzymes involved in this process are summarized in Table T17-1. 

The fate of the glutamate is re-formation of oxoglntarate in the deamination reaction catalysed by glntamate dehydrogenase, in which the NH2 gronp in glntamate is removed as ammonia and the oxoglntarate is formed, as follows ... 

Attempts to establish the structure of the initial adduct by NMR-spectroscopy failed because of the low solubility of 27. This makes it impossible to draw a clear conclusion as to whether the ammonia adds to C-6 (as occurs in the case of the A-methylpyrimidinium salts) or at C-2. Since NMR spectroscopy of a solution of 4,6-diphenylpyrimidine in potassium amide/liquid ammonia strongly supports the formation of an anionic C-2 adduct (75UP1], it is justified to assume that also in the deamination of 27 by liquid ammonia, a C-2 adduct 28 is involved (Scheme III. 16). It is evident that the major part of the deamination (73%) does not involve a ringopening reaction the main deamination reaction occurs by an Sn2 attack of ammonia on the A-amino group in 27. A similar mechanism has also been postulated in the deoxygenation of pyrimidine A-oxides, when they are heated with liquid ammonia (Scheme III.16) [77UP2]. 

Direct extrusion of methyl nitrene has been discounted as an explanation of these deamination reactions, which are apparently induced by attack of the acetylenic ester and thus more likely take place via an intermediate analogous to 176. On the other hand, the products from pyrolysis of 107 at 325° include 1,2,3,4-tetrafiuoronaphthalene (132) and hydrogen cyanide, and it was suggested that methyl nitrene was the precursor of the latter compound (see Section III,D). The adduct (180) of tetrafiuorobenzyne and thiophen extrudes sulfur so readily... 

Barton and Narang" have prepared nitrate esters by treating primary and secondary alky-lamines with dinitrogen tetroxide in the presence of an amidine base like DBU. Wudl and Lee " conducted deamination reactions without any amidine base and reported much lower yields of nitrate ester product. The use of an amidine base is not necessary if the amine substrate... 

This enzyme [EC 5.3.1.10] catalyzes the following isomerization and deamination reaction o-glucosamine 6-phosphate + H2O o-fructose 6-phosphate + NH3. 

Cp was not identified conclusively as such, but its decomposition to authentic Up (a known56 deamination reaction characteristic of 5,6-dihydrocytosines) is strong evidence, supported by the similarity of the pK of 5.56 (measured spectroscopically) to that of other dihydrocytosines. 

Finally, an interesting deamination reaction of aziridines was reported, in which treatment of N-unsubstimted aziridines (152) with dinitrogen tetroxide (2 equiv) in the presence of Et3N results in clean deamination to provide the corresponding alkenes (154) with remarkably high yields (>90%). The reaction is believed to proceed via the N-nitroso intermediate 153, so that the driving force for the reaction is liberation of N O <99SC1241>. 

A hydride transfer from the methylene group to the copper ion followed by the oxidation of the latter by the oxidizing agent is also unlikely, in view of the fact that the deamination reaction is not affected by the addition of nucleophiles like chloride ions, which would be expected to interfere with a pre-equilibrium involving hydride ions. 

Deamination. Amine groups can be removed oxidatively via a deamination reaction, which may be catalyzed by cytochromes P-450. Other enzymes, such as monoamine oxidases, may also be involved in deamination reactions (see below). The product of deamination of a primary amine is the corresponding ketone. For example, amphetamine is metabolized in the rabbit to phenylacetone (Fig. 4.27). The mechanism probably involves oxidation of the carbon atom to yield a carbinolamine, which can rearrange to the ketone with loss of ammonia. Alternatively, the reaction may proceed via phenylacetoneoxime, which has been isolated as a metabolite and for which there are several possible routes of formation. The phenylacetoneoxime is hydrolyzed to phenylacetone. Also N-hydroxylation of amphetamine may take place and give rise to phenylacetone as a metabolite. This illustrates that there may be several routes to a particular metabolite. 

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