Propylamine, deamination

Free radical reactions of purines with amines gave similar products to those produced in alcohol solution although deamination may also occur, probably at the post- rather than the pre-adduct stage. Whereas purine and n-propylamine afforded 6-n-propylpurine (71MI40907), adenine and caffeine produced both the 8-aminoalkyl and corresponding 9-alkyl derivatives (74MI40904). Also irradiation of 8-aminoalkylpurines in methanol furnished the 8-alkyl derivatives. Amino acids as an amine source are of special biochemical interest. They also tend to produce 8-alkylpurines by concomitant deamination and decarboxylation (69CC905). 

Roberts seems to have been the first to propose the existence of a carbonium ion intermediate with a bridging methyl group (a structure that we would now call a corner-protonated cyclopropane), in part as a result of a study on the deamination of propylamine-1-in an aqueous medium, in which it was believed that a small amount of label migration to both C(2) and C(3) of the 1-propanol product was observed (Figure 50). In fact, the analysis of the label position was later shown to be in error but, by then, other experiments had suggested the existence of some kind of protonated cyclopropane. Among these were studies showing the formation of cyclopropanes from deamination of alkylamines in non-aqueous media. This process was subjected to further scrutiny... 

Warrick and Saunders (1962) have reported a comparison of the migratory aptitudes of the benzyl and methyl groups in the deamination of 2,2-dimethyl-3-phenyl-l-propylamine (42, X=NH2) and in the solvolysis of the corresponding tosylate. 

Nevertheless intramolecular proton shifts are competive with deprotonation under these conditions. The hydrocarbon products from the nitrous acid deamination of 1 -propylamine (628) consist of 10% cyclopropane and 90% propene. The 1-propanol (630) obtained from labeled (628) arises mainly by solvolytic displacement leading to isotopically unrearranged (630a) and partly from protonated cyclopropane with isotopic scrambling466. ... 

The rearrangements associated with the deamination of 1 -propylamine (628) are indicative of protonated cyclopropane but do not require the intervention of the... 

An important observation has been made recently by Brosch and Kirmse. They showed that the nitrous acid deamination of optically active [1- H] butylamine and [1- H] methyl propylamine both proceed with complete ( 2%) inversion of configuration. Reaction via a carbocation is unlikely to proceed with complete inversion of configuration reaction of a diazonium ion with a nucleophile must proceed with complete inversion of configuration. Although ion pairs would be involved in the carbocation reaction it is unlikely that they would give a completely inverted product. 

The deamination of n-propylamine by nitrous acid and the deoxideation of n-propoxide both give propene and cyclopropane as the elimination products in a ratio of 9 1 (refs. 619, 620). A similar product ratio is obtained from the thermolysis of 1-diazopropane and this raises the possibility that carbenoid intermediates are also involved in the former reactions. However, the products of deoxideation of 1,1-dideuteropropanol are consistent with a carbonium-ion mechanism involving a 1,3-elimination to give the cyclopropane,... 

The small amount of monodeuterated cyclopropane could have arisen by a carbene insertion but a 1,3-hydride shift to give an isomeric intermediate carbonium ion, which then partitioned to elimination products, was preferred. As supporting evidence for this shift, rather than the normal 1,2-rearrangements, which are usually observed under solvolytic conditions, an earlier investigation of the deamination of carbon-labelled /i-propylamine was cited. Labelled l- C-/i-propylamine gives l- C-n-propanol (92%) and 3- C-n-propanol (8%). This product distribution can be explained only by a 1,3-hydride shift, viz-... 

The nitrous acid deamination appears to be as complex as the nitrosoamide reaction, and in a common solvent it appears that similar mechanisms are followed. For example, the nitrosonaphthamide of 1-phenylethylamine in acetic acid, and the reaction of 1-phenyl-ethylamine with nitrous acid in the same solvent yield 1-phenylethyl naphthoate (Table 7) and 1-phenylethanol respectively, both with 79-81% retention of configuration. These products are the intramolecular products from the respective reactions, and thte stereochemical results suggest that they are formed by a common path. Similar results were also found in the deaminations of S-cholC stanylamine 2-phenyl-2-butylamine ° and 1,2,2-triphenylethyl amine Also pertinent, is the finding that the acetates fi-om the deamination of n-propylamine in acetic acid, by the two methods, contained similar amounts of the isomeric product, isopropyl acetate the amount of isomerization observed was far greater than in the solvolysis of n-propyl tosylate in the same solvent... 

The relationship of the nitrous acid and nitrosoamide methods of deamination is more tenuous in water since only one example of the i nitrosoamide decomposition in aqueous media has been reported. The decomposition of A -nitroso-A -n-propylbenzamide in dimethyl-formamide-water (60/40 by vol) yielded a propyl benzoate fraction containing 9% of the isopropyl isomer and a propanol fraction con- taining 33% of isopropyl alcohoP . The nitrous acid deamination of n-propylamine under the same conditions yielded an alcohol fraction containing 31% of isopropyl alcohoP. The similarity in the isomer contents of the alcohol portions suggests that common intermediates were involved. The less extensive isomerization of the benzoates may be a reflection of the shorter lifetime of the propyl cations trapped by negatively charged coimter ions compared to those trapped by neutral solvent molecules on the other hand, the role of diazopropane must be determined before definitive conclusions are possible. 

The nitrous acid deamination of n-propylamine in acetic acid yields an acetate fraction containing far more isopropyl acetate (32%) than the acetate from the solvolysis of n-propyl tosylate in the same solvent (2-8%) Also, the deamination of n-butylamine in acetic acid yields a butanol fraction containing 35% of 2-butanol, whereas the solvolysis of n-butyl -nitrobenzenesulfonate in the same solvent was reported to give exclusively n-butyl acetate . These results are reasonable in terms of the larger positive charge on the cation formed in deamination, relative to the charge on the more solvated ion formed in solvolysis. 

---