Diazotative deamination

Solvolytic studies provided the first structural indication for almost every carbocation-ic intermediate and the C4H,+ ion is no exception. Roberts observed that the solvolysis of cyclopropylcarbinyl or cyclobutyl systems and the diazotative deamination reactions of cyclopropylcarbinyl amine or cyclobutyl amine gave similar product mixtures consisting of cyclopropylcarbinyl, cyclobutyl and allylcarbinyl derivatives in essentially the same ratio1,2. A common cationic intermediate of C3v structure, the tricyclobutonium ion 1, was... 

Equally, all the attempts of Haginiwa to diazotize 2-amino-4-methylselenazole led to complete decomposition. Later these investigations were taken up by Metzger and Bailly. They tried to prepare selenazoles unsubstituted in the 2-position by means of diazo-tization and a special Sandmeyer reaction. In spite of variations in the reaction conditions, they were not able to deaminate 2-amino-4-phenylselenazole by this method. 

Amino-l,5-diphenyltriazole is deaminated by diazotization in ethanolic solution and warming. 1-Aminotriazoles are deaminated in high yield by treatment with nitrous acid. Removal of a toluene-p-sulfonamido group can be accomplished in two steps by acid hydrolysis followed by diazotization, or in one step by treatment of the 1-toluene-p-sulfonamide derivative with sodium in liquid ammonia. ... 

In the latter case the structure was established by reduction with stannous chloride in acetic acid, which afforded the imidazole derivative (104), thus proving ortho substitution, followed by comparison of the ultraviolet spectrum of 104 with the two possible benzimidazole derivatives of carbazole. Deamination of 103 via diazotization in sulfuric acid afforded 1-nitrodibenzothiophene (105) (54%), being the only recorded route to this compound (Scheme 5). Initial attempts to hydrolyze 102 to the nitroamine (103) had been made with ethanolic hydrogen chloride... 

Three derivatives of 3-aminodibenzothiophene, 110a, 110b, and 110c, have been nitrated, and in each case substitution occurred in the 4-position. Hydrolysis of the products yielded 3-amino-4-nitro-dibenzothiophene, which was different from the previous two nitro-amines and which formed an imidazole different from both 104 and 109. Deamination of this nitroamine via diazotization gave a small amount of 4-nitrodibenzothiophene. An alternative synthesis of the 4-nitro compound is described later. The spectroscopic techniques used above by Sawicki were later extended to determine the positions of substitution in dibenzoselenophene, in this case by comparison with the above-established derivatives of dibenzothiophene. - ... 

Aprotic diazotization of 86 (R = Me or Ph) produced 55% of thianthrene and lesser amounts of 1-phenylthio- (or methylthio) dibenzothiophen (Scheme 14) together with deaminated products. Comparable yields of 2-methyl-, 2-methoxy-, 2,7-dichloro- and 2,8-dichlorothianthrenes were obtained using this synthetic route. It is suggested that ring closure involves an intramolecular homolytic substitution at sulfur with loss of the 5-substituent as a radical [74JCS(P1)1272]. 

Phenylpiperidine has been prepared by warming aniline with 1,5-dibromopentane 4,8 heating 5-anilino-l-bromopentane 6 the dehydration of 5-anilino-l-pentanol over alumina 7 the electrolytic reduction of N-phenylglutarimide 8 the catalytic hydrogenation of l-phenyl-3-hydroxypyridinium chloride 9 the action of bromobenzene on piperidine in the presence of lithium 10 the reaction of fluorobenzene, 1-methylpiperidine, and phenyl-lithium 11 the action of diphenylsulfone on piperidine in the presence of sodamide 12 the diazotization and deamination of l-(2-aminophenyl)piperidine 13 and of l-(4-aminophenyl)piperidine 14 and the present method.18... 

Ridd [5] and Kalatzis and Ridd [6] have written an interesting series of studies and reviews on the interrelationship of nitrosation, diazotization, and deamination. Other reviews covering various aspects of iV-nitroso chemistry are by Leotte [7], Overberger et al. [8], Dusenberg and Powell [9], Lashkarev and Vasyunas [10], Mannschreck et al. [11], Rademachereta/. [12]. Chapter 16 should also be reviewed for background material on nitrosations. 

Donor-substituted 1-aminomethylcyclopropanes 108 110 and tosylhydrazones of 1-donor-substituted cyclopropyl ketones 111 can undergo ring enlargement to cyclobutanones through deamination. To this purpose, aminomethylcyclopropanes were diazotized with sodium nitrite 108-110 or isopentyl nitrite 109 in acidic medium and tosylhydrazones were decomposed in basic medium.111 The rearrangements proceed via diazonium ions and are especially useful for the construction of bicyclic systems. For examples of these rearrangements see 1,108 2,109 3,109 4,110 5,111 6 and 7.1 1... 

Nitrosation, diazotation, and deamination processes take place in the reactions resulting in alcohols and N2 gas as final products. From the studies on the pH-dependence of the rate constants at different temperatures, a mechanism was proposed involving diazonium ions as intermediates. With the prediction that coordination to the metal could stabilize the otherwise extremely reactive diazonium species, the mechanism of these reactions are being studied in organic media. 

Amino-l,2,4-triazole was alkylated with 4-nitrobenzyl bromide by simply refluxing the mixture in isopropanol to give SO in excellent yield. The aminotriazole SO was deaminated with NaNOa in aqueous HCI and the nitro group was reduced with ammonium formate catalyzed by 10% Pd/C to deliver 47 in an improved yield over the route shown in Scheme 17. Diazotization of 47, reduction of the diazonium salt with sodium sulphite and Fischer indolization of the resulting hydrazine with 4-( /, /-dimethylamino)butanol dimethyl acetal was performed in a single step to afford rizatriptan (4) in 45% yield. 

Diazotization has been reported for all the pyrazolopyridines, and in some cases the salts have been isolated. A 7-aminopyrazolo[4,3-c]pyridine (191a) was converted to the corresponding hydroxy compound with sodium nitrite in hot glacial acetic acid.159 Analogous products were obtained from a 3-aminopyrazolo[3,4-b]-15 and 2-aminopyrazolo[l,5-a]pyridine.186 Decomposition of diazonium salts with hydrobromic acid afforded 3-bromo-pyrazolo[3,4-c]-u0 or -[4,3-bjpyridines111 deamination of 3-aminopyra-zolo[3,4-h]pyridines was achieved via treatment of the diazonium salts with hypophosphorous acid,10 titanous chloride,238 or ferrous ammonium sulfate.238 Kocevar et al.236 have made a detailed study of the reactions of the latter diazonium salt. 

Amines also can be used as precursors for the generation of alkyl cations. The classic method of deaminative formation of carbocations involves some type of diazotation reaction producing an equimolar amount of water [Eq. (3.23)]. 

Reductive deamination of 4-isopropyl-2-nitroaniline by diazotization in the presence of ethanol or hypophosphorous acid yields m-nitrocumene and completes the synthesis. 

It is evident that the success of the deamination process is a function of the completeness of diazotization as well as of the reduction. Fortunately, practically any primary aromatic amine is susceptible of diazotization, usually in yields approaching the theoretical. The conditions for this reaction are comparatively standard and are fully described in monographs on the diazo compounds.1... 

In most of the recorded deaminations with ethanol, sulfuric acid has been used rather than hydrochloric or nitric acid. As a general practice this appears to be a good choice since, in certain cases, diazotization with hydrochloric acid involves a risk that the deamination product may contain chlorine in place of a bromine atom or a nitro group originally present in the aromatic amine. ... 

In the deamination of polybromoamines, if the bromine atoms are ortho or para to the amino group and if the diazotization is carried out with hydrochloric add, nuclear bromine is exchanged for chlorine. Bromine atoms meta to the diazo group are not affected.82 46... 

Diazotization in the presence of sulfuric add affords a simple means of avoiding the exchange reaction since diazonium add sulfates do not rearrange. Thus, by treating the diazonium add sulfate of tribromoaniline with boiling ethanol, pure tribromobenzene is obtained in about 80% yield.29 Even pentabromoaniline suffers no loss of bromine when deaminated via the diazonium add sulfate.32... 

As has already been noted in the section on ethanol deaminations, upon diazotizing some nitroamines in hydrochloric acid, a diazonium salt is obtained in which the nitro group has been replaced by chlorine (pp. 272-273). Consequently, hypophosphorous acid reduction gives a deaminated product Containing chlorine in place of the nitro group. For example, when 5-amino-8-nitroisoquinoline (XVIII) is diazotized with hydrochloric acid and then treated with hypophosphorous acid, 8-chloro-isoquinohne (XIX) is obtained in 60-70% yield instead of 8-nitro-isoquinoline.86... 

Conversion of this diamine to triptycene has, however, been accomplished in 40-45% yield by diazotizing with sulfuric acid l-bromo-2,5-diaminotriptycene (XXI) has also been deaminated by this procedure.83... 

The successful deamination of l-nitro-2-aminonaphthalene, 2,5-diamino-triptycene (XX), and l-bromo-2,5-diaminotriptycene (XXI) suggests that 5-amino-8-nitroisoquinoline (XVIII) also could be deaminated to 8-nitroisoquinoline if the diazotization were carried out in sulfuric acid. 

Deamination of 4,5-dimethyl-8-aminoquinoline by hypophosphorous add gives only a 6% yield of 4,5-dimethylquinoline, There is some evidence, however, that the diazotization takes an abnormal course.84... 

A deamination procedure for which general application is claimed has been described by Hodgson and Madden.6 An aqueous solution of the diazotized amine is treated with the molar quantity of naphthalene-1,5-, disulfonic acid or 2-naphthol-l-sulfonic acid, whereupon the stabilized diazonium compound is precipitated. In most cases the stabilized diazo salts require slight variations in technique for their preparation in optimum yield. "The dry salt is reduced at room temperature in ethanol containing zinc or copper. Overall yields of the order of 90% are reported however, the purity of the product is not specified. 

Diazotization of a mixture of diamino derivatives (R,S)-22 afforded the triazolo[l,5-c]pyrimidine 23. When the reaction time and the proportion of sodium nitrite were increased, a second compound 24, resulting from a reductive deamination of the amino group [89JCS(P1)2401] was obtained (Scheme 5). 

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