Reactions with hexamine

Reactions with electrophilic reagents take place with substitution at C-3 or by addition at the pyridine nitrogen. All the aza-indoles are much more stable to acid than indole (cf. 20.1.1.9), no doubt due to the diversion of protonation onto the pyridine nitrogen, but the reactivity towards other electrophiles at C-3 is only slightly lower than that of indoles. Bromination and nitration occur cleanly in all four parent systems and are more controllable than in the case of indole. Maniuch and Vilsmeier reactions can be carried out in some cases, but when the latter fails, 3-aldehydes can be prepared by reaction with hexamine, possibly via the anion of the azaindole. Alkylation under neutral conditions results in quatemisation on the pyridine nitrogen and reaction with sodium salts allows A-1-alkylation. Acylation under mild conditions also occurs at N-1. The scheme below summarises these reactions for the most widely studied system - 7-azaindole. Acylation at C-3 in all four systems can be carried out at room temperature in the presence of excess aluminium chloride. ... 

The resins are hardened by acidic conditions. Phosphoric acid, or more commonly ammonium chloride, an acid donor, is employed. The ammonium chloride functions by reaction with formaldehyde to give hydrochloric acid. Hexamine is also formed during this reaction. 

RDX. Gilpin Winkler (Ref 38b) measured a heat of nitration of — 88.0kcal/mole of hexa-mine for the reaction of hexamine with 97.5% nitric acid. They also obtained a value of — 140kcal/mole of hexamine for the formation of RDX from hexamine and Bachmann reagents (acetic anhydride, acetic acid, ammonium nitrate and nitric acid). Incidentally, Gilpin Winkler interpret their results to mean that hexamine dinitrate is an intermediate in the direct nitrolysis of hexamine to give RDX, while hexamine mononitrate is an intermediate in the Bachmann process of producing RDX... 

Adachi A, Okano A (2008) Generation of cyanide ion by the reaction of hexamine and losartan potassium with sodium hypochlorite. J Health Sci 54(5) 581-583... 

Chapman studied the nitrolysis of symmetrical methylenediamines. The nitrolysis of N, N, N, M-tetramethylmethylenediamine with nitric acid-acetic anhydride-ammonium nitrate mixtures gives both dimethylnitramine and RDX the latter probably arises from the nitroT ysis of hexamine formed from the reaction of ammonium nitrate and formaldehyde released from the hydrolysis of the methylenediamine. The same reaction with some morpholine-based methylenediamines (105) allows the synthesis of l,3,5-trinitro-l,3,5-triazacycloalkanes (106). 

The presence of HMX as an impurity in RDX is not a problem when the product is used as an explosive. However, the need for an analytical sample of RDX makes other more indirect methods feasible. One such method involves the oxidation of 1,3,5-trinitroso-1,3,5-triazacyclohexane (109) ( R-salt ) with a mixture of hydrogen peroxide in nitric acid at subambient temperature and yields analytical pure RDX (74%) free from HMX." The same conversion has been reported in 32 % yield with three equivalents of a 25 % solution of dinitrogen pentoxide in absolute nitric acid. l,3,5-Trinitroso-l,3,5-triazacyclohexane (109) is conveniently prepared from the reaction of hexamine with nitrous acid at high acidity. ... 

However, the yield of DPT from such reactions is often poor (15-25 %). DPT has also been synthesized from the reaction of hexamine dinitrate with acetic anhydride or cold 90 % aqueous sulphuric acid. Both methods under optimum conditions give yields of DPT of approximately 31 The reaction of nitramine (NH2NO2) with aqueous formaldehyde, followed by neutralization of the reaction mixture with ammonia to pH 5.5-6.5, gives DPT in 73 % yield based on the nitramine starting material. This last reaction presumably involves the formation of dimethylolnitramine as an intermediate (Section 5.15.4.2). 

The nitrolysis of hexamine at low temperature has led to the synthesis of a number of cyclic nitramines. The reaction of hexamine dinitrate (241) with 88 % nitric acid at -40 °C, followed by quenching the reaction mixture onto crushed ice, leads to the precipitation of 3,5-dinitro-3,5-diazapiperidinium nitrate (242) (PCX) in good yield PCX is an explosive equal in power to RDX but is slightly more sensitive to impact. The reaction of PCX (242) with sodium acetate in acetic anhydride yields l-acetyl-3,5-dinitro-l,3,5-triazacyclohexane (82) (TAX), which on further treatment with dilute alkali in ethanol yields the bicycle (243). ... 

The reaction of hexamine dinitrate (241) with 98% nitric acid at —30°C, followed by quenching with aqueous sodium nitrate, yields the nitrosamine (244). When the same reaction is cautiously quenched with ethanol the ethoxyether (245) is obtained. Treatment of the ethoxyether (245) with cold absolute nitric acid yields the bicyclic ether (246). ° Treatment of any of the cyclic nitramines (242)-(246) with nitric acid and ammonium nitrate in acetic anhydride yields RDX. ° Hexamine dinitrate is often used in low temperature nitrolysis experiments in order to avoid the initial exotherm observed on addition of hexamine to nitric acid. 

No peroxide has found practical use as an explosive, a consequence of the weak oxygen-oxygen bond leading to poor thermal and chemical stability and a high sensitivity to impact. Hexamethylenetriperoxidediamine (HMTD) (46) is synthesized from the reaction of hexamine with 30 % hydrogen peroxide in the presence of citric acid. HMTD is a more powerful initiating explosive than mercury fulminate but its poor thermal and chemical stability prevents its use in detonators. 

Hexamine dinitrate is reacted with ammonium dinitrate in the presence of acetic anhydride. Unlike the E-method no paraformaldehyde is used, all the necessary methylene groups being provided by hexamine, and the additional amino groups (as in the K-method) by ammonium nitrate. Nitric acid enters into reaction in combination with hexamine and as ammonium dinitrate ... 

The pyrilium salt 30a was obtained from benzo-9-crown-3 in 29% yield in two steps by formylation with hexamine in the presence of CF3CO2H, followed by reaction with 2 equiv of acetophenone in the presence of POCI3 <2002JOC2065>. In the same manner, the Vilsmeier formylation of the /V-phenyl dithiazonine and the subsequent condensation reaction with 2-aminobenzenethiol resulted in substituted benzothiazole 43 in 38% yield < 1999J(P2)1273>. Benzo-9-crown-3 ether trimerizes in the presence of fed and aqueous sulfuric acid to produce tris-(9-crown-3)-triphenylene 28 in 25% yield <2001CJC195>. 

The interaction of alkyl halides, preferably iodides or bromides, with hexamine in chloroform or alcohol solution forms quaternary ammonium salts which on heating with hydrochloric acid are readily converted to primary amines. The procedure has been employed successfully in the reaction of primary, but not secondary or tertiary, aliphatic halides, certain benzyl halides, halo ketones, halo acids, and halo esters. The yields range from 40% to 85%. 

Substituted benzyl halides react with hexamine in boiling alcohol to form addition compounds which decompose on heating with water to give aldehydes. " An excellent discussion of the reaction has been presented, and improvements in the conditions have been made. Aqueous acetic acid (1 1) is recommended as solvent for the entire process, and there is no need to isolate the intermediate salt. The procedure is illustrated by the synthesis of 1-naphthaldehyde (82%). In other instances, the addition compound is first ptrepared in chloroform solution, isolated, and then decomposed with water or dilute acetic acid, as in the synthesis of 2-thiophenaldehyde (53%). ... 

A somewhat similar reaction is the conversion of substituted benzyl-amines to the corresponding benzaldehydes by treating their formaldehyde condensation product with hexamine. ... 

The methods by W. E. Bachmann (in the U.S.A.) and Koffler (in Germany) Vol. HI, p. 111 have now received particular attention in view of the fact that the route with acetic anhydride can lead to the formation of Octogene (HMX), Reed [124] described the reaction of hexamine, nitric acid, trifluoruaceth anhydride in the presence of liquid SO which is a very good solvent for hex amine. Tlie reaction yielded (85%) l-lrifluoroacetyl-3,5-dinitro l, 3,5-triazacyclo hexane, m.p. 131-132 C. 

DeUpine reaction An activated halide reacts with hexamine in a nonaqueous medium to form an iininium salt which is hydrolyzed by ethanolic hydrochloric acid to produce the corresponding amine, as hydrochloride formaldehyde is removed as the volatile diethyl formal. For example, 2,3-dibromopropene-l (I) forms the salt (2), which on hydrolysis affords the amine (3). In this example the... 

Sommelet reaction This reaction also involves reaction of a halide, usually a benzyl-type halide, with hexamine to form a heximinium salt, which is then hydrolyzed in a nonacidic aqueous medium such as water or aqueous alcohol. In the procedure formulated, the reaction of benzyl chloride with hexamine is carried out... 

The bis-imidazolin-4-one derivatives (107), prepared by the reaction of a-halo-acetanilides with hexamine, were hydrolysed to give (108), which were converted into the diazepinones (109) by reaction with base. The authors... 

The cardol present in CNSL, if in high proportion can lead to an exothermic reaction with formaldehyde and also It appears desirable for the phenolic components to have a high proportion of triene in order for the first acid-catalysed side chain oligomerisation stage to proceed. CNSL-formaldehyde polymers have greater flexibility than those from phenol-formaldehyde, due to internal plasticising, they are also more soluble in solvents, and due to their hydrophobicity they have resistance to water penetration, and hence acidic and alkaline media. For some applications highly methylolated cardanol is useful and this can be formed with formaldehyde, by the use of adipic or succinic acid as catalysts, and subsequently rapidly cured with hexamine (ref. 245). 

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