Hexamethylenetetramine, reactions

A study [12] of the novolak-hexamethylenetetramine reaction by differential thermal analysis and thermogravimetric analysis supports the view that the cross-linking reaction proceeds through dibenzylamines. 

It is to be noted that the relative amounts of the various linkages shown above are not intended to have any quantitative significance. Thus the network polymer obtained from the novolak-hexamethylenetetramine reaction has a structure which is predominantly similar to that of the network polymer derived from a resol. 

Two-Stage Resins. The ratio of formaldehyde to phenol is low enough to prevent the thermosetting reaction from occurring during manufacture of the resin. At this point the resin is termed novolac resin. Subsequently, hexamethylenetetramine is incorporated into the material to act as a source of chemical cross-links during the molding operation (and conversion to the thermoset or cured state). 

Hexamethylenetetramine. Pure hexamethylenetetramine [100-97-0] (also called hexamine and HMTA) is a colorless, odorless, crystalline sohd of adamantane-like stmcture (141). It sublimes with decomposition at >200° C but does not melt. Its solubiUty in water varies Htde with temperature, and at 25°C it is 46.5% in the saturated solution. It is a weak monobase aqueous solutions are in the pH 8—8.5 range (142). Hexamethylenetetramine is readily prepared by treating aqueous formaldehyde with ammonia followed by evaporation and crystallisation of the soHd product. The reaction is fast and essentially quantitative (142). 

Whereas the above reactions are appHcable to activated aromatics, deactivated aromatics can be formylated by reaction with hexamethylenetetramine in strong acids such as 75% polyphosphoric acid, methanesulfonic acid, or trifluoroacetic acid to give saUcylaldehyde derivatives (117). Formyl fluoride (HCOF) has also been used as formyl a ting agent in the Friedel-Crafts reaction of aromatics (118). Formyl fluoride [1493-02-3] in the presence of BF was found to be an efficient electrophilic formyl a ting agent, giving 53% para-, 43% ortho- and 3.5% meta-tolualdehydes upon formylation of toluene (110). 

Primary amines through reaction of alkyl halides with hexamethylenetetramine... 

Reaction of alkyl halides 1 with hexamethylenetetramine 2 (trivial name urotropine) followed by a hydrolysis step, leads to formation of primary amines 3 free of higher substituted amines. This method is called the Delepine reaction, a comparable method is the Gabriel synthesis. 

An alkyl halide 1 reacts with hexamethylenetetramine 2 to the quaternary ammonium salt 4, which crystallizes from the reaction mixture ... 

Hexamethylenetetramine can serve as a source of ammonia in the reaction with a 2-(haloacet-amido)benzophenone. The intermediate salts 14, which can be isolated, are readily transformed into benzodiazepinones IS in refluxing ethanol (Method C). Selected examples are given.197 198... 

A. 2-BromoaUylhexamimum bromide. A 2-1. three-necked flask fitted with a Hershberg stirrer,2 a dropping funnel, and a condenser is charged with a solution of 154 g. (1.10 moles) of hexamethylenetetramine (Note 11 in 1250 ml. of chloroform. The solution is stirred and heated under reflux while 200 g. (1.00 mole) of 2,3-dibromopropene (Note 2) is added dropwise over a period of 1 hour. Precipitation of the product is noted soon after the first addition of 2,3-dibromopropene. After the addition is complete, the reaction mixture is stirred under reflux for 3 hours and allowed to stand overnight. The mixture is cooled in an ice bath, and the salt is collected by suction filtration. After air-... 

Bromomethyl-2,3-dimethoxy-7-methylquinoxaline (265) underwent a classical Sommelet reaction and incidental hydrolysis of the methoxy groups to give 7-methyl-2,3-dioxo-l,2,3,4-tetrahydro-6-quinoxalinecarbaldehyde (266) (hexamethylenetetramine, CHCI3, 20°C reflux, 30 min solid from evapora-... 

Primary amines can be prepared from alkyl halides by the use of hexamethylenetetramine followed by cleavage of the resulting salt with ethanolic HCl. The method, called the Delepine reaction, is most successful for active halides such as allylic and benzylic halides and a-halo ketones, and for primary... 

The Delepine reaction Involves nucleophilic displacement of active halides by hexamethylenetetramine, followed by hydrolysis of Intermediate quaternary ammonium salt to release the amine. 

Normally the reaction Is useful for the conversion of alkyl halides to primary amines without concomitant formation of secondary amines.29 Treatment of polymer 17 with hexamethylenetetramine in a mixture of ethanol/THF afforded an insoluble resin. Using diazabicyclooctane (DABCO), we demonstrated that the reaction could be limited to attack by a single nitrogen in a multifunctional amine, so we did not anticipate crosslinking via bis-quat salt formation. Hydrolysis of 2 with anhydrous HC1 in ethanol generated free amino groups as evidenced by a positive ninhydrin test, but quantitative hydrolysis could not be achieved and the product remained insoluble. One would have expected a simple bis-quat to hydrolyse and open the crosslinked structure. 

It is made by the nitration of hexamine (hexamethylenetetramine), itself prepared from formaldehyde and ammonia. Hexamine was originally nitrated with a large excess of concentrated nitric acid at temperatures below 30°C and the product recovered by adding the reaction liquor to an excess of chilled water. Later the yield was improved by adding ammonium nitrate to the reaction as this reacts with the liberated formaldehyde. A much-used process converts the hexamine first to its dinitrate, which is then reacted with ammonium nitrate, nitric acid and acetic anhydride (the last reagent being re-formed from the product by use... 

Part 23 Determination of formaldehyde and hexamethylenetetramine (HMTA) in food simulants In the case of HMTA, it is treated with acid and heated to release formaldehyde. Formaldehyde in simulant is determined colorimetrically by reaction with chromotropic add in the presence of sulfuric acid... 

Paquin in 1948 found that a strongly exothermic reaction occurred when 40% formaldehyde was added to a solution of sulfamide in 25% aqueous ammonia. At once beautiful crystals precipitated they were recrystallized from 96% alcohol to give a compound, C5H10N4SO2, mp 224-225 "C, in 88% yield.245 From the similar character to hexamethylenetetramine, he named this product pentamethylenetetramine sulfone it is 225. One year later, in 1949, Hecht and Henecka at Bayer research laboratory reported that a condensation product from one mole of sulfamide in strong mineral acid and two moles of formaldehyde showed very strong toxicity and was five times more toxic than strychnine. They called this product (226) tetra-methylenedisulfotetramine. 246... 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

The early addition of Dimedon is reported234 to depress the formation of hexamethylenetetramine from formaldehyde in the presence of ammonia. O Dea282 found that the activated methylene center, sometimes formed in periodate oxidations of carbohydrates, reacts appreciably with the formaldehyde formed, thus giving low yields of apparent formaldehyde. He was able to depress this side reaction by the use of lowered temperatures and by the addition of benzaldehyde or of p-hydroxybenzaldehyde. The analyses for formaldehyde have often been more successful at a pH of 7.5 than at lower pH values.57, 68 59a 60 264... 

Experiment 6. Reaction with Ammonia.—Of the formaldehyde prepared 10 c.c. are mixed with a small excess of ammonia and the mixture is evaporated in a small glass dish on the water bath. The colourless crystals which remain consist of hexamethylenetetramine (CH2)6N4 (urotropine.) This reaction proceeds quantitatively. It should be so carried out and the result compared with that obtained by titration. 

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