With Amines

2-Cyanopyrazine with concentrated aqueous ammonia was converted through 2-[A(-(C-imino-C-pyrazin-2-ylinethyl)amidino]pyrazine (43) to 2-carbamoylpyrazine (985), and 2-chloro-6-cyanopyrazine reacted similarly (985). 2-Ethoxy-6-(C-ethoxy-C-iminomethyl)pyrazine was found to be a by-product of the reaction of 2-chloro-6-cyanopyrazine with concentrated ethanolic ammonia and 2-ethoxy(or methoxy)-6-[C-ethoxy(or methoxy)-C-iminomethyl]pyrazine was obtained from 2-chloro-6-cyanopyrazine by the action of ethanol (or methanol) in the presence of triethylamine (985). 2-Cyanopyrazine treated in water with hydroxylamine hydrochloride and sodium carbonate at 70-75° gave 2-(C-amino-C-hydroxyiminomethyl)-pyrazine (62), and 2 yanopyrazine fused with aniline and an equimolar amount of aluminum chloride at 140-220° gave 2-(C-anilino-C-iminomethyl)pyrazine (and similar preparations were carried out with other aromatic amines) (1334,1410). 

2-Chloro-6-cyanopyrazine with aqueous methylamine at 0° gave 2-chloro-6-(A -methylamidino)pyrazine (940), and 2-cyano-6-dimethylaminopyrazine with dimethylamine in the presence of anhydrous aluminum chloride gave 2-dimethyl-amino-6-(C-dimethylamino-C-iminomethyl)pyrazine and similar reactions were observed with other secondary amines (1424). 

A series of 2-cyano-6-substituted aminopyrazines (and imidoesters) refluxed with hydroxylamine in methanol gave 2-(C-amino-C-hydroxyiminomethyl)-6-(substituted amino)pyrazines (943, 1424), and 2-cyano(or thiocarbamoyl)-6-ethylthiopyrazine refluxed with hydroxylamine in aqueous methanol gave 2-(C-amino-C-hydroxyiminomethyl)-6-ethylthiopyrazine (992). 

Tetracyanopyrazine with liquid ammonia in tetrahydrofuran formed 2,6-diamino-3,5-dicyanopyrazine (1180, 1182), and tetracyanopyrazine with piperazine similarly gave 2,6-dicyano-3,5-dipiperazin-l -ylpyrazine (1182). 

2-Cyanopyrazine with dicyanodiamide [(NH2CN)2] gave the 2-(4, 6 -diamino-triazin-2 -yl)pyrazine (63), with o-phenylenediamine in the presence of poly-phosphoric acid at 250 gave 2-(benzimidazol-2 -yl)pyrazine, and with hydrazine gave 2-(C-hydrazino-C-iminomethyl)pyrazine, which condensed with benzil to 2-(5, 6 -diphenyl-as-triazin-3 -yl)pyrazine (64) (1441). 

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CO. Alkynes will react with carbon monoxide in the presence of a metal carbonyl (e.g. Ni(CO)4) and water to give prop>enoic acids (R-CH = CH-C02H), with alcohols (R OH) to give propenoic esters, RCH CHC02R and with amines (R NH2) to give propenoic amides RCHrCHCONHR. Using alternative catalysts, e.g. Fe(CO)5, alkynes and carbon monoxide will produce cyclopentadienones or hydroquinols. A commercially important variation of this reaction is hydroformyiation (the 0x0 reaction ). 

Although benzenesulphonyl chloride has for simplicity been used in the above discussion, tolucne-/>- sulphonyl chloride, CHaCeH SO Cl, is more frequently used in the laboratory, owing to its much lower cost, the latter being due in turn to the fact that toluene-p-sulphonyl chloride is a by-product in the commercial preparation of saccharin. Toluene-p sulphonyl chloride is a crystalline substance, of m.p. 68° the finely powdered chloride will, however, usually react readily with amines in the Schotten-Baumann reaction it does not react so readily with alcohols, but the reaction may be promoted considerably by first dissolving the chloride in some inert water-soluble solvent such as acetone. 

Picrates, Picric acid combines with amines to yield molecular compounds (picrates), which usually possess characteristic melting points. Most picrates have the composition 1 mol amine 1 mol picric acid. The picrates of the amines, particularly of the more basic ones, are generally more stable than the molecular complexes formed between picric acid and the hydrocarbons (compare Section IV,9,1). 

Anion-exchange resins contain a basic radical, such as —NH and =NH, and are prepared by the condensation of formaldehj de with amines such as m-phenylenediainine and urea. These resins can absorb acids by the formation of salts, —NH3CI and =NHjCl, and are regenerated by treatment with sodium hydroxide or sodium carbonate. 

They react with amines to form substituted thioureas ... 

CAUTION - The lower nitroalkanes form shock and/or temperature sensitive EXPLOSIVE compounds with amines and hydroxides. BE CAREFUL, DAMNIT You have been warned. 

In these cases the acyl azides formed have been used to prepare amines via Curtius rearrangement. The acyl chloride or azide intermediates can. however, also be reacted with amines or alcohols to form amides or esters. 

Amines are powerful nucleophiles which react under neutral or slightly basic conditions with several electron-accepting carbon reagents. The reaction of alkyl halides with amines is useful for the preparation of tertiary amines or quaternary ammonium salts. The conversion of primary amines into secondary amines is usually not feasible since the secondary amine tends towards further alkylation. 

Allylation under basic conditions. Allylation can be carried out under basic conditions with allylic acetates and phosphates, and under neutral conditions with carbonates and vinyloxiranes. The allylations under neutral conditions are treated separately in Section 2.2.2.1 from those under basic conditions. However, in some cases, allylations of the same substrates are carried out under both basic and neutral conditions to give similar results. These reactions are treated together in this section for convenience. Allylic acetates are widely used for Pd-catalyzed allylation in the presence of bases tertiary amines or NaH are commonly used[6,7,4l]. As a base, basic alumina or ICF on alumina is conveniently used, because it is easy to remove by filtration after the reaction[42]. Allyl phosphates are more reactive than acetates. The allylation with 40 proceeds stepwise. At first allylic phosphate reacts with malonate and then allylic acetate reacts with amine to give 41(43]. 

The reaction of the vinylcyclopropanedicarboxylate 301 with amines affords an allylic amine via the 7r-allylpalladium complex 302[50]. Similarly, three-membered ring A -tosyl-2-(l,3-butadienyl)aziridine (303) and the four-mem-bered ring azetidine 304 can be rearranged to the five- and six-membered ring unsaturated cyclic amines[183]. 

Thiazole disulfides react with amines in the presence of oxidizing agents to yield 2-sulfenamidothiazoles (314). Results obtained in the ben-zothiazole series (323) indicate that they could be used as starting material to obtain 2-halosulfothiazoles. 

Many biological processes involve an associa tion between two species in a step prior to some subsequent transformation This asso ciation can take many forms It can be a weak associ ation of the attractive van der Waals type or a stronger interaction such as a hydrogen bond It can be an electrostatic attraction between a positively charged atom of one molecule and a negatively charged atom of another Covalent bond formation between two species of complementary chemical re activity represents an extreme kind of association It often occurs in biological processes in which aide hydes or ketones react with amines via imine inter mediates... 

Section 20 12 Esters react with amines to give amides... 

Nucleophilic substitution results when primary alkyl halides are treated with amines... 

Chloroacetic acid can be esterified and aminated to provide useful chemical intermediates. Amphoteric agents suitable as shampoos have been synthesized by reaction of sodium chloroacetate with fatty amines (4,5). Reactions with amines (6) such as ammonia, methylamine, and trimethylamine yield glycine [66-40-6J, sarcosine [107-97-17, and carhoxymethyltrimethylammonium chloride, respectively. Reaction with aniline forms /V-phenylglycine [103-01 -5] a starting point for the synthesis of indigo (7). 

Nickel halide complexes with amines give mixtures of linear polymer and cychc trimers (30). Nickel chelates give up to 40% of linear polymer (31). When heated with ammonia over cadmium calcium phosphate catalysts, propargyl alcohol gives a mixture of pyridines (32). 

With thionyl chloride as catalyst, hydrogen peroxide adds to vinyl ethers in anti-Markovnikov fashion, as do monothioglycols with amine catalysts... 

Salt Formation. Salt-forming reactions of adipic acid are those typical of carboxylic acids. Alkali metal salts and ammonium salts are water soluble alkaline earth metal salts have limited solubiUty (see Table 5). Salt formation with amines and diamines is discussed in the next section. 

Diethyl Ethylphosphonate. A Hquid compound introduced for appHcations similar to those of DMMP is diethyl ethylphosphonate [78-38-6] CgH O P. This material is claimed to be less susceptible to undesirable interactions with haloaHphatic components, such as blowing agents, or with amine catalysts. 

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