Primary aliphatic amines reactions

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

The resulting diazo reagents undergo a wide variety of reactions including those of interest in the manufacture of azo dyes and pharmaceuticals. With primary aliphatic amines the course of the reaction is different N2 is quantitatively evolved and alcohols usually result ... 

Instead of a diazonium salt, a diazo compound is obtained from reaction of a primary aliphatic amine 8 that has an electron-withdrawing substituent at the a-carbon (e.g. Z = COOR, CN, CHO, COR) as well as an a-hydrogen ... 

Reaction of a-isocyano-a, / -unsaturated sulfones with primary aliphatic amines affords 1,5-disubstituted imidazoles 59 (equation 56)48. The reaction of aromatic amines such as aniline is too slow to be of practical use. Results of the preparation of 59 are listed in Table 5. 

This method gives better yields than other methods of preparation of 2-bromoallylamine, and it is the most convenient method for the preparation of large quantities of the compound. The procedure illustrates a reaction, the so-called Delepine reaction, that has been used for the preparation of many primary aliphatic amines.8-12 A number of primary aliphatic amines have been prepared by this method without isolation of the intermediate hexaminium salt.11 Several preparations of aliphatic aldehydes via the hexaminium salt have been described in earlier volumes of this series.13... 

The reaction of diazo compounds with amines is similar to 10-15. The acidity of amines is not great enough for the reaction to proceed without a catalyst, but BF3, which converts the amine to the F3B-NHR2 complex, enables the reaction to take place. Cuprous cyanide can also be used as a catalyst. The most common substrate is diazomethane, in which case this is a method for the methylation of amines. Ammonia has been used as the amine but, as in the case of 10-44, mixtures of primary, secondary, and tertiary amines are obtained. Primary aliphatic amines give mixtures of secondary and tertiary amines. Secondary amines give successful alkylation. Primary aromatic amines also give the reaction, but diaryl or arylalkyl-amines react very poorly. 

Primary (R = H) and secondary aromatic amines react with alkenes in the presence of thallium(III) acetate to give vie- diamines in good yields. " The reaction is not successful for primary aliphatic amines. In another procedure, alkenes can be diaminated by treatment with the osmium compounds R2NOSO2 and R3NOSO (R = t-Bu)," analogous to the osmium compound mentioned at 15-51. The palladium-promoted method of 15-51 has also been extended to diamination. " Alkenes can also be diaminated indirectly by treatment of the aminomercurial compound mentioned in 15-51 with a primary or secondary aromatic amine. 

The reaction of EPM-g-MA with primary aliphatic amines results in amide acids, which at elevated temperature convert to imides [12] (Figure 13.6). The reaction of EPM-g-MA with alcohols yields... 

Woodbum HM, Morehead BA, Chih CM (1950) The reaction of cyanogens with organic compounds. II. Primary aliphatic amines. J Org Chem 15(3) 535-540... 

A number of palladium-catalysed reactions of the triflate 61 have been reported but the nucleophilic displacement with primary aliphatic amines was, surprisingly, very slow in refluxing THF (24-92h). However, under microwave irradiation the reactions were very rapid and gave high yields, although even with microwaves, secondary amines and anilines failed to... 

Moss and coworkers provided an early example of the way in which micellization can control the stereochemical course of a reaction. Deamination of chiral primary aliphatic amines in water proceeds with net inversion and extensive racemization, and the extent of racemization depends upon the lifetime of the carbocation-like intermediate. The situation changes dramatically if the salts of the primary amine can self-micellize, because now the nucleophile, typically water, is directed in from the front-side so that there is extensive retention of configuration (Moss et al., 1973). 

Larger accelerations were observed, using the same principle, for the geometrically less demanding formation of an amide from a primary aliphatic amine and an acyl phosphate (14, Scheme 6). In this case the uridine bases carry an imidazole side-chain (13). After 16 rounds of increasing selection pressure the best catalytic species accelerated the reaction of Scheme 6 over 105-fold... 

Isonitrile Reaction.—Like the primary aliphatic amines of the methylamine type, aniline and its analogues give a characteristic odour with chloroform and alkali. 

M-Substitution of primary aliphatic amines R1NH2 (R1 = t-Bu, CsHn, cyclopentyl, cyclohexyl, PhMeCH etc.) to yield R2CH2NHR1 (R2 = Et, Ph or PhCH2) is accomplished by condensation of the amine with benzotriazole and formaldehyde, followed by reaction of the products with Grignard reagents (equation 45)126. 

Fig. 9.8 presents another, more complex type of phosphate prodrugs, namely (phosphoryloxy)methyl carbonates and carbamates (9-26, X = O or NH, resp.) [84], Here, the [(phosphoryloxy)methyl]carbonyl carrier appears quite versatile and of potential interest to prepare prodrugs of alcohols, phenols, and amines. The cascade of reactions leading from prodrug to drug as shown in Fig. 9.8 involves three steps, namely ester hydrolysis, release of formaldehyde, and a final step of carbonate hydrolysis (X = O) or A-decar-boxylation (X = NH). Three model compounds, a secondary alcohol, a primary aliphatic amine, and a primary aromatic amine, were derivatized with the carrier moiety and examined for their rates of breakdown [84], The alcohol, indan-2-ol, yielded a carrier-linked derivative that proved relatively... 

While primary aliphatic amines are converted to nitro compounds on reaction with ozone these reactions are accompanied by numerous by-products.Such side-reactions are largely suppressed by first dissolving the amine onto silica gel followed by passing a stream of 3 % ozone in oxygen through the solid at -78 °C under anhydrous conditions, where yields of between 60 and 70 % are reported. This route has been used to synthesize the energetic cyclopropane (65) from the diamine (64) (Table 1.7). ... 

The reaction of primary aliphatic amines and nitramines with nitronium salts also leads to deamination and the formation of alkyl nitrates. 

More recently, Menendez et al. reported a closely related four-component access to tetrahydropyridines, the amino alcohol being replaced by a primary amine and an alcohol. Thus, the cerium(IV) ammonium nitrate (CAN)-catalyzed reaction between primary aliphatic amines, 1,3-dicarbonyls, cx,p-unsaturated aldehydes, and alcohols resulted in the formation of 6-aUcoxy-2-methyl-l,4,5,6-tetrahydropyridines with... 

A catalytic reaction also took place under similar conditions with primary aliphatic amines but it led to the formation of symmetrical ureas and the best results were... 

Cyano-4-quinazolinones (4-oxo-3,4-dihydro-2-quinazolinecarbonitriles) 975 are available from 2-[A -(chloro-dithiazole)imino]benzoate esters 973 by reaction with primary aliphatic amines at room temperature <1998JHC659, 2002H(57)1471, 2002TL3993, 2005TL7477>. 

Telomers 422 (n = 2) and other 4-halogeno-l,3-dioxolan-2-ones were shown288 to react readily with ammonia or primary aliphatic amines, with formation of 4-hydroxy-2-oxazolidones (460). The latter, for which the trans arrangement of the hydrogen atoms of the oxazoli-done ring was deduced from H-n.m.r. data, readily underwent replacement of the hydroxyl group by a phenyl group on reaction with... 

As indicated above (Ohme and Schmitz [38a, p. 339]) primary amines converted into the alkylamides of sulfuric acid can be oxidized with sodium hypochlorite to azo compounds. The reaction appears to proceed by way of an intermediate hydrazine, which is ultimately oxidized [38a], The reaction is suitable for the formation of symmetrically substituted azoalkanes. Highly branched primary aliphatic amines have been oxidized with sodium hypochlorite in an aqueous dioxane medium [77],... 

The best known example of the treatment of a primary aliphatic amine with nitrous acid involves the reaction of esters of glycine hydrochloride with sodium nitrite to form esters of diazoacetic acid. This reaction is carried out at low temperatures and under such reaction conditions that any IV-nitroso primary amine which might have been formed is immediately converted to the diazoacetate [15, 16]. Treatment of 1-methyl-2,2,2-trifluoroethylamine hydrochloride, another primary amine, with sodium nitrite in an aqueous system also evidently leads to the corresponding diazoalkane [17]. 

Kelly and coworkers devised a two binding-site host that accelerates an Sn2 reaction between a primary aliphatic amine and an alkyl bromide [17[. Kelly s host (Figure 1.7) acted as template for the two reactants that were able to form three hydrogen bonds to each aminopyridone from the host. The reactants were the aminomethyl- and bromomethylnaphthyridines indicated in Figure 1.7, which bound strongly (K>1O M ) to the aminopyridone moieties from the host. A sixfold acceleration of the Sn2 reaction was observed, but turnover could not be demonstrated (the product precipitated from the CHCI3 solution as the HBr salt). 

Generally, reaction (1) is not successful with non N-substituted, i.e. primary amides, most of which undergo decomposition when nitrated. Primary aliphatic amines also decompose under the action of concentrated nitric acid. 

Cowan, C. T., and D. White, The mechanism of exchange reactions occurring between sodium montmorillonite and various n-primary aliphatic amine salts , Trans. Faraday Soc., 54, 691-697 (1958). 

Primary aliphatic amines, 413 crystalline derivatives of, 424 reactions of, 420, 1072 table of, and derivatives of, 424 Primary aromatic amines, 539 crystalline derivatives of, 652 reactions and characterisation of, 648, 1073 ... 

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