Secondary amines, derivatives preparation

Although in many cases products 256 can be directly prepared by Mannich synthesis, the replacement reaction is particularly convenient (l)in the case of primary amines, as it yields a secondary amine derivative hardly obtainable through other synthetic routes, and (2) in the case of arylamincs, as it makes it possible to avoid engaging an activated, reactive, aryl group in the direct Mannich reaction. Moreover, the method is frequently adopted in the synthesis of polymeric substances (Chap. III). 

For the identification and subsequent characterization of hydroxy compounds as well as primary and secondary amines, by preparing their crystalline acetyl derivatives. 

Note. Secondary amines, etc. in Class (ii) can be identified by their derivatives (C) and (D) above, and by their picrates when these can be readily isolated. The preparation of derivatives (D) requires the dry amine, whereas water does not aifect that of derivatives (C). 

Hinsberg procedure for the separation of primary, secondary and tertiary amines is given under (viii) above, and this method may be used. The following experimental details may, however, be found useful for the preparation of derivatives of primary and secondary amines. 

For this reason, acetic anhydride is generally preferred for the preparation of acetyl derivatives, but acetyl chloride, in view of its greater reactivity, is a better diagnostic reagent for primary and secondary amines. 

Secondary amines having one oi two chiral groups attached to the nitrogen atom are prepared from boronic esters by their conversion into alkyldichlotobotanes, followed by treatment with organic azides (518). The second chiral group can be derived from an optically active azide. 

A -Nitroso derivatives, prepared from secondary amines and nitrous acid, are cleaved by reduction (H2/Raney Ni, EtOH, 28°, 3.5 h CuCl/concd. HCl"). Since many V-nitroso compounds are carcinogens, and because some racemization and cyclodehydration of V-nitroso derivatives of V-alkyl amino acids occur during peptide syntheses, V-nitroso derivatives are of limited value as protective groups. 

The fluoride [NS(0)F]3 is more stable thermally and towards nucleophilic reagents than the corresponding chloride. For example, 8.15a is hydrolyzed by water to NH(S02NH2)2, whereas sulfanuric fluoride is unaffected by cold water. In warm water, however, hydrolysis occurs to give the [N3S304F2] anion. All three fluorine atoms in [NS(0)F]3 can be replaced by primary or secondary amines at 80-90°C in the absence of a solvent. Mono- or diphenyl derivatives can be prepared by treatment of [NS(0)F]3 with PhLi in diethyl ether at -70°C, while the Friedel-Crafts reaction with benzene at reflux in the presence of AICI3 gives two isomers of [NS(0)Ph]3. ... 

Aminoquinazolines have been the subject of considerable investigation and a large number of derivatives have been prepared as potential antimalarials. The secondary and tertiary amino compounds can be prepared from the corresponding chloroquinazolines and the required primary or secondary amines. The reaction depends on the reactivity of the halogen atom, e.g, the 4-chloro atom reacts more readily than the 2-chloro atom in quinazolines and also on the basic strength of the amine used (see 6a). The reaction is... 

Aminonitrile formation on 125 with potassium cyanide and piperidine hydrochloride affords the derivative, 135. Hydrolysis as above gives the corresponding amide (136). Debenzylation is accomplished by catalytic reduction. Alkylation of the secondary amine with the side chain (96) used in the preparation of diphenoxylate affords pirintramide (138) This compound, interest-... 

Photosensitive functions are in many cases also heat sensitive, so the preparation of photosensitive polyimides needs smooth conditions for the condensations and imidization reactions. Some chemical reactants, which can be used for polyamide preparation, have been patented for the synthesis of polyimides and polyimide precursors. For example, chemical imidization takes place at room temperature by using phosphonic derivative of a thiabenzothiazoline.102 A mixture of N -hydroxybenzotriazole and dicyclohexylcarbodiimide allows the room temperature condensation of diacid di(photosensitive) ester with a diamine.103 Dimethyl-2-chloro-imidazolinium chloride (Fig. 5.25) has been patented for the cyclization of a maleamic acid in toluene at 90°C.104 The chemistry of imidazolide has been recently investigated for the synthesis of polyimide precursor.105 As shown in Fig. 5.26, a secondary amine reacts with a dianhydride giving meta- and para-diamide diacid. The carbonyldiimidazole... 

The reaction between epoxides and ammonia is a general and useful method for the preparation of P-hydroxyamines. " Ammonia gives largely the primary amine, but also some secondary and tertiary amines. The useful solvents, the ethanolamines, are prepared by this reaction. For another way of accomplishing this conversion, see 10-54. The reaction can be catalyzed with Yb(OTf)3 and in the presence of a-BINOL is l,l -bi-2-naphthol derivative gives amino alcohols with high asymmetric induction. A variation used Yb(OTf)3 at lOkbar or at ambient pressure. Lithium triflate can also be used. Primary and secondary amines give, respectively, secondary and tertiary amines, for example. 

Ammonia and primary and secondary amines can be added to isocyanates to give substituted ureas. Isothiocyanates give thioureas. This is an excellent method for the preparation of ureas and thioureas, and these compounds are often used as derivatives for primary and secondary amines. Isocyanic acid (HNCO) also gives the reaction usually its salts (e.g., NaNCO) are used. Wohler s famous synthesis of urea involved the addition of ammonia to a salt of this acid. "... 

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