The Addition of Primary and Secondary Amines

0 Aldehydes and ketones react with primary amines to form imines and with secondary amines to form enamines. 

Imines have a carbon-nitrogen double bond. Enamines have an amino group joined to a carbon-carbon double bond (they are alkeneamines). 

A general equation for the formation of an imine from a primary amine and an aldehyde or ketone is shown here. Imine formation is acid catalyzed, and the product can form as a mixture of (E) and (Z) isomers  

The amine adds to the carbonyl group Intermolecular proton transfer from nitrogen 

Protonation of the oxygen produces a good ieaving group. 

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Lithium alkylamides (in situ generated from the amine and either n-BuLi or sec-BuLi) generally give higher yields under milder conditions. Thus, n-BuLi (5%) catalyzes the addition of primary and secondary amines to styrene to afford (-phenethy-lamines in moderate to good yields (e.g., Bq. 4.32) [155]. NH, and PhNHj, however, do not add to styrene under these conditions. a-Methylstyrene and 1,1-diphenyleth-ylene can also be hydroaminated. 

The published data5 14,16,17 29,30,50,54-641 on the relation between the constants of the addition of primary and secondary amines are most discrepant. On one hand, such a situation is due to the different experimental conditions, and on the other hand, to the dissimilar methods of calculating the kinetic constants. Most researchers used the kinetic data for reactions in excess alcohol to estimate the quasibimolecular rate constants of the primary and secondary additions. The constants were estimated assuming the validity of a simple scheme of the successive bimolecular reaction [Scheme (1)]. 

The elimination reaction can be followed only for pH > (pKvm — 2). The rate of the side reaction of the a,(i-unsaturated ketone increases with increasing pH and for phenylvinyl ketone becomes of importance at pH values above about 9. To study the elimination process unaffected by the hydration of the a,[3-unsaturated ketone generated, it was necessary to find a Mannich base the elimination of which would take place at pH << 9, i.e. with a.pKjtB 9. 3-Morpholinopropiophenone proved to be a suitable model (27) this compound has a pK B value of 6.8, so that constants ke and kaa at pH < 9 can be quantitatively evaluated without any effect from cleavage of the a,(3-unsaturated ketone. The validity of the kinetic equations corresponding to scheme (13) was proved both for the elimination of p-aminoketones (27) and for the addition of primary and secondary amines to a, (3-unsaturated ketones (28). 

For the addition of primary and secondary amines, the rate of which is affected by the two acid-base equilibria considered in scheme (7), it is possible to apply equation (8). On the assumption that P STme < P n> equation (8) can be further simplified as follows ... 

Fig. 3. Epoxy-amine reaction scheme. ki and k2 correspond to the non catalyzed kinetic constants for the addition of primary and secondary amines respiectively. k l and k 2 correspond to the catalyzed processes.

Scheme 52). Cherkasov et ah also studied the bis(Kabachnik-Fields) reaction and recent results of the Kabachnik-Fields reaction including the preparation of a-aminophosphine oxides have been reviewed. p-Aminophosphine oxides were obtained by the addition of primary and secondary amines to diphenyl(vinyl)phosphine oxide in water as the reaction medium (Scheme 53). ... 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

The reaction of 49 with alkylamines has been examined in the context of Cp2Mg-MR3-NH3 (M = group 13 metal) mixtures as CVD precursors. Addition of primary and secondary amines to 49 at ambient temperature in toluene affords stable amine adducts in good yield (Table 3). Most adducts can be sublimed at under 100 °C/0.05 torr in... 

Vardanyan [65,66] discovered the phenomenon of CL in the reaction of peroxyl radicals with the aminyl radical. In the process of liquid-phase oxidation, CL results from the disproportionation reactions of primary and secondary peroxyl radicals, giving rise to trip-let-excited carbonyl compounds (see Chapter 2). The addition of an inhibitor reduces the concentration of peroxyl radicals and, hence, the rate of R02 disproportionation and the intensity of CL. As the inhibitor is consumed in the oxidized hydrocarbon the initial level of CL is recovered. On the other hand, the addition of primary and secondary aromatic amines to chlorobenzene containing some amounts of alcohols, esters, ethers, or water enhances the CL by 1.5 to 7 times [66]. This effect is probably due to the reaction of peroxyl radicals with the aminyl radical, since the addition of phenol to the reaction mixture under these conditions must extinguish CL. Indeed, the fast exchange reaction... 

The facile addition of primary and secondary amines to Cjq has been used to synthesize polymer-bound Cjq [126-133]. Solutions of precursor polymers containing primary amino groups in the side chain or secondary amino groups in the main chain [132] were allowed to react with CgQ in a "buckybalT fishing process. Fullerene end capped polymers (type V) are accessible by reaction of amino-terminated polystyrene [128], poly(ethylene glycol) or poly(propylene glycol) [129] with Cgo. 

Whereas the T1 linker involves immobilization of a diazonium salt on an amine resin, the T2 linker is the reversal of this concept. An immobilized diazonium salt 73 was prepared from Merrifield resin 70 in two steps subsequent addition of primary and secondary amines generated triazenes 74. Attachment of hydroxylamine, hydrazines, sulfoximines, and phenols (to give azo coupling products) proceeds equally well (Scheme 6.1.16). 

The addition of primary or secondary amines to acrylonitriles, followed by catalytic reduction of the /S-amino cyanides, constitutes a good synthesis of y-aminopropyfamines. The yields in the first step are usually in the range of 60% to 95% and in the second about 50% to... 

The addition of aliphatic and aromatic amines to other unsaturated ketones has been discussed/ a,/3-Unsaturated aldehydes like acrolein and crotonaldehyde combine with two moles of amine to form unsaturated 1,3 diamines, RCH(NRj)CH=CHNRj/ The addition of primary or secondary amines to acrylic esters has provided a good route to the N-alkyl-/3-amino-... 

Dehydrohalogenation of amide chlorides affords a-chloroenamines, which undergo cycloaddition with IV-diphenylmethylaldimines to furnish azetidinium salts (303 equation 161). From these salts the diphe-nylmethyl group can be removed by hydrogenation, subsequent deprotonation yields 2-amino-1-aze-tines. The addition of primary or secondary amines to nitrilium salts gives rise to formation of amidinium salts and amidines respectively, e.g. (304 equation 162). In a similar reaction from copper(I) imidazolide, r-butyl bromide and nitriles amidines (305 equation 163) were prepared. ... 

Ph4SbOTf is an effective Lewis acid catalyst of nucleophilic addition of primary and secondary amines to oxiranes (Scheme 14.70) [142]. Ph4SbOH catalyzes the azidation of oxiranes with MejSiNj [143], the regioselectivity being dependent on the substituents of fhe oxiranes (Scheme 14.71). Ph4SbOMe promotes intramolec-... 

Pailer, M. and O. Sulm Pyrolysis of tobacco additives Fachl. Mitt. Osterr. Tabakregie 14 (1973) 258-266. Pailer, M., K. Vollmin, C. Karninen, and H. Kuhn tlber das Vorkommen von primaren und sekondaren Aminen im Zigarettenrauch [On the occurrence of primary and secondary amines in cigarette smoke] Fachl. Mitt. Osterr. Tabakregie 10 (1969) 165-168. 

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