Amines aminoalkylation

Aminoalkylation of N-[pyridyl-(2)]thiazolyl-(2)-amine yields the C-5-substituted compound (208) (Scheme 131) (132. 382. 383). 

Complex cyclic compounds may be named by adding the suffix -amine or the prefix amino- (or aminoalkyl-) to the name of the parent compound. Thus three names are permissible for... 

Cationic Starches. The two general categories of commercial cationic starches are tertiary and quaternary aminoalkyl ethers. Tertiary aminoalkyl ethers are prepared by treating an alkaline starch dispersion with a tertiary amine containing a P-halogenated alkyl, 3-chloto-2-hydtoxyptopyl radical, or a 2,3-epoxypropyl group. Under these reaction conditions, starch ethers are formed that contain tertiary amine free bases. Treatment with acid easily produces the cationic form. Amines used in this reaction include 2-dimethylaminoethyl chloride, 2-diethylaminoethyl chloride, and A/-(2,3-epoxypropyl) diethylamine. Commercial preparation of low DS derivatives employ reaction times of 6—12 h at 40—45°C for complete reaction. The final product is filtered, washed, and dried. 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Thus, deprotonation of the aminium radical from a secondary or primary amine will at last form an amino radical instead of an aminoalkyl radical and a CH2CH2CN radical. This amino radical will then serve as one of the active species for the initiation of polymerization. 

Acid-catalyzed aminomethylations of 5W-dibenz[/>,/]azepine (5) in ethanolic solution with formaldehyde and a secondary amine yield the 2-(aminoalkyl) derivatives, e.g. 6.186 If acetic acid is used as the solvent, however, then 2,8-bis(aminoaIkylatiou), e.g. formation of 7, results. 

Photoredox systems involving carbonyl compounds and amines are used in many applications. Carbonyl compounds employed include benzophenone and derivatives, a-diketones [e.g. benzil, cainphoroquinone (85),2W 291 9,10-phenanthrene quinone], and xanthone and coumarin derivatives. The amines are tertiary and must have a-hydrogens [e.g. N,A7-dimethylani 1 ine, Michler s ketone (86)]. The radicals formed are an a-aminoalkyl radical and a ketyl radical. 

The reaction between the photoexcited carbonyl compound and an amine occurs with substantially greater facility than that with most other hydrogen donors. The rate constants for triplet quenching by amines show little dependence on the amine a-C-H bond strength. However, the ability of the amine to release an electron is important.- - This is in keeping with a mechanism of radical generation which involves initial electron (or charge) transfer from the amine to the photoexcited carbonyl compound. Loss of a proton from the resultant complex (exciplex) results in an a-aminoalkyl radical which initiates polymerization. The... 

Phenols, secondary and tertiary aromatic amines, pyrroles, and indoles can be aminomethylated by treatment with formaldehyde and a secondary amine. Other aldehydes have sometimes been employed. Aminoalkylation is a special case of the Mannich reaction (16-15). When phenols and other activated aromatic compounds are treated withA-hydroxymethylchloroacetamide, amidomethylation takes place " ... 

Corrosion inhibition is primarily associated with acidizing. Buffered hydrofluoric acid compositions have been shown to be less corrosive (147). Corrosion inhibitors are designed to reduce the rate of reaction of fluid with metal surfaces, generally by forming films on the surfaces. Acetylenic alcohols and amines are frequently components of corrosion inhibitor blends. Other compounds that have been used include nitrogen heterocyclics, substituted thioureas, thiophenols, and alpha-aminoalkyl thioethers (148). 

In some instances, reducing sugars are present that can be reductively aminated without prior periodate treatment. A reducing end of a monosaccharide, a disaccharide, or a polysaccharide chain may be coupled to a diamine by reductive amination to yield an aminoalkyl derivative bound by a secondary amine linkage (Figure 1.96). Also see Section 4.6, this chapter, for an extensive discussion on carbohydrate modification techniques. 

In solution, l-(ot-aminoalkyl)benzotriazoles 562 are in equilibrium with iminium cation 563 and hence with their benzotriazole-2-yl isomers 564 (Scheme 89). Protonation or complexation of the benzotriazolyl moiety (e.g., Mg, Zn, B, A1 reagents) facilitates the transformation. Intermediate iminium cations 563 can be trapped by nucleophiles providing synthetic pathways to various amines. Many such reactions are described in CHEC-II(1996) <1996CHEC-11(4)1 >, and some newer results are compiled in reviews <2005T2555>. 

When one of the substituents on the amine nitrogen atom is ready to trap a radical formed by treatment of iV-(a-aminoalkyl)benzotriazole with Sml2, cyclization may occur. Such a situation is depicted in Scheme 102. Thus, (4-penten-l-yl)amine derivative 652 is reduced to radical 653 that is then rapidly trapped by the alkenyl group and... 

The comparison of the BDE of hydrocarbons and amines proves the strong effect of the amino group on the BDE of the a-C—H bond. This is the result of the strong interaction of the a-C atom free valence of the aminoalkyl substituent with the p-electron pair of nitrogen atom. The energy of such interaction demonstrates the difference in the BDE of the a-C—H bond in hydrocarbons and amines (AD = Dc h(RCH3) — Dc H (RNH2)). 

Similarly alcohols and amines are oxidized with chain propagation via two kinds of peroxyl radicals, namely aminoalkyl peroxyl and hydroperoxyl according the following scheme ... 

In a recent patent, Hu et al. reported a similar procedure where the acceptor aldehyde contains aminoalkyl substituents in place of chloride. Subsequent to lactol oxidation and amine deprotection, these intermediates can directly undergo Paal-Knorr cyclization with the appropriate diketone to produce atorvastatin, thus avoiding the use of cyanide chemistry. 

The alkylation with alcohols and amines can lead to alkyl derivatives or a-hydroxy and a-aminoalkyl derivatives according to the nature of the heteroaromatic base and the reaction conditions. The intermediate products in both cases are, however, the a-hydroxy and a-aminoalkyl dihydro derivatives, which can be aromatized by disproportionation or oxidation, while the loss of water or ammonia leads to the alkyl derivatives (Scheme 7). 

In view of the ability of nitromethane to undergo a cyclizing bis-aminoalkylation when reacted with dialdehydes in the presence of amines 80,61) its application to other nitromethylene compounds seems an obvious extension. This reaction has already been verified when glutar-aldehyde is allowed to react with nitromethane and benzylamine in a 1 2 4 molar ratio in water, lr-methyl-l-nitro-2c,6c-bis-benzylamino-cyclohexane (110) is obtained in 56% yield 2) xhe same product is isolated in even higher yield (83%) on treatment of the nitroethane-glutaraldehyde cyclization product (6) with benzylamine However, further work is required to evaluate the preparative utility of this reaction principle for the synthesis of C-methyl branched triaminosugars. 

The a-aminoalkyl radical intermediates from electrochemical oxidation of amines show a strong tendency to lose a further electron and form an immonium ion. This process shows an anodic polarographic wave at negative electrode poten-... 

The benzotriazole moiety of iV-(a-aminoalkyl)benzotriazoles is readily replaced by hydride upon reduction with sodium borohydride, or with a carbanion by reaction with Grignard or lithium reagents. These are two most important reactions of benzotriazole derivatives from which versatile routes have been developed for the synthesis of primary, secondary, and tertiary amines. 

---