Methyl groups, 24 Aliphatic amines

The relatively low basicity of aniline relative to aliphatic amines results from the interaction of the lone pair of electrons at nitrogen with the aromatic ring this can only occur when the system is completely planar as in 8.8, because the lone pair of electrons at nitrogen needs to be in a p orbital that is parallel to the p orbitals of the x-system. However, in 8.9, the NMej group is forced to twist out of the plane of the ring to avoid interaction with the ort/zo-methyl groups this amine is more basic. 

The reaction of ACPC with linear aliphatic amines has been investigated in a number of Ueda s papers [17,35,36]. Thus, ACPC was used for a interfacia] polycondensation with hexamethylene diamine at room temperature [17] yielding poly(amide)s. The polymeric material formed carried one azo group per repeating unit and exhibited a high thermal reactivity. By addition of styrene and methyl methacrylate to the MAI and heating, the respective block copolymers were formed. 

Since the discovery of the exceptional basicity of l,8-bis(dimethylamino)-naphthalene (Alder et al., 1968) and its unusual kinetic behaviour (Hibbert, 1973, 1974, 1975) there has been considerable interest in the acid-base properties of hindered diaminonaphthalenes. 1,8-Bis(dimethylamino)naph-thalene (pK — 12.1 at 25°C and ionic strength 0.1 mol dm-3) (Alder et al., 1968 Hibbert, 1974 Chiang et al., 1980) is more basic than most aliphatic amines and the pAT-values of the partially methylated diamines [52] illustrate the dramatic effect of introducing the fourth methyl group (Alder et al., 1968). Reaction of protonated l,8-bis(dimethylamino)naphthalene with... 

As in carboxylic esters it is possible to substitute alkoxy groups of Fischer-type carbene complexes by non-carbon nucleophiles, such as other alcohols [73,214,218], enols [219], aliphatic amines [43,64,66,220-224], aniline [79], imines [225], or pyrroles [226]. Strong nucleophiles can also lead to a dealkylation of methoxy-substituted carbene complexes (5 2 at the methyl group, [227]), in the same way as methyl esters can be cleaved by nucleophiles such as iodide. Carbon... 

The enzyme found in the liver will deaminate secondary and tertiary aliphatic amines as well as primary amines, although the latter are the preferred substrates and are deaminated faster. Secondary and tertiary amines are preferentially dealky la ted to primary amines. For aromatic amines, such as benzylamine, electron-withdrawing substituents on the ring will increase the reaction rate. The product of the reaction is an aldehyde (Fig. 4.30). Amines such as amphetamine are not substrates, seemingly due to the presence of a methyl group on the a-carbon atom (Fig. 4.27). Monoamine oxidase is important in the metabolic activation and subsequent toxicity of allylamine (Fig. 4.31), which is highly toxic to the heart. The presence of the amine oxidase in heart tissue allows metabolism to the toxic metabolite, allyl aldehyde (Fig. 4.31). Another example is the metabolism of MPTP to a toxic metabolite by monoamine oxidase in the central nervous system, which is discussed in more detail in chapter 7. 

Phthalimide protection is stable towards acids and bases, but can be cleaved with strong nucleophiles, such as hydrazines or sulfides, or by reduction with sodium boro-hydride [230]. More sensitive towards nucleophilic attack than unsubstituted phthalimide is tetrachlorophthalimide [33]. This group has been successfully used as N(a) protection of amino acids in the solid-phase synthesis of peptides (deprotection N2H4/DMF (15 85), 40 °C, 1 h coupling DIC/HOAt/amino acid (1 1 1), 3 equiv. of each, DMF, 25 °C, 4 h [294]). Typical conditions for the removal of phthaloyl protection on cross-linked polystyrene include treatment of the resin with hydrazine hydrate [295,296], with methyl hydrazine [297], or with primary aliphatic amines [298] in DMF, EtOH, or solvent mixtures for several hours at room temperature or above [296,299,300]. Illustrative examples are sketched in Figure 10.15. It has been claimed that the hydrazinolysis of polystyrene-bound phthalimides proceeds more readily in DCM or DCE than in DMF [301]. 

Support-bound quinazolin-2,4-diones can be N-alkylated, either with alkyl halides under basic conditions or with aliphatic alcohols by means of the Mitsunobu reaction (Entries 12-14, Table 15.29). The methyl group of a 2-methylquinazolin-4-one is sufficiently acidic to undergo aldol condensations with aldehydes [343]. Aminations of chloroquinazolines are discussed in Section 10.1.2. 

For [CoII(2,3,17,18-TDC)]+, the association constant Kt was found to increase in the range 102-104M 1 as the pKa of 4-substituted pyridines increased.254,265 The Kx is linearly correlated to the pATa in the [Co11 (ODC)]+-N-donor system (equation 3V).269 Though the for L = Im fits the equations, aliphatic amines show lower Kx values than expected from their pK values, suggesting some metal-axial ligand n interaction. The steric hindrance of the 2-methyl group lowers K by a factor of 103. 

Sulfite ion forms a complex of structure III (Refs 44 80), which is a source of yield loss during the purification of TNT if the pH exceeds 8. Cyanide ion also forms a compd of structure III (Ref 44) the kinetics of this reaction has been studied (Ref 76), TNT, as the anion I, can react with itself to form adducts of type II it can similarly react with 13 >5-trinitrobenzene (Ref 57). Primary and secondary aliphatic amines form a-complexes (Refs 46 58), but tertiary amines (in an aprotic solvent), and aromatic amines, form ir-complexes instead. Upon soln in liq ammonia, a complex of type III is initially formed, with no evidence of I (Ref 105). With time, a second NH2 group becomes attached to the ring carbon with the methyl group this compd has cis- and transisomers. Removal of the ammonia gave a red... 

Although the anodic generation of a cation in a-position to nigrogen in aliphatic amines is not difficult, this type of reaction is not always useful to the synthesis of alkaloidal compounds, since the cation is not stable and a simple dealkylation is the usual follow-up reaction. N-monomethyl and N,N-dimethylanilines are, however, useful starting materials for the synthesis of the skeleton of tetrahydroquinoline. The anodic methoxylation of N,N-dimethylaniline 20 takes place at the methyl group, and an iminium ion intermediate 22 is easily generated by treatment of the methoxylat-ed product 21 with Lewis add. This intermediate can be trapped in situ with a variety of nucleophiles such as electron-rich olefins yielding tetrahydroquinolines 23 16). 

In general, catalysis by 84a and 85c resulted in good to excellent enantioselec-tivities in the reduction of lcetimines derived from methyl aryl ketones and aromatic amines (80, R1, R3 = aryl, R2 = Me), where the electronic effects of substituents in both aromatic groups did not show any significant influence [79, 80]. On the other hand, imines obtained from aliphatic amines (80, R3 = alkyl) gave virtually racemic products with 85a [80b]. In the reduction of non-aromatic imines, such as 80c, only catalyst 84a maintained high enantioselectivity (Table... 

Aliphatic and cyclic amine NH protons absorb from S 3.0 to 0.5 aromatic amines absorb from S 5.0 to 3.0 in CDC13 (see Appendix E) because amines are subject to hydrogen bonding, the shift depends on concentration, solvent, and temperature. Amide, pyrrole, and indole NH groups absorb from 8 8.5 to 5.0 the effect on the absorption position of concentration, solvent, and temperature is generally smaller than in the case of amines. The nonequivalence of the protons on the nitrogen atom of a primary amide and of the methyl groups of N, /V-dimethylamides is caused by... 

Kelly et al. (51,52) designed a two-binding-site host that accelerates an Sn2 reaction between a primary aliphatic amine and an alkyl bromide. Their host (Figure 14) acts as a template for the two reactants, amino-methyl- and bromomethyl-naphthyridine each aminopyridone group of the host forms three hydrogen bonds to each reactant. This binding is rather strong (K s > 10 M ). The authors observed a sixfold acceleration of the Sn2 reaction but could not prove or disprove that turnover was catalytic. 

Deprotonation of N-methylamines. Aliphatic N-methylamines are metallated exclusively on the methyl group by icc-butyllithium and potassium t-butoxide when excess amine is used as solvent. Deprotonation cannot be effected with -BuLi/KOC(CH,), or t-BuLi/KOC(CH3)j. The resulting carbanion reacts readily with alkyl halides, but gives... 

It furnishes a good synthesis for amines of the type ArCH(R )NHR where the two R groups may be widely varied to include those from many Grignard reagents and primary aliphatic amines, e.g., N-methyl-1,2-diphenyl-ethylamine (95%) ° and 1-ethylamino-l-phenylbutane (90%)/ The reaction of aliphatic aldimines and Grignard reagents has been found to proceed less readily. ... 

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