Group methylaniline

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

In the NMR spectrum of the N-methylaniline enamine of cyclohexanone (135), the vinylic proton appears at a much lower field, i.e., at 324 Hz (75). Here the electron pair on nitrogen tends to conjugate with the phenyl group thus exhibiting a very small degree of overlap with the enamine double bond. 

The Paloc group was developed as an amino acid protective group that is introduced with the p-nitrophenyl carbonate (H2O, dioxane, 68-89% yield). It is exceptionally stable to TFA and to rhodium-catalyzed allyl isomerization, but it is conveniently cleaved with Pd(Ph3P)4 (methylaniline, THF, 20°, 10 h, 74-89% yield). ... 

Unlike unsubstituted and 3,4-disubstituted 1H-azepine-1 -carboxylates, which dimerize on heating, methyl 2-methyl-l//-azepine-l-carboxylate remains unchanged at 130 C, but on heating to 200°C ring contracts to Ar-(methoxycarbonyl)-2-methylaniline (64% mp 60°C).115 Similarly, the 4,5-dimethyl- and 3,6-dimethyl-l//-azepine-1-carboxylates, in which [6 + 4] dimerization is sterically retarded by the methyl groups, give only the A-arylurethanes. Methyl 2,7-dimethyl-1//-azepine-1-carboxylate is particularly stable and remains unchanged even after 24 hours at 200 C. 

Penton and Zollinger (1979, 1981 b) reported that this could indeed be the case. The coupling reactions of 3-methylaniline and A,7V-dimethylaniline with 4-methoxy-benzenediazonium tetrafluoroborate in dry acetonitrile showed a number of unusual characteristics, in particular an increase in the kinetic deuterium isotope effect with temperature. C-coupling occurs predominantly (>86% for 3-methylaniline), but on addition of tert-butylammonium chloride the rate became much faster, and triazenes were predominantly formed (with loss of a methyl group in the case of A V-di-methylaniline). Therefore, the initial attack of the diazonium ion is probably at the amine N-atom, and aminoazo formation occurs via rearrangement. 

Note As in related series, the addition of pyridine or (better) A,A-dimethylani-line (free of A-methylaniline, a common contaminant in some grades of this reagent) to phosphoryl chloride, appears to improve the yield of chloroqui-noxaline, especially if electron-withdrawing passenger groups are present. 

A solution of the sodium salt of yV-methylaniline in HMPA can be used to cleave the methyl group from aryl methyl ethers ArOMe + PhNMe —> ArO + PhNMca- This reagent also cleaves benzylic groups. In a similar reaction, methyl groups of aryl methyl ethers can be cleaved with lithium diphenylphosphide (PH2PLi). " This reaction is specific for methyl ethers and can be carried out in the presence of ethyl ethers with high selectivity. 

The complexity of the metabolism of alachlor, acetochlor, butachlor, and propachlor has led to the development of degradation methods capable of hydrolyzing the crop and animal product residues to readily quantitated degradation products. Alachlor and acetochlor metabolites can be hydrolyzed to two major classes of hydrolysis products, one which contains aniline with unsubstituted alkyl groups at the 2- and 6-positions, and the other which contains aniline with hydroxylation in the ring-attached ethyl group. For alachlor and acetochlor, the nonhydroxylated metabolites are hydrolyzed in base to 2,6-diethylaniline (DBA) and 2-ethyl-6-methylaniline (EMA), respectively, and hy-droxylated metabolites are hydrolyzed in base to 2-ethyl-6-(l-hydroxyethyl)aniline (HEEA) and 2-(l-hydroxyethyl)-6-methylaniline (HEMA), respectively. Butachlor is metabolized primarily to nonhydroxylated metabolites, which are hydrolyzed to DEA. Propachlor metabolites are hydrolyzed mainly to A-isopropylaniline (NIPA). The base hydrolysis products for each parent herbicide are shown in Eigure 1. Limited interference studies have been conducted with other herbicides such as metolachlor to confirm that its residues are not hydrolyzed to the EMA under the conditions used to determine acetochlor residues. Nonhydroxylated metabolites of alachlor and butachlor are both hydrolyzed to the same aniline, DEA, but these herbicides are not used on the same crops. 

Lack of reactivity towards SN2 reactions at nitrogen would in itself account for low mutagenic activity. However, the tert-butyl groups on 31c f and 32a,b are well removed from the reactive nitrogen and, as well, SN2 reactions of mutagens 31c e with A-methylaniline in methanol at 303 °C occur with relatively similar rate constants to that of unsubstituted 28a, and of mono tert-butylated systems 28i and 31 a,b (Table 18). 

Intramolecular [4 + 2]cycloaddition of an enaminelenal(enone). Generation in situ of an aldehyde enamine of a substrate also containing an enal or enone group can result in a facile intramolecular [4 + 2]cycloaddition resulting in bicyclic dihydropyrans. Although several sec-amines can be used, N-methylaniline is particularly suitable because of the stability of the adducts. 

N-Alkylation of primary aromatic amines increases their nucleophilic character, making them couple much more readily, the introduction of the azo group occurring in the 4-position. Thus, in contrast to aniline, N-methylaniline couples readily and N,N-dimethyl-aniline very readily with simple diazonium salts. Diphenylamine also couples in the 4-position, but less readily than N-methylaniline. 

Amino groups may act not only as proton acceptor, but also as proton donor. Acidic N—H protons interact with basic solvents. In these cases an ortho-nitro group in an aniline system competes with the solvent by an internal hydrogen bond66, as depicted in 12. The stretching frequencies (by IR spectra in carbon tetrachloride) of vnh of complexes between A-methylaniline or diphenylamine (and some nitro-anilines66) and solvents depend on the proton accepting ability of the solvent (which is a moderate base)67. The frequency shifts are linearly related to the solvent s donor number (DN)3. 

Let us now compare the pA, values (in AN) of the cation-radicals derived from aniline, N-methylaniline, and A-phenylaniline 5.5, 4.2, and 1.8, respectively (Jonsson et al. 1996). An N-methyl substitnent produces only a marginal effect on the pA, valne of the aniline cation-radical. At the same time, the effect of the A-phenyl snbstitnent in aniline is considerable. The phenyl group (electron-withdrawing) effect on the aniline cation-radical acidylation is self-obvious. 

Amine substrates whose rings are strongly deactivated with nitro groups are Al-nitrated with relative ease 2,4-dinitro-A-methylaniline undergoes Al-nitration on treatment with 70 % nitric acid at room temperature. It is known that the Al-nitration of anilines is favoured by... 

More recently, Polish chemists have reported a synthesis of both aryl and aliphatic secondary nitramines by treating amine substrates with ethyl magnesium bromide followed by reaction with n-butyl nitrate (Equation 5.8). This method, which uses nonpolar solvents like hexane or benzene, has been used to synthesize aliphatic secondary nitramines, and At-nitro-A-methylanilines which otherwise undergo facile Bamberger rearrangement in the presence of acid. The direct nitration of At-unsubstituted arylamines usually requires the presence of an electron-withdrawing group. Reactions are retarded and yields are low for sterically hindered amines. 

As we move to A-methylaniline, we see only a modest change in pK ,. This is undoubtedly due to the electron-donating effect of the methyl group, and this would be expected to stabilized the conjugate acid, increasing observed basicity. There is a modest increase in basicity, but it is apparent that the resonance effect, as in aniline, is also paramount here, and this compound is also a weak base. However, diphenylamine (A-phenylaniline) is an extremely weak base this can be ascribed to the resonance effect allowing electron delocalization into two rings. 

Nucleophilic attack by iV-methylaniline is favoured by electron-withdrawing groups on the amide and acyloxyl side chains. A series of / ara-substituted Af-acetoxy-Af-butoxy-benzamides (138) (Table 6) gave a weak but positive Hammett correlation with a constants (p = 0.13, r = 0.86) °. The analogous reactions of pyridine with para-substituted phenacyl halides in methanol afforded a similar Hammett correlation a, p = 0.25) . The bimolecular rate constants for the limited series of Ai-benzoyloxy-A-benzyloxybenzamides (139) in Table 6 correlated strongly with Hammett a constants (p = 1.7, r = 0.97) °. Stabilization of developing carboxylate character supported the computed charge redistribution in the transition state ... 

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