V-methylation

The more complex Lamepon and Igepon type of amides, including the sarcoskie (AJ-methylglyckie) [107-97-1] and /V-methyl taurkie (A/-methylamkio-ethanesulfonate) types shown ki Table 4, are used primarily as specialty surfactants ki shampoo and toothpaste formulations. These rather complex stmctures have limited use ki very specialized appHcations. 

Allyl or benzyl groups on the nitrogen facilitate the process. The rearrangement appears to be intramolecular (13), proceeding by a cycHc mechanism as in the case of /V-2-buteny1-/V-metby1 aniline oxide giving /V-methyl-0-1-methylallyl-/V-phenyl-hydroxylamine. 

In the presence of sulfuric acid, aniline reacts with methanol to form /V-methyl- and /V,/V-dimethylaniline. This is a two-step process... 

Mixtures of /V-alkylanilines can usually be separated by fractional distillation. Mixtures of the methyl or ethyl derivatives have also reportedly been separated by converting the V/-ethyl or the /V-methyl derivative to the nonvolatile salt with -toluenesulfonic acid (12) or phthaUc anhydride (13), followed by distillation. 

The replacement of the /V-methyl group on the nitrogen atom of the piperidine ring of morphine and analogues by aHyl, isopropyl, or methyl cyclopropyl, an isopropyl isostere, results in compounds which antagonize opioid responses, especially respiratory depression. Naloxone [465-65-6] C22H2 N04 (10... 

Mocimycin has been chemically converted to aurodox by protection of the 4-hydroxy group at the pyridone moiety as the benzoylformate, followed by /V-methylation and hydrolytic removal of the protective group (1,55). Whereas aurodox esters are active growth promotors in animals, goldinamines that are A/-acylated by acids other than goldinonic acid, such as acetic, benzoic, or arylsulfonic acids, lack useful antimicrobial or growth-promoting activity (1). 

On reaction with /V-methyl- /V-phenylhydrazine, however, the hydrazone (47) can be isolated, which on further treatment with anhydrous trifluoroacetic acid gives an A/-aLkenylpyrazole (48) (eq. 9). 

Hydroxyisoquinolines. Hydroxy groups in the 5-, 6-, 7-, and 8-position show phenoHc reactions for example, the Bucherer reaction leads to the corresponding anainoisoquinolines. Other typical reactions include the Mannich condensation, azo-coupling reactions, and nitrosation. Both 0-methyl and /V-methyl derivatives are obtained from the methylation of 1-hydroxyisoquinoline, indicating that both tautomeric forms are present. Distillation of various hydroxy compounds, eg, 1- and 4-hydroxyisoquinoline, with zinc dust removes the oxygen. Treatment of 1-isoquinolinol with phosphoms tribromide yields 1-bromoisoquinoline [1532-71 -4] (178). 

V-methyl- /V-trimethyl-silyltrifluoroacetami de /-butyl dimethyl silylimid- a2ole [24589-78-4] MSTFA (CH3)3SiN(CH3)COCF3... 

Methyl violet [8004-87-3] Cl Basic Violet 1 (17), is made by the air oxidation of dimethyl aniline in the presence of salt, phenol, and a copper sulfate catalyst. Initially, some of the dimethyl aniline is oxidized to formaldehyde and /V-methyl aniline under those conditions. The formaldehyde then reacts with dimethyl aniline to produce N,N,]S7,1S7-tetramethyldiaminodiphenylmethane, which is oxidized to Michler s hydrol [119-58-4]. The hydrol condenses with... 

V-methyl aniline formed in the initial step to give the leuco base of methyl violet. Treatment with aqueous acid produces the dye. Because Michler s hydrol may also react with dimethyl aniline instead of the /V-methyl aniline to give crystal violet, commercial-grade methyl violet is usually a mixture. A cobalt complex has converted 4,T-dimethylaminodipheny1methane and dimethyl aniline in the presence of atmospheric oxygen to crystal violet in one step (50). 

Vinyl chloride forms a photo [2 + 2] cycloadduct with 1-isoquinolone [491-30-5] and its /V-methyl derivative (57). 

In the case of nicotinamide, the color yield is often low. This problem can be circumvented by either hydrolysis to nicotinic acid or by conversion of the amide to a fluorescent compound. Treatment of nicotinamide with methyl iodide yields the quaternary ammonium salt, /V-methyl nicotinamide (5). Reaction of this compound with acetophenone yields a fluorescent adduct (49). Other carbonyl compounds have also been used (50—54). 

Almost all actinomycins have the same chromophore, a planar phenoxa2inone dicarboxyUc acid called actinocin. In dactinomycin, the stmcture of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-aHo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes /V-methyl isoleucine instead of /V-methylvaline. The lactone ring is always present. 

Discrimination between exposed and unexposed areas in this process requires the selection of thia zolidine compounds that do not readily undergo alkaline hydrolysis in the absence of silver ions. In a study of model compounds, the rates of hydrolysis of model /V-methyl thia zolidine and A/-octadecyl thiazolidine compounds were compared (47). An alkaline hydrolysis half-life of 33 min was reported for the /V-methyl compound, a half-life of 5525 min (3.8 days) was reported for the corresponding V/-octadecyl compound. Other factors affecting the kinetics include the particular silver ligand chosen and its concentration (48). Polaroid Spectra film introduced silver-assisted thiazolidine cleavage to produce the yellow dye image (49), a system subsequentiy used in 600 Plus and Polacolor Pro 100 films. 

To overcome hydrolysis of vinyl sulfone dyes during appHcation under neutral dyeing of wool, Hoechst introduced dyes with the /V-methyl taurine... 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

Value for V-methyl derivative cf. Chapter 4.13. Table 5 H NMR Spectral Data for Ring Hydrogens of Azoles Containing Oxygen ... 

Phensuximide (/V-methyl-2-phenylsuccinimide) [86-34-0] M 189.2, m 71-73". Crystd from hot 95% EtOH. 

Magnesium ionophore II (ETH 5214), [A/,A/"-octamethylene-bis(A/ -heptyl-)V"-methyl methylmalonamide)] 1119110-37-1] M 538.8. Reagent ca 700mg) can be purified by flash chromatography on Silica Gel 60 (30g) and eluting with CH2Cl2-Me2CO (4 1). [Anal Chem 61 574 1989.]... 

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