N-methyl group

The salts of some enamines crystallize as hydrates. In such cases it is possible that they are derived from either the tautomeric carbinolamine or the amino ketone forms. Amino ketone salts (93) ( = 5, 11) can serve as examples. The proton resonance spectra of 93 show that these salts exist in the open-chain forms in trifluoroacetic acid solution, rather than in the ring-closed forms (94, n = 5, 11). The spectrum of the 6-methylamino-l-phenylhexanone cation shows a multiplet at about 2.15 ppm for phenyl, a triplet for the N-methyl centered at 7.0 ppm and overlapped by signals for the methylene protons at about 8.2 ppm. The spectrum of 93 ( = 11) was similar. These assignments were confirmed by determination of the spectrum in deuterium oxide. Here the N-methyl group of 93 showed a sharp singlet at about 7.4 ppm since the splitting in —NDjMe was much reduced from that of the undeuterated compound. 

It has been found empirically that central analgesics that possess some degree of activity as antagonists of the effects of morphine tend to show a reduced propensity for causing physical addiction. Again empirically, it was noted that this could often be achieved by replacement of the N-methyl group by allyl, cyclopropylmethyl, or cyclobutylmethyl additional nuclear modifications often contributed to this activity. 

This material sinters at a temperature above about 125°C and melts at 130 to 135 C UV absorption X maximum 255 m/j, X minimum 240 m/j. It contains one ester group and no N-methyl groups. 

Structural Formula The N-methyl group in vinblastine (which see) is replaced by N-CHO. Chemical Abstracts Registry No. 2068-78-2 57-22-7 (Base)... 

If the enaminone contains one N-methyl group as in 733 a, a mixture of the pyridine 732 and the substituted benzene 735 is obtained, whereas with two N-al-... 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Oxostephasunoline (4) was isolated from the roots of Stephania japonica(4). The UV spectrum of oxostephasunoline (4) showed an absorption maximum at 286 nm, and the IR spectrum depicted bands at 3550,3500, and 1670 cm, indicating the presence of a hydroxyl group and a y-lactam. The mass spectrum (Table VI) exhibited the most abundant ion peak at m/z 258, and the H-NMR spectrum (Table II) revealed the presence of three methoxyl and one N-methyl group. The downfield shift (53.06) of the JV-methyl resonance indicated that oxostephasunoline (4) was a y-lactam, which was further supported by the IR band at 1670 cm 1, significant features of the mass spectrum (Table VI), and the 13C-NMR spectrum (Table III). On exhaustive H-NMR analysis similar to the case of stephasunoline (17), the structure of oxostephasunoline (4) including the stereochemistry was practically proved (4). 

Tarpey, W. Source of the N-Methyl Group in the Preparation of Demerol. 

The PE spectra of four 2-substituted 1,3-dimethylimidazolidines (58) have been recorded and analysed using AMI and PM3 quantum chemical calculations106. A single broad band is found for the two hn ionizations and the energies of the two mn orbitals are split by only 0.0-0.3 eV indicating little n/n interaction. This is consistent with envelope conformations of the five-membered ring of 58 and an axial-equatorial orientation of the two N-methyl groups. 

Theoretical studies on N-methylborazine and N-dimethylborazine predict an electron-density on the boron atoms adjacent to the N-methyl group which is greater than that for the parent borazine molecule. This fact would lead to the expectation that para substitution is favored in the reaction of photoexcited N-methylborazine with ammonia, due to the lower electron density at the para site. However, B NMR data and H- N coupling constant results predict a lower electron density at the ortho site. The photochemical results are in accord with this latter prediction. Beachley produced 70% para B-chloro-N-methylborazine in the substitution reaction of HgCl2 with N-methylborazine in isopentane solution. Because this reaction has been shown to occur by a bimolecular exchange mechanism, these results can be explained by steric factors in the same manner as the HN(CH3)2 and CH3OH photochemical results. 

In open-chain systems nmr indications of predominant O- (or C-) protonation are the restricted rotation around the Q-N bond and the slowness of NH-exchange. The nmr spectrum of j3-dimethylamino-acrolein in aqueous perchloric acid shows that the non-equivalence of the two N-methyl groups is retained (Kramer and Gompper, 1964). S-Benzylaminoacrolein is also mainly 0-protonated (Kramer, 1966). 

The extremely low yield of vincristine (2) from intact plants has made pursuit of its biosynthesis a very challenging problem, which at this point in time remains unsolved. Kutney et al. have used both anhydrovinblastine (8) (227) and catharanthine N-oxide (107) (233) as precursors to vincristine (2) in a cell-free preparation, but incorporation levels were extremely low. Therefore, the question of whether vinblastine (1) is an in vivo, as well as an in vitro, precursor remains to be answered. Several possibilities exist for the overall oxidation of vinblastine (1) to vincristine (2), including a direct oxidation of the A-methyl group or oxidative loss of the N-methyl group followed by N-formylation. 

The structural feature of aminopyrine is similar to antipyrine except that aminopyrine has a substituent (dimethylamino group) at the C-4 position (Fig. 4). The exceptional efficacy of the aminopyrine breath test derives from the presence of multiple N-methyl groups that are readily removed by oxidative N-demethyla-tion. Hence, further oxidation of several formaldehyde molecules produced by demethylation of aminopyrine gives large volumes of labeled COj that is readily quantified. Some of the metabohtes of aminopyrine are given in Fig. 4 [30, 85, 87-90]. 

Figure 13.6 (a) Mechanism for the hydroxy I ation of lysine N-methyl group leading to dehydroxylation and release of formaldehyde, succinate and CO2. 

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