SUBJECTS exhaustive methylation

Problem 18.58 An optically active amine is subjected to exhaustive methylation and Hofmann elimination. The alkene obtained is ozonized and hydrolyzed to give an equimolar mixture of formaldehyde and butanal. What is the amine ... 

Structural Analysis of a Polysaccharide A polysaccharide of unknown structure was isolated, subjected to exhaustive methylation, and hydrolyzed. Analysis of the products revealed three methylated sugars in the ratio 20 1 1. The sugars were 2,3,4-tri-O-methyl-D-glucose 2,4-di-O-methyl-D-glucose and 2,3,4,6-tetra-O-methyl-D-glucose. What is the structure of the polysaccharide ... 

Antihistaminics, being tertiary amines, are analysed after reaction with an analogous reagent [566] with pentafluorobenzyl chloroformate a derivative is formed with a high ECD response and good GC properties, e.g., on OV-17. Hucker and Miller [567] subjected amitriptyline and other tertiary amines to exhaustive methylation and analysed the products from the reaction (Hoffman). Whereas the initial substances gave considerable tailing on 3% of QF-1, the derivatives provided sharp and symmetric peaks. 

In analogy to piperidines, some 3-piperideines were subjected to the Hofmann exhaustive methylation. 5-Dimethylamino-l,3-pentadiene... 

Problem 23.6 What products would be expected if I and II were subjected to exhaustive methylation and elimination ... 

DL-Dimethylcoclaurine was synthesized by the Bischler-Napieralski method starting with homoveratrylamine and p-methox3q)henylacetyl chloride. The 3,4-dihydroisoquinoline derivative first obtained was hydrogenated in the presence of palladium. The necessary comparison with material from the optically active alkaloid was achieved by subjecting the synthetic dimethylcoclaurine to exhaustive methylation, which robs Ci of the tetrahydroisoquinoline system of its asymmetric character. The meth-... 

What is formed when coniine is subjected to exhaustive methylation (Ref. Stewart, Recent Advances in Organic Chemistry, 1918, pp. 125-6.)... 

Pethidine, the active ingredient in the narcotic analgesic Demerol, was subjected to two successive exhaustive methylation-Hofmann elimination sequences, followed by ozonolysis, with the following results ... 

The structure of cryptowoline iodide (2) was determined by a similar set of reactions. Both O-methyl and 0-ethyl ethers were subjected to exhaustive meth-ylation, elimination, reduction, and ozonolysis. The key compounds obtained from the ethyl ether were 26 and 6-aminopiperonal. The amine fragment showed the methylenedioxy group to be at the 9,10 position in cryptowoline, and the fact that the same aldehyde 26 was obtained from 0-ethylcryptowoline iodide fixed the position of the free OH as in cryptaustoline to C-2. 

Methyl and benzyl halides were the earliest alkylating agents for the Friedel-Crafts alkylation of arenes. In fact Friedel and Crafts themselves reported the alkylation of benzene with methyl and benzyl chloride catalyzed by AlCb. ° An earlier review by Price covers the field until 1946, but more extensive treatment of this subject was presented by Olah in 1964 and 1973. Further developments up to 1984 have been dealt with by Roberts and Khalaf in their book. No repetition of the detailed and exhaustive discussion of the topic is, therefore, necessary. Instead, we point out briefly some of the significant work carried out to highlight the most important aspects of the reaction. 

A solution of 1,3,5-trinitrobenzene in N-methylformamide was subjected to electrolysis at —0.70 V (Path A, Scheme 18). The controlled-potential electrolysis was stopped after a passage of one electron per each molecule. The formed anion-radical species of 1,3,5-trinitrobenzene were allowed to react with N-methyl-formamide. Under the used experimental conditions the o -complexes were the only species present in the reaction mixtures. Exhaustive oxidative controlled-potential electrolysis at 1.30 V gave A-methyl-iV-(2,4,6-trinitrophenyl)formamide (Sn product) in good yield (80%). Without a preliminary reductive electrolysis (Path B, Scheme 18), the same type of o -complexes proved to be formed, and after exhaustive oxidative controlled-potential electrolysis at 1.30 V, A-methyl-iV-(2,4,6-trinitrophenyl)formamide (Sn product) was obtained in 20% yield. 

Alternatively, furan may also be brominated and then subjected to an exhaustive methanolysis. A zinc chloride-catalysed double enol ether condensation with 1-propenyl methyl ether (Miiller-Cunradi-Pieroh reaction) gives finally the crystaUine (aU )-Cio-dialdehyde in an overall yield of >50 %. 

The next steps in the assay are acidification and extraction of the urine, and preparation of the methyl esters. The methylated material is then subjected to pH 10 hydrolysis. After this reaction is ccm-plete the pH 10 aqueous phase can be extracted exhaustively with organic solvent. By this means neutral and basic catpounds are removed while PGF-M remains in the aqueous phase as the C-1 acid, C-16 methyl ester derivative. The sample is then acidified to pH 2, left for 1 hour at roan temperature and returned to pH 8. The 6-lactone derivative of PGF-M is extracted into dichloroethane leaving almost all the urinary acids in the aqueous phase. Subsequently the metabolite is converted to the methyl ester t-BDMS ether derivative, purified further by TIG and analyzed by GC-MS. 

Chen (393) has reported that the di-ethiodide of the main alkaloid present in Chinese C. pareira when subjected to exhaustive Hofmann degradation affords the same nitrogen-free derivative as does (+)-tubocurarine when treated similarly. It is stated that the fully iV,0-methylated derivative of the alkaloid is identical with a mixture of equal amounts of the AT,0-methylated (+)- and (—)-curine derivatives in other words, the original alkaloid should simply be racemic curine, i.e. hayatine as at present commonly understood. The mystery continues ... 

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