Carbon reductive methylations

In striking contrast to the above observations is the finding that both reduction and reductive methylation of the tetrahydropyranyl ether of 17a-ace-toxypregnenolone (71) afford the expected products (72a, b) in 85-88 % yields by direct crystallization of the crude reaction products. Clearly, the complications in the reduction of the 16-en-20-one system are attributable primarily to reactions of the carbon-carbon double bond rather than to the a-carbanion (73), which is the final intermediate in both the reduction of the 16-dehydro compounds and the 17-acetoxy ketones. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Me have studied the Co-I-PPh catalyzed reductive carbonylation of methanol, dimethyl ketalsf dimethyl carbonate and methyl esters ( 10 JL5 >2 ) 0 goal was to achieve high acetaldehyde... 

A sample of the methanolic oxidation product was treated directly with powdered sodium borohydride. Water was added, the solvent allowed to evaporate, and the aqueous solution extracted with carbon tetrachloride. Methyl vinyl carbinol was shown to be the major product, but about 10% impurities were present. Reduction by stirring overnight with 1.0 Af sodium sulfite followed by extraction with carbon tetrachloride produced a solution which analyzed as methyl vinyl carbinol with about 1% impurities. 

Many of the commonly used solvents for precision cleaning are being eliminated due to their suspected involvement in reduction of the earth s ozone layer. Production of these chemicals, known as ozone depleting substances (ODS), is being eliminated by an international treaty known as the Montreal Protocol. This is an international agreement, first proposed in 1987 and entered into force in 1989, which limits production of chlorofluorocarbons (CFCs) and halons due to concerns that these substances were damaging the earth s ozone layer. The Montreal Protocol was modified in 1990 and again in 1992 to completely eliminate the production of chlorofluorocarbons, carbon tetrachloride, methyl chloroform (1,1,1 -trichloroethane) and halons by 1996. 

An exception to the formation of equatorial alcohols is in the reduction of certain 12-oxo-steroids with lithium/ammonia or sodium/alcohol. These reductions provide predominantly the slightly less stable, axial alcohol (Table 3). Apparently, the direction of reduction is influenced by the nature of the side chain substituent at carbon-17 and may be associated with a shielding of the oxygen in the 12-position by the carbon-21 methyl group of the steroidal side chain. Furthermore, MMX calculations suggest that the equatorial 12/i-alcohol is only marginally more stable than the a-alcohol (12/1/12a 55 45). 

FH4 is carried out by the crucial enzyme thimidylate synthetase (Fig. 4-13). It should be noted that this is a reductive methylation where the tetrahydrofolate coenzyme serves both as a one-carbon donor and reductant. The resultant FH2 must be reduced back to FH4 by folate reductase, thus offering further opportunity for DNA synthesis inhibition at this point. Thymidylate synthetase is the sole de novo path to thymidylate there are no alternate routes. The interest of this point as a target for anticancer agents is obvious. 

A key enzyme in pyrimidine biosynthesis, thymidylate synthetase, catalyzes the reductive methylation of 2 -deoxyuridylate (dUMP) to thymidylate (dTMP) with the concomitant conversion of 5,10-methylene-H4-folate to 7,8-dihydrofolate. The cofactor serves both as a 1-carbon carrier and a reductant. There is substantive evidence based on direct and indirect studies with the inhibitor 5 -fluoro-2 -deoxyuridylate, which will not be reviewed here, that the dUMP is covalently bound to the enzyme, possibly through a thiol group [59]. The intermediate ternary complex is hypothesized to have the following structure (10), where the CH2 unit is attached through the N-5 of H4-folate. The ring opening of the 5,10-methylene-H4-folate is... 

Reductive methylation (4,441-442). Further examples of reductive meth-ylation by this complex metal hydride have been reported. In aU cases methylation takes place exclusively at a benzylic carbon atom activated by a phenyl group as shown in the examples. 

Thus, the C-l/C-q model self-consistently accounts for the three NOE experiments, and the C-3/C-q model does not. The dominant regioisomer of the reductive methylation of perylene has methyl groups at C-l and the adjacent nonprotonated carbon (see Scheme II). 

DECACYCLENE CHEMISTRY. Unlike perylene, which consumes 2 mol of K per mole of perylene, decacyclene consumes between 2.2 and 3.0 mol of K per mole of decacyclene. As with perylene, we wanted to determine if reductive methylation could yield a product with a methyl group on a quaternary carbon, as in the C-3/C-q dimethyldihydrodecacyclene isomer depicted in Scheme III. 

Raney nickel, 13, 54, 76, 109, 119, 172, 337,401,502-503, 651,667 Reductive acetylation, 4 Reductive methylation, 528 Reformatsky reaction, 293, 674-675 Retro Diels-Aldet reaction, 379 Retro Michael cleavage, 284 Rhodium on alumina, 503 Rhodium on carbon, 503 Rhodium carbonyl, 504 Rhodium trichloride Silica, 504 Rhodium trichloride hydrate, 504 Ring expansion, 162-163, 194, 252-253,... 

Oxidation and reduction reactions alternately happen among products to form gases of nitrous oxide and carbon monoxide. Methyl nitrate would be oxidized through spontaneous decomposition path at 300 °C. 

This reaction was initially reported by Eschweiler in 1905, and subsequently by Clarke and co-workers in 1933. It is the preparation of tertiary methylamines from primary or secondary amines by means of the treatment of those amines with an excess amount of aqueous formaldehyde and formic acid. Therefore, it is generally known as the Eschweiler-Clarke methylation. In addition, this reaction is also referred to as the Eschweiler-Clarke condition," Eschweiler-Clarke A -methylation, Eschweiler-Clarke procedure, -) Eschweiler-Clarke reaction, s.3j,7 Eschweiler-Clarke reductive methylation, Eschweiler-Clarke reductive -methylation, Clarke-Eschweiler methylation, Clarke-Eschweiler reaction,or Clarke-Eschweiler procedure. In this reaction, the formate anion donates its proton to reduce the imine or iminium salt, so that carbon dioxide is evolved. Thus the whole process is a reductive amination of formaldehyde. This reaction is very useful for the reductive amination, without the application of hydrogen gas, catalyst (e.g., Pd/C), and high-pressure apparatus and has been widely applied to alkaloid chemistry. A special case of such reductive amination that occurs on phenylethylamine and results in the formation of tetrahydroisoquinolines is also referred to as the Clarke-Eschweiler cyclization. In a few cases, the methylation also occurs on an aromatic ring during the reductive amination. J... 

Ozone depletion is the reduction of the protective ozone layer within the stratosphere caused by the emissions of ozone-depleting substances (such as chlorofluorocarbons (CFC), carbon tetrachloride, methyl chloroform, and halon etc.). CFC-11 is generally used as the reference compound. 

The synthesis of 6-deoxy-D-glucose (see D-Quinovose, p, 99) is carried out from 2,3,4-tri-0-acetyl-6-bromo-6-deoxy-a-D-glucosyl bromide. The dihalide is converted to the methyl 2,3,4-tri-0-acetyl-6-bromo-6-deoxy-i -D-glucoside by treatment with silver carbonate and methyl alcohol, and the bromine is exchanged for a hydrogen atom by reduction with zinc and acetic acid 227). 

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