Elimination, direction methyl

Direct Blue 218 had reported sales of 623 t valued at 4.4 million ia 1987. It is produced from Direct Blue 15 (76) by metallizing and elimination of methyl groups from the methoxide to form the copper complex. Direct Blue 15 (76) is prepared by coupling o-dianisidine [119-90-4] to two moles of H-acid (4-amiQO-5-hydroxy-2,7-naphthalenedisulfonic acid) under alkaline pH conditions. Other important direct blues iaclude Direct Blue 80 (74), (9-dianisidine coupled to two moles of R-acid (3-hydroxy-2,7-naphthalenedisulfonic acid [148-75-4]) followed by metallizing to form a bis copper complex, and Direct Blue 22 (77), an asymmetrical disazo dye, prepared by coupling o-dianisidine to Chicago acid [82-47-3] and 2-naphthol. Direct Blue 75 (78) is an example of a trisazo dye represented as metanilic acid — 1,6-Q.eve s acid — 1,6-Q.eve s acid — (alb) Ai-phenyl J-acid. 

With proof-of-concept on the direct methylation in hand, the optimization of the methylation with respect to regioselectivity, yield and isolation conditions was initiated to eliminate the use of 1,4-dioxane and LiH (Table 6.3). Under similar reagent/base conditions (Me2S04, LiOt-Bu), better selectivity was observed in nonpolar solvents (entries 2 and 3) than in polar (entry 1) and aprotic solvents (entries 4 and 5). Mel was a better methylation reagent than dimethyl sulfate under otherwise the same reaction conditions (entries 5 and 7). 

For the reaction of sym-tetrabromoethane with iodide ion in methanol a secondary isotope effect (Ah/ d) of 1.28 at 80°C was observed . On theoretical grounds, an inverse isotope effect ( h/ d — 0.7) is predicted for a rate-determining displacement reaction and a normal isotope effect for an elimination reaction . Methyl and bromine substituents have similar spatial requirements, so it is thus not surprising that the direct elimination mechanism, which is observed for 2,3-dibromobutane, is followed by jyw-tetrabromoethane. 

By microscopic reversibility, the forward and reverse reactions of a thermal process must follow the same path. In this case, if the labeled CO ends up cis to Me in the elimination direction, the CO to which a methyl group migrates in the insertion direction must also be cis to methyl. We are fortunate in seeing the kinetic products of these reactions. If a subsequent scrambhng of the COs had been fast, we could have deduced nothing. 

The treatment of o-phenyl-substituted benzotrifluoride 22 led to the formation of mixture of three products as shown in Scheme 22 [39]. This result can be explained as the common benzyl cation intermediate 23 underwent direct methylation, intramolecular Friedel-Crafts-type reaction, or p-H elimination to be converted into each product. 

Both spiro and methyl migration rearrangements are proposed to occur when the pentamethyloctalin 153 is subjected to reaction with sulfuric acid in acetic acid (239). Isomers 154 and 155 are formed by decalyl spiro rearrangement followed by angular methyl shift and elimination. The minor product 156 however, arises by direct methyl migration. 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

Except for the biochemical example just cited the stractures of all of the alcohols m Section 5 9 (including those m Problem 5 13) were such that each one could give only a single alkene by p elimination What about ehmmahon m alcohols such as 2 methyl 2 butanol m which dehydration can occur in two different directions to give alkenes that are conshtutional iso mers Here a double bond can be generated between C 1 and C 2 or between C 2 and C 3 Both processes occur but not nearly to the same extent Under the usual reachon con dihons 2 methyl 2 butene is the major product and 2 methyl 1 butene the minor one... 

Interest in the synthesis of 19-norsteroids as orally active progestins prompted efforts to remove the C19 angular methyl substituent of readily available steroid precursors. Industrial applications include the direct conversion of androsta-l,4-diene-3,17-dione [897-06-3] (92) to estrone [53-16-7] (26) by thermolysis in mineral oil at about 500°C (136), and reductive elimination of the angular methyl group of the 17-ketal of the dione [2398-63-2] (93) with lithium biphenyl radical anion to form the 17-ketal of estrone [900-83-4] (94) (137). 

The direction of elimination is also affected by steric effects, and if both the base and die reactant are highly branched, steric factors may lead to preferential removal of the less hindered hydrogen. Thus, when 4-methyl-2-pentyl iodide reacts with very hindered bases such as potassium tricyclohexylmethoxide, there is preferential formation of the... 

There are conflicting reports regarding the direction of elimination from isomeric 12-methyl-12-hydroxy compounds. Levine found little dependence on hydroxyl orientation, whereas Coxon found the tra -diaxial requirement overwhelming. 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

The reaction of OH radicals with dimethyl sulfoxide in aqueous solution was studied already in 1964 by Norman and coworkers37 38. They used the system T1m-H202 to produce OH radicals and using ESR/rapid mixing techniques they were able to demonstrate elimination of a methyl radical during the OH induced oxidation. Further studies showed the formation of sulfmic radicals in this reaction either directly or by spin trapping experiments39-44. 

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