Alcohols, acetylation dehydration

Other examples include the formation of 3-acetyl-2-methoxychromene from 4-methoxybut-3-en-2-one (80MI22400) and 2-morpholino-3-phenylchromene (93) from AC-styrylmorpholine (81TL2113, 82JCS(pl)l 193). The latter is surprising in view of the earlier report that this reaction affords an isoflavone via the alcohol (66JOC1232). It seems likely that the alcohol is dehydrated under the experimental conditions. 

A second synthesis for the preparation of 2H5V (29) starts by condensation of o-nitrobenzenediazonium chloride withT-hydroxyaceto-phenone. The azo compound was reduced with zinc and sodium hydroxide without reduction of the carbonyl group of the acetyl group. After acetylation, 2(2-acetoxy-5-acetylphenyl)2H-benzotriazole (2A5A) was reduced with sodium borohydride and the secondary alcohol was dehydrated with potassium hydrogen sulfate after hydrolysis, 2H5V was... 

Sodium borohydride reduction of either 3-acetyl- or 3-benzoyl-4-hydroxy-2H-l,2-benzothiazine 1,1-dioxides (e.g., 21, 89, 93) produced the corresponding 3-alkylidene compounds 108.4 Evidently the intermediate alcohols are dehydrated under the conditions of the reaction. The authentic ben-zylidene derivative 108 (R1 = Ph, R2 = Me), prepared4 by another route (Eq. 20), was identical to the product isolated from the borohydride reduction of compound 107. 

In each case, the synthetic route involved Friedel-Crafts acylation of the Cp-metal complex followed by hydride reduction of the acetyl carbonyl function to an alcohol, and dehydration. This approach is illustrated in equation (2) for monomer 5. 

Step 2 of Figure 29.12 Isomerization Citrate, a prochiral tertiary alcohol, is next converted into its isomer, (2, 35)-isocitrate, a chiral secondary alcohol. The isomerization occurs in two steps, both of which are catalyzed by the same aconitase enzyme. The initial step is an ElcB dehydration of a /3-hydroxy acid to give cfs-aconitate, the same sort of reaction that occurs in step 9 of glycolysis (Figure 29.7). The second step is a conjugate nucleophilic addition of water to the C=C bond (Section 19.13). The dehydration of citrate takes place specifically on the pro-R arm—the one derived from oxaloacetate—rather than on the pro-S arm derived from acetyl CoA. 

Quinoxalinecarbaldehyde (64) gave 2-(p-cyanostyryl)qumoxaline (65) [Ph CH2CN, trace of HN(CH2)5 or Na0H-H20, EtOH, 20°C, briefly 60%] other well-activated methylene synthons likewise gave products such as 2-(2,2-diacetylvinyl)- (66, Q = R = Ac) (66%), 2-(2-acetyl-2-benzoylvinyl)-(66, Q = Ac, R = Bz) (94%), or 2-(2,2-dimethoxycarbonylvinyl)quinoxaline (66, Q = R = C02Me) (58%) but some such synthons produced only the intermediate secondary alcohols, such as 2-(l-hydroxy-2-nitroethyl)quinoxa-line (67) (36%), without final dehydration under these conditions. ... 

The p-acetoxystyrene monomer, precursor of polymer III, is prepared from p-hydroxyacetophenone using the procedure of Corson et al. (14) which involves acetylation of the phenolic group followed by catalytic hydrogenation of the ketone and dehydration of the resulting benzylic alcohol as shown in Scheme 3. 

Methylfluorene has been prepared by cleavage of ethyl 9-methyl-9-fluorenylglyoxylate,4 by the decarboxylation of 9-methylfluorene-9-carboxylic acid,4 by the decarboxylation of 9-fluorenylacetic acid,6 by the cleavage of 9-methyl-9-acetyl-fluorene with alcoholic potassium hydroxide or soda-lime,6 by the reduction of 9-methyl-9-fluorenol with hydriodic acid in acetic acid,7 by the reaction of 9-fluorenyllithium 8 or -sodium 9 with methyl iodide or methyl sulfate,9 by the cyclization of diphenylmethyl carbinol over platinum-on-carbon at 300°,10 by the reaction of ethyl 9-methoxymcthyl-9-fluorcnylcarboxylate,11 by the diazotization and heating of 2-ethyl-2-aminobiphenyl,12 by the dehydration and then reduction of 9-mcthyl-9-fluorcnol,13... 

The preparation of various alkenylbenzo[6]thiophenes by dehydration of side-chain alcohols is discussed in Section VI, J. l,l-Di(2-benzo[6]thienyl)ethylene may be prepared by treating 2-benzo[6]-thienyllithium with acetyl chloride,132 and the olefins (158a-d) may... 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

Next step of this synthesis consisted in the conversion of alcohol (17) to pisiferic acid (1) and this has been described in Fig. (3). The alcohol (17) in hexane was treated with Pb(OAc)4 in presence of iodine at room temperature to obtain the epoxy triene (19) (51%) whose structure was confirmed by spectroscopy. Treatment of (19) with acetyl p-toluene-sulfonic in dichloromethane yielded an olefinic acetate (20) and this was hydrogenated to obtain (21). The compound (22) could be isolated from (21) on subjection to reduction, oxidation and esterification respectively. The conversion of (22) to (23) was accomplished in three steps (reduction with sodium borohydride, immediate dehydration in dichloromethane and catalytic hydrogenation). Demethylation of (23) with anhydrous aluminium bromide and ethanethiol at room temperature produced pisiferic acid (1). Similar treatment of (23) with aluminium chloride and ethanethiol in dichloromethane yielded methylpisiferate (3). 

Reference to some Russian contributions to the study of dehydration of alcohols and of the pinacoline rearrangement was made by Dolgov (67). This included work on dehydration of unsaturated alcohols. In connection with the current studies of Favorskil s school on vinyl-acetylene derivatives, the work of Zakharova on dehydration of acetyl-enylcarbinols to vinylacetylenes should be mentioned (430). 

Increased steric hindrance in the 9a -methyl-11 -oxo-oestrone derivative (137) does not prevent attack by methylmagnesium bromide to give the 9a, 1 la-dimethyl-11/3-alcohol (138), opening the way to novel patterns of substitution in ring C (Scheme 3).143 The acid-catalysed dehydration of the 11/3-alcohol (138) with rearrangement is noteworthy, giving the novel ll,ll-dimethyl-8-ene (139). Acetylation of the hindered tertiary alcohol (138) was effected with refluxing acetic... 

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