The final steps of Baran's 2009 total synthesis of vinigrol, 1146, (52) are summarized in Scheme 7.36. Using this procedure, benzophenone hydrazone (15) afforded an 85% yield of diphenylmethane (16) in 4 h. Other conditions, including the use of DMSO at 40 and 100 °C, were explored, but with less success. Thus, on using excess hydrogen chloride the reaction proceeds exhaustively to give 1,1-diphenylcyclohexane, while a dimeric product is obtained with only 3 equiv. By working in DMSO the conventional product (376) is obtained. 54-56. http:\/\/id.loc.gov\/authorities\/subjects\/sh85038497> ; http:\/\/www.worldcat.org\/title\/-\/oclc\/41980117>. These steps are summarized in Scheme 7.35. He studied the initial stages with acetophenone and t-butylphenyl ketone. Nuclear substitution is only a minor pathway when methyl 2-bromomethylfuran-3-carboxylate is treated with cyanide in aqueous benzene but in ethanol the methylene group reacts with the formation of (379) and (380). 1,2-Benzodiazepine oxides (840) react with sodium methoxide with extrusion of N-2 to give quinolines 〈76CC419〉. 3-Phenylproprionic acid (150 mg, 1.0 mmol) was dissolved in CH2Cl2 (10 ml) in a 25-ml round-bottomed flask cooled in an ice bath. As summarized in Scheme 3,8,14 the reduction is thought to occur on the zinc metal surface, and involves protonation of the carbonyl function and a concomitant electron transfer process to give an organozinc intermediate (A). (a) Illustrate the following name reactions giving suitable example in each case : (i) Clemmensen reduction (ii) Hell-Volhard-Zelinsky reaction 186-188. Microwave irradiation has been recommended to effect the reduction of a range of acetophenone and benzophenone derivatives in the presence of potassium hydroxide <1999SL1573>. However, a modified Clemmensen reduction is an effective method to reduce isolated aliphatic carbonyl groups directly to methylene groups, and typical examples are shown in equations (4)–(6).11,13,16, In deuterium-labeling experiments, 4,4-diphenylcyclohexanone (2) reacted with zinc dust/deuterium chloride (prepared from trimethylchlorosilane and deuterium oxide), and gave 4,4-dideuterio-1,1-diphenylcyclohexane (3) as the major product (isotopic purity of 81% di, 10% d, 6% d3 and 3% d4; equation 7),8 while the ketone (4) was converted to (5) in 83% isotopic purity, along with the trideuterio compound (17%), under rather vigorous conditions (equation 8).17, In conjugated carbonyl systems, the usual Clemmensen conditions may give rise to reduction and isomerization of the CC double bond. Your Web browser is not enabled for JavaScript. Sargent, F.M. 163-167. The mechanisms are discussed at length in a review 〈B-73MI20800, B-73MI20801〉; earlier references will be found in the papers 〈64JOC2124, 59JA6029〉. These metrics are regularly updated to reflect usage leading up to the last few days. The functional group transform for reduction with hydrazine or of the dithiane is, Michael B. Smith, in Organic Synthesis (Fourth Edition), 2017, When a carbonyl group must be removed from a molecule, the acidic conditions of the Clemmensen reduction (Section 7.11.6) are not always compatible with other functional groups that may be present. It has been demonstrated that, if the intermediate hydrazone is isolated first, the reaction can be carried out in DMSO at room temperature <62JA1734>. The subsequent reactions showed that the tosylhydrazone 1124a gave the best results. of iodoform but benzaldehyde does not. The reagent shares an advantage with semicarbazide: these reagents do not support the formation of azines when treated with anhydrous base, and both are stable enough to be isolated and purified. Given that the base-induced decomposition of the hydrazone occurs at very high temperatures, generating the hydrocarbon occurs at temperatures more than 150 °C above the boiling point of the product. After 2 h stirring, the solvent was removed and benzoic acid (245 mg, 2 mmol), and then benzene (10 ml), was added to the residue. The dianion from the tosylhydrazone was generated and quenched with methyl iodide at − 50 °C, well below the decomposition temperature of the dianion, to give the methylated product 1125. Zinc reduction of conjugated alkenoic acids. Chem. The mechanism for the Clemmensen reduction is not yet fully understood and there are two principal proposals: the ‘Carbanionic Mechanism’ and the ‘Carbenoid Mechanism’. In the presence of base, a hydrazone anion intermediate (Section 13.4.6) can be formed that removes a proton from the acidic solvent leading to reduction. The bicyclic ketones of the camphor system were attractive targets for the Wolff-Kishner reduction early in its development, as we discussed in Chapter 2 (43) while describing Kizhner’s first papers.