2- Naphthyl methyl ketone, preparation

This method may be used for the preparation of larger quantities, a batch twenty times this size giving a yield of 87 per cent. It may be used also for the preparation of other aromatic acids where suitable ketones are available. Methyl a-naphthyl ketone prepared by Caille s method is not suitable for the preparation of a-naphthoic acid as it contains at least 30 per cent of the methyl d-naphthyl ketone. 

A wide variety of substituents are tolerated. The group R can be alkyl, halogen, alkoxy, -amido, azi-domethyl, ester, aryl, aryloxy and aryloyl, and at least one ortho substituent is permissible with no loss in yield. TTie aromatic ring can also be 2-naphthyl, 9,10-dihydro-2-phenanthryl, 3-pyridyl, thiophen-2-yl or pyrrol-3-yl. The group R can be hydrogen, yl, acyl or acetic acid. Beyond Ae antiinflammatory targets, successful reaction substrates include the methyl ketones of a binaphthyl crown ether, a morphinane and a polyaromatic hydrocarbon. The preparation of ibuprofen methyl ester (38) is shown in equation (37) as a typical example. ... 

Formation.—Phenyl-, 2-naphthyl-, 2-thienyl-, and 2-furanyl-thiets are prepared from aryl methyl ketones, dimethylamine, and methanesulphonyl chloride. X-K y crystal structures establish that the compounds arising from the cycloaddition of alkynes to thioxanthones are thiets, and not spiro-dihydropyrans, as originally proposed. Additional work shows that alkynyl sulphides also give thiets with thioxanthone, and that the adduct (104) is in rapid equilibrium with the open form (105) in solution, although they can be isolated separately. Thiet (106) was isolated after thermolysis of a Dewar thiophen—azide adduct. ... 

Prepare a solution containing about 100 g, of potassium hypochlorite from commercial calcium hypochlorite ( H.T.H. ) as detailed under -Dimethylacrylic Acid, Section 111,142, Note 1, and place it in a 1500 ml. three-necked flask provided with a thermometer, a mechanical stirrer and a reflux condenser. Warm the solution to 55° and add through the condenser 85 g, of p-acetonaphthalene (methyl p-naphthyl ketone) (1). Stir the mixture vigorously and, after the exothermic reaction commences, maintain the temperature at 60-70° by frequent cooling in an ice bath until the temperature no longer tends to rise (ca. 30 minutes). Stir the mixture for a further 30 minutes, and destroy the excess of hypochlorite completely by adding a solution of 25 g. of sodium bisulphite in 100 ml. of water make sure that no hypochlorite remains by testing the solution with acidified potassium iodide solution. Cool the solution, transfer the reaction mixture to a 2-litre beaker and cautiously acidify with 100 ml. of concentrated hydrochloric acid. Filter the crude acid at the pump. 

The commercial product, m.p. 53-55°, may be used. Alternatively the methyl -naphthyl ketone may be prepared from naphthalene as described in Section IV,136. The Friedel - Crafts reaction in nitrobenzene solution yields about 90 per cent, of the p-ketone and 10 per cent, of the a-ketone in carbon disulphide solution at — 15°, the proportions ore 65 per cent, of the a- and 35 per cent, of the p-isomer. With chlorobenzene ns the reaction medium, a high proportion of the a-ketone is also formed. Separation of the liquid a-isomer from the solid p-isomer in Such mixtures (which remain liquid at the ordinary temp>erature) is readily effected through the picrates the picrate of the liquid a-aceto compound is less soluble and the higher melting. 

Addition of triethylamine to the oxazaborolidine reaction system can significantly increase the enantioselectivity, especially in dialkyl ketone reductions.79 In 1987, Corey et al.80 reported that the diphenyl derivatives of 79a afford excellent enantioselectivity (>95%) in the asymmetric catalytic reduction of various ketones. This oxazaborolidine-type catalyst was named the CBS system based on the authors names (Corey, Bakshi, and Shibata). Soon after, Corey s group81 reported that another fi-methyl oxazaborolidine 79b (Fig. 6-6) was easier to prepare and to handle. The enantioselectivity of the 79b-catalyzed reaction is comparable with that of the reaction mediated by 79a (Scheme 6-36).81 The -naphthyl derivative 82 also affords high enantioselectivity.78 As a general procedure, oxazaborolidine catalysts may be used in 5-10 mol%... 

A remarkably high diastereoselective excess was obtained in the addition of the anion of (S)-(-)-methyl 1-naphthyl sulfoxide to n-alkyl phenyl ketones. The sulfoxide was prepared in optically pure form by oxidation of the complex of methyl 1-naphthyl sulfide and 13-cyclodextrin with peracetic acid followed by crystallization. Desulfurization of the adducts provided enantiomerically pure tertiary alcohols (393]. 

Other hemiacetals which have been prepared include the methyl 8<9a>, ethyl 9b), and isopropyl hemiacetals 81) of tetramethylcyclopropanone, the phenyl, a- and (3-naphthyl hemiacetals of cyclopropanone 82>, and the benzyl hemiacetal of 2,3-di-f-butylcyclopropanone. 13> In the last case, the benzylic methylene protons display an AB pattern in the PMR spectrum indicating that the two Ybutyl groups are trans to one another. Although derivatization of this di-f-butyl ketone was possible, carbonyl addition may be hindered by steric factors as suggested by the lack of reaction of 2,2-diY-butylcyclopropanone with methanol. 55a>... 

Lactams with larger rings, e.g. seven-,143,144 eight-,145 nine-,148 eleven-, and thirteen-membered lactams,147 yield acyclic amino-ketones as the sole products, as is to be expected. With the seven- and thirteen-membered rings, the existence of both forms might be expected, and the salts of 1-methyl-2-a-naphthyl-l-aza-2-cycloheptene and l-methyl-2-a-naphthyl-l-aza-2-cyclotridecene have been prepared in both the cyclic enamine and the acyclic amino-ketone forms.148 The structure of the products also depends upon the Grignard reagent used. 

A one-pot approach giving a series of l-(2-naphthyl)methylene- or l-(3,4-dimethoxybenzyl)pyrrolidines 432 has been developed, as illustrated by the reductive cyclization of the four-carbon precursor 433, which was prepared by conjugate addition of the a-(alkylideneamino)nitrile 434 to methyl vinyl ketone (Scheme 55) <2005S945>. 

To conclude this chapter we will be occupied with an old, long-known reaction The Elbs reaction130, suited for a simple preparation of polycyclic aromatic hydrocarbons containing the anthracene moiety, by heating diarylketones with an ortho-placed methyl group at 400-450°. Our mechanistic proposal, applied to the cycliza-tion of the 2-naphthyl-(2 -methylnaphthyl-l )ketone (365) which yields the dibenzo-(a,h)anthracene (369) may involve an electrocyclic step followed by an elimination ... 

Acetylation of naphthalene gives methyl naphthyl ketone, and sulfonation followed by alkaline fusion gives naphthol (Scheme 4.60). The methyl and ethyl ethers of naphthol are prepared from naphthol by reaction with the corresponding alkyl sulfate under basic conditions. These ethers are usually known by the shorter names of yara and nerolin, respectively. Yara, nerolin and methyl naphthyl ketone possess floral odours and are moderately important perfume ingredients. 

Ci2H10O, Mr 170.21, 6pi.7kPa 171-173 °C, df 1.171, ng° 1.6752, has been identified in some essential oils. It smells like orange blossom and is a colorless crystalline solid (mp 56 °C). It is usually prepared by Friedel-Crafts acetylation of naphthalene (with acetyl chloride, acetic anhydride, etc.) in the presence of aluminum chloride. In polar solvents (e.g., nitrobenzene), the percentage of the simultaneously formed a isomer is lower. Methyl P-naphthyl ketone is used in eau de cologne, soap perfumes, and detergents. It is a good fixative. 

Methyl 8-benzhydryl-l-naphthoate added to excess methyllithium prepared from methyl iodide and lithium in ether, and the product isolated after 5 hrs. refluxing methyl 8-benzhydryl-l-naphthyl ketone. Y 92%.—A second mole of methyllithium enolizes the ketone with formation of methane, a general type of reaction of hindered alkyl ketones. Phenyllithium yields a tert. carbinol since enolization of the intermediate is not possible. R. L. Letsinger and P. T. Lans-bury, Am. Soc. 81, 935 (1959). 

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