THE PREPARATION OF SOME ARYL METHYL KETONES*

By P. M. POJER,? E. RITCHIE,~ and W. C. TAYLOR?

For another project, sizable quantities of p-diacetylbenzene were required. Of the methods for its preparation described in the literature, the two best appeared to be the chromia aoid oxidation of p-ethyla~etophenone,~ and the acid hydrolysis of the acylation product of acetoacetic ester by terephthaloyl ~hloride,~ but even these were rather unattractive. However, i t seemed that the little-used method of Wolfram and Brown,3 which consists of the reduction of a diazoketone by hydriodic acid a t room temperature, might be successful. In the event, the method fulfilled all expectations and the purpose of this note is to draw attention to its utility.

Terephthaloyl chloride, obtained almost quantitatively by the action of thionyl chloride on the acid, was converted in very high yield into the bis-diazo- ketone by excess diazomethane as described by Ross.4 Reduction of the diazoketone by concentrated hydriodic acid then yielded pure p-diacetylbenzene in nearly 70% overall yield. In a slight variation of the procedure, the hyclriodic aoid was replaced by potassium iodide and phosphoric acid but the yield was then about GO0/,.

In a similar manner, isophthalic acid was converted into rn-diacetylbenzene in high yield, but all attempts to prepare o-diacetylbenzene were unsuccessful. The product obtained by treating phthaloyl chloride with excess diazomethane even at about -40" was brown and anlorphous in contrast to the highly crystalline bis-diazoketones from the isomeric acid chlorides. Any manipulation of the brown material rapidly caused further decomposition and treatment with hydriodic acid gave no recognizable product. The failure of the procedure in this instance does not appear to be due to a purely steric or electronic effect, since o-nitrobenzoyl chloride afforded o-nitroacetophenone in good yield.

The possibility of using o-acetylbenzoic acid was examined. I t has been shown5 that acids of this type exhibit ring-chain tautomerism (I + 11) in which the position of equilibrium varies with the state and with structural features. The product obtained by the action of thionyl chloride a t room temperature on o-acetylbenzoic

* Manuscript received December 14, 1967. t Department of Organic Chemistry, University of Sydney, N.S.W. 2006.

Williams, J. L. R., J. Am. chem. Soc., 1953, 75, 2779. Schofield, K., and Theobald, R. S., J. chem. Soc., 1949, 2404. Wolfram, M. L., and Brown, R. L., J. Am. chem. Soc., 1943, 65, 1516. ROSS, W. C. J., J. chem. HOG., 1950, 752. Finkelstein, J., Williams, T., Toome, V., and Traiman, S., J. org. Chem., 1987, 32, 3229,

and references therein.

1376 SHORT COMMUNICATIONS

acid was assigned structure (111) by Halford and Weissmann6 on unstated grounds. Later Renson7 concluded as a result of i.r. spectral studies that the produot had the ring structure (IV); this conclusion was readily confirmed in the present work by an examination of the n.m.r. spectrum which had a 3-proton singlet a t 6 2.22 (CDCI,). It was therefore not unexpected to find that (IV) reacted slowly with diazomethane and gave instead of the desired diazoketone dark ill-defined products.

Some observations on certain other substances related to o-acetylbenzoic acid were also made. Erley et ~ 1 . ~ measured the n.m.r. spectrum of a methyl derivative of o-acetylbenzoic acid, which had been prepared by an unspecified method, and interpreted the results in terms of an equilibrium between structures (V) and (VI). In the present work, the methyl derivative prepared by the action of diazomethane on the acid had spectral properties (see Experimental) consistent with the normal ester structure (V) and no evidence for the existence of an equilibrium with (VI) was apparent. Halford and Weissmann6 assigned structure (VII) to the product from the reaction between aniline and their "acid chloride" ; the n.m.r. spectral properties (see Experimental) again proved to be decisive and showed that the product had structure (VIII). When o-acetylbenzoic acid or its methyl ester was refluxed with aniline a different produot was formed; from its spectral properties it was clearly (IX) which had previously been obtainedg by heating aniline and phthalylideneacetic acid in acetic acid.

Halford, J. O., and Weissmann, B., J. org. Chem., 1952, 17, 1646. Renson, M., Bull. SOC. chirn. Belg., 1961, 70, 77. Erley, D. S., Potts, W. J., Jones, P. R., and Desio, P. J. , Cherny Ind., 1964, 46, 1915. Honzl, J. , Colln Czech. chem. Cornmum., 1956, 21, 725

SHORT COMMUNICATIONS 1377

Evidence has been obtainedl0Jl that o-formylbenzoic acid exists, a t least in some circumstances, predominantly as the cyclic (XI) rather than the normal structure (X); both methyl derivatives (XII) and (XIII) have been obtained.ll The true ester (XII) is more readily prepared by the action of diazomethane on the acid. When this ester or the acid was heated with aniline the new substance (XIV) was formed. The i.r. and n.m.r. spectra were in agreement with this assignment, and the major significant peaks in the mass spectrum may be rationalized by Scheme 1.

Scheme 1

Melting points are uncorrected. Light petroleum had b.p. 40-60'. 1.r. spectra were measured in Nujol mulls unless stated otherwise, and n.m.r. spectra on a Varian A60 spectrometer in deuterochloroform solution with tetramethylsilane as internal standard; mass spectra were determined by an AEI MS9 mass spectrometer.

The bis-diazoketone (18 g) from terephthdic acid was added during 1 hr to a vigorously stirred mixture of chloroform (200 ml) and 47 % hydriodic acid (90 ml). After stirring for a further 0.5 hr, water (300 ml) was added. The chloroform layer combined with a chloroform extract of the aqueous layer, was washed successively with water, 10% Na,S,O,, water, saturated KaHCO,, dilute HC1, and brine. The crude product obtained by evaporating the solvent mas best purified by chromatography on alumina deactivated by ethyl acetate. Material eluted by light petroleum-benzene (2 : 1) on recrystallization from light petroleum gave pure p-diacetyl- benzene, m.p. 113" (lit.2 113-114') in 68% overall yield from terephthalic acid. v,,, 1690 om-l; n.m.r. spectrum: s, 4, 8.03, 4 xArH; s, 6, 2.63, 2 xCOCH,.

lo Bernatek, E., Acta chern. scand., 1960, 14, 785. l1 Grove, J. F., and Willis, H. A., J. chem. Soc., 1951, 877.

1378 SHORT COMNUNICATIONS

When the reduction was carried out with syrupy phosphoric acid (63 g), potassium iodide (225 g ) , and water (155 ml) instead of hydriodic acid, the yield was 62%.

The bis-diazoketoneZa from isophthalic acid on reduction by hydriodic acid as above gave m-diacetylbenzene which was purified by distillation (b.p. 124-125"/1 mm), in 80% yield. The product had m.p. 31-32' (lit.18 32'); v,,, 1690 cm-I; n.m.r. spectrum: m, 4, 8.55-7.41, 4 x ArH; s, 6, 2.64, 2 xCOCH,.

The crude product from reduction of o-nitrodiazoacetophenoneZ4 was purified by filtering its solution in benzene through a column of silica gel, followed by distillation (b.p. 127'/0.8 mm) to give a pale yellow solid (66% yield), m.p. 27-28' (lit. 27-28').

Methyl o-Acetylbenzoate (8)

An ethereal solution of o-acetylbenzoic acid was treated with ethereal diazomethane in the usual way. The product obtained in almost quantitative yield was a colourless oil, b.p. 114'11 mm; v,,, (film) 1720, 1696 om-l; n.m.r. spectrum: m, 4, 7.9-7.25, 4 x ArH; s, 3, 3.89, COOCH,; s, 3, 2.52, COCH,.

This substance, prepared by the method of Halford and Weis~mann,~ crystallized from light petroleum on cooling in an acetone-dry-ice bath as colourless needles, m.p. 57' (lit.Q7-58'); v,,, 1690 cm-l; n.m.r. spectrum: m, 4, 8.0-7.5, 4 x ArH; s, 3, 2.22, CH,.

3-Anilino-3-methylphthalide (VII I )

Reaction between the above chloro compound and aniline in dry ether a t room temperature was slow. The product isolated in the usual manner crystallized from benzene-light petroleum in colourless needles, m.p. 157-159" (lit.6 156-157'); v,,, 3361, 1682 em-'; n.m.r. spectrum: m, 9, 7.70-7.15, 9 x ArH; s (b), 1, 3.8 (exchangeable with D,O), KH; s, 3, 1.56, CH,.

3-Alethylene-2-phenylphthali~nidine (IX)

o-Acetylbenzoic acid (0.95 g) or its methyl ester was refluxed with aniline (10 ml) for 6 hr. The mixture was dissolved in ether and the solution washed thoroughly with dilute HC1. The product crystallized from light petroleum as light yellow needles (0.7 g), m.p. 99-100' (lit.9 100'); v,,, 1700, 1642 cm-l; n.m.r. spectrum: m, 9, 8.1-7.2, 9xArH; AB q, 1+1, 5 .2 and 4.8, J 2 c/s, C=CH,.

Methyl o-Pormylbenzoate (XII )

The action of ethereal diazomethane on an ethereal solution of the acid gave the ester, b.p. 96"/0.7mm; v,,,(film) 1721, 1699cm-l; n.m.r.spectrum: s, 1, 10.58,CHO; m,4, 8.1-7.5, 4 x ArH; s, 3, 3.93, COOCH,.

3- Anilino-2-phenylphthalimidine ( X I V)

The above ester (1 g) or the related acid was refluxed with aniline (10 ml) for 6 hr and the product isolated in the usual way. I t crystallized from methanol as colourless needles (1.2 g), m.p. 162" (Found: C, 79.7; H, 5.4; N, 9.5; mol. wt., 300. Ca,Hl,N,OrcquiresC, 80.0; H, 5.4; N, 9.3; mol. wt., 300). v,,, 3360, 1680 om-l; n.m.r. spectrum: m, 14, 8.0-6.5, 14 xArH; d (approx.), 1, 6.5-6.2 (on edge of aromatic proton band), C-H; d (b), 1, 4.6-4.3, N-H; on exchange with D,O the latter signal disappeared and the signal from CH became a singlet a t 6.33.

l2 Ruggli, P., and Knecht, K., Helv. chim. Acta, 1944, 27, 1108. 13 Ruggli, P., and Gassenmeier, E., Helv. chim. Acta, 1939, 22, 496. 14Arndt, F., Eistert, B., and Partale, W., Ber. d t , chem. Ces., 1927, 60, 1364.