83 1
NEWCOMPOUNDS
Yovember, 1964
TABLEI
X'I
I I XI
xz
H
I
H
Br C1
H Br
I
a
I
Br Br Br I C1 Lit.8 1n.p. 250".
Mp.,
oc.
247-24Sa 200-202 200-201 207-209 179-181 183-154 188-189 * Crude yield.
Yield,
%
7s 64 41 94* 1OOb 56* 6gb
Found, C
43.19 55.14 28.09 26.81 31.69 31.55
Calcd., %
9% H
2.89 3.63 1.74 1.58 2.02 1.90
C
43.30 55.06 26.97 26.97 31.39 31.11
H
Formula
2.91 3.70 1.51 1.51 1.76 1.74
CiE"zIz04 CJhBr204 Ci6HnClzO1 CJLoBrJ204 Cl6HloBrJaOc ClsHloBraOl CisH1oClzI204
Anal. Calcd. for C19H17NO: C, 82.87; H, 6.22; N, 5.09. Found: C,82.70; H,6.51; N, 5.03. Methyl 5-Cyano-2,2-diphenylpentanoate.-Dehydration of the STUART s. KULP AND STANLEY A. I O B S T ~ above amide ester with phosphorus oxychloride9 gave the cyano ester in 797, yield. It had b.p. 220-225" (6 mm.) and n1.p. Department 0.f Chemistry, Moravian College, 68-66.6' after recrystallization from methanol. Anal. Calcd. for CI9Hl9-UO2:C, 77.82; HI 6.48; 9,4.78. Bethlehem, Pennsulcania Found: C , 7 7 . 6 7 ; H, 6.81; N,4.83. 2,2-Diphenyl-5-cyanocyclopentanone.-To a stirred, refluxing h'meived Jiily 9,1964 solution of 0.0793 mole of potassium t-butoxide in 150 ml. of dry t-butyl alcohol was added a solution of 21.7 g. (0.0741 mole) The structural relalionships of substituted 2,2-diphenylcycnloin 3.50 ml. of t-butyl of methyl 2,2-diphenyl-5-cyanopentanoate pentanones t o the methadone class of analgetics have been alcohol over 2.5 hr. After completion of the addition, the soludiscussed. 2 - 4 A previous report6 mentions several unsuccessful tion was refluxed for 8 hr. About two-thirds of the solvent was attempts to synthesize 2,2-diphenyl-8-cyanocpclopentanone. removed under reduced pressure and a white solid formed. After This keto nitrile has now been prepared from methyl 2,2-dicooling, a solution of 5 ml. of acetic acid in 200 ml. of water was phenyladipate. added, and the solid redissolved. Concentration of the resulting solution to about half its volume gave white crystals which were filtered. The product, 17.6 g. (91.2Y,), melted a t 97-101". Experimental6 Aft,er several recrystallizations from methanol, the m.p. was 103.5-106'. Methyl 2,2-diphenyladipate was synthesized as reported6 ilnal. Calcd. for ClsH&O: C, 82.76; H, 5.75; N, 5.36. except 5-chloro-2,2-diphenylpentanenitrile was converted to the Found: C,82.61; H,6.01; 5 , 5.28. corresponding dinitrile in 99% yield in 3 hr. by using dimethyl The infrared spectrum (CCla solution) had absorption peaks sulfoxide as solvent'.' at4.42(CS)and5.64p(CO). 5-Carbomethoxy-5,5-diphenylpentanoicAcid.-A solution of Hydrolysis with 80% sulfuric acid for 1 hr. then dilution to 73.4 g. (0.225 mole) of methyl 2,2-diphenyladipate in 200 ml. 40%, and refluxing for 6 hr. gave 2,2-diphenylcyclopentanone, of methanol was heated under reflux with vigorous stirring. After m.p. 86-88'. A mixture melting point of this material Kith an dropwise addition of 117.5 ml. of 2 N NaOH (0.235 mole) over authentic sample3 was not depressed. 1 hr., the solution was refluxed for an addit,ional 2 hr. The methanol was removed by distillation and the remaining solu(9) A. R. Surrey, "Organic Syntheses," Coll. Vol. 111, John Wiley and tion was diluted with 500 ml. of water. Acidification with Sons, Inc., New York, 3. Y.. 1955, p. 535. concentrated HC1 gave a yellow oil which soon solidified. The crude product, 67.8 g. (96.67,), melted a t 103-103". A sample recrystallized from methanol had m.p. 107-110" (lit.* 105106'). The method of Salmon-Legagneur and Xeveua gave inseparablc miutiires.5 Some 2,3-Disubstituted Quinazolonesl Methyl 5-Carbamoyl-2,2-diphenylpentanoate.-A mixture of 37 g. (0.222 mole) of thionyl chloride and 63 g. (0.202 mole) of K. KISHOR, R.K U J I A R , AXD SURESDR.4 S.PARMAR the above acid ester stood overnight, was heated a t 80" for 1 hr., and the excess thionyl chloride was removed under reduced pressure. The acid chloride was dissolved in 100 ml. of dry Department of Pharmacologu and Therapeictics, K . G . Medical dioxane then dropped into 1000 ml. of concentrated XH40H a t College, Lucknow C'nitiersity, Lzicknow, India 0" over 1 hr. After warming to room temperature, filtration gave 64.6 g. (99yo) of crude product melting a t 88-100". ReReceived J l a y 29, 1964 crystallization of a sample from methanol-water raised the m.p. to 98-100". I n a series of 2,3-disubstituted quinazolonesz possessing hypnotic activity,3 2-methyl-3-(o-tolyl)-4quinazolonewas found to (1) Taken from the Senior Honors thesis of S. A. I., Iforavian College, be a potent anticonvulsant, superior to sodium phenobarbital 1964. against pentylerietetrltzole seizures.4 Furthermore, Darwin, (2) P. K. Craig and I. H. Witt, J . A m . Chem. Soc., 72, 4925 (1950). ( 3 ) N. R. Easton and S. J. Nelson, ibid.. 76, 640 (1953).
Synthesis of 2,2-Diphenyl-5-cyanocpclopentanone
(4) N. R. Easton. H. E. Reiff. G. Svarnas. and F'. R. Fish. ibid., 74, 260 (1952). ( 5 ) S.S. Kulp, V. R. Fish, and K. R. Easton. J . Med. Chem., 6 , 516 (1963). (6) JIelting points are corrected and nere determined in a Jlel-Temp
apparatus. ( 7 ) L. Friedman and H. Shechter, .I. Or@. Chrm.. 26, 879 (1960). (8) F. Salmon-Legagneur and C. Neveu, Bull. sac. chim. France, [ 5 j 23, 929 (1956).
(1) T h e authors uish t o express their thanks t o the State RIedical Research Council (U.P.) for a research grant and t o the Indian Council of Medical Research for financial assistance t o R. K. (2) I. K. Kacker and 5.H. Zaheer, .I. I n d i a n Chem. Soc.. 28, 344 (1951). ( 3 ) M. L. Qujral, R. P. Kohli, and P. N . Saxena, J . Assoc. I'husiciane I n d i a , 2, 29 (1955). (4) M. 1,. Gujral. P. N. Saxena, and R. P. Kolili, Indian J . M e d . Res., 45, 207 (1957).
