Lack of time and material does not permit US to obtain additional evidence regarding these alternate linkages. Logical approaches would be by the use of the Edman method on the aspartyl-glutaminyl-leucine peptide' and by partial acid degradation of the nonapeptide mentioned above. Details of this and the earlier work will be reported shortly. EXPERIMENTAL THERAPEUTICS A Y D KATHERINE S. HOWARD MEDICINAL CHEMICAL SECTIONS ROBERT G. SHEPHERD RESEARCH DIVISION E. ANNEIGNER AMERICASCYANAMID COMPAXY DAVIDS. DAVIES STAMFORD, CONNECTICUT PAVLH. BELL RECEIVED MAY11, 1963
agents such as hydrogen over platinum to the corresponding hydroquinone. I can be converted to a variety of stable substitution products (11-VII) which have some chemical properties analogous to those of substituted benzoand naphthoquinones. X
11,
x = c1
111, X = Br
V, X = -0CH3 VI, X = -NHu YII, x = -OH
0
I reacted with chlorine or bromine in acetic acid to yield the yellow halogen derivatives I1 and 111, respectively. I1 had m.p. 114-115'. Anal. Calcd. PHENYLCY CLOBUTADIENOQUINONE for CloHsOzCl: C, 62.36; H, 2.62. Found: C, Sir: H , 2.54. I11 had m.p. 128-129'. Anal. No authentic cylobutadiene derivatives appear to 62.20; Calcd. for C10H602Br:C, 50.66; H , 2.13. Found: have yet been prepared except for biphenyleneIa and related substanceslb)?.Bwhere the four-niem- C, 50.64; H , 2.13. Reduction of I11 with amalgamated zinc and hydrochloric acid gave phenylcybered rings are part of fused-ring system^.^ The clobutane. 111 reacted rapidly with alcoholic silfailure to detect cyclobutadiene or its non-fused ring ver nitrate and, with sodium iodide in acetone, derivatives among the products of appropriate yielded IV, m.p. 163-165' (dec.). Anal. Calcd. synthetic reactions can be ascribed either to excesCloH50zI: C, 42.26; H, 1.77. Found: c, sive ring strain or unfavorable electronic configura- for 42.38; H , 1.87. Methanolysis of 111 afforded pale t i o n ~ . ~Strong ,~ evidence that ring strain is not the yellow V, m.p. 151-152' (Anal. Calcd. for most important factor is now provided by a syntheCI'Ha03: C, 70.20; H, 4.28. Found: C, 69.51; sis of the quite stable phenylcyclobutadienoquinH , 4.16) while ammonia in dry benzene gave the one (phenylcyclobutendione, I ) which to a first ap- colorless essentially neutral amino derivative (VI), proximation is expected to have the same degree of m.p. 279-281' (dec.). Anal. Calcd. for C U I H ~ O ~ N : ring strain as phenylcyclobutadiene. C, 69.36; H, 4.07; N, 8.09. Found: C, 69.37; H, 4.04; N, 8.08. With dilute acetic acid, 111 CBHb- / =O was hydrolyzed to colorless VII, m.p. 205-208' I1 (dec.). VI1 is soluble in water, is an exceptional I O strong acid for a C, H, 0 compound ( ~ K A 1) and gives a magenta color with ferric chloride soluPhenylacetylene with trifluorochloroethylene a t tion. Anal. Calcd. for CloHaOs: C, 68.96; H, 120' for 24 hours gave 1,1,2-trifluoro-2-chloro-3-3.48; neut. equiv., 176. Found: C, 68.87; H, phenylcyclobutene6; b.p. 52-53' (0.4 mm.), n% 3.61; neut. equiv., 174. VI1 is converted to V 1.,5117. Anal. Calcd. for Cl~H6F3C1:C, 54.92; with diazomethane. H, 2.77. Found: C, 54.83; H, 2.89. Hydrolysis6 The stable existence of I-VI1 suggests the possiof the adduct with 92% sulfuric acid a t 100' af- bility that quinone-type derivatives of unknown forded bright-yellow crystalline I in 73% yield; cyclic polyolefins such as pentalene and heptalene m p . 152-1 53' (dec.) after recrystallization from might be more stable than the parent hydrocarbons. acetone. Anal. Calcd. for C10H602: c, 75.94; Investigation of the chemical and physical propH , 3.52; mol. wt., 155. Found: C, 76.00; H , erties of I-VI1 is being continued. 3.85; mol. wt. (Rast), 151. I had Amax = 286 mp, CONTRIBUTION No. 2000 E 2.3 X lo5and strong infrared absorption a t S.6 p . GATESAND CRELLINLABORATORIES EDGAR J. SMUTNY -1chloroform solution of I with 30%. hydrogen per- CALIFORNIA INSTITUTE OF TECHNOI,OGY J O H N D. ROBERTS oxide yielded phenylmaleic anhydride, m.p. 119- PASADENA 4. CALIF. 120', which did not depress the m.p. of an authenRECEIVED MAY20, 1955 tic sample.' Reduction of I with amalgamated zinc and hydrochloric acid yielded phenylcyclobuNEW REAGENT FOR RESOLUTION BY COMPLEX tane which was identified by comparison of its in- A FORMATION ; THE RESOLUTION OF PHENANTHROfrared spectrum with material previously prepared.6 13.4-cl PHENANTHRENE' I is much more stable to water and oxygen than o- Sir: benzoquinone. It is apparently not reduced by We wish to report the synthesis of 2-(2,4,5,7-tet(1) (a) W. C. Lothrop, THISJ O U R N A L , 63, 1187 (1941); (h) 64, ranitro-9-fluorenylideneaminooxy)-propionic acid, 1098 (1942). 111, a useful reagent for the optical resolution of cer(2) R . F. Curtis and G. Viswanath, Chem. ond Ind., 1174 (1954). tain aromatic compounds which do not have the (3) M. P. Cava and J. F. Stucker, ibid., 440 (1955). functional groups usually needed to effect resolution (4) An excellent survey of attempts t o prepare non-fused ring cyclobutadiene derivatives was recently presented by E. R . Buchman, Ahst. by conventional reagents. of A.C.S. meeting, Sept. 13. 1954, p. 9-0. The dextro and levo forms of 111 were made by ( 5 ) For references and discussion see J . D. Roberts, A. Streitwieser, condensing 2,4,5,7-tetranitrofluorenone,I, with Jr.. and Clare hl. Regan, THISJ O U R N A L , 7 4 , 4579 (1952).
-
.
(6) Cf.J . D. Roberts, 0 . R . Kline and H. E. Simmons, J r . , ibid., 76, 4765 (1953). ( 7 ) I , . E. Ililler, H. R . Staler and n. J . hlann, Ibid., 71, 374 (1949).
I
I
(1) A p a r t of this material was presented before t h e Division of Organic Chemistry a t t h e 127th meeting of t h e American Chemical Society, Cinclnnatl, Ohio, >larch, 19n5.
