VOl. 77
COMMUNICATIONS TO THE EDITOR
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recent study confirms Busch’s initial hypothesis zan rearrangement in the present study and hence and, furthermore, suggests that the rearrangement lend credence to the (1H)-tetrazolium structure is probably intramolecular.s However, we have assigned to 111. found that the interaction of 1-(5’-tetrazolyl)-3We have employed the procedure described above phenyltetrazene (I) and benzaldehyde yields a rela- for the preparation of a variety of 3,5-diaryl-1-(5’tively stable benzaltetrazene (11), m.p. 116-117 dec. tetrazolyl) (1H)tetrazolium betaines by introducing (Anal. Calcd. for C14H12N8: C, 57.52; H, 4.14; electronegative substituents in the benzene residue N, 38.34. Found: C, 57.30; H, 4.33; N, 38.04) of I together with the use of substituted benzaldeinstead of the corresponding formazan (IV). Oxida- hydes. These compounds will be described in detion of this yellow solid (11) with cold concentrated tail in a future communication. nitric acid gave 3,5-diphenyl-l-(5’-tetrazolyl) (1H)- DEPARTMENT OF CHENISTRY tetrazolium betaine (111), m.p. 300” (Anal. Calcd. ILLISOISISSTITUTEOF TECHNOLOGY JEROME P. HORWITZ A. GRAKAUSKAS ILLINOIS VYTAUTAS for CllHlON8: C, 57.92; H, 3.47; N, 38.61. CHICAGO, RECEIVED SOVEMBER 8, 1955 Found: C, 58.12; H, 3.76; N, 38.50). That the oxidation product (111) was, indeed, a tetrazolium betaine was established from the degradation of MOLECULAR DISSYMMETRY AND OPTICAL INthis solid with hot concentrated hydrochloric acid ACTIVITY which gave a mixture of 5-hydroxytetrazole (GO% Sir: yield) and 2,5-diphenyltetrazole (98% yield). We wish to report the synthesis of (dextro)However, the degradative evidence did not permit the unequivocal assignment of the relative posi- menthyl (levo)-menthyl 2,6,2’,6‘-tetranitr0-4,4’-ditions of the tetrazolyl and N-phenyl substituents. phenate (I) Thus, it is conceivable that structure V might afford the same degradation products. CsHi-S-NHz
\
?io* OzN/
I
N=N
I
I
CaHaCHO
an optically inactive and configurational2y pure compound1 whose individual molecules are asymmetric. Despite the total lack of molecular reflection symmetry, ;.e., the absence of plane, point of 4n4 fold alternating axis of symmetry, rotameric interconversions ensure statistically equal populations of enantiomeric conformations and thus account for the observed optical inactivity.2 I Compound I may be variously regarded either as C (I) a meso diastereomer for which no symmetric HN/ \ S conformation is possible, or as (2) a non-resolvable 1 N=?i racemic mixture of conformational type. I n m.p. 116-117’ dec., either case I appears unique in that its enantiomeric yellow conformations are interconverted by rotameric I1 changes which cannot involve passage through any symmetric conformation.? An adequate discussion of this and related matters requires the reexamCeHs-S-N ination of certain fundamental generalizations perI $)C-CeHS taining to molecular dissymetry and optical activX=K ity, a task which we hope to approach in full publiI 1 cation. The stereoisomers of I were prepared as follows. I I, ! Action of copper on methyl 4-chloro-3,5-dinitroX=====K N=====N benzoate gave methyl 2,6,2’,6’-tetranitro-4,4’-dim.p. 209-210’ m.p. 300” phenate, m.p. 192-192.503 (Found: C, 42.9; H , \I11 2.0; N, 12.5), acid hydrolysis of which yielded Quite fortunately, Kuhn and Kainer had earlier 2,G,2’, 6’-tetranitro-4,4’-diphenicacid (II), m .p. described the synthesis of 2,5-diphenyl-3-(5’-tetra- 338-342” (Found: C, 40.2; H, 1.8; N, 13.0). zolyl)(2H)tetrazolium betaine (V), m.p. 209-210”, Conversion of I1 to the acid chloride with thionyl which was obtained by the oxidation of the corre- chloride, followed by treatment with (-)-mensponding formazan (IV) with N-bromosuccini- thol in pyridine, gave ( -)-menthyl 2,6,2’,6’-tetramide.6 Compound IV, m.p. 143”, possesses the nitro-4,4’-diphenate (111), m.p. 225-22G0, [ a ] ” D red color that characterizes the formazans2and was -59.4” (benzene); Found: C, 58.5; H, 5.6; N,8.3. obtained by the action of benzenediazonium chlo- Similar treatment of the acid chloride of I1 with ride on benzal 5-tetrazolylhydrazone. (+)-menthol yielded (+)-menthyl 2,6,2’,6’-tetraThe differences noted between I1 and IV, and I11 nitro-4,4’-diphenate (IV), m.p. 225-226”, [ a I z 8 D and V preclude the possibility of a tetrazene-forma(1) As distinguished from a racemate or racemic mixture.
%AN I
~
( 5 ) H. Hauptmann and A. C. de M. Perisse, Experienfia, 10, 60 (1 954). (6) R. Kuhn and H. Kainer, Angew. Chem., BS, 442 (1953).
( 2 ) K. Mislow, Science, 120, 232 (1954). (3) F. Ullmann and J. Bielecki, B e y . , 34, 2174 (1901), report m.p. 1730.
Dec. 20, 1955
COMMUNICATIONS TO THE EDITOR
+60.0° (benzene); Found: C, 58.7; H, 5.7; N, 8.0. The racemate, formed by recrystallization of a mixture of equal quantities of I11 and I V from benzene-methanol, melted a t 264-265". Partial hydrolysis of I11 with sodium hydroxide in aqueous dioxane yielded (-)-menthyl hydrogen 2,6,2',6'tetranitro-4,4'-diphenate (V) , m .p. 216-2 18O , [a] lD -38.6" (acetic acid); Found: N, 9.7, 9.5; neut. eq. 562. Treatment of V with thionyl chloride, followed by addition of (-)-menthol in pyridine, gave I11 (m.p., mixed m.p., [ a ] ~ )Similar . treatment of the acid chloride of V with (+)-menthol afforded I, m.p. 247-248.5' (Found: C, 58.4; H, 6.3; N,8.1). The optical activity of I was zero, as measured in pyridine and benzene solutions a t 589, 578, 546 and 435 mp.
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and IV solvolyzed a t closely similar rates and showed one-fourth the logarithmic rate reduction of the tetradeutero derivative. TABLE I ACETOLYSIS RATESOF DEUTEROCYCLOPENTYL TOSYLATES Tosylate of
lO5k (sec.-')(l 50'
A A F =k (per D) cal./mol'e
Cyclopentanol 4.21 .. trens-Cyclopentanol-2-d 3.62 99 cis-Cyclopentanol-2-d 3.47 125 Cyclopentano1-2,2,5,5-d( 2.05 116 a 0.1Msolutions in acetic acid, 0.117M in sodium acetate. Rates were run in duplicate; reproducibility was 1%.
The results are clearly inconsistent with a common interpretation of resonance structures such as WM. H. NICHOLSCHEMICAL LABORATORY 11. The results are completely consistent with a NEW YORKUNIVERSITY KURTMISLOW RICHARDBOLSTAD molecular orbital viewpoint formulated as in Fig. 1. NEW YORK53, N. Y . RECEIVEDOCTOBER 14, 1955
THE STEREOCHEMISTRY OF HYPERCONJUGATION
Sir: The most important recent evidence for the concept of hyperconjugation has been the finding of decreased reactivity in solvolytic reactions of tertiary halides and secondary sulfonates in which 0hydrogen atoms are substituted by deuterium. The accepted explanation has involved the decreased effectiveness of hyperconjugation (I 11) because of the greater strength of the carbon-ieuW terium bond. Changes in inductive effect are not 01 s involved for H D has no dipole moment. The imFig. 1.-Transition state of a solvolytic reaction of plied analogy between hyperconjugation and elimination reactions' and the suggested importance of cyclopentyl tosylate illustrating a molecular orbital viewthe trans-hydrogen in 113have been scrutinized by point of hyperconjugation. a study of the stereospecificity of the deuterium The sp3hybrid orbitals of the P-C-H bonds are not isotope effect. orthogonal to the developing p orbital a t the reac6+ 6tive center; consequently, overlapping will occur. H-CRt-CRz. . . .X t)H' CR*=CRz X A molecular orbital of the proper symmetry may I I1 be constructed from the methylene hydrogen atoms Reaction of cyclopentene oxide with lithium alu- which, by overlapping with the component p orminum deuteride gave trans-cyclopentanol-2-d (111) bital of the P-carbon, forms a conjugated system containing 0.98 f 0.03 atom of D per molecule, with the developing p orbital formally analogous which was converted to the tosylate, m.p. 28-29', to that in an allyl carbonium ion. Because the two and displaced by tetramethylammonium acetate in methylene hydrogens are acting as a unit in a molecpure acetone to afford, after hydrolysis, cis-cyclo- ular orbital, substitution of either one by deuterium pentanol-2-d (IV). The infrared spectra of I11 will have the same efect on the energy of Ihe pseudo-a and I V were different in many respects and demon- bond, to a close approximation. strated that each deuteroalcohol was free from its DEPARTMENT OF CHEMISTRY AND epimer. CHEMICAL ENGINEERING ANDREWSTREITWIESER, JR. Ten exchanges of cyclopentanone with excess UNIVERSITY OF CALIFORNIA ROBERT H. JAGOW weakly basic deuterium oxide gave cyclopentanone- BERKELEY 4, CALIF. SHIGETO SUZUKI RECEIVED OCTOBER 15, 1955 2,2,5,5-d4, which was reduced with lithium aluminum hydride a t -80" to cyclopentanol-2,2,5,5-d4 (V) containing 4.1 f 0.1 atoms of D per molecule. THE CARCINOSTATIC ACTMTY OF SOME 2-AMINOThe tosylate had m.p. 28-29'. 193,4-THIADIAZOLES The acetolysis rates were determined a t 50' for Sir: the tosylates of 111, IV, V and cyclopentanol (Table During screening of compounds for their carcinoI). There is no important stereochemical effect static activity, several 2-amino-1,3,4-thiadiazole for deuterium substitution. The tosylates of I11 derivatives were found to be active against several (1) V. J. Shiner, Jr., THISJOURNAL, 7 6 , 2925 (1953); 76, 1603 transplanted animal tumors. A representative (1954). group of the derivatives and analogs synthesized (2) E. S. Lewis and C. E. Boozer, ibid., 76, 791 (1954). and tested are listed, along with the results ob(3) G. Baddeley, A n n . Refits. o n Progress Chem. (Chem. SOC. London), 61, 169 (1954). tained, in Table I. The synthesis of these particu-
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ls2
