COMATUNIC ~ T I O S STO
504
TIIF
EDITOR
I-01. SI
search Fund; and to the National Institutes of Health for a summer research appointment.
petroleum ether, These extracts were fractionally vacuum distilled. The substituted decaboranes were characterized by elemental composition and DEPARTMENT OF CHEMISTRY UNIVERSITY OF KAXSAS ALBERTW. BURCSTAHLERcryoscopic molecular weight. LAWRENCE, KANSAS ZOE J . BITHOS The n-alkyl fluorides were prepared by4 adding RECEIVED NOVEMBER 19. 1958 mercuric fluoride slowly to an alkyl bromide or ioThe product was then vacuuni dide, a t 40-50'. distilled and redistilled a t atmospheric pressure. GRIGNARD SYNTHESIS OF ALKYL DECABORANES Acknowledgment.-The authors are indebted to Sir : Marshall Wheeler for technical assistance, Phyllis Inorganic Grignard reagents derived from dec- Ii'heeler for analyses, and James V. Lowe, Jr., for aborane, and the condensation reaction to pre- the preparation of the alkyl fluorides. The enpare benzyldecaborane recently have been re- couragement of Drs. Sol Skolnik and F. A. H. Rice ported.' We subsequently found that these re- is gratefully acknowledged. agents could not be used readily to prepare a series (4) 4 . L Henne and T XIIrlgley, THIS JUORNAL, 68, 884 (1936). of alkyl decaboranes by the normal Grignard conJOHN GALLAGHAN U S. NAVAL PROPELLANT PLAYT densation reaction, using n-alkyl chlorides, bro- INDIAN HEAD,MD. BERNARD SIECEL mides and iodides. Seeking a general method for RECEIVED O C r O B E R 11, 1958 preparing alkyl decaboranes, other types of condensing agents were tried with B1~H13?"lgX. Success with a tri-alkyl oxonium salt, R 3 0 B F ~ led , 2 us TRANSANNULAR SULFUR-CARBONYL INTERACTION to believe that alkyl fluorides might be used as condensing agents. Although alkyl fluorides have not Sir: been used in Grignard condensation reactions3 (preWe have now obtained evidence of transannular sumably because of the strong carbon-fluorine sulfur-carbonyl interaction across an eight-membond in n-alkyl fluorides), we found that BI0H13- bered ring in the model compound l-thiacycloMgX could be condensed successfully with a series octan-5-one (I). Prediction of the occurrence of of n-alkyl fluorides, and an alicyclic fluoride. The substituted decaboranes prepared by this principle are shown in Table I. TABLE I Substituted decaborane
Yield,
%
Butyl' 25 Amyl" 40 Hexyl" 24 Cyclohexyl* 6 Heptyl" 23 OctylQ 16 Colorless liquid.
--Elemental -Theoretical--C R
analyses, -,Y , ----Found-B
26.9 12.4 60.1 31.3 1 2 . 5 5 6 . 3 35.0 12.6 58.4 35.3 11.8 52.9 38.2 12.7 49.0 41.0 1 2 . 8 46.1 * White solid, m.p.
C
I H
25.6 12.5 31.2 12.7 35.1 1 2 . 8 3 3 . 8 11.8 3 7 . 5 12.7 40.9 12.6 90-91'.
B
59.7 58.1 53.2 51.9 51.1 44.9
Since this reaction appeared to be of general interest to organic chemistry, we tested i t with a simple organic Grignard reagent that could not be alkylated with the usual n-alkyl halides. Accordingly, after ethylmagnesium bromide failed to react with n-butyl bromide, the former was treated with n-butyl fluoride. This resulted in a substantial yield of n-hexane (1170) and 3-methylpentane (7'%); the latter were identified by their mass spectra. Experimental.-B1oHl8MgBr was prepared by the reaction of equivalent quantities of decaborane and C&MgBr, using 5 to 6 g. of decaborane. The ether solvent was then distilled and a two-fold excess of alkyl fluoride was added. The resulting solution was stirred for 48-64 hours under nitrogen, a t ambient temperature; in some cases an ice-bath was necessary initially. After the prolonged standing the highly volatile components were distilled and the residues were extracted with dried (1) B. Siegel, J. Mack. J. Lowe and J. Gallaghan, THISJOURNAL, 80, 4523 (1958). ( 2 ) H. Meerwein, et al., J . prakl. Chem., 164, 83 (1939). (8) T h e only report on this subject was a recent Russian article in which, in the specialized instance of several tertiary fluorides, greater yields of condensation were obtained than was the case with tertiary chlorides: A. D. Petrov, et al., Chem. Abslracfs, 60, 16057 (1950).
Ia
such interaction was made earlier,' as methods were being developed for the detection of nitrogencarbonyl interaction in cyclic aminoketones and aminoacyloins of medium ring size.2 Compound I was obtained (45y0 crude yield) by the Dieckmann cyclization of diethyl y,7'-thiabis-butyrate3using potassium t-butoxide in xylene under high dilution conditions, with high speed stirring under n i t r ~ g e n ,then ~ hydrolysis and decarboxylation, and was purified by recrystallization from ether-pentane and sublimation, colorless needles, m.p. 53.2-54.2' (And. Calcd. for C7HlzOS: C, 58.29; H, 8.39. Found: C, 58.21; H, 8.36).5 A by-product, when the addition rate of the sulfide diester was relatively rapid (25 hours),6 was the sixteen-membered ring compound, 1,9dithiacyclohexadecane-5,13-dione, colorless needles, m.p. 65-66', ':zv 1715 cm.-l (Anal. Found: C, 58.64; H, 8.25; mol. wt., 252 (calcd. 288)). Indication of the contribution of S-Cco "interacted" forms (Ia) of I-thiacyclooctan-5-onewasfound in the infrared carbonyl maximum (shoulder) a t 1684 (1) N. J. Leonard, R. C. Fox and M. a k i , THISJOURNAL, 76, 5708 (1954). (2) For the most recent articles in the series on transannular nitrogen-carbonyl interaction, see: (a) N. J. Leonard, J. A. Adamcik, C. Djerassi and 0. Halpern, ibid., 80, 4858 (1958); (b) N. J. Leonard, D. F. hlorrow and M. T. Rogers, ibid., 79, 5476 (1957). (3) Made in this laboratory in 1954 by T. Hashizume. private communication. (4) N. J. Leonard and R. C. Sentz. ibid., 7 4 , 1704 (1952). ( 5 ) This product was identical with a sample of the same material kindly forwarded t o us by Dr. Charles G. Overberger of the Polytechnic Institute of Brooklyn and described in the accompanying Communication by C. G. Overberger and A. Lusi; see also: A. Lusi, Master's Thesis, Polytechnic Institute of Brooklyn, 1959. (6) N. J. Leonard, h l . o k i and S. Chiavarelli, ibid., 77, 6234 (1955).
Jan. 20, 1959
505
COMMUNICATIONS TO THE EDITOR
cm.-l, accompanying the strong maximum a t 1703 cm.-l (0.01 M s o h . in CC14)7corresponding to “non-interacted” conformations of I. By contrast, under the same conditions, tetrahydro-4H-lthiapyran-4-one (11)8and 1-thiacycloheptan-4-one (III)g exhibited single maxima a t 1716 and 1711 cm.-’, respectively. The dipole moment of the eight-membered ring compound (I),3.81 D in benzene, was higher than that of the seven-membered ring compound (111) (3.04 D; 1.73 D for II).2b I t is important to note that S-Cco interaction occurs to a lesser extent than N-Cco transannular interaction in the electronic ground state by comparison (infrared especially) of 1-thiacyclooctan-5-one with l-methyl-l-azacy~looctan-5-one.~ Finally, the ultraviolet absorption maxima of I in cyclohexane, a t 226 mp ( E 2445) and -232 mp ( E 2150), are associated with excitation of the interacting S-CCO system A,(: 223 mp ( E 695), XES, 233 mp ( E 507). lo (7) N. J. Leonard, M. d k i , J. Brader and H. Boaz, T ~ r JOURNAL, s 7 7 , 623 (1955). (8) E. A. Fehnel and M. Carmack, ibid., 70, 1813 (1948). (9) C. G. Overberger and A. Katchman, i b i d . , 78, 19G5 (1956). (10) E. Fehnel and M. Carmack (zbid.,71’84 (1949)) have suggested earlier that the difference between the ultraviolet spectrum of tetrahydro-4H-l-thiapyran-4-one(11) and those of its acyclic analogs is attributable t o direct interaction between t h e 1,4-atoms in the excited state. (See also V. Georgian, Chemisfvy and I n d u s f u y , 1480 (1957).) If this is correct, the four- to five-fold increase in intensity for the eight membered ring over the six-membered ring may be regarded as manifestation of the greater contribution of transannular interaction in the medium-ring compound, (11) Sinclair Refining Co. Fellow in Organic Chemistry, 1957-1968. Work done under the sponsorship of the Sinclair Research Laboratoiies, Inc.
dehydrogenase, DPN reduction (reaction l), pyruvate dismutation, and reduction of free lipoic acid (reaction 2).a,6 These activities were restored by
CH8COOP03‘
+ Lip(SH)t + COZ (2)
addition of FAD, but not of F M N (Table I). The dihydrolipoic transacetylase activity of the preparation was not affected by removal of flavin. TABLE I REACTIVATION OF SPLIT PYRUVATE DEHYDROGENATION SYSTEM WITH FAD Assay system
Before splitting
Specific activities’ -After splittingWithout With FAD FAD0
870 214 544 228 Lipoic DeHb 486 144 870 214 DismutationC Reaction Id 156 20 62 20 32 64 32 Reaction 2e 90 112 100 110 100 Lip. transac.’ Expressed as pmoles/hr./mg. protein based on assays described previously. * Ref. 7 , P H 7. Ref. 3. Ref. 8. Ref. 6, pH 7, 5 prnoles DL-lipoamide employed. f Ref. 8. 0 Aliquots of split complex incubated 10 min. a t 30’ with FAD or FMN before assay. Final concentration of added flavin in assays was 10-6 to 10-6 M .
These data indicate that FAD is an essential component of the enzyme complex, presumably associated with dihydrolipoic dehydrogenase. The data are consistent with the reaction sequence21a shown for oxidative decarboxylation of pyruvate by the enzyme complex.
+ T P P 2[CHaCHO-TPP] + COz S + SI>. 2HS)R + T P P CHaCOS
THENOYESCHEMICAL LABORATORYKELSOXJ. LEONARD CHzCOCOzH UKIVERSITY OF ILLINOIS THEODORE L. BROWS URBASA,ILLINOIS TERRY W. M I L L I G A N ~[CH3CHO-TPP] ~ RECEIVED DECEMBER 4, 1958
COA-SH
Sir:
ON THE MECHANISM OF OXIDATIVE DECARBOXYLATION OF PYRUVATE
+ COZ + DPNH + H +
+
(1)
(3)
(4)
I_ CHaCOS CHaCOSCoA
+
Extracts of Escherichia coli contain an enzyme system which catalyzes an oxidative decarboxylation of pyruvate represented by reaction 1.1,2-3
acetyl CoA
With FMNV
-3
+
+ HS “>R
HYR FAD + I R FADHl HS R = -CHZCHZCH(CHp)&O-enzyme
(5)
(6)
I
The reduced flavoprotein produced in reaction 6 apparently can interact with DPN (cf. reaction 1) and free lipoic acid (cf. reaction 2).
( 6 ) I. C. Gunsalus, Federalion Proc., 13, 715 (1954). We have obtained highly purified preparations (7) L. P . Hager and I. C. Gunsalus, THISJOURNAL, 76, 5767 (1953). (250-fold purification) of this system from extracts (8) L. P. Hager, Thesis, University of Illinois, 1953. of the Crookes strain. It is apparently an enzyme (9) During this investigation Dr. V. hlassey. Biochim. el bioghys. ~ o m p l e x and , ~ sediments in the ultracentrifuge (1 acfa, 30, 205 (1958) communicated t o us his significant finding (ref. 9) to 2 hr. a t 144,000 X g) as a dark yellow, fluores- t h a t highly purified diaphorase exhibited strong dihydrolipoic dehydrocent pellet. The complex contains a flavin which genase activity. BIOCHEMICAL has been tentatively identified as FAD. Release CLaYTON FOUNDATION INSTITUTE AND DEPARTMENT OF CHEMISTRY of the flavin by precipitation of the enzyme com- UNIVERSITY OF TEXAS MASAIIIKO KOIKE plex with ammonium sulfate a t pH 3.6 resulted in a ACSTIN,TEXAS LESTERJ. REED decrease in the enzymatic activities : dihydrolipoic RECEIVED NOVEMBER 25, 1958
(1) S. Korkes, e l al., J . Biol. Chem., 193, 721 (1951). (2) I. C. Gunsalus, in “The Mechanism of Enzyme Action,” The Johns Hopkins Press, Baltimore, Md., 1954, p. 545. (3) L. J. Reed, el al., J . Bioi. Chem., 232, 123, 143 (1958). (4) Abbreviations: D P N , diphosphopyridine nucleotide; CoA. coenzyme A; TPP, thiamine pyrophosphate; FAD, flavin adenine dinucleotide; Lip&, free lipoic acid; Lip(SH)o, free dihydrolipoic acid; RSa, protein-bound lipoic acid. (5) R. S. Schweet. PI ol., J . R i d . C h o n . . 196, 563 (1952); 11. R. Sauadi. u l ui , t h i d . , 197, 851 (1!152).
CHELATION AS A DRIVING FORCE IN SYNTHESIS. A NEW ROUTE TO a-NITRO AClDS AND a-AMINO ACIDS
Sir: Dibasic a-iiitro acids (I) are converted in weakly basic i i i c d i a to acid salts which rapidly decarbos-
