1552
NELSONJ. LEONARD, PAULD. THOMAS AND VIRGILIT.GASH /CONTRIBUTION FROM
Unsaturated Amines. IV.
THE
Vol. 77
NOYESCHEMICAL LABORATORY, UXIVERSITY OF ILLINOIS]
Structures and Reactions of the Dehydrosparteines and their
BY NELSONJ. LEONARD, PAUL D. THO MAS^ AKD VIRGILW. GASH RECEIVED SEPTEMBER 10, 1954 The dehydrogenation of ( - )-sparteine by means of mercuric acetate leads successively to ( - )-P-dehydrosparteine and ( - )-A5,11-didehydrosparteine. These structures have been established by a variety of methods available for the detection of a,O-unsaturated tertiary amines (enamines). The salts corresponding to these unsaturated bases have been shown t o contain the A1(6)-dehydrosparteiniumand ~1(6),1i(1s)-didehydrosp~rteinium cations, respectively. Advantage has been taken
+
-+
of the attack by nucleophilic reagents on the >C=S< >C-S< group present ill these salts, for the preparation of 6cyanosparteine, 6,11-dicyanosparteine, and a series of 6-alkyl- and 6-aralkylsparteines,
By a combination of methods,5-i it has been shown that the mild dehydrogenation of quinolizidine (I) by means of mercuric acetate results in A1(lO)-dehydroquinolizidine(11), which forms salts of the a j ( l o ) dehydroquinolizidinium type (111). 2 With such knowledge available for this representative bicyclic system, i t was of interest to return to a consideration of the mercuric acetate dehydrogenation*of the tetracyclic alkaloid sparteine (IV), C1&?&-2, which consists effectively of two fused quinolizidine moieties. The products, called dehydrosparteine, ClbH24N2, and a-didehydrosparteine,
I
I1
The placement of the second double bond introduced into the sparteine molecule at the 11,12position is required because of the over-all change in stereochemistry a t C-11 effected by catalytic hydrogenation of a-didehydrosparteine.8-11On the basis of the analogy of the removal of hydrogen from a tertiary carbon (C-11) during the second step of the mercuric acetate dehydrogenation of sparteine and the further analogy of the removal of the Clg-hydrogen from quinolizidine (I + 11),2 it would be expected that the first double bond introduced into (-)-sparteine also would appear a t a tertiary carbon (C-6), making dehydrosparteine "( - )-A5-dehydrosparteine" (VII) and cr-didehydrosparteine "( - )-A5, "-didehydrosparteine" (VIII) (stereochemistry indicated)." While these structures have been regarded as correct representations of the dehydro products for some time both in
VI I
C15H22N2, which resulted successively from the action of mercuric acetate on Z-sparteine,8 were assigned structures V and V I (stereochemistry not i indicated) by Winterfeld and his co-workers.9,l o ; re-examination of the structures V and V I and those of their salts is facilitated by our present knowledge of the stereochemistry of the C15 family of lupin alkaloids. l~~~ (1) A section of this paper was presented a t t h e 5th Summer Seminar i n t h e Chemistry of Natural Products a t t h e University of New Brunswick, Fredericton, h-.B., Canada, August 19, 1953. (2) Paper I11 in this series: PI'.J. I,eonard, A. S . H a y , R . W. Fulmer and 1 ' . W. Gash, THISJ O U R N A L , 77, 439 (1955). ( 3 ) This work was supported in part by a grant from the Research Hoard of t h e University of Illinois. (4) Sinclair Refining Company lielloiv in Orgaiiic Chcmi,tr)-, 1953-1954. \Vork done under t h e sponsorship of the Sinclsir Iiesearch Laboratories, Inc. (3) R . Adams and J. E. hlahan, T H I S J O U R N A L , 64, 2588 (1Y43). (D) N . J. 1,eonard a n d V. W. Gash, ibid., 76, 2781 (1954). ( 7 ) N . J . Leonard and D. M. Locko, i b i d . , 77, 437 (1955). (8) R. Winterfeld aud C. Rauch, Arch. Phav7?7.,2 7 2 , 273 (1934). (9) 1;.U'interfeld and €1. E . Riinsberg, i b i d . , 274, 48 (1936). ( 1 0 ) K. Winterfeld and H. Besendorf, i b i d . , 282, 33 (1044). (11) 1.. Llarion and N J , T.ronnrd, Con J . C h e n . , 29, 3.55 (1951). [ 1 2 ) 2Iaria P r i y t i y l s k a a n d \V. I i Barnes, ..iili! C v y r l , 6 , 377 ( 1 9 5 3 )
T'III
this Laboratory and our present results offer conclusive evidence in support of V I 1 and V I I I . T o begin with, the dehydrosparteine of IVinterfeld and Rauch was known to possess the same skeletal structure as its precursor, sparteine, because of the regeneration of sparteine upon catalytic hydrogenation.8 The assignment of the entering double bond to an cu,p-position with respect to nitrogen has now been reached-thus definitely ruling out structure V as a possibility-by a compelling accumulation of evidence. The infrared spectrum of the C15H2,N2compound in chloroform showed absorption a t 1650 cm.-', while the monoperchlorate salt in the same solvent had an intense absorption maximum a t 1692 c m - l (1695 cm.-' in Nujol mull). The shift toward higher infrared frequency in going from an unsaturated tertiary amine to its salt has been shown to be indicative of a,p-unsaturation in the amine (>Ca-c-XCH-C=X
CH-C-N
C = N < function (conjugated) see, for example: A. Kaufmann and A. Albertini, B e y . , 42, 3776 (1909); A. Kaufmann and A. Albertini, i b i d . , 44, 2052 (1911); A Kaufmann, i b i d . . 61, 116 (1918); A. Kaufmann, J. Chem. Soc., 114, 187 (1918); A. Kaufmann and A. Albertini, B e y . , 42, 1999 (1909); R. D. Haworth and W. H. Perkin, J. Chcm. Soc., 127, 1434 (1925); (unconjugated), N. J. Leonard a n d A . S. Hay, THISJ O U R N A L , in press.
+
(17) For reactions of Grignard reagents with t h e > C = N < function (conjugated) see, for example: M. Freund, B e y . , 36, 4257 (1903); 37, 4666 (1904); M. F r e u n d a n d H. H . Reitz, i b i d . , 39, 2219 (1906); M. Freund and K. Lederer, ibid., 44, 2353, 2356 (1911); E. Spath a n d J. Gangl. .Monatsh., 44, 103 (1923); M. Freund a n d L. Richard, Bcr., 43, 1101 (1909); M. Freund and H. Beck, i b i d . , 37, 4679 (1904). (18) N J. Leonard and R. ti. Beyler, THISJ C J I T R N A I . , 73, 131G (1950).
trometric titrations indicated a progressive increase in the first pK’, value for sparteine (3.3), dehydrosparteine (5.0) and a-didehydrosparteine (6.8), and the second PK’a value for a-didehydrosparteine was 13.0 in 66% DMF. That two separate enamine functions (IX) were present in the a-didehydrosparteine also was indicated by a comparison of the ultraviolet absorption spectra of the same C15H26N2r CIF,H~~NZ and Cl5Hz2Nz compound^.^ Moreover, a-didehydrosparteine diperchlorate reacted with potassium cyanide in methanol to give a dicyanosparteine, C17H24N4, in excellent yield. The existence of dual structures X in the salt was proved further by the proximity of one entering nitrile group to each of the nitrogens in the dicyanosparteine, as shown by the low PK’, values for the latter (66% DMF): (1) l8was treated with (14.1 millimoles) of freshly distilled l-ethyl-2-methyl-A2- 72% perchloric acid until acid t o congo red. Recrystallizatetrahydropyridine prepared by the method of Ladenburg.% tion of the precipitated salt was accomplished from water containing a few drops of perchloric acid, m.p. 270' dec. Evolution of carbon dioxide was vigorous. After one hour (reported 25708 (no analysis), 262-2630i9). a t 60", the reaction mixture was cooled, rendered basic with Anal. Calcd. for CLjH~~C12S2O8: C, 41.77; H , 5.61; 40% aqueous sodium hydroxide solution, and extracted with N, 6.50. Found: C, 41.63; H, 5 4 2 ; N, 6.35. ether. The residue obtained on evaporation of the ether extracts was distilled, b.p. 14L5-1460(reported for l-ethyl-2The infrared spectrum of a Nujol mull had an intense ~nethylpiperidine,~~ 145-147'), n'% 1.4478, yield 1.40 g. band a t 1690 cm.-l. Active hydrogen: calcd. for one ( 7 8 % ) . The picrate, prepared in ether and recrystallized as active hydrogen, 0.23%; found, 0.25%. pk";, (66% gold-colored plates from ethanol, melted a t 189-190" (re- DMF): (1) 6.8; (2) 13.0. ported for 1-ethyl-2-methylpiperidine picrate,38188-189'). ( - )-AS~ll-Didehydrosparteine (VIII).-The amiiie, ob'4nui. Calcd. for C14H?oSaOi: C, 47.19; H, 5.66; N, tained from the perchlorate above by basification and ether extraction, was sublimed at 100-110" (0.5 mm.), m.p. 10515.72. Found: C, 47.27; H , 5.81;K,15.66. 10'7", [ u I z 5 D -698" (c 1.96 in benzene) (reported for uReduction of ( - )-A6-Dehydrosparteinewith Formic Acid; didehydrosparteine, [ a ] -647',8 ~ -627"9). The infrared -To 2.0 g. (44 millimoles) of 98-100~oformic acid a t 60 was added dropuise 6.58 g. (28.3 millimoles) of freshly dis- spectrum of a 10% solution in chloroform had a strong band 1645 tilled A6-dehydrosparteine while the system was swept con- a t 1646 cm.-l (previously reported for the tinually with a stream of nitrogen. Heating was continued cni.-*). The ultra\-iolet absorption spectrum in ether has until the evolution of carbon dioxide ceased (ca. 2 hours). been reported previously,' and the statement in ref. 18, p . 1322, referred to the absence of a maximum, in ethanol the reaction mixture \vas then added to 20 tnl. of 18% hydro(e.g. 281 chloric acid and extracted with ether. The aqueous layer solution,42typical of C=C-C=C-N ( - )-A5a11-Didehydrosparteine was recovered unchanged was basified and the amine recovered by ether extraction was distilled through a Holzman column, b.p. 113" (0.5 mm.), from attempted reduction with lithium aluminum hydride, sodium and liquid ammonia, and sodium and ethanol. yield 5.0 g. (750jo). The derivatives were identical wit: Reduction of ( - )-%ll-Didehydrosparteine with Formic those of ( - )-sparteine; monoperchlorate, n1.p. 170-171 Acid.-To 0.87 g. (3.8 millimoles) of A5~"-didehgdrosparteine dec. (reportedlo 173'); dihydrobromide, m.p. 194-197'' was added dropwise 0.74 g. (16 millimoles) of 98-100% (reported4l 19.t-195 "). Clemmensen Reduction of A1t61-Dehydrosparteinium formic acid. From this point, the reaction mixture was Bisulfate.-A solution of 4.75 g. (11.2 millimoles) of this treated as that from A5-dehydrosparteine and formic acid. The product, m . p . 102-log", was identified by direct comialt, m . p . 224-226' dec. ( r e p o r t e d s ~225-226'), ~~ prepared from ( - )-AE-dehydrosparteine, in 20 ml. of 12 -V hydro- parison as ( - )-a-isosparteine (I-cu-isosparteine)*sl*; dichloric acid, was added cautiously to zinc amalgam made picrate, m.p. 220-221' dec.; bisulfate, m.p. 264" dec.; diperchlorate, m.p. 235-257' pK', (66% D M F ) : from 18 g. of mossy zinc and 2 g. of mercuric chloride. (1)
