TOTAL SYNTHESIS
Sept. 5, 1958
[CONTRIBUTION FROM
THE
OF O X Y G E N A T E D
DEPARTMENT OF CHEMISTRY OF
4659
LUPINA L K A L O I D S
THE
UNIVERSITY OF WISCONSIN ]
Total Synthesis of Oxygenated Lupin Alkaloids’ BY EUGENE E.
VAN
TAMELEN AND JOHN S. BARAN
RECEIVEDMARCH10, 1958 Details of the first total syntheses of various oxygenated lupin alkaloids, including cytisine, anagyrine and thermopsine, are described.
Collectively, the lupin alkaloids bear the quinolizidine ring (I) as a common structural unit, al-
Guided by the biogenetic schemes, e . g. \’, promulgated by Robinson and others, we initiated a COOH C H 2 0 - . . i- - C H , - - - C H o / ~
CH2OH I
/
I
I1
though, individually, niembers may differ with regard to such features as stereochemistry, oxidation state and number of additional rings. Thus, lupinine (11) represents the simplest, bicyclic type, the first in the family attained by synthesk2 The alkaloids3p4 possessing the bridged, tetracyclic skeleton I11 contrasts with the lupinine case as well as that of cytisine (IV), an almost unique repre-
T‘
HOOC
laboratory approach which, in the case of cytisine, involved the projected twofold Mannich condensation of benzylamine, formaldehyde and 2-(a-
CHzO
CHCOOH
I
COOH
> >CH2 s-
‘CH?C( COOHj :: \’I I CsHsCH2KH
C H 2 - n )CH, s-
\CH~CHCOOH VI11
(1) First reported in Communications to the Editor, THISJOURNAL, 77, 4944 (1955); 7 8 , 2913 (1956). acid VI11 could be obtained either by thermal de(2) G. R. Clemo, W. McG. Morgan and R. Raper, J. Chem. SOC., carboxylation of the malonic acid or by initially 965 (1937). carrying out the condensation with prolonged heat(3) S . J. Leonard in Manskc and Holmes, “The Alkaloids,” ing and with benzylamine hydrochloride instead Academic Press, Inc., New York, S. Y.,1953, Vol. 111, pp. 12@199. of the free base. Attempts to introduce a second (4) F. Galinovsky, “Progress in the Chemistry of Natural Products,” Springer-Verlag. Vienna, 1951, Vol. V I I I , pp. 245-277. methylene unit and thereby secure the desired bi(5) (a) N. J. Leonard and R . E. Beyler, THISJOURNAL, 70, 2299 cyclic intermediate IX, were unsuccessful. These (1948); (b) G. R. Clemo, R. Raper and W. S. Short, Nature, 162, 268 (1948; (c) F. Sorm and B. Keil, Collection Cacchoslow. Chem. Commun., (9) R. Robinson, “The Structural Relations of Natural Products,’’ IS, 564 (1948); F. Galinovsky and G. Kainz, Monalsh., 80, 112 Oxford University Press, London, 1955, p. 77. (1949); (e) M. Carmack, B. Douglas,E. W. Martin and H. Suss, THIS (10) T h e physiological-type synthesis claimed by E. Anet, G. K. JOURNAL, 77, 4435 (1955). Hughes and E. Ritchie, Auslv. J. Sci. Reseauch, Ser. A , 9 , 635 (1950). ( 6 ) E. Spath and F. Galinovsky, B e y . , 66, 1526 (1932). has been discredited by C. Shopf, G. Renz, F. Rraun, H. Hinkel and R . (7) H. R. Ing, J. Chem. Soc., 2778 (1932). Rokohl, Airgew. Chem., 66, 161 (1953). (8) T. A. Henry, “Plant Alkaloids,” T h e Blakiston Co., Philadel(11) W. von E. Doering and R. A. Well, THIS JOURNAL, 69, 2463 phia, Pa., 1949, fourth edition, p. 153. (1947).
EUGENE E. VAN TAMELEN AND
4GGO
attempts included the treatment with formaldehyde of the monocarboxylic acid VI11 or its ester; the triester (X, R = C2H6) and the triacid (X, R
= H), which were available from an alternate approach (vide infra); the amino alcohol X I (X =
p
c11>-y--4' CsIISCHiSH 'CH* \ / 'CH2CHCHtX S I CH 2 - ( , r \ \ A -4 RSH >cl-r, ,, + c H 2 c I - I c H ~ XII
'
OH), obtained by lithium hydride reduction of the ethyl ester of VIII; and the quaternary salt XI1 (R = COH~CHZ-), provided by cyclization of the primary bromide X I (X = Br) derived from the corresponding amino alcohol. Although the plan to build up the bicyclic intermediate I X from 2-(cr-pyridyl)-ethylmalonic acid had failed, we hoped to preserve the essence of the approach by utilizing instead 2- (a-pyridy1)-allylmalonic acid (XIII), which already possesses the methylene group which we failed to insert in our adherence to scheme (A). This acid seemed well suited for the kind of synthetic operation envisioned, in that the Mannich reaction would in this case be accompanied by the mechanistically sound conjugate addition of the benzylic nitrogen to the vinylpyridine system.I2 The diethyl ester of the starting material already had been described,13 and can be prepared in reasonable yield by the reaction of sodiomalonic ester and 2-(a-pyridyl) allylacetate, carried out in dimethylformamide benzene. The diacid XI11 was secured as a crystalline solid (imp. 115" dec.); however, a dilute aqueous solution, obtained by addition of an amount of mineral acid exactly equivalent to the base used for saponification, was usccl for actual synthetic operations. Heating of the malonic acid solution with benzylamine and slightly more than one mole /=====-7xd
CH*==?C~HSCHIKHZ ,CHz --j. CH20 CH(COOH)z S I 1 1
€I*XIV (12) A . H. Summers, Rl. Freifelder, 13. B. Wright and A. W.Westou, TSIIS J O U R N A L , 75, 57 (1953). (13) F. Bohlmann, N. O t t a w a and ICIi,OIi
c 2
XXIII
move. Sodium ethoxide in refluxing ethanol produced an 89% yield of the imide, m.p. 137-138', which could be prepared more expeditiously from the starting pyridylacetamide without isolation of the intermediate addition product XXI. Hydride reduction of the glutarimide X X I I to X X I I I failed, seemingly because of the several ac(16) R. Adams and S. Miyano, THISJOURNAL, 76, 3108 (1954),reported t h a t ethyl a-pyridyl acetate and methylene malonic ester yield, in the presence of sodium ethoxide, the addition-cyclization product (i).
HsCzOOC-
H
k d -c )>
2-
0
(17) Treatment of this amide diester with aqueous ammonia led t o t h e triamide X X I b , independently secured by amination of t h e triester X X I a obtained b y addition of ethyl pyridylacetate t o methylene malonic ester. This result a t this stage excluded the alternate structure ii for the a-pyridylacetamide-methylene malonic ester addition product.
(HsCZOOC)2CHCHzNHCOCHz ii
II,NCSCH~ h.-.
iii
iv
was introduced into the reaction serirs by converting a-pyridylacetamide t o t h e thioamide iv through treatment with phosphorus pentasulfide in refluxing toluene (yield l5-20TO). Addition of this anionic agent t o methylene malonic ester proceeded smoothly, affording t h e thioamide diester v, which readily cyclized, on treatment with ethanolic base, t o the yellow-orange, crystalline thioimide vi. Desulfurization of this imide gave a mixture of products, from which there could be isolated a 23% yield of a colorless crystalline product, m.p. 140.4141.5', possessing t h e formula ClrH14NsOa. The analytical results required the simple loss of a n -SH unit and thereby implied the presence of a new double bond. T h e unsaturation revealed itself in the
V
0
A-
vi
0
ultraviolet, where its conjugation with t h e pyridine ring was indicated by absorption at 307 mp ( e 17,500). We therefore consider t h e desulfurization product t o possess structure vii. Further reduction
/=====\
of vii seemed feasible; however, efforts along these lines were unattractive, and the sequence involving thioamides was abandoned.
EUGENE E.
4662
VAN
TAMELEN AND JOHN S. BARAN
which utilizes the Mannich-ring closure step was the more satisfactory, with respect to operational facility and over-all yield. The sequence of steps designed to lead from the piperidine alcohol to the cytisine system is encompassed by the formulas XXV-XXVII. -Although
XX\' f -=-== '
XXV I
Br-
,
>
--/
CsHaCHzN' \--
\x< ---/
- \
\\
0
XXVI I
the conversion of the aminoalcohol to the corresponding bromide XXV and the quaternization of the latter seemed secure, oxidation of the salt XXVI to the pyridone XXVII was suspect. Preparation of pyridones by alkaline ferricyanide oxidation of quaternary salts (XXVIII) derived from pyridine itself is well known,20yet the operation cannot be applied to a-alkylpyridinium salts (XXIX) or to the simplest member (XXX) of the tetrahydroquinolizinium salt classi3 to which the tri-
XXVIII
XXIX
XXX
cyclic intermediate XXVI also belongs. Reflection on the nature of the structures involved leads to the conclusion that attachment of hydroxyl to a pyridinium salt followed by oxidation, observed with the simplest type XXT'TIT, is not the only path-
XXXI
way open to the 2-alkyl type, which can instead eliminate to the anhydro base X X X I ; ensuing oxidation may then proceed abnormally, atid the expected a-alkyl-a'-pyridone is not formed. Turning to the item of particular interest, we see that, on account of the restrictions explicit in Bredt's rule, the tricyclic cutiopL X X 1 T is not convertible to an anhydro base. Consequently, i t may be concluded, insofar as oxidation of pyridinium salts to pyridones is concerned, that the case for which model experiments portended failure is in fact the very case with the structural feature allowing success. Turning again to the account of the experimental, refluxing of the aminoalcohol XVIII with 48Vo ( 2 0 ) t . g . , li. A. P r i l l R I I ~ S. I t . h I c B l v a ~ n , Gilman's "Org.inic Syntheses," John R'ilcy and S o n s , S e w Uork, S . X-.,1013, Coll. Yol. 11, p. 419.
Vol. 80
aqueous hydrobromic acid resulted in formation of the bromide XXV; the free base was not isolated, but cyclized, on brief heating in benzene, to the crystalline quaternary bromide. When aminoalcohol secured by hydride reduction of unepimerized ester (XIV, K = C2Hs) was used in this step, the over-all yield arnounted to 25%; on the other hand, base treatment of the ester preliminary to the same series of operations raised the over-all yield to 5GYG. Oxidation of the tricyclic salt, carried dut with alkaline ferricyanide in aqueous solution a t approximately loo", produced N-benzyldl-cytisine (XXVII), m.p. 137.5--139.0'. The identity of the synthetic product was demonstrated by infrared spectral comparison with N-benzyl-lcytisine, obtained by direct alkylation of the alkaloid with benzyl chloride. In order to complete the synthesis there remained, apart from the resolution, the requirement of removing the benzyl group from the N-benzylated base. After satisfying ourselves that the reductive cleavage could not be managed readily by a catalytic process, we resorted to constant-boiling hydriodic acid, using the conditions prescribed by for regeneration of cytisine from various N-alkylated products. This last operation afforded :I .XY'I,yield of dl-cytisine, m.p. 146-147', which was purified by sublimation, followed by recrystallization from acetone-ether. The infrared spectra of the synthetic and the natural bases, both in chloroform solution, were indistinguishable. Resolution was accomplished by working with d-camphor-10-sulfonic acid as the resolving agent. Crystallization of the salt by addition of acetone to equimolar amounts of the components dissolved in methanol resulted in complete resolution, as evidenced by the identity of the isolated product, m.p. 283-28s3, with the d-camphor-10-sulfonate of natural cytisine. Further, the base regenerated from the. salt obtained in the resolution possessed ;t melting point, I .i-4..i-l.i3.c50,and rotation, /cy]% - 1116..3" (water'i, substantially identical with those recorded for natural cytisine. The mixed melting point deterriiiriation of the resolved synthetic base and the natural base (imp. 154.5-153.3"! showed no depression, and the infrared spectra measured on samples dissolved in chloroform were identical. Two alkaloids which have been demonstrated to be simple N-alkyl derivatives of cytisine are caulophylline N-methylcytisine)2 2 and rhombifoline (N-butenylcytisine).21 The first has been detected in a fair iiuniber of Legunzinosae, while the second has been isolated from only one plant, Thermopsis rhovnb(fo1in (Nutt), Richards; both have been obtained from natural cytisine by appropriate N-alkylation . ' 2 i . 2 3 With the parent now accessible by total synthesis, 'these two substances may therefore be regarded similarly. Synthesis of Oxygenated Tetracyclic Lupin Alkaloids.-Of the great variety of lupin alkaloids the tetracyclic bases are the more numerous and, therefore, more representative. The reported syn'21) 'A'. F. Cockburn and L. l\Iarion, Can.J . C h e w . , 30, 93 (1932) ('22) J. L-. Lloyd, Puoc. A m , Phavm. Assoc., 41, 115 (1893); I:. F? Power and A H. Salway. J . C h e m . Snc.. 103, 191 (1018) ( 2 3 ) A , P x t h e i l , Ber., 24, 633 (lS91).
Sept. 5, 1958
TOTAL SYNTHESIS OF OXYGENATED LUPINALKALOIDS
theses of the sparteine system are simple and effective ; however, because of the particular symmetry properties of the oxygen-free system, synthetic techniques can be employed which are not amenable to the oxygenated class. It appeared that the first of the two cytisine approaches described above might be modified so as to allow an entry into the oxygenated tetracyclic group, and the account below is concerned with details of such attempts. 1-Anagyrine, a t times referred to as monolupine, rhombinine or alkaloid 111, is a distillable oil first 4
5
H
4663
In addition to the obvious fact that the bridged system of anagyrine requires that the potential bridgehead hydrogens be cis, we note that the hydrogen a t position-11 is trans to that a t the bridgehead, as depicted by the conformational expression XXXVI.
HH
XXXVll
A noteworthy feature of the molecular system is the axial 11,12-bond, one of three axial attachments to ring C. In operating within the tetracyclic SSSII H H isolated by Partheil and SpasskiZ4from Anugyris framework, production of the more stable, equaarrangement a t C-11 (for example, converfoetida, and since detected in many other lupin torial sion of sparteine to a-isosparteineZ8or the catalytic alkaloid sources. The efforts of Galinovsky, Ing, reduction of anagyrine to 1upanine2’) is commonly Clemo, Rydon and others resulted in the accep- effected; on the other hand, generation of an axial tance of structure XXXII, a ring homolog of cytihas not been realized, and therefore prosine, which substance anagyrine markedly re- linkage for the required stereochemistry a t C-11 of sembles. Lupanine, appearing variously as the d-, vision 1- or dl-forms, also gained the attention of nu- anagyrine should be made before the bridged sysmerous investigators; and clear recognition of its tem is locked in place. The all-axial status of ring C in the bridged system corresponds to the conforstructural nature (XXXIII) resulted from the mationally inverted form of an all-equatorial syswork of Clemo25$26 and Ing.27 tem, and thus, in order to achieve the less stable stereochemical arrangement present in anagyrine, there is required simply the most stable, allequatorial form XXXVII of intermediate XXXV. However, consideration of the chemical changes (HOOC)*CH iJ. during which the three asymmetric centers in the AX-, XI11 CHO, tricyclic intermediate I X are created, force the conL./ clusion that dependable stereochemical predictions are not possible. I n the first place, a choice between the erythro and threo forms for the monocarboxylic acid XXXIV which results from the decarboxylation step is difficult. Secondly, as pointed out earlier, the nature of the proton transfer COOH to the penultimate product in sequence C, the CYInitiation of the anagyrine synthesis involves pyridyl anion, is uncertain. Fortunately there can brought to use a mechanistic device which, in the Mannich reaction between 2- (a-pyridy1)-allyl- be effect, allows equilibration of all the asymmetric malonic acid (XIII) and 5-aminovaleraldehyde, accenters in XXXV, and therefore ensures acquisition companied by cyclization to 3-(a-pyridyl)-quinoliof the required stereochemical isomer. That zidine-1-carboxylic acid (XXXIV) (sequence C) . treatment of the ester with anhydrous alcoholic In practice, an aqueous alcoholic solution of the alkoxide will effect at C-5 conversion to the anion unsaturated pyridylmalonic acid and the solid tri- and thus to the more stable configuration, is well mer of A’-piperidine was heated on a steamprecedented requires no further comment. bath; isolation of the acidic material was followed, IVhether suchand a process can be brought into operawithout purification, by esterification under Fischer tion a t the similarly activated C-3 position is less conditions, fractional distillation of the resulting is evidence that abstraction of a product affording the liquid ethyl ester XXXV of certain-there the acid XXXIV. Thus, by putting to use two proton from an a-pyridylmethine carbon under readily available starting materials, it was possible these conditions is a relatively slow process.29 to assemble, in a single laboratory operation, a Nevertheless, direct equilibration a t a second suitably oxidized tricyclic intermediate possessing asymmetric center seems likely. Galinovsky and ~ ~ demonstrated that d-isopellethe entire carbon-nitrogen skeleton of the tetra- c o - w ~ r k e r shave tierine or N-methyl-d-isopelletierine (XXXVIII) , cyclic lupin system. During the course of the multiple operations de- although stable in acidic media, suffers fairly scribed above there arise three asymmetric centers. (28) K. Winterfeld and C. Ranch, Arch. Phavmne. B e y . drscn. phav(24) (25) (26) (27)
A. Partheil and L. Spasski, A p o f h . Z., 10, 903 (1895). G. R. Clemo and G. C. Leitch, J . Chem. SOL.,1811 (1928). G. R. Clemo, R. Raper and Ch. Tenniswood, i b i d . , 429 (1931). H. R. Ing, ibid., 504 (1933).
maz. Gcs., 272, 273 (1934). (29) W.v. E. Doering and V.Z. Pastemak, THISJOURNAL, 72, 143 (1950). (30) F. Galinovsky. G. Bianchetti and 0. Vogl, M o i i o t s h . , 84, 1221 (1953).
EUGENE E.
4664
VAN T A M E L E N AND
JorrN
s. BARAN
Vol. 80
rapid racemization in weakly basic aqueous solution at room temperature or below; the change was considered as due t o a 8-elimination-addition process which momentarily destroys the asymmetric center. Accordingly, the action of reflux/\ /'\ 0
pure perchlorate (m.p. 315°).32 Since we gained no evidence for the formation of diastereoisomers after the step involving equilibration of the tricyclic ester X I , we regard this total synthesis as stereoselective. Since lupanine has been secured by catalytic reduction of anagyrine, the synthesis described above also embraces, in a formal sense, the structure of the former alkaloid. I t was apparent that by building upon the k foundation of total syiithesis now established cering anhydrous alcoholic base would be expected to tain other minor quinolizidine alkaloids should be induce in XXXV temporary elimination to a 10- attainable without great difficulty. One such case is represented by thermopsine. This alkaloid, isolated as the d-form from Lzrpinits genera and as the L-form from Ticerntopsis genera,2 was demonstrated by Marion and Leonard to possess the tetracyclic pyridone structure XLII, i.e., diastereomembered heterocyclic ring and lead, therefore, ultimately to the required all-equatorial isomer HP -__ XXXVII.3' t (cat.) In order to prepare for conversion to the tetracyclic stage, the equilibrated pyridyl ester was I-I reduced by means of lithium aluminum hydride to t clear again. The solution was heated on the steambath (vessel should be stoppered to prevent evaporation of solvent) for one day, cooled and extracted with five 15nil. portions of benzene. The combined benzene extracts were dried over anhydrous sodium sulfate, freed of solvent in unczio, and the residue distilled in a 10 mu.diameter glass t u b e (sealed a t one end), by heating in an appropriate aluminum block, to give 114 rng. (41Yc) of dl-anagyrine, b . p . IX-l'iS" (0.1 mm.) a light yellow glass a t room temperat ure. .Ifreshly prepared sample, 114 mg. (0.47 mmol.), was (liw~lverlin 6 ml. of methanol and neutralized with 4.63 inl. of 0.101 N perchloric acid. The solution was evaporated to dryness, and the crystalline residue recrystallized from absolute methanol to give 114 mg. (81y0)of colorless, cottony needles, m.p. 315". Anal. Calcd. for CI5HY10J2C1: C, 62.25; H, 6.14. Found: C, 62.20; II, 6 . 1 . A sample of dl-anagyrine regenerated from pure dlanagyrine perchlorate was distilled for analysis to give a colorleis plaw, b . p . I X o jn.1 mm.!. The infrared spectra
[COSTKIBUTIOS FROM
THE
Vol.
so
in carbon disulfide solution, and ultra1 iolet spectra in 95TL ethanol, of dl-anagyrine and authentic 1-anagyrine were indistinguishable. dl-Thermopsine.-Thirty-five mg. (0.143 m ~ n o l). of dlanagyrine (regenerated from its perchlorate) was dissolved in 6 ml. of 5yoaqueous acetic acid. T o tlie solution in a 1:ml. graduated centrifuge tube was added 365 mg. (1.14 mmol.) of mercuric acetate. After the mercuric acetate dissolved, a slow, fine stream of nitrogen was passed through the solution, and the solution was heated on a steam-bath for two hours. The volume of solvent was kept constant by the addition of 5% acetic acid. rlfter heating, the solution was cooled to 0" and the precipitated mercurous acetate (100 tng.) was centrifuged. The aqueous solution was then saturated with hydrogen sulfide, 5 drops of concentrated hydrochloric acid and 3 drops of concentrated sulfuric acid were added to the mixture, and the mixture was heated (111 :i steam-bath until the mercuric sulfide coagulated. Then the mercuric sulfide was centrifuged, and the clcar aqueous layer was evaporated to dryness in uacuo. T h e residue was dissolved in water and the solution made basic. Since the dehydrogenation product is unstable, the basic soiution was rapidly extracted with four 15-ml. portions of chloroform, which were subsequently dried over anhydrous sodium sulfate for several minutes. The chloroform solution was filtered, evaporated under a stream of nitrogen, and 10 ml. of absolute methanol mas added t o the residue. The methanolic solution was shaken with two 50-mg. portions of Raney nickel, filtered, and hydrogenated over :if1 mg. of 6% palladium-on-strontium carbonate at 1 a t m hydrogen for 5 minutes. The hydrogenation m filtered, the solvent evaporated completely, and the residue (31.5 mg.) mas chromatographed on a colunin of 400 mg. of silicic acid in chloroform (ratio of height to width of column was 3 : 1 ) . The mixture was placed on the column with 5 drops of chloroform solution and eluted n i t h lyL methanol in chloroform. .I band which immediately separated with 1% methanol in chloroform was collected and the residue obtained after evaporation of solvent was sublimed at 0.1 mm. to give 6 mg. of a n oil, b.p. 150-170° (1 mm.). On scratching, the oil crystallized to material melting a t 155-165'. The solid was recrystallized from :i very small amount of acetone-ether and resublimed t o gi\-e ail oily solid, m.p. 160-168". This solid \vas washed in the sublimation tube with a little ether and then resublimed to give 2 mg. of dl-thermopsine, m.p. 170-172'. .A mixed m . p . with authentic dl-thermopsine was 170-172'. The infrared spectra in carbon disulfide solution, and the ultraviolet spectra in 9570 ethanol of synthetic and authentic samples of dl-thermopsine were identical.
MADISOX, '\T~Isc
DEPARTMEST OF CHEMISTRY, USIVERSITYOF DELAWARE]
Observations on the Mechanism of Addition Reactions of Olefins; Criteria for Mechanism in Mixed Aqueous Solvents BY
HAROLD KWVART A N D LEWISB. WEISFELD' RECEIVED DECEMBER 18, 1957
The rate of racemization of optically active 3-p-menthene has beeii found to be equal to the rate of addition to the double bond in highly acidic aqueous alcoholic solutions. These results are consistent with the hydration mechanism proposed by Taft and co-workers2and exclude a reaction sequence in which a carbonium ion is formed in a preliminary proton equilibrium step. The addition rates are well correlated by the activity postulate and the acidity scale suggested by Grunwald and co\wrkers.7,9,10This latter observation has been interpreted to establish a reaction mechanism whereby a r-complex is formed in a primary proton equilibrium followed by a rate-determining transition to carbonium ion with the exclusion of solvent from the major transition state. The acetoxylation of 3-p-menthene in glacial acetic acid with trifluoroacetic acid as catalyst is found to be mechanistically analogous to the hydration-etherification reaction. Criteria are developed for kinetic analysis of lyonium ion catalyzed reactions in other than purely aqueous media.
formative studies on the detailed mechanism of H + Introduction series of experiments reported by Taft and ~ 0 - addition reactions of common Olefinic substances. 'OnstitUte the most recent and most in- ; c ) R. R'. T a f t , Jr., A b s t r a c t s of Papers, 125th Meeting A.C.S., (1) E. I. du Pont de Nemours, Fellow 1955-1956. 12) (a) R W. Taft, Jr., TFIISJ O U R N A L , 74, 5372 (1952): (b) J. B I , e r y , R. U'. T a f t , Tr., a n d L . P Nammett, ibid.. 76, 1253 (1953);
Kansas City, Mo,, March, 1934, p. 12P; (d) R. W. T a f t , Jr., E. L. Purlee, P. Riesz and C. A. DeFasio, THISJ O U R N A L , 77, 1584 (1955); (e) P. Riesz, R. W. T a f t , Jr., and R . H. Boyd, ibid., 79, 3724 (1957).
