Dec. 20, 1952
6299
NOTES
of the compounds prepared are stated in Table I. Previously reported compounds are noted therein. Experimental a-(pEthy1benzenesulfonamido)-isocaproicAcid.-A solution of 7.72 g. (0.038 mole) of 9-ethylbenzenesulfonyl chloride, prepared as described elsewhere,* in 25 ml. of acetone was added slowly from a separatory funnel t o a mechanically stirred solution of 5.0 g. (0.038 mole) of t-leucine in 55 ml. of 2 Nsodium hydroxide and 25 ml. of acetone. During the addition the mixture was cooled in an ice-bath. Water was added t o dissolve the precipitated sodium chloride. The acetone was removed under vacuum a t 60' and the cooled solution was acidified t o thymol blue with concd. hydrochloric acid. The precipitated crystals were collected and dried. The yield of crude material was 5.48 g. or 48% of the theoretical amount. Recrystallization from hot water gave crystals, m.p. 117-118', used in the analyses. a ( p Ethylbenzenesulfonamido) isocapramide.-Three grams (0.01 mole) of the acid as prepared above was dissolved in 10 ml. of purified thionyl chloride and heated on a steam-bath t o solution. The gaseous products and excess thionyl chloride were removed under vacuum leaving a viscous liquid. Excess concd. ammonium hydroxide was added to this liquid. The crude reaction mixture was treated with 200 ml. of water. The crystals were collected and dried. The yield was 1.96 g. or 65% of the theoretical amount. Recrystallization from 95% ethanol gave crystals, m.p. 202-203', used in the analysis.
- -
-
Acknowledgment.-The authors are indebted to the Research Committee of the College of Arts and Sciences of the University of Louisville for a grant in support of this work.
sirup; yield 80 g. The sirup was dissolved in 1000 ml. of water and placed on a 290 X 105 mm. (i.d.) column of Darco G6Os:Celite6 (1: 1 by wt.) and washed with 10 1. of water. This solution was evaporated under reduced pressure to a sirup which failed t o crystallize; yield 17 g. The column was then washed with 10 1. of 5% ethanol. Upon evaporation under reduced pressure, this solution yielded a sirup (13 g.) which was crystallized by dissolving in the minimum amount of warm water, cooling t o room temperature, adding ethanol (95%) t o incipient crystallization and allowing to stand a t room temperature. The column was again washed with 10 1. of 10% ethanol. Upon evaporation this solution yielded 35 g. of sirup which crystallized from water-ethanol as described above. A further yield of sirupy material was obtained by washing the column with 10 1. of 20% ethanol. The sirup from this fraction showed only a slight tendency t o crystallize. This residue was combined with the mother liquors from the 5 and 10% ethanol washings and evaporated to a sirup which was extracted with 500 ml. of boiling 85% ethanol t o yield a further amount of 6 g, of crystals. The combined crystalline material was recrystallized from water by the addition of ethanol; yield of recrystallized material 39 g., m.p. 101-105' (sealed tube), [ ~ ] Z S D f131.3' (c 4.5, water). These constants are in good agreement with those given in the literature for stachyose tetrahydrate. * (5) Decolorizing carbon; a product of Darco Department, Atlas Powder Co., New York, N . Y. (6) No. 535, a siliceous filter-aid produced by Johns-Manrille Co. New York, N. Y.
DEPARTMENTS OF CHEMISTRY AND AGRICULTURAL BIOCHEMISTRY THEOHIOSTATE UNIVERSITY COLUMBUS 10, OHIO
OF
(3) R. H. Wiley and R. P. Davis, THIS JOURNAL, 74,6142 (1952).
DEPARTMENT OF CHEMISTRY COLLEGE OF ARTSAND SCIENCES OF LOUISVILLE UNIVERSITY 8, KENTUCKY LOUISVILLE
Improved Preparation of Stachyose
The Reaction of Phosphorus Pentachloride with Epimeric 2-Aminocycloalkanol Hydrochlorides BY EUGENEE. VAN TAMELEN AND RICHARD RECEIVED AUGUST7, 1952
s. WILSON'
During the course of work being carried out in BY M. L. WOLFROM, R. C. BURRELL, A. THOMPSON~ AND this Laboratory, it became desirable to investigate S. S. FURST the synthesis of diastereoisomeric 2-chlorocycloalRECEIVED AUGUST8, 1952 The tetrasaccharide stachyose was iirst isolated by von Planta and Schulze2 from the root sap of Stuchys tuberifera. Although stachyose has been found in a number of other plants, the tuber of Stachys tuberifera is still one of the better sources of this sugar. The method of isolation has been modified by Tanret.3 We wish to report herein a simple procedure for obtaining stachyose from the tuber of Stachys tuberif'era wherein the organic solids in the extract of the tuber were adsorbed on a column of carbon and removed selectively by washing with increasing strengths of ethanol, according to the general adaptation of Whistler and D ~ r s o . From ~ the eluates the sugar could readily be crystallized. Experimental Fresh tubers of Slachys tuberifera (1 kg.) were ground in a food chopper and were refluxed on a water-bath with 1750 ml. of 85% ethanol for 80 min. in the presence of 2.5 g. of precipitated calcium carbonate. The liquid was removed by filtration and the extraction was repeated with 500 ml. of 75% ethanol for 60 rnin. The extract was 6ltered and combined with the first filtrate t o produce a clear brownish solution which was concentrated under reduced pressure to a (1) Corn Industries Research Foundation Associate. (2) A. von Planta and B. Schulze, Bcr., PS, 1692 (1890). (3) G Tsnret, Bull. JOC. shim , 141 IS, 176 (1913). (4) R. L. Whistler and D P.Durso. TEN!JOUBNAL, 72, 677 (1960).
kylamines through the reaction of phosphorus pentachloride with cis- and trans-2-aminocycloalkanol hydrochlorides. The results of these studies, together with evidence for the stereochemistry of the products, are presented below. The synthesis of a 2-chlorocyclohexylamine hydrochloride (IIa) from trans-2-aminocyclohexanol hydrochloride (Ia) by this route was first reported by Osterberg and KendaL2 Direct evidence for the cis configuration (and therefore displacement by phosphorus pentachloride with inversion) has been presented by Carter, et al.,3and, more recently, by Paris and Fanta.* The isomeric 2-chlorocyclohexylamine and derivatives have been obtained by several methods.'-' Attempts to obtain this trans isomer through the action of phosphorus pentachloride on the hydrochloride of cis-2-aminocyclohexa(1) Abatracted from a research report submitted by Richard S. Wilson in partial fulfillment of the requirements for the Master of Sdence degree, University of Wisconsin, February, 1952. (2) A. E. Osterberg and E. C. Kendall, THIS JOURNAL, 42, 2616 (1920). (3) G. E. McCasland, R. K.Clark, Jr., and H. E. Carter, ibid., 71, 637 (1949). (4) 0. E. Paris and P. E. Fanta, ibid., 74, 3007 (1952). (5) G. E. McCasland and D. A. Smith, ibid., 72, 2190 (1950); 71, 637 (1949). (6) W. S. Johluon and E. N. Schubert, i b i d . , 71, 2187 (1950). 17) T. L. Ceirna, P. J. Graham. P. L. Bnrrick and K. S.Schreiber, J . Or#. Cham., 17, 761 (1962).
6300
NOTES
no15 (IVa) failed; only dark-colored resins could be isolated. lye have, however, been able to supple111ent the evidence for the stereochemistry of tlie two 2-chlorocyclohexylamines. The p-nitrobensamide6 (VIa) of the tranr isomer was converted, although in poor yield, to the oxazoline' (VIIa) by brief heating in alcoholic sodium hydroxide solution, tlie p-nitrobenzamides (IIIa) of the ~ 1 iso) mer, on the other hand, was recovered after siitiilar treatment. These results are consistent with the established conceptyof an internal displacentent (of halogen) with inversion; oiily the from-chloromitle is f'ivornbly oriented for such a process
VOl. 74
and trans-2-aminocycloalkanols proceeds with inI ersioii. XII interesting feature of trans-N- (p-nitrobenzoyl) -2-chlorocyclohexylamine (VIa) is its predoniinant hydrolysis, upon prolonged treatment with base, to p-nitrobenzoic acid and (presumably) tram2-chlorocyclohexylamine, rather than ring closure to the oxazoline. The latter reaction appears to be exclusive in the cyclopentane series, but proceeds only to the extent of 3.574 with VIa. Molecular models show that the amide VIb is decidedly better oriented for ring closure than is VIa. Experimentalll
Ring-closure of trans-N-(p-nitrobenzoyl)-2-chlorocyclohexylamine (ma).-To 1.10 g. of frans-X-(-(p-nitrobenzoyl)2-chlorocyclohexylamine6 (VIa) dissolved in 20 ml. of ethmol a t 70°, was added with stirring 8.0 ml. of 1.09 N sodium hydroxide in 80% ethanol a t 70'. The resulting solution was kept a t 70' ofor three minutes and then poured into 10 ml. of water a t 0 . The white precipitate (A) that formed was collected by filtration and dried. Recrystallization from 80% ethafol gave 0.13 g. (12%) of starting material, m.p. 177-180 The filtrate from (A) deposited a small amount of precipitate on standing, which was filtered off with suction. This solid (B) was a mixture and IIIa,b was ectracted with dilute hydrochloric acid to remove oxaioline. The eutract, upon treatment with excess, dilute sodium hydroxide, yielded a white precipitate which melted a t 108-114". A single recrystallization from ethdl101 gave 80 mg. (3.5'%) of 2-p-nitrophenyl-4,5-tetramethyleneoxazoline, m p. 116.5-118.5'. -4 mixed melting point with authaitic material6 was undepressed. The filtrate from ( B ) was acidified with dilute hydrochloric acid. The precipitated material ( m p . 236-239") was identified as p rtitrobenzoic acid by a mixed melting point determination. The yield in the present experiment (15%) could be raised considerably by longer treatment of the chlorocyclohexylxmide with base. Similar treatment of the corresponding cis-2-chloroamide I1138 resulted only in the recovery-of starting material. Refluxing with dilute base for 30 minutes resulted in considerable darkening, and again the only material isolated in a relatively pure state was starting amide. cis-2-Chlorocyclopentylamine Hydrochloride ( IIb ) .-To l*IIa,ti 6.0 g. of trans-2-aminocyclopentanol hydrochlorides in il flask surrounded by an ice-bath was added 11.0 g. Parallel reactions in the cyclopentane series were 500-ml. of phosphorus pentachloride dissolved in 100 ml. of dry benattended by more success. trans-2-Aminocyclo- zene a t 0". The contents were stirred for 30 minutes. pentanol hydrochloride (Ib) was smoothly con- Then the viscous mixture was filtered by suction, and the yield to czs-2-chlorocyclopentylam- precipitate was washed several times with dry carbon tetraverted in Five and six-tenths grams (83%) of the chloroine (IIb) ; similarly, the cis-aminoalcoholj (IVb) chloride. cyclopentylamine salt (m.p. 162-167') was obtained. Reafforded trans-2-chlorocyclopentylamine (Vb), al- crystallization from dry benzene-absolute ethanol raised the though in poorer yield. Again, the structures of rnrlting point to 168.0-170.5". The free base was not isolated, but converted to the solid these products were established by treatment of S-(p-nitrobenzoylj derivative IIIb. Crystallization from their N- (p-nitrobenzoyl) derivatives (IIIb and VIb) 80% ethanol afforded colorless needles, m.p. 160.5-162.0". with strong base. The czs-amide, after being Anal. Calcd. for C12Hd?Z03Cl: C, 53.64; €1, 4.88. heated to 170" for one minute with ethanofic sodium Found: C, 53.52; H, 4.80. hydroxide, was recovered unchanged; longer reactrans-2-Chlorocyclopentylylamine Hydrochloride (VIb).tion times gave only black, unpromising mixtures. cis-2-Aminocyclopentanol hydrochloride6 (2.65 g.) was The trans-amide (VIb), on the other hand, can be placed in a 500-ml. flask, and a solution of 5.0 g . of phosphorus pentachloride in dry benzene a t 0" was added. The retransformed with ease under identical conditions sulting mixture was stirred a t room temperature for six to cis-2-p-nitrophenyl-4,5-trimethyleneoxaz0line~~~~ hours. The suspended crystals were filtered arid theri (VIIb). The amide VIb was identical with the washed several times with dry carbon tetrachloride. After N-(p-nitrobenzoyl)-2-chlorocyclopentylamine ob- drying thoroughly, the product melted a t 209-213' and 1.15 g. (39%). The analytical sample (m.p. tained by the rearrangement of cis-2-aminocyclo- weighed 212.5-214.0°) was obtained by one recrystallization from pentyl fi-nitrobenzoate hydrochloride.l o dry benzene-absolute ethanol. Thus the well-defined differences in reactivity beAnal. Calcd. for CjHtlNC12: C, 38.48; H, 7.10. Found: tween cis- and frtrii~--"-cliloroamides establish their C, 38.38; H, 6.84. configurations, which in turn iiiclicate that the reacThe chloroamine hydrochloride was converted to the Ntion of phosphoruy petitaclilnritle wit!? both C I \ - ( p-nitrobenzoyl) derivative in the usual fashion (to prevent i111gtl~,.ure of the product to the oxazoline, exactly two (8) M ' I 1,etHer and K 4dams, 1111s IOVR\AL 6 9 , 2.252 f 1 ' 1 4 7 J i l i o i e 5 of txsr irere d d e d carefully to the aqueous solution
.
(9) 7 n ' l n - t v p nnd H l i o s ~ h ~ rhrd n 73 4669 i l n W ) ( l e i t.: I < i * l i l turnel
