M a y , 1942
CHEMICAL CONSTITUENTS OF DISTILLED LIMEOIL [CONTRIBUTION FROM THE
9.59
RESEARCH LABOIUTORIES OF FRITZSCHB BROTHERS, INC.]
An Investigation of the Chemical Constituents of Distilled Lime Oil (Citrus Medica, L., Var. Acida, Brandis) (Citrus Auranfifolia, Swingle)* BY ERNESTS. GUENTHER AND EDWARD E. LANCENAIJ The oil distilled from the juice of the whole crushed fruit of Citrus medica, L., var. acida, Brandis (Citrus aurantifolk, Swingle) has long been produced in the West Indies and Mexico; this is the oil known in commerce as distilled lime oil. I t must not be confused with the expressed oil which is obtained either by the dcuelle method or by crushing the whole fruit and subsequently separating the oil from the juice by means of a high speed centrifuge. Since a thorough study of distilled lime oil has not been reported previously in the literature, this investigation was undertaken to determine the chemical constituents of a normal oil. Burgess and Page' investigated a distilled lime oil from which the terpenes had been removed by distillation. They established the presence of 1-a-terpineol as the main oxygenated constituent and the presence of bisabolene (their "limene") as the main constituent of the higher boiling fraction. The present investigation has confirmed the presence of these two constituents. The a-terpineol isolated by Burgess and Page differs somewhat from that obtained in this investigatioq in respect to its optical rotation. These earlier investigators reported a rotation of - 20" for the purified alcohol in a supercooled state; the a-terpineol isolated in this Laboratory showed a specific rotation of - 11'. From the mother liquor of the phenylurethan derivative of a-terpineol, Burgess and Page2 isolated a second phenylurethan which crystallized in needles, m. p. 1.72'; they suggested this might be an unknown isomeric terpineol. Following the procedure outlined by them, we were unable to isolate a phenylurethan of m. p. 132". Possibly the crystals obtained by them may have been an impure form of bornyl phenylurethan (m. p. 138-139') which we obtained in the form of long thin needles upon recrystallization from alcohol. According to Parry,s distilled lime oil contains * Original manuscript received May 26, 1942.
pinene, limonene, dipentene and cymene ; however, he gives no experimental data to substantiate this statement. The present investigation has established the presence of a-pinene, p-pinene, limonene, and dipentene; the presence of p cymene was not established.
Experimental The oil used in this investigation was distilled in Mexico from the juice of green crushed fruit: dls 0.866; +OD 1.4761; ~ O +41°6'; D solubility a t 20", 4.5 to 5 volumes and more of 90% alcohol; aldehyde (as citral), 1.15OJo.' Twenty-seven pounds of oil was fractionated under vacuum in a commercial still having a 6-foot column: the four main fractions and residue of Table I were obtained.
Fraction I The first lo%, removed by distillation at 20 mm. with a 36-inch column of the Young type having 22 disks and bulbs, was repeatedly fractionated under vacuum. A final distillation a t atmospheric pressure yielded fractions boiling a t 150-160°, 160-170°, and 170-175'. Identification of a-Pinene.-The fraction 150-160" (4 cc.) was rectified over metallic sodium a t 20 mm.: dls 0.860; CPD +12"20'; PPD 1.4674. A nitrosochloride was prepared by the procedure of Wallach6: small shiny plates were obtained, m. p. 102-103"; a mixed m. p. with the nitrosochloride prepared from the corresponding fraction of American turpentine oil showed no depression. Identification of Furfural.-The fraction 160-170" (4 cc.) possessed a strong musty odor suggestive of furfural. The aldehyde was separated by washing the oil with water and extracting the washings with ether; 0.3 g. of a yellow oil was obtained. A drop added to 2 cc. of 4% freshly distilled aniline in glacial acetic acid gave the intense red color characteristic of furfural. The oxime melted at 8990" after three recrystallizations from dilute alcohol; a mixed m. p. with the oxime of furfural showed no depression. Identification of 8-Pinene.-The fraction 16&170" was now rectified over metallic sodium a t 20 rnm. : d l s 0.862; a% +30'25'; 1.4748. These properties differ considerably from the accepted constants of pure @-pinene, and indicate that only a small amount of this terpene could be present. The oil was oxidized with alkaline potassium permanganate by Wallach's method6: the nopinic acid obtained melted a t 124-126 '. There was insufficient material for a recrystallization. According to Wallach,6 pure nouinic acid melted a t 12C-127'.
(4) Aldehydes were determined by the following procedure. To a 5.0-g. sample was added 26 cc. of a neutral 0.6 N hydroxylamine hydrochloride solution; after fifteen minutes the liberated hydro(1) Burgess and Page, J . Chum. Soc., 86,414 (1904). chloric acid was titrated with 0.1 N d i u m hydroxide walution w i n g (2) Burgess and Page, ibid., 86, 1829 (1904). (3) Parry, "The Chemiitry of Emntial 0118 and Artificial Pu- hrom phenol blue as indicator. (5) Wallach, Aan., 146, 251 (1888). fumes," fourth edition, D.Van Noatrand Co.. he., New York, N. Y., (6) Wallach, 4bddd,866,228 (1907)h 1921. VOl, I , p, 440.
ERNESTS. GUBNTHER AND EDWARD E. LANGENAU
1-01. 65
TABLE I Fraction I
Per cent. of original oil Boiling , ! : range
{
dls uZoD 7t"D
Fraction I1
Fraction I11
Fraction IV
Residue V
2.4 14.9 3.8 3.4 Up to 68" at 68' a t 14 t o 76' a t 12 to 105' at 12 to 129' a t Above 129' at 12 14 76" a t 12 12 105' a t 12 0.853 0.865 0.931 0.896 0.934 +54'15' +2G040' -7'0' -17'55' Too opaque 1.4740 1.4805 1.4825 1.4923 1.5062 2.4 0.5 2.3 0.3 2.7 0.0 0.9 2.7 5.4 8.8 13.2 0.9 0.9 3.7 13.0
75.0
Aldehyde (as citral). % Acid number Ester number Ester number after acetylation 0.9 4.5 vols. a m . Solubility at 20' 90% alc.
34.4 219.5 70.6 80.6 5 vols. a.m. 1.5vols. a.m. Clear up to 1 vol. Clear up t o 1.5 vols. 90% alc. 60% alc. 95% alc.; cloudy 95% alc.; cloudy w.m. to 2.5 vols.; w.m. clear again in 2.5 vols. a.m.
The aldehydes of the residual 90% were removed with sodium bisulfite. Five liters of oil was shaken with 2.5 liters of 40y0 sodium bisulfite solution for eight hours; '5 the crystals which after standing for seven days at , formed were filtered off and repeatedly washed with ether. I 'pon regeneration with IOC;', sodium carbonate solution dlld extraction with ether, 0.88 g. of a yellow oil having a pronour~crdodor of ii. fatty aldehyde was obtained: n% I .421u Identification of n-Octyl Aldehyde.-The semicarbazone of the regenerated aldehydes melted a t about 88-92' after six recrystallizations froin dilute alcohol. In an attempt to resolve this mixture, the semicarbazones were acidified with dilute sulfuric acid and the mixture steam distilled: a distillate of 100 cc. was collected, from which the liberated aldehydes were extracted with ether. The recovered aldehydes were fractionated by a micro-technique.' The semicarbazone of the first fraction (about 0.2 9.) melted at 96.5-97.5"after two recrystallizations from dilute alcohol. The semicarbazone of n-octyl aldehyde melted a t 97-98 "; mixed m. p. 96.5-97.5'. One liter of the aldehyde-free oil was fractionated at 20 mm.; nine 100-cc. fractions were collected; these showed the following rotations: (1)+50"20'; (2)+54"50'; (3) +56"25'; (4) +57"10'; (5) +57'58'; (0) -I-58'21'; (7)+58'29'; (8)+5T038'; (9)+57'0'; (residue) +46"0'. Identification of d-Limonene.-The sixth and seventh fractions, having the highest rotations, were combined and rectified over metallic sodium a t atmoSpheric pressure: dls 0.850; a '% +58"30'; nZoD 1.4730; b. p. 175176'. The tetrabromide melted at 103-104 O after recrystallization from dilute acetic acid and from ethyl acetate; a mixed m. p. with limonene tetrabromide, prepared from the terpene fraction of sweet orange oil, showed no depression. Identification of Dipentene.-The crystals of limonene tetrabromide described above were recrystallized from boiling ethyl acetate. When crystals first appeared, they were removed immediately from the warm solution by filtration; the crystals obtained were again treated in this manner. Dipentene tetrabromide was separated from the (7) Emich, "Microchemical Laboratory Manual" (English Translation). John Wiley & Sons, New York, N.Y.,1933,p. 34.
more soluble limonene tetrabromide by this procedure. The silver-white crystals melted at 123.5-124.5' after two recrystallizations from dilute methyl alcohol and a further recrystallization from boiling ethyl acetate; a mixed m. 1). with dipentene tetrabromide showed no depression. A second I-liter portion of the aldehyde-free oil was fractionated over nietallic sodium at atmospheric pressure with a 20-inch Hempel column packed with glass brads: the presence of phellandrene, pcymene, or terpinene coultl not be established in the fractions boiling at 177- 178 ', 1%
179', 179-180'. Fractiofl If The aldehydes were removed with sodium bisulfite solution; upon regeneration, 0.5 g. of a yellow oil having a pronounced odor of a fatty aldehyde was obtained: nLoD
1.4340, I d c n t i h t i o n of n-Nony1aldehyde.-The semicarbazone of the regenerated aldehydes melted a t 98-99' after two recrystallizations from dilute alcohol; a mixed m. p. with the semicarbazone of n-nonylaldehyde showed no depression. The primary and secondary alcohols were removed with phthalic anhydride. A mixture of 205 g. of the aldehydefree oil, 205 g. of phthalic anhydride, and 205 g. of benzene was retluxcd on a steam-bath for four hours. Upon cooling to room temperature, a considerable quantity of excess anhydride crystallized from the solution and was removed by filtration. The filtrate was shaken with two 500-c~. portions of 20% sodium carbonate solution and washed with 500 cc. of water. The combined aqueous layers were saponified with 800 g. of 50% sodium hydroxide solution, and the liberated alcohols were extracted with ether: 1 g. of a yellow oil having a n odor suggestive of borneol and geraniol was obtained. Idsntificlrtion of Borneol.-The phenylurethan of the recovered primary and secondary alcohols melted at 138139' after two recrystallizations from petroleum ether; a mixed m. p. with the phenylurethan of borneol showed no depression. Since Fraction I1 had not been saponified, borneol is present as a free alcohol. Fraction 11, freed of aldehydes and primmy and secondary alcohols, was fractionated at 20 mm.: the presence
May, 1943
CHEMICAL CONSTITUENTS OF DISTILLED LIMH; OIL
96 1
the above fractions melted at 187-195". The derivatives were combined; repeated recrystallizations from alcohol yielded a small amount of yellow needles, m. p. 200Fraction III 201"; a mixed m. p. with the naphthocinchoninic acid Citral, an important constituent of expressed lime oil, is derivative of citral showed no depression. Attempts to destroyed under the influence of heat and acid; in the secure crystals of sharp m. p. from the mother liquors production of distilled lime oil, a small amount of this proved unsuccessful. aldehyde might possibly escape decomposition. As TieThe unidentified aldehyde proved very susceptible to mann has shown,' sodium bisulfite solution is unsatispolymerization: a small amount exposed to the air factory for the isolation of citral because of the formation of yielded a very viscid oil with an acid number of 4.0, india stable addition compound; he recommended the use of a cating polymerization rather than oxidation had occurred. solution of sodium sulfite buffered with sodium bicarbonate Nor was a solid acid obtained by oxidation with hydrogen for the preparation of the soluble labile compound. peroxide. After seven days, the aldehyde had become so The aldehydes of Fraction I11 were removed bfr a modiviscid that it poured with difficulty. A rectification a t 3 fication of Tiemann's method. Eighteen hundred grams mm. of the combined fractions was necessary to separate of oil was shaken with a solution of 126 g. of sodium sulfite the unpolymerized aldehyde: more than 50% remained as and 168 g. of sodium bicarbonate in 2 liters of water for a residue. However, the aldehyde polymerizes very eight hours; after standing for seven days at 5", the q s slowly if dissolved in ether and protected from light. tals which formed were filtered off and repeatedly washed The sodium bisulfite addition compound appears to be with ether. Upon regeneration with 10% sodium carvery soluble: 0.5 cc. of the aldehyde yielded no solid bonate solution and extraction with ether, 7.5 g. of a yellow addition compound with 10 cc. of saturated sodium bioil was obtained, having a pronounced odor of a fatty sulfite solution. A pronounced loss of odor indicated that aldehyde. Identification of n-Decy1aldebyde.-The regenerated reaction had occurred. This offers a possible means of aldehyde was rectified a t 5 mm.: dlb 0.830; 4% 10"; removing citral, if citral is the interfering substance. Unfortunately, there remained i n s d c i e n t material to t r y nmD 1.4278; b. p. 80-81' a t 5 mm.; oxime, m. p. 6&69' this technique. We hope at a later date t o isolate a larger after recrystallization from dilute methyl alcohol. The amount and to identify the aldehyde with the odor suggessemicarbazone melted at 1 W 1 0 1O after two recrystallizative of cuminic aldehyde. tions from dilute alcohol; a mixed m. p. with the semi'The aldehyde-free oil was saponified with alcoholic carbazone of n-decylaldehyde showed no depression. hodium hydroxide solution. After removal of the alcohol The buffered sodium sulfite solution (which contained the soluble labile addition compound of any citral that by distillation, the saponified oil was washed with water: these aqueous washings were treated in the manner demight have been present in Fraction 111) was thoroughly scribed under "Acidic Consthents." washed with ether. During the process of regeneration After saponification, the primary and secondary alcohols with 20% sodium hydroxide solution, the free aldehydes were removed with phthalic anhydride: 6 g. of a viscid oil were protected from the continued action of the alkali by the addition of 1 liter of ether. Upon evaporation of the was obtained. Identification of Geraniol.-The recovered p r i m and ether layer, 6 g. of a pale yellow oil having an odor suggestive of cuminic aldehyde was obtained: n% 1.4925; secondary alcohols were distilled at 20 mm.: three 2-cc. a% +0°40'. To these aldehydes were added the corre- fractions were collected. The first fraction was semi-solid and readily yielded sponding aldehydes of Fraction IV. The Presence of an Unidentified Aldehyde and the colorless plates of borneol upon crystallization from Identification of Citral.-The semicarbazone of these re- petroleum ether: m. p. 204-206°; [a]*'D -31'0' (10'7, generated aldehydes melted at about 124-129 "; repeated alcoholic solution) ; phenylurethan, m. p. 138-139". The second and third fractions; having the odor of recrystallizations from ethyl, methyl, isopropyl alcohols, and from benzene and from ether raised the m.p. t o 130- geraniol, were combined and purified through the calcium chloride addition compound of Jacobsen.lo Rectification 137'. In a n attempt to separate these aldehydes, they were of the resulting oil yielded pure geraniol: a"D *O"; 1.4781; dl6 0.884. One gram, oxidized with chromic fractionated at 16 mm. with a h k having a two-inch column packed with small beads. Arbitrary fractions and sulfuric acids, gave a distinct odor of citral. The diwere collected at 103-106"; 108-110"; 110-115"; all phenylurethanll melted at 81.5-82.5' after two recrystalwere pale yellow oils of similar odor: n% 1.4882, 1.4900, lizations from dilute alcohol; a mixed m. p. with the di1.4912, respectively. Semicarbazones of these three phenylurethan of geraniol showed no depression. Fraction 111, freed of aldehydes, esters, and primary and fractions melted at 132-136" after two recrystallizations from dilute methyl alcohol. The third fraction was secondary alcohols, was fractionated at 20 mm.: the slightly darker in color than the first and second, and was properties of the fractions, after rectification a t atmospheric considerably more viscid. The fact, which was uncovered pressure, are given in Table 11. Identification of Linalool.-Fraction IIIA was redislater in this investigation, that these aldehydes polymerize very readily, may well account for the differences in proper- tilled a t atmospheric pressure. The desired phenylurethan of the portion boiling a t 196-200' was separated from the ties of these three fractions. Doebner's' naphthocinchoninic acid derivative of each of less soluble derivative of terpineol with petroleum ether. (8) Tieman, k., 81,8297 (1898). (10) Jacobs=, Ann., 167, 284 (1871).
of phellandrene and p-cymene could not be established in the fraction 180-182" (762 mm.).
( 0 ) Doebna, ibid., ST, 2020 (1SW.
(11) Erdmann and Eurth. 1.pr&. Ckm., [2] 6 4 2 7 (1897).
ERNESTS. GUENTHER AND EDWARD E. LANGENAU
(302
TABLR I1
VOl. 65
After saponification of the aldehyde-free oil, the primary and secondary alcohols were removed with phthalic anhydride: 0.4 g . of a viscid brown oil was obtained. Fraction I I I A Up to 212 .. ... An attempt to prepare a phenylurcthan proved U ~ S L I C FractionIIIR 212-214 0 . 9 3 6 -8'23' 1.4808) FractionIIIC 214-216 0 . 9 3 8 -8"28' 1.4818 3 t o 3 . 5 ~ 0 1 - cessful. FractionIIID 216-218 0 . 9 3 9 -9'55' 1.4832 umes and Fraction IV, freed of aldehydes, esters, and primary and Fraction I I I E 218-220 0 . 9 4 0 --10°28' 1.4839 more60% secondary alcohols, was fractionated a t 4 mm.: a main FractionIIIF 220-222 0 . 9 4 0 -11'17' 1.4848 alcohol. fraction boiling at 110-112" was obtaiiied. ~'mctionI I I C 222-2'24 0.940 -11'35' I 484'1 J Identification of Bisabo1ene.-This fraction had properI t nielted a t 6% 66" after four recrystallizations from dilute ties that approximate the values given i n the 1iteraturelGfor alcohol; a mixed ni. p. with the phenylurethan of linalool bisabolene: d15 0.891; -24"25'; . n Z o ~1.4982; showed no depression. solubility a t 20' = 5 volunies aut1 more of 9scZ alcohol. Identification of a-Terpineol.-Fractions IIIB to IIIG A trihydrochloridc.,l*prepared by passing dry hydrochloric inclusive were viscid, colorless liquids having a pronounced acicl into a cold ethereal soluiioii of the oil, melted at 79odor of terpineol. All could be congealed at - 5 " to a 80' after recrystallization froni alcohol. This is in agreesemi-solid mass upon seeding with a crystal of solid ment with the value reported in the literature. A lo'% terpineol. The phenylurethan of these fractions melted a t rhloroforrriic solution of these crystals was optically ill111-112" after two recrystallizations from dilute methyl active. alcohol. The iiitrosochloride of Fractions IIIB, IIIE and Anal. Calcd. for Cl5Hzd.3IICI: C1, 33.92. Found: IIIG, prepared by the method of &'allach,L~ melted at 121.c1, 33.79. 122". From the combined Fractions I I I D and IIIE, solid Residue V terpineol was separai ed by chilling, seeding and filtering. The aldehydes were removed with sodium bisul6te soluAfter two recrystallizations from ether, large colorless tion: upon regeneration, 0.14 g. of lauric aldehyde was plates were obtained: m. p. 34-38"; [ a I z o D - 11 "0' (105; obtained. alcoholic solutiori); phenylurethaii, m . p. 111--112°: niAfter saponification of the aldehyde-free oil, the primary trosochloride, m. p. 121-122'. and secondary alcohols were removed with phthalic anhyIt is to be noted that the m. p. of the nitrosochloride dride: 2.5 g. of a viscid oil was obtained. and the phenylurethan correspond to the values given in the Identification of Lauric Alcohol.-After standing a t literatureI3 for the inactive dl-modification. Probably 5" lor twelve hours, a white waxy x!id separated: m. p, these derivatives were formed because of the relatively about 19' after recrystallization froni ether. The phenylsmall excess of l-terpineol over the d-modification : the urethan melted a t 74-75' after recrystallization from specific rotation of an optically pure I-a-terpineol is petroleum ether; a mixed m. p. with the phenylurethan of - 1oo.5L.': lauric alcohol showed no depressiori. :iincc: this alcohol Attempti to secure the phenylurethan, m. p. 132", was not identified in any other fraction, it is likely that i t described by Burgess and Page,' were unsuccessful. occurs as a high boiling estl'r. Residue V, freed of aldehydes, esters, arid primary antl Fraction IV secondary alcohols, was fractionated a t 4 mm., yielding a The aldehyde5 were removed by the modified method of Tiemanri. The aldehydes regenerated from the bu5ered fraction boiling a t 106-110° which was found to consist sodium sulfite solution, 1 g., had an odor and index (nmo primarily of bisabolene, a fraction boiling at 1 1 5 119' which contained some bisabolene but no cadineiir, a frac1.4926) similar to the corresponding aldehydes of Fraction tion boiling a t 120-115" which had an intense blue color, 111; they were combined. From the crystalline bisulfite addition compound, 4 g. of a yellow oil having the odor of a and a residue which showed the absence of parafinic hydrocarbons when treated with fuming sulfuric acid. fatty aldehyde was obtaiued. Separation of an Azulenic Compound.-The fraction Identification of Lauric Aldehyde.-The regenerated 15 cc. having the intense blue color, 3 g., was shaken with aldehyde was rectified a t 10 mm.: di5 0.838; a 2 " '~0 " ; of ice-cold phosphoric acid, following the procedure of ~ * ' J D1.43iO; b. p. 130-131" a t 10 mm.; oxime, ni. p. 74--a i3 after two recrystallizations' from methyl alcohol. Sherndal": 0.2 g. of an intense blue-green oil was 01,tained. A minute amount of this oil dis5o:ved in ethrr The sernicarbazone melted a t 100-101 after recrystallizagave the yellow-green color characteristic of distilled linic tion from methyl alcohol and from isopropyl alcohol; a mixed m. p. with the semicarhazone of lauric aldehyde oil. Acidic Constituents showed no depression. After standing a t 5" for twelve hours, a semisolid mass The combined aqueous washings froni the saponificaresulted. Upon drying between filter paper, the solid tions of Fraction 111, Fraction IV, and Residue V were aldehyde nielted a t 10-11 this is the low melting form of evaporated t o 1 liter. After washing with ether, the lauric aldehyde. A drop of dilute hydrochloric acid con- solution was acidified and steam distilled : distillation was verted this aldehyde into a solid, m. p. %-56'; this is continued as long as the runnings were acidic to litmus. probably the dimer reported by Zaar with a m . p. of 57" l6 Sodium carbonate was added until the distillate was alkaline; any phenols that might be present were extracted (12) Wallach, A n n . , STT, 120 (1893). (13) Sirnousen, "The Terpenes," University Press, Cambridge, with ether. Roiling range,
oc.
d,,
Sohbi ILt y at 20
a%
1 ~
O;
1931, Vol. I, p. 227. (14) Puller and Kenyon, J . Ckem. Soc., 116, 2304 (1924) (16) zw, 1.p d r . Cbcnr., 121 $19, 168 ( l e a l ) .
(16) Sirnousen, LOG. dit., Vol. 11, p. 493. (17) Sherndal, T H IJOWSNAL, ~ W, 167 (1916)
May, 1943
A*-CYCLOHEXENONES AND CYCLOHEXANONES INTO SPIROHYDANTOINS
Separation of a Phenol.-Evaporation of the ether yielded 0.2 g. of an oil with a phenolic odor suggestive of carvacrol. One drop, dissolved in 1 cc. of alcohol, gave au intense yellow color with ferric chloride solution; ihc color won changed I O a deep orange. L1!pOn recrystallization from ether, the phenylurethan separated as a cluster of yellow ncedles, m. p. 134-137'. l h e r r was insufficient material for furl her purification. The alkaline distillate was evaporated to 500 cc., acidified with sulfuric acid, and extracted with ether: 4,2g. of an oily liquid were obtained. These free acids were distilled at atmospheric pressure: a fraction boiling a t 95-110" was collected; the residue was rectified a t 13 mm. Identification of Acetic Acid.-The toluidide of the first fraction melted a t 146-147"; a mived m. p. with the toluidide of acetic acid showed no depression. The silver salt was ignited after recrystallization from boiling water. Anal. Calcd. for C ~ H S O ~ AAg, ~ : 64.64. Found: Ag, 64.22. Identification of n-Octylic Acid.-The toluidide of the rectified residue melted a t 69-70' after repeated recrystallizations from dilute alcohol; a mixed m. p. with the toluidide of n-octylic acid showed no depression. Identification of n-Decplic Acid.-The rectified residue deposited a solid acid upon standing a t 5" for twelve hours: m. p, about IOo. A toluidide of this solid acid melted at 74-75' after repeated recrystallizations from dilute alcohol. The toluidide of n-decylic acid melted a t 75-76'; mixed In. p. 14.5-15.5'.
[COXURIBUTION FROM
THE
963
Summary An investigation of the chemical constituents of a Mexican distilled lime oil has established the presence of the following: a-pinene, P-pinene, d limonene, dipentene, bisabolene, furfural, n-octylaldehyde, n-nonylaldehytle, n-decylaldehyde, lauric aldehyde, citral, I-borrieol, geraniol, a-terpineol linalool, lauric alcohol, esters of acetic, n-octylic and n-decylic acids. Borneol, geraniol and a-terpineol occur as free alcohols, and possibly also as esters; lauric alcohol probably occurs as an ester. A high boiling oil of an intense blue-green color, probably an azulenic compound, was separated. An unidentified aldehyde with an odor suggestive of cuminic aldehyde was not obtained in a state of sufficient purity for identification. The presence of a trace of a phenol or phenolic ester was also established, although it was not identified. The presence of phellandrene, p-cymene, terpinene, cadinene, or high boiling paraffinic hydrocarbons could riot be established. NEWYORK,N. Y.
RECEIVED FEBRUARY 25, 1943
DEPARTMENT OB CHEMISTRY, THE UNIVERSITY OF TEXASJ
Conversion of A2-Cyclohexenonesand Cyclohexanones into Spirohydantoins' B\' HENRYK. HENZE,ROBERTCURTISWILSON2 AND ROBERT w.TOWNLEY* During the past few years a considerable number of derivatives of hydantoin have been prepared in this Laboratory. These compounds have been tested elsewhere4 and many have been shown to possess mild pharmacological activity, some as anticonvulsants and others as soporifics. As in the case of the barbiturates, some correlation may be noted between the type of activity and the structure of the substituents attached a t the 5-position of the hydantoin nucleus. To date very few spirohydantoins6 had been prepared for the purpose of being tested; this study supplied some examples of the desired type. (1) From the P h . D dissertation of R . C. Wilson. June, 1941.
(2) Prevent address. General Aniline and Film Corporation, Gr~sselliNew Jersey (3) Present s t a l u a : 1'iist A\.;istant Public Hygiene Engineer IT. S. Piillic Health Siervict.. ( 4 ) a i r indeblrdurss tu Park,., I h v i s and Company fc,r this w v i c c is y~atrfullyackuuwiedptd. ! 5 ) Henze and SpeIr ['IUS JUohNL. 64, 6 U (lY42)] rec'ordnl the rorlting points of Q few enarnplcs. hut omit details of prepurntion and 0 harmacological activity
Substituted cyclohexanones react readily with aqueous-alcoholic solutions of potassium cyanide and ammonium carbonate to yield the anticipated substituted spirohydantoins. However, when A2-cyclohexenones are condensed, addition of two equivalents of hydrogen cyanide leads to the formation of cyanospirohydantoins. When certain A2-cyclohexenonesare treated with alkali bisulfite and the products exposed to the action of potassium cyanide and ammonium carbonate solution, spirohydan toins containing a sulfonic acid substituent are obtained. Five of these spirohydantoins have received preliminary pharmacological testing through the courtesy of Parke, Davis and Company. The spirohydantoin derived from 3-ethyl-$methylcyclohexanone exhibited neither hypnotic iinr mticonvulsant activity. However, the phenyl arialog, namely, 2,4-dioxo-'i-rnethyl-Y-phenyl-l,3diazaspiro(4,5)decane, did evidence a mild degree
