2 782 READ AND COOK: CCCLXXXII1.-Researches in the Menthane Series. Part I . By JOHN READ and SON MARY RITCHIE COOS. THE information hitherto available respecting dl-menthone is derived mainly from the work of Pickard and L i t t l e b q on the catalytic reduction of thymol (J. 1912 101 109) and a note by Wallach on the catalytic reduction of synthetic dl- Al-p-menthen-%one (Annden 1913 397 217). It is questionable whether a pure specimen of dl-isomenthone had been prepared and recog-nised it8 such prior to the work of Hughesdon Read and Smith on the reduction of piperitone (J. 1923 123 2916). The " inactive menthone" prepared by Wallach gave the semicarbazone (m. p. 212") characteristic of dl-isomenthone whilst the derived oxime (m. p. 79-80") corresponded with dl-menthone.These and other apparent inconsistencies in the literature of the subject have now been satisfactorily explained and it has been found possible to convert dl-piperitone at will into derivatives of either series. Alkaline reduction of dl-piperitone (1 below) yields a mixture of liquid and solid menthols in which it has not proved possible to detect &-menthol or dl-ncomenthol ; a preliminary examination of the menthols concerned indicates that they are derived from dl-isomenthone rather than from dl-menthone. By means of the operations summarised below this material was transformed suc-cessively to dl-isomenthone (3) d-menthol (4) and dl-menthone (5). In a further series of operations (6 7 and 8) a more direct passage from d-piperitone to dl-isomenthone and dl-menthone was secured : ( 1 ) d-Piperitone I (Hydrogen and palladium) I + 1 .1.J. 1 I (Sodium and alcohol) dl-&oMenthols I I (Chromic acid) Q-isoMenFhone (6) d-isoMenthone (Sodium 'and alcohol) (Sodium &d alcohol) + J. dl-Menthol [ + d-iaoMenthols] (7) Q-Menthol [ + d-hoMenthols] I I (Chromid acid) J. dl-Menthone (Chromic 'wid) 4 (8) dl-Menthone relationships may be explained on the basis of the establish-ment of definite dynamic equilibria between isomenthone an RESEARCHES IN THE MENTHONE SERIES. PART I. 2783 menthone in the presence of alkali and under other influences. The main product of the alkaline reduction of dl-imenthone is dl-menthol which may be separated to a large extent in the c-l-line form from the rtssociated liquid material.The latter is probably composed largely of dl-menthol accompanied by a liquid mixture of dC-isomenthols. From the above considerations it is clear that by repeated oxidation and reduction this liquid by-product may be used as a source of further quantities of crystdine d-menthol. When dl-menthol is oxidised by chromic acid in the final operation it yields practically pure dl-menthone which shows little tendency to isomerise into dl-isomenthone in the presence of this reagent. By treating the resulting d-menthone with alcoholic alkali how-ever it may be transformed info the equilibrium mixture of dl-menthone and W-iaomenthone. Through the careful avoidance of disturbances due to the use of alkaline reagents it has been p i b l e to prepare a number of pure derivatives of d-menthone and dl-isomenthone the melting points of which are indicated in the following summary : Derivative.dl-GoMenthone. dl-Menthone. Wallch's value. Oxime ........................... 99-100" 81-42' 79-80" Beneoyloxime .................. 55.5 72-73 69-70 tkooxime ........................... 94-95 114-1 15 Semicarbezone (a) ............ 225 185-186 219 87-88 - 9 ) (8) ............ 177- 178 161 The melting points of the semicarbazones of dl-isomenthone were observed by Eughesdon Smith and Read (loc. cit.). The values quoted in the laat column suggest that the " inactive menthone " described by Wallach (loc. cit.) consisted of dl-isomenthone from which the oxime was prepared in an alkaline medium. dLd80-Menthoneoxime is remarkable by reason of its capacity for forming well-developed crystals so that for the first time it becomes F i b l e to submit a menthoneoxime to a complete goniometric examination.dl-Menthone and W-isomenthone may most readily be discriminated by preparing the oximes or semicarbazones in weakly acid solutions. Up to the present attempts to reduce piperitone to menthol or menthone in an acid medium have been unsuccessful the ketone being practically unaltered by such reagents as tin and concen-trated hydrochloric acid or zinc dust and glacial acetic acid. Dis-tinct evidence was obtained of the formation of an appreciable amount of dl-a-phellandrene during the alkaline reduction of dl-piperitone the relationship being of particular interest in view of the occurrence together of the laevo-modifications of these two subbnces in various eucalyptus oils 2784 READ AND COOK: EXPERIMENTAL.Produd obtained through an Initial Alkaline Reduction of dl-Pipen'tone.-l. The piperitone used throughout this work wm extracted from the essential oil of Eucalyptus dives using sodium bisulphite ( J . sot. c h m . Id. 1923 42 339~). 2. In order to avoid all possibility of the formation of optically active products the piperitone (a0 g.) was racemised by means of alcoholic sodium ethoxide prior to reduction with sodium and alcohol (J. 1923 123 2270 2918). Altogether 880 g. of dl-piperi-fone yielded 820 g. of crude menthol which was submitted fo two systematic distillations under diminished pressure. The first fraction (b.p. to 87"/10 mm.) had an odour similar to that of a-phellandrene its physical characteristics (J. 1923 123 1660), together with the ready formation of a nitrosite melting at 106-107" and resembling that of dl-a-phellandrene indicated that the fraction consisted essentially of this terpene. A further series of reductions carried out with piperitone which had been carefully freed from phellandrene by two successive fractional distillations under diminished pressure gave a crude product (223 g.) containing 9.1% of a similar fraction with the following physical characteristics : b. p. to 87"/10 mm. ahe -1958" (1-dcm. tube) n r 1.4798. It therefore appears conclusive that dl- a-phellandrene is formed to an appreciable extent in the alkaline reduction of dl-piperitone.The total yield of menthols was 4204%. 3. Upon oxidation with chromic acid (AnnaZen 1889 250 325), a total quantity of 410 g. of the liquid product (b. p. 95-97"/10 mm.) yielded 332 g. of a liquid possessing the characteristic odour of menthone. When distilled twice under diminished pressure 37% of the product distilled up to 82"/8 mm. (ab' -0.18" nhF 1.4553), and 40% at 82-85"/8 mm. (ar -0-34" n;' 1.4571). The latter fraction was used in preparing the derivatives described below and appeared to consist essentially of dl-igomenthone. 4. Upon reduction with sodium and alcohol in the usual manner, a specimen of the dl-isomenthone just described (24.7 g.) yielded a product (24.0 g . ) which distilled almost completely a t 10Q-105"/15 mm. Three distinct fractions each boiling over a range of one degree between 102" and 105"/15 mm.and having n',"'= 1-4640, deposited crystalline material on cooling the liquid becoming permeated in each instance with h e radiating needles reachmg a length of 2 em. When separated and dried on porous plate the three specimens melted a t 32-34" and yielded the characteristic dl-menthyl hydrogen phthalate. 5. The menthone obtained by oxidising the crystalline dZ-mentho RESEARCHES IN THE MENTHONE SERIES. PART I. 2785 from the preceding operation resembled the product described under (8) below and thus consisted essentially of dl-menthone. Prodwh obtained through an Initial Caddytic Reduction of dl-Pipfi'tone.4. Carefully purified dl-piperitone (50 g.) wm hydrogenated at the ordinary temperature under a pressure of 0.25 atmosphere in presence of colloidal palladium (J.1923 1x3, 2921). The mixed yields from four operations when systematically distilled under diminished pressure gave a main fraction b. p. 90-93"/18 mm. n:' 1.4580; this was optically inactive and appeared to be practically identical with product (3) thus con-sisting of d-isomenthone. 7. Upon reducing 18 g . of the preceding product with sodium and alcohol a yield of 15.5 g. of crude menthol was obtained. This failed to crystallise but when fractionally distilled the portion passing over a t 107-112"/23 mm. (9.3 g.) furnished 2.3 g. of crystals, which possessed the pronounced odour of ordinary menthol and melted a t 32-34". Not only these crystals but also a liquid fraction of somewhat lower boiling point (105-107"/23 mm.; ng. 1.4686) yielded the characteristic dl-menthyl hydrogen phthalate (Pickard and Littlebury Zoc. cit.). 8. dl-Menthol (m. p. 32-34"; 54 g.) was oxidised with chromic acid in the usual manner except that the temperature wit8 raised to 70" in order to decompose the black crystalline chromium compound. The crude product (45.1 g.) when distilled passed over almost completely a t 85-89"/12 mm. and had ng 1.4641. The preparation of the derivatives described below showed it to consist essentially of dl-menthone so that it was identical with product ( 5 ) and differed from products (3) and (6). dl-Menthone possesses a characteristic peppermint odour which is if anything even more pronounced than that of I-menthone.dl-isoMenthone, on the other hand has a decidedly fainter odour of the same general character. De?imtices of dl-isoMEnthne.-dl-isoMenthneoxime was pre-pared from d-isomenthone (b. p. 82-85'/8 mm.) obtained in preparation (3) above by treatment in the usual way with hydroxyl-amine acetate (J. 1922 121 586) 92-4 g. of the ketone yielded 100-4 g. of crude oxime which crystallised partly when kept for a short time in a vacuum desiccator. The crystalline material (35 g.) dried on porous plate melted indefinitely between 85" and W" but attained a constant m. p. 99-100" after three recrystallisations from warm light petroleum. The substance is readily soluble in organic solvents but when pure it crydallises from light petroleum with great ease in magnificent transparent prisms distinguished by their high lustre.The crystals wer 2786 READ AND COOK: kindly measured by Mr. T. V. Bsrker M.A. of the Department of Mineralogy University of Oxford who reports that they are anorthic with forms a m b M c & and rarely 0 developed in the proportions indicated by Fig. 1. The elements a b c = 2.049 1 1.281; a = 112" 12' p = 116" 17' y = 86" 57' were computed from the following results of measurement of four crystals : a(100). m ( i ~ o ) . b(010). ~ ( 1 1 0 ) . ~(001). &(oil). o(ii1). ... 0" 0' 0' 0' 0" 0' 0" 0'*67" 48' *134' 18' 134" 18' p ... 0 0 56 51(14) *82 6 *110 17 *62 48 75 23(3) 52 18(20) Optically t,he extinction is nearly straight with the vertical edge, and an optic axis lies just within the field (Found C 71.1 ; H, 11.1.CIoH,,ON requires C 71.0; H 11.2%). The mother-liquors from the recrystallisation of the oxime dl-isoMenthoneoxime. deposited an oily product when con-centrated by evaporation ; when kept for some time this material furnished a further quantity of the crystalline oxime described above but no other crystalline oxime could be isolated. The lower fraction of dl-isomenthone (b. p. to 82"jS +mm.) from preparation (3) behaved similarly when oximated. dl-isoMenthone prepared by the catalytic reduction of &I-piperitone (6) gave a similar product which however, furnished a considerably higher pro-portion of the crystalline oxime. Fractions melting indefinitely between 60" and 75" were obtained from the mother-liquors but no indication was forthcoming of the presence in these of dl-menthoneoxime.Benxo~l-dl-isomentitoneoxime was prepared by benzoylation in pyridine solution its a viscid oil which was induced to crystallise with great difficulty. The crude product after drying on porous plate melted at 52-54". After three successive recrystallisations from light petroleum in which the derivative is very soluble the melting point became constant at 55.5" the pure substance separat-ing in massive transparent prisms suitable for goniometric ex-amination. The product obtained by benzoylating the oily mother-iquor from the crystalline oxime could not be induced to crystallise (Found C 74.7 ; H 8.9. C,,H,O,N requires C 74.7 ; H 8.8%). dl-isoMenthoneisooziiize prepared by dissolving crystalline dl-iso-menthoneoxime in cold concentrated sulphuric acid (Wallach, Annulen 1894 278 304) crystallised from hot water containin RESEARCHES IN THE MENTHOSE SERIES.PART I. 2787 a little alcohol in fine glistening needles m. p. 94-95'. The product of the reaction appeared to be homogeneous (Found: C 70.2; H 11-1. CloH,,ON requires C 71.0; H 11.2%). Derimtizm of dl-Ment7mne.4-Menthone from preparations ( 5 ) and (8) above when oximated in the manner described for piperitme (J. 1922 121 586) yielded d-menthoneoxime (m. p. 81-82") associated with a considerable amount of oily material. Unlike the stereoisomeric dl-isomenthoneoxime this derivative could not be obtained in crystals sufliciently well developed for goniometric examination. Attempts to benzoylate the crystalline oxime by the Schotten-Baumann method gave unsatisfactory results but by the use of pyridine an oily product was obtained which after extraction with ether and keeping in a vacuum desiccator crystallised spontaneously.The substance crystallised from light petroleum in small trans-parent plates or glistening prisms m. p. 72-73". BenzoyE-dl-. menthoneoxime is very soluble in all the usual organic solvents ; it does not form such well-developed crystals as benzoyl-dl-iso-menthoneoxime (Found C 74-7 ; H 8.6. Cl,H,Oa requires C 74-7; H 8.8%). The oily material from the mother-liquor of the crystalline dZ-menthoneoxime yielded a viscid liquid when benzoylated in pyridine solution. dl-Me~~thoneisooxime prepared from crystallised d-menthone-oxime in the manner indicated above crystallised from hot water containing a little alcohol in fine soft needles m.p. 114-115', and was readily obtained pure (Found C 69-9; H 10.9. C,&€,,ON requires C 71.0; H 11.2%). Upon allowing d-menthone (10.5 g.) to react with semicarbazide in the manner described in a previous paper (J. 1923 123 2920), a crystalline product (10.2 9.) was readily isolated. By continued fractional crystallisation from hot methyl alcohol a small fraction of dl-mentbne- a-semicarbazone was eventually obtained this forms characteristic and well-defined glistening prisms m. p. 185-186" (Found C 62-1 ; H 10.2. CllH210N3 requires C 62.5; H, 10.O~o). The bulk of the product however consisted of small, glistening needles of dl-menthone- p-semicarbcczone m. p. 161-162" ; this derivative is more soluble than the isomeric compound (Found : C 62.7; H 10.3y0). No semicarbazone characteristic of dl-iso-menthone could be isolated from this product; an intermediate product melting at about 177" when mixed with dl-isomenthone-p-semicarbazone (m. p. 177-178"; J. 1923 123 2922) softened a t 158" and melted indefinitely between 169" and 176'. It may be remarked that dl-isomenthone- a-semicarbszone (m. p. 225") is by far tlhe least soluble of the semicarbazones of the optically inactive 5 B 2788 COLVIN THE IONIC ACTIVITY PRODUCT menthones ; its absence from the above reaction-product thus affords a criterion of the freedom of the specimen of dl-menthone from dl-komenthone. We express our thanks to the Department of Scientific and Indmtrial Research for a maintenance grant to one of the authors (A.M.R.C.). The investigation is being continued. UNITED COLLEGE, UNIVERSITY OF ST. ANDREWS. [Received July 6th 1926.