574 READ AND SMITH:

LXVI1.-Piperitone. Part I I . Benxylidene-dl-piperitone. By JOHN READ and HENRY GEORGE SMITH.

IN a recent preliminary paper (T., 1921,119, 779) dealing with the chemistry of the eucalyptus ketone, piperitone, we described the pre- paration of benzylidene-dl-piperitone and indicated the importance of this very distinct'ive derivative in differentiating piperitone from closely related ketones. At the same time, we suggested that the remarkable ease with which the derivative is formed was likely to prove of interest in connexion with the question of the constitution of piperitone. For these reasons it was thought advisable to examine more fully the physical and chemical characteristics of benzylidene-dl-piperitone and to carry out supplementary experi- ments bearing on its formation. Some of the results af these investigations are recorded in this communication. In particular,

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PIPERITONE. PART 11. BENZYLIDENE-DL-PIPERITONE. 575

the dimorphism of benzylidene-dl-piperitone, of which an indication was given in our first paper, has proved to possess highly characteristic and interesting features.

Among the work not fully described, may be mentioned certain attempts to prepare definite benzylidene or dibenzylidene derivatives of carvone; these experiments were carried out with the object of gathering further evidence regarding the constitutional peculiarities which allow of this condensation. Our observations confirmed Wallach's statement (Annalen, 1899, 305, 274) that carvone con- denses readily with benzaldehyde in alkaline solution to give ill- defined products. By using alcoholic sodium ethoxide as a con- densing agent, in the way described for piperitone (Zoc. cit., p. 785), it was found that carvone reacted with great ease with two molecular proportions of benzaldehyde ; the product, however, could only be obtained in the form of a yellow, vitreous mass. When one molecular proportion of benzaldehyde and one-fifth the preceding amount of sodium were used, the product was a pale yellow oil of indefinite boiling point, the bulk of which distilled below 240°/20 mm. At this point in the investigation the recent paper by Muller (Ber., 1921,54, [B] , 1471) came under our notice, describing the production of a solid and a liquid monobenzylidenecarvone by carefully con- trolled alkaline condensation. Further work in this direction was accordingly abandoned. Incidentally, we may point out that the substance melting at 233-234" obtained by Muller (loc. cit. , p. 1480) in small yield by the action of phenylcarbimide on benzylidenedi- hydrocarveol and on a- and (3-benzylidenecarvones is probably not a phenylurethane, as stated. The high melting point of this substance, which apparently was not analysed, suggests that it was carbanilide, and thus the presumed identity of the reduced a- and p- benzylidenecarvones with benzylidenedihydrocarveol cannot be accepted as established.

E x P E R I M E N T A L.

Dimorphic Forms of Benzylidene-dl-piperitone. In the original crystallisations of benzylidene-dl-piperitone (loc.

cit., p. 787) two forms of crystals were observed; these were char- acterised by distinctive habits, one form being prismatic and the other tabular. As a result of goniometric measurements, the crystals of prismatic habit (now named the a-form) were assigned to the monoclinic system, but owing to incomplete development of the observed crystals the axial ratios could not be determined in full. In an attempt to secure more perfect crystals of this kind by recrystallisation from ethyl-alcoholic solution, a striking trans- formation occurred and the whole of the material separated as

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576 READ AND SMITH:

crystals of tabular habit (the p-form). Further recrystallisations confirmed t'his result; it appeared impossible, in fact, to reproduce the effect of the original crystallisation. Ultimately, however, by inoculating a supersaturated alcoholic solution of the substance with a portion of a powdered crystal of prismatic habit, a homo- geneous separation of crystals of this type was obtained. Similarly, inoculation with material from a crystal of tabular habit resulted in a separation consisting entirely of crystals of the second type. In brief, by suitable inoculation, it was found possible to induce benzylidene-dZ-piperitone to crystallise wholly in either of the forms mentioned ; perfectly homogeneous separations of the a- and p-form being thus obtainable a t will. Crystallisation was effected in all cases at the ordinary temperature, the solvent being either methyl alcohol or ethyl alcohol. The tendency of the substance to form supersaturated solutions has already been mentioned ; a perfectly sterile alcoholic solution of this kind may be kept indefinitely in a closed vessel without crystallisation occurring at all.

a-BenzyZidene-d l -~ i~e~ i~o~e forms pale yellow prisms, of ten exceeding 1 cm. in length and exhibiting high transparency and lustre. The powdered crystals are almost colourless. The crystals appear to be quite stable when kept in the dark, but after several months' exposure to diffused light they gradually lose their lustre and become gummy. This effect is greatly accelerated in bright sunlight ; after a few minutes' exposure a distinct change is notice- able; after an hour or so, opalescence begins to radiate from numerous centres ; and eventually, after several hours, this appear- ance becomes general, whilst the faces assume a vitreous aspect and the crystals cohere. If the exposure has been made in a closed glass tube, a distinct odour of benzaldehyde becomes evidenb a t this stage.

Crystals from five different preparations melted in each instance over the range 59-61", when powdered and heated in a capillary tube in the usual way. No preliminary sintering was observed, and after resolidification the specimens melted with somewhat greater precision, the mean range being 59-60".

These crystals show a strongly developed tendency to assume the simple forms already illustrated (Zoc. cit., p. 786), and hour-glass structure is a very typical feature. It was only after numerous attempts, extending over several months, that crystals were obtained of suitable development to permit of full crystallographic character- isation. The appended supplementary report was kindly supplied by Miss Marie Bentivoglio, B.Sc., of the Department of Geology, University of Sydney :

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" Recently obtained crops of crystals of a-benzylidene-dl-piperit- one have yielded individuals exhibiting two extra pyramidal forms : consequently, it has now been possible to determine the complete axial ratios. These forms (Fig. 1) are d ( i l l ) , a long narrow face, and e(121), a small form only observed on two crystals. The prismatic crystal habit remains unaltered.

" AxiaE ratios.-a : b : c = 0.9321 * : 1 : 0.3899. p = 72" 36'. No. of

measure- Limits. Observed. Form. ments. 9 P $ P d(I11) 6 1'3" 11'-li" 45' 22" 22'-21" 52' 17' 28' 22" 14' e(121) 2 8" 58'- 9" 15' 38" 00'-38" 23' 9" 07' 38" 12'

" The calculated + and p for 4121) are, respectively, 9" 06' and

FIG. 1. FIG. 2. 38" 18""

p-BenzyEidene-dl-piperitone forms lustrous, transparent crystals having a pronounced yellow colour and attaining a length of 2 or 3 cm. The yellow colour is equally evident in the powdered crystals ; indeed, powdered specimens of the cc- and p-forms of this substance may easily be differentiated by reference to their colour alone. The crystals are quite stable in diffused daylight, and even when exposed to bright sunlight no alteration is apparent until the lapse of about a fortnight. On prolonged exposure, however, the crystals gradually become gummy, although no opalescence is developed. As with the a-form, the change appears to be accompanied by the production of minute amounts of benzaldehyde.

It may be remarked in this place that the last-named observation cannot be interpreted as an indication of any pronounced tendency on the part of this derivative to revert to benzaldehyde and piperit- one under ordinary chemical influences. Attempts to hydrolyse

* The value of a has been corrected from 0.9331 to 0.9321.

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578 READ AND SMITH:

i t with hot aqueous mid and alkali showed that benzylidene-dl- piperitone is practically unaffected by these reagents. Thus, up to the present, it has not proved possible to utilise this readily accessible derivative for the regeneration of pure dl-piperitone : such a process would be very desirable in view of certain objections associated with the semicarbazone process, to which attention will be directed in a later communication.

Crystals from five different preparations of p-benzylidene-dl- piperitone melted in each instance over the range 63-64', with a slight preliminary sintering a t about 61 '. After resolidification in the capillary tube, each of these specimens melted a t 59-60'.

Crystals of the p-form invariably exhibit striations, but the hour-glass structure, characteristic of the a-form, is not evident. A goniometric examination of these crystals was also made by Miss Bentivoglio, to whom we are indebted for the following particulars :

" The crystals of p-benzylidene-dl-piperitone are transparent and light yellow in colour. Although varying much in size, they preserve a perfect tabular habit, the brachypinacoid being the largest form present (Fig. 2). The prism zone is well developed and contains the form b(010) having a smooth surface, and the forms 1(250), n(470), m(110), and p(310), all of which are strongly striated, so that very accurate readings could not be obtained. The dome d(013) is invariably present and has smooth faces. A well-marked cleavage was observed parallel to b(010).

" Crystal system-Rhombic, normal. " Axial ratios.+ : b : c = 0.4841 : 1 : 0.9334.

No. of measure-

Angle. ments. Limits. Observed. Calculated. bl =010: 250 10 39" 15'-40" 14' 39" 51' 39" 34' bn =010 : 470 12 49" 14'--49" 54' 49" 34' 49" 44' bm=010: 110 19 63" 45'-64" 23' 64" 10' 64' 10' bp =010 : 310 27 SO" 39'-81" 19' 81" 02' SO" 50' bd =010: 013 24 72" 17'-72" 59' 72" 43' 72" 43' dd =013 : 013 11 34" 09'-34" 51' 34" 34' 34" 34'

" It would appear, therefore, that the two forms of crystals are in no way correlated. The prismatic crystals are monoclinic; the tabular ones are rhombic. This difference is also observed in optical properties. The tabular crystals possess rectangular extinction directions, parallel to the two edges of the crystal; in the monoclinic crystals (the ortho-zone being usually absent), indined extinction was observed. Moreover, a biaxial interference figure was obtained for the tabular crystals, symmetrical about the centre of the microscope field."

The fact that the dimorphic substance, benzylidene-dl-piperitone,

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PIPERITONE. PART 11. BENZYLIDENE-DL-PIPERITONE. 579

tends to separate from alcoholic solutions at the ordinary tempera- ture in the 8-form, taken in conjunction with the comparatively sluggish response of this form to the influence of sunlight, might perhaps be accepted as an indication that the @-form is stable and the a-form labile at the ordinary temperature. If this supposition were correct, the dimorphism would obviously be monotropic, in view of the higher melting point of the 8-form. Further experiments, however, demonstrated that the a-form is the stable modification at the ordinary temperature. When a saturated mother-liquor in contact with rhombic crystals is seeded with monoclinic material, the rhombic crystals are rapidly etched and dissolved, while mono- clinic crystals develop a t their expense, until, after the lapse of one or two days, all the original rhombic crystals have disappeared. The particularly well-developed monoclinic crystals described above were obtained in this way. It follows, therefore, that the a-form is the less soluble and the more stable at the ordinary temperature; further, since the 8-form has the higher melting point, the dimorphism is enantiotropic. No accurate determinations of solubility or density have yet been made, but the behaviour of the two forms when raised gradually to the region of the melting point suggests that the transition temperature is situated not far below that region. It may be added that either modification may be preserved indefinitely when allowed to remain in contact with its saturated mother-liquor in a closed vessel.

When molten benzylidene-dl-piperitone is allowed to solidify, it invariably assumes the cc-form. This fact accounts for the pro- duction of the original monoclinic crystals, the solution having been seeded with material obtained in this way. Probably, the rather unusual relationships which have been observed between these dimorphic modifications may be explained by assuming that their difference of stability is much less pronounced than is customary in such cases. Thus, the molten material undergoes a preliminary solidification to the cc-form, which, although labile a t the melting point, is sufliciently stable to persist until the temperature has fallen below the transition temperature. Similarly, solutions crystallising a t the ordinary temperature yield a preliminary deposit of the labile 8-form, which, however, is so stable at this temperature that it exhibits no apparent tendency to undergo transformation into the less soluble and theoretically more stable a-form, unless it is brought into contact with that form. Benzylidene-dl-piperitone thus appears to present one of the

best-dehed cases of enantiotropic dimorphism yet recorded in organic chemistry, the ease with which each form is procurable in a state of freedom from the other being especially remarkable.

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580 READ AND S M I T H :

The only solvents yet applied in studying the relationships concerned are methyl alcohol and ethyl alcohol, and no appreciable difference has been observed in their effects. Cold alcoholic solu- tions of benzylidene-dl-piperitone exhibit a pale yellow colour, which deepens appreciably on heating and pales to the original tint as the solution cools.

When the substance, after being heated considerably above the melting point, until it becomes quite mobile, is poured into ice- water it forms a pale yellow, semi-fluid, plastic mass, which after standing for about ten minutes becomes crystalline.

Since benzylidene-dl-piperitone is an externally compensated substance, it seemed desirable to ascertain whether it is capable of optical resolution by spontaneous separation of its enantiomers in distinct crystals, according to the first method of Pasteur. From the above description i t is apparent that neither of the dimorphic modifications exhibits asymmetry of form, and in conformity with this observation large individual crystals of both types yielded optically inactive solutions when dissolved in alcohol.

In view of the interesting results now recorded, it seems likely that the colour changes noted in the case of benzylidene-dl-piperit- oneoxime (loc. cit., p. 788) may also be ascribed to the occu'rrence of polymorphic forms. We propose to undertake further investiga- tions in this field of work.

The Addition of Hydrogen Bromide to Benxylidene-dl-piperitone. The ready manner in which such substances as benzylidene-

menthone and benzylidenecamphor combine with hydrogen bromide rendered it of interest to apply a similar reaction to the benzylidene derivative of dl-piperitone. The derivative was dissolved in eight times its weight of a 32 per cent. solution of hydrogen bromide in glacial acetic acid. The resulting dark red solution deposited brick red crystals, from which, after a few days, the supernatant liquid was decanted. The crystals dissolved readily in alcohol, acetone, or ether, forming colourless solutions which deposited the original benzylidene derivative when allowed to evaporate a t the ordinary temperature, When triturated with cold benzene, in which they were insoluble, the crystals gave a bright yellow, crystalline mass, with apparent loss of hydrogen bromide. The yellow substance, which melted and sublimed at 91-95', was stable in dry air, but in contact with water, alcohol, acetone, etc., it reverted to the benzylidene derivative, with the liberation of one molecular pro- portion of hydrogen bromide (Found : HBr = 22.7. C,,H2,0 + HBr requires HBr = 25.2 per cent.).

Very similar colour changes were observed when benzylidene-dl-

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PIPERITONE. PART 11. BENZYLIDENE-DL-PIPERITONE. 581

piperitone was dissolved in a mixture of concentrated sulphuric acid and acetic anhydride. The original deep orange solution changed to red, and soon yielded a thick, yellow, crystalline mass, which, after the lapse of an hour, changed to a dark brown liquid.

These observations recall the interesting work of Vorlander and his pupils on the addition of acids to certain unsaturated ketones (Ber., 1904, 37, 1644; Annalen, 1906, 345, 155).

The Reduction of Benzylidene-dl-piperitone. For reasons which will be indicated later, it was considered of

importance to investigate the reduction of benzylidene-dl-piperitone. The derivative (26 grams) was accordingly dissolved in absolute alcohol (250 c.c.) and reduced vigorously in hot solution with sodium (30 grams). From the clear, pale yellow solution which resulted was isolated, by following the usual procedure, a faintly yellow and rather viscous oil (15.5 grams) ; this product boiled a t 197-210"/18 mm. and showed no tendency to crystallise, even after keeping for several months. When dissolved in chloroform, it decolorised bromine immediately, and from the analysis given below it evidently possessed the composition of a benxyl-p-menthenol, C17H240. Attempts to effect a more vigorous direct reduction of the benzylidene derivative resulted in the production of resinous matter.

When heated on the water-bath with phenylcarbimide, the reduction product reacted without difficulty to form a phenyl- urethane ; this compound crystallised readily from warm benzene in lustrous, feathery needles, melting a t 140-141" (Found : C = 79.31 ; H = 8-03. C,,H,,O,N requires C = 79-28; H = 8.05 per cent.). At the same time, an appreciable amount of carbanilide was produced, the identity of which was established by analysis and melting point (241", corr.). Incidentally, hot nitrobenzene was found to be an excellent solvent for this substance.

Further Observations on the Condensation of Piperitone with Benmldehyde.

A specimen of l-piperitone, having [a]: = - 45.2", reacted readily with benzaldehyde, in the manner described for dl-piperitone (loc. cit., p. 785), to yield a dark reddish-brown liquid product. By inoculation with a-benzylidene-dl-piperitone, it proved possible to isolate crystalline material from this crude, undistilled product. The resulting crystals consisted of a-benzylidene-dl-piperitone, and not only these crystals but also the oily mother-liquor failed to exhibit optical activity in benzene solution. It is thus apparent that complete racemisation occurs during the reaction, since the

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582 READ, SMITH, AND BENTIVOGLIO :

method of purification adopted in this case precludes the possibility of subsequent racemisation.

The great ease with which this condensation occurs in the presence of a little sodium ethoxide rendered it of interest to investigate the effect of hydrogen chloride as a condensing agent in the reaction concerned. This method of condensation, which was shown by Wallach (Annalen, 1899, 305, 261) to give excellent results in the case of menthone, yielded, however, only about 20 per cent. of the quantity of benzylidene-dl-piperitone obtained in the alkaline condensation.

We acknowledge our indebtedness to the McCaughey Research Fund of theuniversityof Sydney for a grant in aid of these researches, which are being continued.

DEPARTMENT OF ORUANIC CHEMISTRY, UNIVERSITY OF SYDNEY. [Received, January 2lst, 1922.1

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