THE SYNTHESIS FROM THUJAKETONE OF SOME NEW

[CONTRIBUTION FROM THE CHEMICAL

LABORATORIES OF COLUMBIA UNIVERSITY]

THE SYNTHESIS FROM THUJAKETONE OF SOME NEW HYDROTERPENOIDS JESSE WERNER AND MARSTON TAYLOR BOGERT Received November 5, 1958

It is rather surprising, in view of the ease with which thujaketone can be obtained from thuja-leaf oil (Thuja occidentalis), that this interesting compound has not been used more frequently in recent years for syntheses in the terpene and related fields. Structurally, it resembles quite closely the important methylheptenone:

/"

MeCOCHzCHzC

\\

(Methylheptenone)

CMez

/CHMez

MeCOCHzCHzC

\\

(Thujaketone)

CH2 It is worth noting also that its carbon skeleton is identical with that of the side-chain of ergosterol and calciferol (vitamin Dz), and that one of the products of the oxidation of alpha-ergostenol acetate is dihydrothujaketone'. Although thuja-leaf oil has been investigated carefully' by J a b 2 , Wallacha, Semmlel-4, Tiemand, and others, no mention was made in their reports of the fact that pure thujone can be isolated easily and in excellent yield (46.501,) by a single fractionation. The first series of syntheses is shown in Flow Sheet A and may be described briefly here. 1 (a) GUITERAS, NAKAMIYA, AND INHOFFEN, Ann., 494,116 (1932); ( b ) HEILBRON, SIMPSON, AND WILKINSON,J . Chem. Soc., 1699 (1932). 2 JAHNS, Arch. Pharm., 221, 748 (1883). ( a ) WALLACH, Ann., 272,99 (1893); ( 6 ) 276, 164 (1893); (c) 309,24 (1899); ( d ) 336, 263 (1904); ( e ) 381, 81 (1911). 4 (a) SEMMLER, Ber., 26,3343 (1892); ( b ) 33,275 (1900). 6 TIEMANN AND SEMMLER, Ber., SO, 429 (1897). 578

579

SYNTHESIS FROM THUJAKETONE

In the oxidation of thujone (I) by potassium permanganate, at room temperature, Wallach3=obtained both alpha (11) and beta (111) forms of

Flow Sheet A Me

Me

I

CH-CH-CO (111 \ CHz-C-CHz

-+A

I

I

CH-CO

I

I

(111)

(11) -+

I

CHMez Me

COOH

I

I

Hz-C-CHz

CHMez Me CHz-CO

COOH

\

CHz--C=CIH

I

CHz-CO

- 1

(IV)

CHz-C=CH%

'

CHMez I

CHMez

/

\ \

L

1(

Me

(VI)

Me

A(OH)-CH2COOR

CHz-

I

I

CH~-C=CHZ I

Me

I

C1

CH=

-+

CH2-CO

(XI)

CHz--C=CHz

I

I

(V>

CHz-CO

I

CHMez I

I

I

I

I

""-YO

ye CHz-C( OH)-CHzCOOH CH,,-C=CHZ

I

CHMez

(XI11

I

CHMez

\\

\

' \ ' \ 1 '

1 ''

\\

' \

Me

Y

Me Me I I I CH~-~(OH)-CH~COOH C H ~ ~ C H C O O-+ H CH~-&CH~ (VIII) I (1x1 I (XI I CH2-CHCHI CHz--C=CHz CHz-C=CHz I

&HM%

I

I

CHMez

I

bHMe2

580

JESSE WERNER AND MARSTON TAYLOR BOGERT

thujaketonic acid, whereas Thornson* found only the former. Our own results agreed with the findings of Thomson. Distillation of the dpha acid (11),at atmospheric pressure, gave a good yield of the thujaketone (IV) desired, presumably through the intermediate formation of the beta acid, although Wallachabhas claimed that the yield from the alpha acid is poor, but good from the beta isomer. It was oxidized by permanganate, as described by Tiemann and Semmler5,and the omega-dimethylacetonylacetone (V) isolated as the oxime. The ketone was next subjected to the usual Reformatsky reaction with ethyl bromoacetate and zinc, and the resulting ester (VI) hydrolyzed to the free acid (VII). Catalytic reduction of this acid, yielded the corresponding saturated hydroxy acid (VIII), the odor of which was more agreeable than that of (VII). The latter was dehydrated by phosphorus pentoxide to the diene acid (IX), distillation of which gave the diolefin (X), a hydrocarbon with sweet, pleasant odor. This same dihydroterpene (X) was prepared by dry distillation of the olefin hydroxy acid (VII). Its structure was established by analysis, physical constants, and oxidation to omega-dimethylacetonylacetone (V). In attempting to prepare an isomeric hydroterpene, following a German patent’ for the conversion of methylheptenone into an unsaturated chloride, thujaketone was subjected to the action of phosphorus pentachloride and a vinyl chloride (XI) obtained which, on oxidation, yielded methyl isopropyl ketone (XII). Probably because of its tertiary carbon union, this chloride refused to react with either sodiomalonic ester or methylmagnesium iodide. A second group of reactions, using thujaketone as initial material, is exhibited in Flow Sheet B. Rupe and Schlochoff*have reported that they were unable to obtain a satisfactory yield of the cyanohydrin (XXII) from methylheptenone (XXI), and that the small quantity of impure material secured broke down to methylheptenone again when distilled. We were more fortunate in this reaction and succeeded in preparing the pure cyanohydrin without serious difficulty and in good yield. Further, the product distilled undecomposed under reduced pressure. The same reaction was therefore applied to thujaketone, with equally good results. Unfortunately, however, this cyanohydrin (XIII) could not be hydrolyzed satisfactorily by either acid or alkali, nor did its dehydration by phosphorus pentoxide yield a pure product. Its aroma strongly

* THOMPSON, J . Chem. soc.,

97, 1502 (1910). GRIESHEIM-ELEKTRON, German pat. 118,351; Friedlaender, * RUPEA N D SCHLOCHOFF, Ber., 38, 1502 (1905).

VI, 1252 (1900-1902).

58 1


resembled that of peach essence, whereas the cyanohydrin of methylheptenone exhaled only a very faint cyanide type of odor.

Flow Sheet B Me

Me

I

CHz-COI

CH2-C(OH)CN

I

CHz-&OH)

I

+-

CHz-C=CHz

+

CHz-C=CHz CHMe2 I (IV)

//,

1

k/

Me

I

I

Me

CHz-C=CHz

I

I

CHMe2 (XIII)

Me

I

',

CHMe2 (XIV)

L

Me

Me

I

CH2-C(0H) Ci3Hi3(n)

CHz-C(OH) CllH2a

CHZ--&(OH) CsHii

CHr--C=CH2

CH2--C=CH2

CHz-C=CHz

I

I

I

Me CHZ-C(OH) I CsH~s(n)

I

I

CHMez

I

CHMez

CHMez (XVII)

T

(xx) MezCHCHtCHBrCeHla

(XIX)

t Me2CHCH2CH(0H)CsHl3 (XVIII)

bH2-cH--CHa CHMa I

T MesCHCHzCHO

(XVI) Me

Me

CH2-&=C( CN) COOEt

I

CH2-CH

II

CMea (XXIII)

Me

I

I

CHZ-CO + -

1

CH2-CH (=I)

CH2--C(OH)CN --+

I

CH2-CH

II

CMe2 (XXII)

Since the action of methylmagnesium iodide upon methylheptenone leads t o the formation of a useful perfume alcoholg,five analogous tertiary alcohols (XIV, XV, XVI, XVII, XX) were prepared from thujaketone 9 ( a ) GRIGNARD, These de Doctorat, Univ. Lyons, p. 81 (1901); ( b ) HARRIE~S AND WEIL, Ber., 37, 845 (1904).

582


for a comparison of their odor values. This comparison showed that the pleasingness of their perfume was decreased by increasing the molecular weight of the hydrocarbon radical introduced by the Grignard reaction, but was increased by hydrogenation of the olefin bond. Thus, of the five, the odor of (XIV) was most agreeable, and (XVI) had a finer aroma than (XV). Finally, the Knoevenagel reaction was applied to methylheptenone, following in general the method of Copelo,and the cyanoacetic ester condensation product (XXI) was obtained easily and in excellent yield. Endeavors to saponify this ester, by the action of alcoholic potassium hydroxide solution, under various conditions, failed to yield the corresponding acid, so no attempt was made to apply the same reaction to thujaket one. Acknowledgment.-Our grateful thanks are due to Mr. Frederick H. Leonhardt, President of Fritzsche Brothers, Inc., New York, N. Y., who generously supplied the thuja-leaf oil and methylheptenone necessary for this research. EXPERIMENTAL

The thuja-leaf oil used as initial material possessed the following properties: color, straw-yellow, normal; thujone, 61.8%; specific gravity a t 15', 0.920; optical rotation, -12" 39'; refractive index at 20', 1.4568; ester value, 18.7; ester value after acetylation, 32.1; acid value, 0.5. In the following experiments, the melting-point determinations were made in a Thiele apparatus; and distillations under reduced pressure were performed with the aid of a barostat11 which controlled the pressure to f O . l mm. All thermometers were checked against a set of total immersion thermometers crtlibrated by the U. S. Bureau of Standards. Densities were measured with a pyknometer of about 1.5 cc. capacity, and were accurate t o f 0.0002. Refractive indices were determined with an Abbe refractometer, kept a t 25" (f0.01') by circulating water from the thermostat through the thermoregulator12 by means of a gear pump. The readings were correct to f 0.0002. The analyses were carried out in these laboratories by Mr. Saul Gottlieb. d-Thujone (I).-Ten pounds of thuja-leaf oil was distilled, with the assistance of a very efficient 25-cm. Vigreux column, and the fraction boiling a t 198-203' was collected. I t consisted of a pale-yellow oil of piney odor, and amoupted to 2110 g., or 46.5% of the original oil, and showed n t 1.4521. According to other investigators, the b.p. of pure d-thujone is 200-201"ad, and its nD is 1.4510918, 1.4522014,or 1.4525216. COPE,J . Am. Chem. Soc., 69, 2327 (1937). Cox, Ind. Eng. Chem., Anal. Ed., 1, 7 (1929). 11 HEISIGAND CAMERON, ibid., 6, 420 (1933). 13 WALLACH,Be?., 28, 1965 (1895). lo

11

l4

16

BRUHL,ibid., 82, 1% (1899). TSCHUGAEFF, ibid., 38, 3122 (1900).


583

Tribromide.-Prepared by Wallach's method ab? 16. White plates from ligroin, m.p. 121-122" (corr.) (literature, m.p. 122"). 8,4-Dinitrophenylhydrazone.-Orange needles (from ethanol), m.p. 106-107" (corr.). Anal. Calc'd for Cl&N~O~:C, 57.82; H, 6.07. Found: C, 58.06; H, 6.25. Strain1' has reported the melting point of such a hydrazone as 106-107.5", and Macbeth and Price18 as 116-117", but in neither article is the origin or form of the thujone stated. alpha-Thujaketonic acid (11) has been prepared by permanganate oxidation of thujone by a number of investigetorsso, 4111 6, 8 , 19, but we found i t desirable t o modify these methods in various respects and operated as follows: After stirring vigorously for 10 minutes a mixture of 490 g. of potassium permanganate with 9310 cc. of water, 350 g. of thujone was added and the stirring was continued for 3 hrs. a t room temperature. After removal of the manganese dioxide precipitate, 90 g. of unoxidized thujone was recovered from the mixture by extraction with ether. The residual aqueous solution was made acid to Congo Red by concentrated hydrochloric acid, saturated with salt, and extracted with ether; the extracts were distilled, and the residue was dried by adding dry benzene and distilling i t off again. The liquid mass left behind solidified completely t o white foliated crystals when cooled and scratched; yield, 239 g., or 75.6%. Recrystallized from an etherpetroleum ether mixture, it melted a t 74-75" (corr.); m.p. reported in the literature, 74.5O4o,6, and 75-76'6. No beta-thujaketonic acid was encountered in this process. 0dme.-M.p. 175-176" (corr.) ; previously reported, 174-175"'. Thujaketone (IV).-The decarboxylation of the thujaketonic acid, as carried out by Wallach", has been modified and the yield greatly improved. In a 500-cc. distilling flask, 239 g. of alpha-thujaketonic acid was heated in a bath of molten Wood's metal the temperature of which was raised slowly from 275" t o 325'. To the distillate, benzene was added, the solution was cleared by calcium chloride, and the filtrate was distilled with the aid of a 25-cm. Vigreux column. The fraction boiling at 183-188" consisted of the desired ketone, and more was recovered by redistillation of the fore and after runs. The product was a pale-yellow liquid, of amyl acetate odor; yield, 113.6 g., or 62.4%; n: 1.4430. Previously reported: b.p. "9

184-18Bo3*, 182-185"";

n:

1.44104&.

8emicarbazone.-White plates, m.p. 141-142" (corr.) ; previously reported, 143OZ0. 8,4-Dinitrophenylhydrazone.-Microscopic orange needles (from ethanol), m.p. 73-74' (corr.). Anat. Calc'd for ClsHaoN404: C, 56.24; H, 6.29. Found: C, 56.33; H, 6.58. Oxidation of thujaketone with permanganate, following the directions of Tiemann and Semmlei-6, and our own experience in the oxidation of thujone, gave a very poor yield of omega-dimethylacetonylacetone (V), which was isolated as its dioxime; white microscopic needles, m.p. 128-130" (m.p. previously reported, 132"". Ethyl 3-hydroxy-3, 7-dimethyl-6-methyleneoctanoate(VI) .-A mixture of 140.2 g. WALLACH, Ann., 286, 109 (1895). STRAIN,J. Am. Chem. SOC., 67, 760 (1935). 18 MACBETH AND PRICE,J . Chem. SOC.,1936, 151. 19 RUZICKA AND KOOLHAAS, Helv. Chim. Acta, 16, 94.4 (1932). zo WALLACE,Bes., 30, 423 (1897). 15

17

584


of thujaketone, 167.1 g. of ethyl bromoacetate, 72 g. of zinc (sheet zinc, sandpapered and cut into small pieces), 250 cc. of dry benzene, and 250 cc. of dry toluene, in a flask equipped with an efficient condenser and drying tube, was heated carefully with a free flame until the reaction started. The flame was then removed, and the very vigorous reaction was controlled by cooling with ice water from time t o time. When the reaction was over, the mixture was refluxed for 30 minutes, cooled, and decomposed by agitation with 600 cc. of ice-cold 10% sulfuric acid. The upper layer was removed, washed twice with water, filtered, and the solvents were distilled off under diminished pressure. The remaining liquid was distilled in an atmosphere of nitrogen at a pressure of 3 mm., and a fraction was collected at 113-114", amounting t o 173.4 g., or 76%, as a very pale-yellowish liquid of pleasant, fruity aroma; d i 6 0.9440; n: 1.4500; Mn calc'd 64.97, obs. 65.02. Anal. Calc'd for ClsH2rOs:C, 68.38; H, 10.59. Found: C, 68.65; H, 10.46. Free acid (VZZ).-This was secured by saponifying the ester with alcoholic potassium hydroxide solution and distilling the crude product under reduced pressure in an atmosphere of nitrogen. The fraction collected boiled at 144-146" at 3 mm. and was a pale-yellow liquid, of mild, agreeable odor, and amounted t o 132.5 g., or 87%. Its constants were: d i 6 0.9904; n t 1.4646; MDcalc'd 55.73, obs. 55.86; neutral. equiv. calc'd 200.3, obs. 199.7. Anal. Calc'd for Cl1HzOOs: C, 65.97; H, 10.07. Found: C, 66.21; H, 10.23. 3-Hydroxy-J,6,7-trimethyloctanoicacid (VIII).-Ten grams of the above unsaturated acid (VII), 100 cc. of 80% methanol, and 1 g. of palladium on charcoal, were placed in a Parr-Adams hydrogenator, and the hydrogenation was conducted for 24 hrs. at a pressure of two atmospheres. The mixture was filtered, the methanol was distilled from the filtrate, and the residue was extracted with ether. The ether extract was washed with water, dried with sodium sulfate and distilled, with reduction of the pressure after the elimination of the ether. The fraction collected boiled a t 164-166" at 6 mm., was a pale-yellow oil of agreeable, sweet odor, amounted t o 7 g., or 70%, and showed the following constants: d i s 0.9952, n: 1.4646; MD calc'd 56.20, obs. 56.15; neutral. equiv. calc'd 202.3, obs. 203.1. Anal. Calc'd for C1lHBO1: C, 65.31; H, 10.71. Found: C, 65.03; H, 10.57. 3,7-Dimethyl-6-methyleneocten-2-oicacid (IX).-To a solution of 132.5 g. of the methylene octanoic acid (VII) in 200 cc. of dry benzene, there was added 175 g. of phosphorus pentoxide, and the mixture was refluxed for 6 hrs. at 100". It was then filtered; the residue was extracted twice with 200-cc. portions of dry benzene; the extracts were added to the original filtrate, and the whole was distilled under reduced pressure, under an atmosphere of nitrogen after removal of the benzene. The fraction boiling at 127-128" at 2 mm. was collected. It was a pale-yellow oil, of mild, pear-essence odor; yield, 32.5 g., or 28%; d: 0.9611; n: 1.4840; MI,calc'd 53.73, obs. 54.25; EM +0.52, which is similar to that reported by Tiemann21 for geranic acid; neutral. equiv. calc'd 182.3, obs. 181.8. Anal. Calc'd for CllH1802:C, 72.49; H, 9.96. Found: C, 72.55; H, 10.11. 2,6-Dimethyl-S-methyleneheptene-l(X).-Fifty grams of the octanoic acid (VII) was distilled slowly over a naked flame. The distillate was washed with sodium 21

TIEMANN, Ber., 31, 823 (1898).


585

carbonate solution, dried over calcium chloride, and distilled; the fraction boiling a t 158-159" was collected. This was a colorless oil, of very sweet smell; yield, 17.5 g., or 50%; d:' 0.7698,nf 1.4418;M D calc'd 47.45,obs. 47.50. Anal. Calc'd for CloHls: C, 86.88; H, 13.12. Found: C, 86.64;H, 13.21. Distillation of the octenoic acid (IX), gave a 25% yield of the same hydrocarbon. Oxidation with potassium permanganate, as in the case of thujaketone, yielded only a small quantity of omega-dimethylacetonylacetone (V), identified by its dioxime, microscopic white needles, m.p. 128.5-130" (corr.); mixture with the corresponding dioxime from thujaketone, m.p. 128-129.5' (corr.). 2-Chloro-6-methyl-5-methyleneheptene-2(XI) .-To 84 g. of phosphorus pentachloride, cooled by a mixture of ice and salt, there was added dropwise 56 g. of thujaketone. The reaction mixture was left in the ice bath for 15 minutes longer, then maintained a t room temperature until the vigorous evolution of hydrogen chloride ceased, and finally heated at 100' for 2.5 hrs. It was next placed in an ice pack, hydrolyzed by the careful addition of water, and distilled with steam. The distillate was extracted with benzene, the benzene was distilled off, and the residue was fractionated a t 18 mm. pressure, the cut which boiled a t 95-96' was collected. This was a colorless oil, of terpene odor, 25.1 g., or 40%, in amount, with the following constants: d:' 0.9310, n t 1.4730;M Dcalc'd 47.72,obs. 47.81. Anal. Calc'd for CsH1,CI: C, 68.12;H, 9.53; C1, 22.35. Found: C, 67.91; H, 9.66;C1, 22.34. Oxidation of this compound with potassium permanganate, yielded a small quantity of methyl isopropyl ketone (XII); identified by its semicarbazone, map. 110112" (oorr.) [mixed with an authentic sample of m.p. 112-113' the m.p. was 110.5112' (corr.)], and by its 2,4-dinitrophenylhydrazone,m.p. 115-116' (corr.) [mixed with an authentic sample of m.p. 116-117" the m.p. was 115-116' (corr.)]. 2-Hydro~y-2~6-dimethylhepten-S-oic nitrile (XXII).-To 42 g. of methylheptenone, in a flask equipped with sealed stirrer, dropping funnel, and exit tube to the hood, there was added a solution of 34.7g. of sodium bisulfite in 65 cc. of water. The mixtuye was stirred for 20 minutes, cooled in ice and water, and a solution of 21.7 g. of potassium cyanide in 35 cc. of water added dropwise with vigorous stirring. At the end of the cyanide addition, the cooling bath was removed, the mixture was stirred for 2 hrs., the upper layer was separated, and the lower layer was extracted twice with ether. The ether extracts and the separated upper layer were united, washed with concentrated sodium bisulfite solution, then twice with dilute sodium chloride solution, dried over sodium sulfate, the ether was distilled off, and the residue was fractionated under 2 mm. pressure; the portion that boiled a t 115-117' was collected. This amounted to 28.7 g., or 56.3%, and was a pale-yellow oil of cyanide odor; d:' 0.9224;n; 1.4501;MD calc'd 44.64,obs. 44.68. A n d . Calc'd for CpHlaNO: C, 70.55;H, 9.87. Found: C, 70.51;H, 10.14. Z-Hydroxy-2,6-dimethyl-5-methyleneheptanoic nitrile (XIII) .-This was prepared from thujaketone and potassium cyanide in essentially the same way as the foregoing nitrile was synthesized from methylheptenone. It was a pale-yellow liquid, b.p. 116-118' at 2 mm., with a sweet odor strongly recalling that of peach essence, and on standing turned red first and then yellow; yield, 14.2g. from 23.4 g. of the ketone, or 51%; d:' 0.9103;nt 1.4498;M, calc'd 49.26,obs. 49.41. Anal. Calc'd for CloHlrNO: C, 71.81; H,10.25. Found: C, 71.94;H, 10.24.

586


The alcohols listed below were synthesized by the standard Grignard reaction, either from thujaketone (XIV, XV, XVII, XX) or isovaleraldehyde (XVIII), or (XVI) by reduction of the corresponding unsaturated alcohol. 2,6-Dimethyl-5-methyleneheptanol-2 (XIV). 2,6-Dimethyl-3-methylenedodecanol-6(XV). 2-Cyclohexyl-6-methyl-5-methyleneheptanol-2(XVII). 2,6-Dimethyl-3-methylene-7-isobutyltridecano1-6 (XX). 2,3,6-Trimethyldodecanol (XVI). 2-Methyldecanol-4 (XVIII). The details are given in the accompanying Table. TABLE ALCOHOL

XIV

xv

XVI

XVlII

73

73

~~

Yield (%). . . . . . . . 80 Appearance. . . . . . . Paleyellow oil Odor. . . . . . . . . . . . . Sweet, minty

69 Paleyellow oil Agreeable

46.5

45

PalePaleColorless Colorless yellow oil oil yellow oil oil Mildly Sweet, Very Slightly sweet pleaspleaspiney ant ant

149-151" 123-125" B * p. . . . . . . . . . . . . . 97-99' a t 150-153' 122-124" 157157.5' at 3 at 17 at 12 19 mm a t 15 at 2 mm. mm. mm. mm . mm.

a;as . . . . . . . . . . . . . . . . 0.8390 n D. . . . . . . . . . . . . .

1 -4453 M,, calc'd.. . . . . . . 49.44 MD obs. . . . . . . . . . 49.60 C calc'd.. . . . . . . . 76.86 C f o u n d . . . . . . . . . 77.04 H calc'd.. . . . . . . . 12.90 H found.. . . . . . . . 12.90

0.8375 1.4535 72.56 72.67 79.57 79.49 13.36 13.35

0.8937 1,4749 70.36 70.68 80.28 80.36 12.59 12.77

0.8384 1.4542 95.62 95.81 81.01 81.28 13.60 13.77

0,8351 1.4472 73.03 73.11 78.87 78.89 14.12 13.82

0.8168

1.4310 54.55 54.60 76.67 76.43 14.04 13.90

2,3,6-Trimethyldodecanol-6(XVI). was obtained from the unsaturated alcohol (XV), by reduction for 2 hrs. in 95% ethanol, in a Parr-Adams hydrogenator, at two atmospheres pressure, in the presence of platinum oxide catalyst. The crude product was fractionated under diminished pressure, and the properties of the pure compound are recorded in the foregoing Table. 2-Methyl-4-bromodecane (XIX).-After refluxing for 5.5hrs. 43.2 g. of 2-methyldecanol-4 (XVIII) with 136 cc. of 48% hydrobromic acid, the Supernatant layer was separated, washed with concentrated sulfuric acid, water, and dilute sodium bicarbonate solution, dried over calcium chloride, and distilled at 17 mm. pressure. The fraction boiling a t 115-118"consisted of the bromide sought, and was a colorless oil of agreeable odor; yield, 39.3 g., or 60%; d16 1.0439;n t 1.4525;M D calc'd 60.79,obs. 60.85. Anal. Calc'd for C l 1 H ~ ~ BC,r : 56.17;H, 9.86. Found: C, 56.43;H, 10.16. Ethyl 3,7-dimethyl-2-cyanooctadien-2,6-oate (XXIII) .-A mixture of 34.7g. of


587

methylheptenone, 60 cc. of glacial acetic acid, 5 drops of acetic anhydride, 5 g. of acetamide, and 28.3 g. of ethyl cyanoacetate, was heated so that the temperature of the vapor was maintained a t 105-117" and 62 cc. of liquid distilled in 4.75 hrs. The residue in the flask was cooled, washed with two 50-cc. portions of water, and distilled under a pressure of 12 mm. The fraction boiling at 151-152' consisted of the desired condensation product, and was a pale-yellow oil, of sweet, fruity nitrile odor; yield, 47 g., or 85%; di6 0.9751, n: 1.4820; MD calc'd 62.77, obs. 64.70; EM f1.93. Cope10 has noted a similar exaltation in the case of analogous compounds. Anal. Calc'd for ClaHtoNOn:C, 70.55; H, 8.79; N, 6.33. Found: C, 70.38; H, 8.67; N, 6.31. SUMMARY

1. New hydroterpenoids have been synthesized from thujaketone by application of the Reformatsky, Grignard, Knoevenagel, cyanohydrin, and other standard reactions. 2. Insofar as the odors of these new products are concerned, they differ from, and are more.pleasant than, those of the analogously constituted compounds prepared from methylheptenone. In the case of the tertiary alcohols synthesized by the Grignard reaction, the agreeableness of the odor decreased with increase in the molecular weight of the hydrocarbon radical introduced.

THE SYNTHESIS FROM THUJAKETONE OF SOME NEW

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