Chemistry

Z. G. Isaeva, I. S. Andreeva

On the Isomerization of $\Delta^3$-Carene Oxide in Reaction with Alcohols in the Presence of Acids

(Presented by Academician B. A. Arbuzov on 3 V 1963)

In 1949 we (¹) found that $\Delta^3$-carene oxide, in reaction with primary alcohols in the presence of sulfuric acid, forms products of addition of the alcohol to the oxide—tertiary monoalkyl ethers of careneglycol; under the action of secondary alcohols, along with the reaction of addition of the alcohol to the oxide, isomerization of the oxide into a carbonyl compound is also observed—an “unsaturated aldehyde of undetermined structure”; in the case of reaction with a tertiary alcohol, only isomerization of the oxide into an aldehyde takes place.

Later Kuchinskii and co-workers found that, under the action of sulfuric acid in tert-butyl alcohol (²) and acetic acid (³), $\Delta^3$-carene oxide gives a mixture of reaction products consisting of hydrocarbons (mainly p-cymene), $l$-caranone-3, an unsaturated monocyclic ketone, and $\beta$-careneglycol (or its monoacetate in the case of reaction with acetic acid); the “unsaturated aldehyde” was not found among the reaction products. Kuchinskii and co-workers explain this discrepancy between the data on the study of the isomerization of $\Delta^3$-carene oxide under the action of acids by assuming that the $\Delta^3$-carene oxide used by the authors was contaminated with $\alpha$-pinene oxide, which is readily isomerized into campholenic aldehyde; the presence of campholenic aldehyde in the isomerization products of $\Delta^3$-carene oxide caused a positive reaction with fuchsine-sulfurous acid and moist silver oxide. Such an explanation seemed unlikely to us, since, first, the “impurity” of $\alpha$-pinene oxide would have to be present in rather substantial quantities in order to give one of the main isomerization products; second, a semicarbazone with m.p. 216–217°, characteristic of the “unsaturated aldehyde of undetermined structure,” and the semicarbazone of campholenic aldehyde (m.p. 136–139°) can hardly be called close in melting point.

In order to clarify the causes of the indicated discrepancy and to study in greater detail the reaction of isomerization of $\Delta^3$-carene oxide under the influence of acids, we repeated our experiments on the interaction of $\Delta^3$-carene oxide with alcohols in the presence of sulfuric acid. The mechanism of the acid-catalyzed isomerization reaction of $\alpha$-oxides generally accepted at present includes, as one of the intermediate stages, the formation of a carbonium ion, which can be stabilized by several pathways: addition of the reagent anion (formation of an addition product), electrophilic rearrangement (isomerization into carbonyl compounds), and abstraction of a proton from the $\beta$-position (isomerization into $\alpha,\beta$-unsaturated alcohols). A transformation of bicyclic terpene oxides analogous to the last of these is observed in their reaction with acetic anhydride, with the formation of acetates of $\alpha,\beta$-unsaturated alcohols. In the products of isomerization of terpene oxides in the presence of acids, $\alpha,\beta$-unsaturated alcohols had not previously been detected.

In addition to the results obtained earlier (¹), we found that, first, opening of the oxide ring of $\Delta^3$-carene oxide in a reaction cataly-

by an acid, proceeds in both directions: the product of addition of methyl alcohol to the oxide contains, in addition to 4-methoxycaranol-3 (I) (or the tertiary monomethyl ether of carenglycol), 3-methoxycaranol-4 (II), 3,5-dinitrobenzoate, m.p. 128–129° (yields 75% and 6%, respectively); secondly, isomerization of $\Delta^3$-carene oxide into carbonyl compounds under the action of acid takes place to a very slight extent already in the reaction with primary alcohols: in the products of the reaction with methyl alcohol, $l$-caranone-3 ($^4$) was identified (yield 4%); semicarbazone, m.p. 199–200°; 2,4-dinitrophenylhydrazone, m.p. 158–159°. 4-Methoxycaranol-3 was isolated in pure form by saponification of its 3,5-dinitrobenzoate with m.p. 112–113°; b.p. 83–84°/3 mm, $n_D^{20}$ 1.4810, $d_4^{20}$ 1.006, $[\alpha]D=-2.0^\circ$; $MR$ found 52.04; $\mathrm{C}}\mathrm{H{20}\mathrm{O}_2$, 3-membered ring $MR$ calculated 52.24. On oxidation with the chromic anhydride–pyridine complex, 4-methoxycaranol-3 gave 4-methoxycaranone-3 (III): b.p. 109–111°/11 mm, $n_D^{20}$ 1.4752, $d_4^{20}$ 1.0013, $[\alpha]_D=+36.7^\circ$; $MR$ found 51.19, $\mathrm{C}$. 4-Methoxycaranone-3}\mathrm{H}_{18}\mathrm{O}_2$, 3-membered ring $MR$ calculated 50.95; semicarbazone, m.p. 213–214°; 2,4-dinitrophenylhydrazone, m.p. 147–148°. The IR spectrum of 4-methoxycaranol-3 has a band at a frequency of 1713 cm$^{-1

proved to be unstable toward acids. In the course of hydrolysis of the semicarbazone in the presence of acids, molecules of methyl alcohol are split off from 4-methoxycaranone-3 and unsaturated ketones of composition $\mathrm{C}{10}\mathrm{H}}\mathrm{O}$ are formed. According to IR spectra, the products of hydrolysis of the semicarbazone with m.p. 213–214° by a saturated solution of oxalic acid with simultaneous steam distillation contain approximately equal amounts of 4-methoxycaranone-3 and unsaturated ketones (equal intensities of the bands at 1713 cm$^{-1}$, corresponding to $\nu_{\mathrm{C=O}}$ of a ketone of the cyclohexane series, and 1666 cm$^{-1}$, characteristic of an unsaturated ketone in the molecule of which the CO group is conjugated with two double bonds). The products of hydrolysis of the semicarbazone of 4-methoxycaranone-3 in the presence of sulfuric acid consist mainly of ketones $\mathrm{C{10}\mathrm{H}$. Their structure has not been established by us, but the data given below allow them to be assigned to the series of $p$- and $m$-menthadienones.}\mathrm{O

In one of the experiments on the hydrolysis of the semicarbazone of 4-methoxycaranone in the presence of sulfuric acid, a product was obtained (yield 71.6%), separated into two fractions (ratio 1:2): 1) 97–112°/12 mm, $n_D^{20}$ 1.5245, $d_4^{20}$ 0.9787, $[\alpha]D=-8.35^\circ$; 2) b.p. 112–116°/12 mm, $n_D^{20}$ 1.5365, $d_4^{20}$ 0.9794, $[\alpha]_D=-1.7^\circ$. According to IR spectra, both fractions, in addition to ketones, contained phenols (bands at frequencies of 1620 cm$^{-1}$, 1594 cm$^{-1}$, 1512 cm$^{-1}$, 810 cm$^{-1}$). The phenol isolated from the hydrolysis products by extraction with sodium hydroxide solution (yield 18.5%) proved to be carvacrol ($^5$): b.p. 82–84.5°/2.5 mm, $n_D^{20}$ 1.5220, $d_4^{20}$ 0.9767, $MR$ found 46.84; $\mathrm{C}_3$ $MR$ calculated 46.30; 3,5-dinitrobenzoate, m.p. 95–96°; $\alpha$-naphthylurethane, m.p. 117–118°. Mixed samples with the corresponding derivatives of carvacrol* melted without depression of the melting temperature. The ketone portion}\mathrm{H}_{14}\mathrm{OF

* Carvacrol was obtained by isomerization of $d$-carvone over palladized charcoal: 3,5-dinitrobenzoate, m.p. 93–94°; $\alpha$-naphthylurethane, m.p. 117–118°.

of the hydrolysis products (37%), after separation of carvacrol by distillation, was divided into 2 fractions: 1) 101–112°/7 mm—1.3 g, (n_D^{20}) 1.5250, (d_4^{20}) 0.9758, ([\alpha]D = -17.0^\circ); 2) b.p. 112–115°/7 mm—1.7 g, (n_D^{20}) 1.5383, (d_4^{20}) 0.9762, ([\alpha]_D = -2.0^\circ). Products from the first and second fractions gave two 2,4-dinitrophenylhydrazones: 1) m.p. 179–180° and 2) m.p. 145–146°. The IR spectra of the products of these fractions have bands with frequency 1670 cm(^{-1}), which may be assigned to (\nu) of menthadienones with a CO group conjugated with two double bonds. Upon isomerization over 10% palladized carbon ((^6)), the product with b.p. 101–112°/7 mm gave two phenols: 1) carvacrol; 3,5-dinitrobenzoate, m.p. 94–95°, and 2) 2-methyl-4-isopropylphenol; 3,5-dinitrobenzoate, m.p. 151–152°. Consequently, ketones of the (n)- and (m)-menthadienone series are present in the mixture of products of hydrolysis of 4-methoxycaranone-3 semicarbazone with sulfuric acid.

In order to determine the relative arrangement of the C=C and C=O bonds

[
(\mathrm{C}=\mathrm{C}-\mathrm{C}=\mathrm{C}-\mathrm{C}=\mathrm{O})
\quad \text{or} \quad
\mathrm{C}=\mathrm{C}-\mathrm{C}-\mathrm{C}=\mathrm{C})
\tag{7}
]

[
\begin{gathered}
|\
\mathrm{C}
\end{gathered}
]

in the molecules of the unsaturated ketones, the product with b.p. 112–115°/7 mm was oxidized with alkaline hydrogen peroxide. However, no mono- or diepoxy ketones were found in the oxidation reaction products, and only carvacrol was detected.

The data obtained in studying the reaction of (\Delta^3)-carene oxide with isopropyl and tert-butyl alcohols proved interesting. As before ((^1)), we found that, upon the action of isopropyl alcohol on (\Delta^3)-carene oxide, a product of addition of the alcohol to the oxide and carbonyl compounds are formed. In addition, (n)-cymol (6%) and (\beta)-carenglycol (yield 12%), m.p. 73–74° (monohydrate) ((^8)), were identified. The addition product (yield 10%), 4-iso-propoxycaranol-3, was obtained in pure form by saponification of the 3,5-dinitrobenzoate with m.p. 151–152°: b.p. 95–97.5°/2.5 mm, (n_D^{20}) 1.4695, (d_4^{20}) 0.9585, ([\alpha]D = +6.9^\circ), (MR) found 61.65; (\mathrm{C}}\mathrm{H{24}\mathrm{O}_2), 3-membered ring. (MR) calculated 61.70; 3,5-dinitrobenzoate, m.p. 153°. The carbonyl compounds proved to be a mixture of three products: 1) an aldehyde (\mathrm{C}}\mathrm{H{16}\mathrm{O}) (yield 3%), IR spectrum, (\nu) C=O 1725 cm(^{-1}), semicarbazone, m.p. 190–191°, identical with the aldehyde from the reaction of (\Delta^3)-carene oxide with acetic anhydride (to be described in greater detail in one of the following communications), 2) (l)-caranone-3 (yield 7%), semicarbazone, m.p. 200–201°, and 3) a ketone (\mathrm{C}}\mathrm{H{16}\mathrm{O}) (yield 39.5%), giving the same semicarbazone* with m.p. 216–217°, which we had assigned to an unsaturated aldehyde ((^1)). By hydrolysis of the semicarbazone with m.p. 219–220° (a mixed sample with the semicarbazone, m.p. 216–217°, melted without depression of the melting point), the ketone was isolated in pure form: b.p. 67–67.5°/3.5 mm, (n_D^{20}) 1.4719, (d_4^{20}) 0.9565, ([\alpha]_D = -89.6^\circ), IR spectrum, (\nu) C=O 1709 cm(^{-1}); (MR) found 44.50, (\mathrm{C})). A mixed sample of the 2,4-dinitrophenylhydrazones of the product of isomerization of (\Delta^3)-carene oxide and (l)-isocaranone-3 (m.p. 135–136°) melted without depression of the melting point.}\mathrm{H}_{16}\mathrm{O}), 3-membered ring; (MR) calculated 44.69; semicarbazone, m.p. 219–220°; 2,4-dinitrophenylhydrazone, m.p. 136.5°. By its constants the ketone is identical with (l)-isocaranone-3; however, the melting point of its semicarbazone is somewhat higher than that reported by Kuchinsky and Khabudzinsky ((^9)) for (l)-isocaranone-3 (214.5°). We synthesized (l)-isocaranone-3 by oxidation with chromic anhydride of (l)-isocaranol-3—one of the products of hydrogenation of (\Delta^3)-carene oxide over Raney nickel ((^{9,10

Repeated investigation of the reaction of isomerization of (\Delta^3)-carene oxide with sulfuric acid in tert-butyl alcohol gave more complete information about the course of the reaction, although somewhat differing from the data of Kuchinsky and Khabudzinsky ((^2)).

* The melting point of the same semicarbazone obtained for the product of isomerization of (\Delta^3)-carene oxide with sulfuric acid in tert-butyl alcohol is 221–222° ((^1)).

We found that, in the reaction with tert-butyl alcohol, $\Delta^3$-carene oxide forms $l$-caranone-3 (yield 27%), $l$-isocaranone-3 (yield 14%), in small amounts the ketone $C_{10}H_{16}O$, IR spectrum, $\nu C-O$ 1705 cm$^{-1}$, semicarbazone, m.p. 199–199.5°, not identical with the semicarbazone of $l$-caranone-3, caren-4(7)-ol-3 (11) (10%), $n$-cymene (4%), and $\beta$-careneglycol (21%). An aldehyde with semicarbazone melting point 192–193° was not detected here. Consequently, in addition to the reaction products described in the analogous work of Kuczyński and Chabudziński, we identified $l$-isocaranone-3 and caren-4(7)-ol-3, but did not find the monocyclic unsaturated ketone.

Thus, the product of isomerization of $\Delta^3$-carene oxide described by us earlier proved to be a mixture of carbonyl compounds; one of the components of this mixture—$l$-isocaranone-3—forms a semicarbazone, m.p. 219–220°. The unsaturation of the isomerization product and its reactions with fuchsin-sulfurous acid and moist silver oxide were apparently due to impurities of the aldehyde characterized by a semicarbazone with m.p. 192–193° and to the presence of previously unidentified unsaturated alcohols.

Scientific Research Chemical Institute
named after A. M. Butlerov
of Kazan State University
named after V. I. Ulyanov-Lenin

Received
28 IV 1963

CITED LITERATURE

1. Z. G. Isaeva, B. A. Arbuzov, ZhOKh, 19, 893 (1949).
2. H. Kuczyński, A. Hendrich, Roczn. Chem., 33, 293 (1959).
3. Z. Chabudziński, H. Kuczyński, Roczn. Chem., 33, 871 (1959).
4. H. Kuczyński, Z. Chabudziński, Roczn. Chem., 29, 437 (1955).
5. M. Goryaev, I. Pliva, Methods for the Study of Essential Oils, Alma-Ata, 1962, p. 552.
6. Ch. Balant, Ch. A. Vodoz, H. Kappeler, H. Schinz, Helv. chim. acta, 34, 722 (1951).
7. E. Weitz, A. Scheffer, Ber., 54, 2327 (1921).
8. B. A. Arbuzov, Studies in the Field of Isomeric Transformations of Bicyclic Terpene Hydrocarbons and Their Oxides, Kazan, 1936, p. 182.
9. H. Kuczyński, Z. Chabudziński, Roczn. Chem., 35, 227 (1961).
10. B. A. Arbuzov, Z. G. Isaeva, DAN, 121, 105 (1958).
11. B. A. Arbuzov, Z. G. Isaeva, DAN, 122, 73 (1958).