US2889339A - Dialkyl substituted 2, 3-epoxyacid esters - Google Patents

Description

United States Patent DIALKYL SUBSTITUTED 2,3-EPOXYACID ESTERS Joseph Levy, Paramus, and Robert M. Lusskin, Haworth, N.J., assignors to The Trubek Laboratories, East Rutherford, N .J a corporation of New Jersey No Drawing. Application July 2, 1956 Serial No. 595,095

6 Claims. (Cl. 260-348) This invention relates to aliphatic saturated beta, beta-dialkyl substituted-2,3-epoxyacid esters or glycidic acid esters and to methods of producing the same.

In our copending application Serial No. 595,059, filed July 2, 1956, now abandoned, we have described new alkyl poly-substituted aldehydes, and in accordance with a preferred method described therein for producing such aldehydes, saturated beta, beta-dialkyl substituted-2,3- epoxyacid esters may be produced as intermediate products. These intermediate products are themselves new compounds which further have been found to possess characteristic odors rendering them suitable for use in producing perfumes or perfumed products and as flavoring agents.

-While it is well known that glycidates containing aromatic substituents possess odors rendering them useful in perfumes and flavoring compositions, 2,3-epoxyacid esters or glycidates containing only alkyl substituents have not previously been noted to possess such characteristics to a pronounced degree. It now appears that when aliphatic glycidic acid esters are dialkyl substituted in the beta position and one of the alkyl groups is a branched chain alkyl so that the compound is an ester of a saturated 3,4-dialkyl substituted-2,3-epoxyacid, the product will have pronounced odor and flavoring prop erties. Therefore, the preferred compounds of the present invention may be said to have the composition indicated by the following formula:

wherein R, R' and R" are saturated alkyl radicals and R'" may be a saturated or unsaturated radical.

The principal object of the present invention is to provide a new class of odor and flavoring agents consisting of aliphatic saturated beta, beta-dialkyl-substituted- 2,3-epoxyacid esters. I

Another object of the invention methods for producing'such esters.

A particular object of the invention is to provide esters of aliphatic saturated 3,4-dialkyl substituted-2,3- epoxyacids which may be employed in the production of perfumes, perfumed products and flavoring agents.

These and other objects and features of the present invention will appear from the following description thereof in which reference is made to particular compounds and procedures for the purpose of indicating the nature and character of the invention but without intending to limit the invention thereby.

The compounds of the present invention vary considerably in odor in that some possess a fruity odor, others have a berry-like odor, while still others have what may be described as an herby odor. The particular odor developed in any compound will depend largely upon the nature and location of the various aliphatic radicals.

is to provide novel The alkyl groups which may be present in the compounds can be varied greatly. Among those groups which may be present are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl and the like as well as their various branch chain isomers. In general, the alkyl groups present in the most important members of the series contain from 1 to 4 carbon atoms. When longer alkyl groups are present in the compound, the product is generally less volatile and therefore has a weaker odor or one which is less significant. However, such higher alkyl compounds may be used as blending or odor modifying agents or as additives for use with perfumes or perfumed products.

A further important characteristic of the compounds of the present invention resides in their stability in the presence of soap. Thus, when mixed with soaps, they do not cause discoloration or rancidity and therefore are particularly useful for perfuming soaps.

Compounds of the present invention may be prepared by reacting an appropriately alpha-substituted aliphatic ketone, containing, say 6 to 11 carbon atoms, with an ester of chloracetic acid or bromacetic acid in the presence of an alkaline condensing agent such as sodium, sodium methylate or other sodium alkoxide, sodamide, or the like. The reaction may be represented by the following general equation:

If the alkyl group of the sodium alkoxide or other condensing agent used differs from the alkyl group of the chloracetic ester (that is if the R and R" of the foregoing equation are different), the epoxyacid esters produced will be mixed esters. Such mixtures of esters may be separated by fractional distillation or other methods, if desired, or the mixtures of esters may be used as a blend wherein the differently odored esters combine to produce a distinctive new effect.

When desired a lower aliphatic ester of the epoxyacid may be converted into a higher aliphatic ester by alcoholysis, as by heating the lower ester with a higher alcohol in the presence of a catalyst such as sodium, anhydrous sodium methylate or the like.

The aliphatic ketones required in producing many of the products of the present invention are not commercially available, but they may be produced by condensing an aliphatic aldehyde with an aliphatic ketone containing at least four carbon atoms to obtain an alpha substituted beta-hydroxyketone. Various aldehydes and ketones may be selected as starting agents depending upon the nature of the particular end product to be obtained. Among the aldehydes which may be used are acetaldehyde, propanal, butanal, isobutanal, pentanal, heptanal, octanal, decanal and their various branched chain isomers. Similarly among the ketones which may be used are methyl ethyl ketone, diethyl ketone, dibutyl ketone, methyl propyl ketone, methyl amyl ketone, methyl nonyl ketone, and the like. If desired, unsaturated aldehydes and ketones may be used.

The selected aldehyde and ketone required for producing any desired end product are condensed and dehydrated to produce an alpha substituted unsaturated ketone. In the preferred practice of the invention, the starting materials employed are alkylaldehydes and dialkyl ketones selected to produce an alpha-substituted, alpha, beta unsaturated ketone upon condensation. The general equa tion' for such a reaction is as follows:

Either alkaline or acid condensing agents may be usedand in general, the alkaline agents are preferred. Thus, sodium hydroxide; potassium hydroxide, barium hydroxide, hydrochloric acid, zinc chloride, or the like may be used. However, if R is such that the aldehyde has a branched chain inthe alpha position and R" of the ketone is methyl, an acid condensing agent is preferred in order to assure attack of the aldehyde upon the methylene group of the ketone.

The alpha-substituted unsaturated ketone obtained by such condensation is thereafter hydrogenated to the alpha substituted saturated ketone and the latter then converted into an ester of a beta, beta-disubstituted-Z,3-epoxy or glycidic acid. For this purpose the alpha-substituted saturated ketone is preferably reacted with an ester of chloracetic acid or bromacetic acid in the presence of an alkaline condensing agent such as sodium, sodium methylate or other sodium alkoxides, sodamide, or the like. The reaction proceeds as represented by the following, equation:

In order to illustrate typical procedures which may be employed in the practice of the present invention, the following examples are cited.

Example I 968 gms. of acetaldehyde were added with stirring at -5 C. in 6 hrs. to a mixture of 4752 gms. methyl ethyl ketone and 33.6 gms. potassium hydroxide dissolved in 166 gms. methanol. After stirring for 1 hr. at 0-5 40 gms. oxalic acid was added and the precipitated potassium oxalate removed by filtration. The unreactedmethyl ethyl ketone was then distilled out to 94 C. (pot temp.=l56). After cooling to 100 C., an additional 40 gms. oxalic acid was added and the mixture again distilled to give 2080 gms. crude product (plus some water) distilling from 80170 C. The water was separated and the product redistilled to give 1276 gms. 3-methyl-3- pentene-Z-one distilling at 137-142" C.

1224 gms. of the 3-methyl-3-pentene-2-one thus obtained was charged into an autoclave with 24.5 gms. of 5% palladium-charcoal catalyst and hydrogenated at about 25 and at a pressure of to 50 pounds per square inch of hydrogen gas. Reduction of the carboncarbon double bond wascompleted in about 3 /2 hours after which absorption of hydrogen ceased. The catalyst was removed by filtration and the product distilled to give about 96% yield of 3-methyl-pentanone-2. The pure compound distilled at 121.

A mixture of 456 gms. 3-methylpentanone-2 and 793 gms. methyl chloracetate was cooled to about 10 C. and 394 gms. anhydrous sodium methylate added in-portions during 2 /2 hours with stirring and cooling so that the temperature did not rise above 0 C. Thetemperature was then gradually raised to about 25 during a period of 1 /2 hours and then allowedto stand overnight. The mixture was then heated at reflux for 1 hour, cooled to about 30 C. and treated with about 30 g. acetic acid until acid to litmus paper followed by 228 gms. water. The. oil layer was separated and distilled. Unreacted ketone along with other by-products were recovered in the? fraction distilling from 37-100 C. at mm. of pressure;- end; then 369.4 guts. of. methyl-3,4-dimethylr2,3-epoxy,-

hexanoate was obtained distilling at -85 at 5 mm. of pressure. This compound has a mild berry-like odor and may be represented by the formula CH -GH;OHO OHCOOCH Example 11 A mixture of 77.5 gms. methyl-3,4-dimethyl-2,3-epoxyhexanoate, 133.3 gms. isobutyl alcohol, and 2.1 g; anhydrous sodium methylate, as catalyst, were heated in afiask fitted with a fractionating column while slowly distilling out methanol formed in the reaction. As the temperature of the mixture was gradually raised from about 99 C. to about 131 C. duringa period of four hours, there was obtained gms. of distillate boiling from 67 to 108 C. and consisting of a mixture of methanol and isobutanol. The material in the flask Was cooled to about 25"" C. and treated withabout 2.5 gms. acetic acid followed by 300 cc. saturated salt solution. The oil layer was separated and distilled giving 842 gms. isobutyl-3,4-dimetl1yl-2,3--epoxyhexanoate distilling at 123l24 C. at 10 mm. of pressure. This compound has a mild herb-like odor and may be represented by the formula 3-methylpentanone-2 was reacted with ethyl chloracetate with anhydrous sodium methylate as the condensing agent according to the general procedure of Example I to give a mixture of the methyl and ethyl esters of 3,4-dimethyl-2,3-epoxyhexanoic acid' distilling at 118l24 C. at 20 mm. of pressure. The ethyl ester separated. from this mixture has an odor reminiscentof raspberries but :difl'ering quite characteristically from that of the corresponding methyl ester. formula OH -GH CHOCH-COOC H CH CH Example IV Following the general procedures of Example I, acetaldehyde was reacted with diethyl'ketone and the product dehydrated (with iodine instead of oxalic acid) to give 4-methyl-4-hexene-3-one (B.P.=l6l C.). Reductionof the double bondgave 4-methylhexanone-3 (B.P.= 135-8) and reaction of this ketone with ethyl chloracetate in the.

presence of anhydrous sodium methylate gave a mixture ofthe methyl plus ethyl esters of 4-methyl-3-ethyl-2;3-- epoxyhexanoic acid (B.P.=-105 at 5 mm: pressure);

The ethyl ester separated from this mixturahasa pungent:

It may be represented by the assasse herb-like odor. The compound may be represented by the formula CHrCHrCHC CH-COOCHg-OH (3H H. an,

Example VI Following the general procedure of Example I, heptaldehyde was reacted with methyl ethyl ketone and the product dehydrated (with iodine instead of oxalic acid) to give 3-methyl-3-decene-2-one distilling at 100-105 C. at 5 mm. pressure (Nd at 20=1.4545). Hydrogenation of this compound gave 3-methyldecanone-2 distilling at 92-95 at 5 mm. pressure (Nd at 20=1.4280) and reaction with methyl chloracetate in the presence of anhydrous sodium methylate gave the desired methyl-3,4-dimethyl-2,3-epoxyundecanoate distilling at 1219 C. at 2 mm. pressure. This compound has no very significant odor in itself, but may be used as a blending agent or fixative in producing perfumes or perfumed products. It is represented by the formula 50 g. methyl 3,4-dimethyl-2,3-epoxyhexanoate, 138.8 g. geraniol and 1.9 g. anhydrous sodium methylate as catalyst were heated in vacuo at 100 C. in a flask fitted with a fractionating column until methanol no longer was evolved. The excess geraniol was then distilled away from the mixture and after cooling to about 25 the crude product was acidified with dilute acetic acid and extracted with benzene. After removal of the benzene the product was distilled in vacuo to give geranyl 3,4-dimethyl-2,3-epoxyhexanoate distilling 141-2 at 0.6 mm. of pressure. This material had a weak and very mild odor, but may be used as a blending agent in perfumes and perfumed products. It may be represented by the formula may be varied over a wide range to produce compounds having quite different and distinctive odor and flavor 6 characteristics. Furthermore, the compounds of the present invention may be employed as indicated in our copending application Serial No. 595,059, filed July 2, 1956, as intermediates in the production of new aldehydes and other compounds or products.

While numerous typical compounds of the series to which this invention relates have been specifically referred to or described above, and preferred methods described for producing such compounds, it will be apparent that many other compounds embodying the present invention may be produced. Moreover, it is pointed out that the odor of the compounds varies over a wide range in both character and intensity depending upon the type, location and the relative positions of the various substituents in the carbon chain as well as those of the ester group. Those compounds having relatively high boiling points ordinarily possess less odor and accordingly, compounds containing no more than about 20 carbon atoms are preferred for most purposes. However, even the higher boiling compounds and those containing more than 20 carbon atoms may be used as blending agents or modifiers in perfumes and perfumed products.

It will also be evident that the ketones used in the preferred methods of procedure described may be produced or obtained in any suitable way and it is possible that the epoxyacid esters themselves may be produced by methods other than those herein described.

In view thereof it should be understood that the particular compounds referred to above and the methods for their production described in the various examples cited have been chosen for the purpose of indicating the general nature of the invention and are not intended to limit the scope thereof.

We claim:

1. A lower alkyl ester of 3,4-dimethy1-2,3-epoxyhexanoic acid.

2. Methyl-3,4-dimethyl-2,3-epoxyhexanoate.

3. Ethyl-3,4-dimethyl-2,3-epoxyhexanoate.

4. Isobutyl-3,4-dimethyl-2,3-epoxyhexanoate.

5. Methyl-3-methy1-4-ethyl-2,3-epoxyhexanoate.

6. Methyl-4-methyl-3-ethyl-2,3-epoxyhexanoate.

References Cited in the file of this patent UNITED STATES PATENTS 1,873,430 Knorr Aug. 23, 1932 1,899,340 Knorr Feb. v28, 1933 2,680,109 Stevens June 1, 1954 OTHER REFERENCES Beilstein, vol. #17-19, 1st supp., p. 436 (1934). Beilstein, vol. 18, p. 263 (1952).

Claims (1)

1. A LOWER ALKYL ESTER OF 3,4-DIMETHYL-2,3-EPOXYHEXANOIC ACID.