Title of Invention

"A PROCESS FOR THE PREPRATION OF GERANYL NITRILE FROM LEMON GRASS OIL"

Abstract

The invention relates to a process for the preparation of geranyl nitrile (3,7-dimethyl-2, 6-octadienoic acid nitrile) of the formula 1 from lemon grass oil comprising citral as one of the major constituents. The preparation of geranyl nitrile directly from essential oil is novel and economical. Process steps are: reacting the oil and hydroxylamine hydrochloride at a specific pH, separating the aldoximes from the solution followed by conversion to desired compound by treatment with a dehydrating agent.

Full Text

The invention relates to a process for the preparation of geranyl nitrile (3,7-dimethyl-2, 6-octadienoic acid nitrile) of the formula 1 from lemon grass oil comprising citral as one of the major constituents. Geranyl nitrile is an important perfumery compound which has not been reported from any natural source but has been developed as a synthetic product. It has found wide applications in soap, detergent and perfumery industry. (Mitchell, P.W.D. and Blumenthal, J.A, U.S. Patent 3553, 110 (1971) Chem. Abs; 74 : 57204 and Mitchell, P.W.D and Blumenthal, J.A., U.S. Patent 3, 65, 422 (1972), Chem. Abs; 76: 153969). It is also used in refrigerators and air-conditioners as a leakage detecting agent due to its pungent lemony odour (Vanek, E.A, U.S. Patent 4, 294, 716 (1981) Chem. Abs; 96: 54464). For example, photochemical rearrangement of formula 1 gave cyclopentane derivative (Wolff, S. and Agosta, W.C., J. Org. Chem. 1978, 43 (18) p 3627-8 and Wolff, S., Barney, F. and Agosta, W.C., J. Am. Chem. Soc. 1980, 102 (7) p 2378-86). It also reacts with thioacetic acids to give thiopheneacetonitriles (Boden, R.M., Mc. Colie, J.A., U.S. Patent 4, 883, 774 (1989) Chem. Abs; 112: 216680). Photosensitised oxygenation of 1 furnished cyclic ethers (Butsugam, Y., Yoshida, S., Bito, T., Muto, M, Synth. Chem. 1973 (8)p 1617-20). Aroma or taste enhancing thiocyclic ethers were obtained when geranyl nitrile was reacted with thioacetic acid,. (Boden, R.M. Mc. Colie, J.A. Euro. Patent, 369. 668 (1990) Chem. Abs. 113: 172378). Photoxygenation of geranyl nitrile followed by esterification furnished new perfumery products (Wu Guosheng, Ma Yunfer, Gne, M, Von. B., Liu, Z., Sci, China Ser. B. 1989 32 (10)p 1164-71). Synthesis and odour evaluation of new gemdimethyl cyclohexane derivative was carried from cyclogeranic acid nitrile a cyclisation product of geranyl nitrile. A monograph on geranyl nitrile which includes its toxicity, irritation. Sensitization and metabolism has also appeared (Opdyke, D.L.J., Food Cosmet. Toxicol. 1976, 14 Suppmt. 787). There are two general methods of synthesis of geranyl nitrile. In one of the methods, mixture of Citral a and b (isolated from a natural source or prepared synthetically) is converted into corresponding aldoximes and the aldoxime mixture is then converted to nitrile using acetic anhydride (Bhatt, M.V.Prasad, H.N. Venketesh, World Rev. Nutr, Diet 1978, (31)p 141-8 Chem. Abs. 90: 168788) or by any other dehydrating agent (Trofimor, B.A., Mikhaleva, A.I., Korostova S.E., Balabanova, L.N., Vasilev, A.N., Izv, Akad, Nauk SSSR Sr, Khim 1978 (3)p 690-1, Chem. Abs; 94: 179841). In another method 1 is synthesised from methyl heptenone (6-methyl-hept-5-ene-2-one) by reacting with 2-halo-ethyl nitrile. The intermediate after dehydration furnishes geranyl nitrile in good yields (Hercules Ino. Isreal Patent IL 51, 253 (1983), Chem. Abs; 100: 120538). Citral is also converted directly to geranyl nitrile by catalytic oxidation with nickel sulfate-potassium persulfate in presence of ammonia (Yamazaki, S., Yamazaki, Y., Chem. Lett. 1990 (4)p 571-4). In another variation of its synthesis a Japanese patent discloses its synthesis from 3-chloro-2, 6—dimethyl-1, 5-heptadiene and sodium cyanide in presence of quaternary ammonium salts as catalyst (Suzuki, S., Fujita, Y., Shino, M., Kanehira, K., Onishi, T. Nishida, T., Japanese Patent 60, 36, 549 (1985), Chem. Abs; 104: 168640). The most common methods of preparing geranyl nitrile and related analogues involve reaction of substituted alkenones with an alkyl nitrile in presence of a strong base (Bordyukova, O.O. Erman, M.B., Aul Chenko I.S., Bogorodskaya, LP., Falleva, LP., USSR Patent 1, 049, 476 (1983)., Chem. Abs; 100: 39396; Rhone-Pouleno, S.A., Belg. Patent 829, 793 (1975), Chem. Abs., 85: 93876: Desomone, R.S., U.S. Patent, 3, 960, 923 (1976), Chem. Abs., 85: 123387; Rhone-Pouleno, S.A., French Patent 2, 312, 490 (1976) chem. Abst; 87: 101982. Desomone, R.S., Ger. Patent 2, 656, 065 (1975), Chem. Abst; 87: 133919; Von Fraunberg, karl, Ger. Patent 2, 343, 055 (1975), Chem. Abst; 82: 155428; Mitchell, P.W.D, Blumenthal, J.H., French Patent 1, 555, 952 (1969), Chem. Abs: 72: 42861. Mitchell, P.W.D. and Blumenthal, S.A., U.S. Patent 3,553, 110 (1971) , Chem. Abs; 74: 57294. In another variation of above reaction, substituted ketones were reacted with malononitrile and the product was decarboxylated to yield the desired nitrile (Cell; C.J.L., Plattier, M., Teisseire, P.T., Ger. Patent 2, 333, 265 (1974), chem. Abs; 80: 82224). It is obvious from the literature review that most of the work carried out on geranyl nitrile and its analogues on their synthesis and uses is patented and most common route of their synthesis comprises reacting substituted alkenones with alkyl nitriles followed by dehydration of intermediate. Citral is another important source which is being converted into desired nitrile 1 by various methods. However isolation of citral from natural source such as essential oil of lemon grass may either be achieved by fractional distillation of the oil or by derivatisation such as bisulfite formation which is followed by liberation of citral by treatment with alkali solution. Lemon grass oil (Cymbopogon pendulus fam. Grahminae) contain almost 65-70% of citral which is a mixture of two stereoisomers, viz. citral a (65%) and citral b (35%) (Sharma, J.R., Lai, R.K. Mishra, H.O. and Naqvi, A., current science 197, 56, 30; and Patra, P and Dutta, P.K. Res. & Ind. 1986, 31, 358). A direct approach towards the preparation of geranyl nitrile from lemon grass oil will not only obviate the need of an additional step of isolating the pure citral from the oil but also would prove more economical in ultimate analysis. Thus preparation of geranyl nitrile directly from essential oil is both novel as well as more economical. Accordingly the present invention provides a process for the preparation of geranyl nitrile (3,7-di methyl-2,6-octadienoic acid nitrile) of the formula 1 from lemon grass oil, which comprises: reacting lemon grass oil with hydroxylamine hydrochloride at pH in the range of 7-12 in a polar medium in presence of alkali solution (50% sodium hydroxide), stirring the mixture to obtain aldoximes, separating the resulting aldoximes from unreacted oil by known methods, dehydrating aldoxime mixtures with a dehydrating agent followed by hydro distillation or steam distillation to obtain the pure product. In a preferred embodiment of the invention the essential oil of lemon grass (Cymbopogan penduius. family Grahminae) is reacted with hydroylamine hydrochloride and rhe pH of the mixture is maintained between 8-11 by adding strong alkali solution then stirring the mixture till a uniform emulsion is formed. The diluted emulsion is extracted with a non-polar solvent such as hexane, petroleum- ether, benzene, dichioromethane and the like to remove the unreacted material. The aqueous layer is then acidi" fied with dilute acid solution to pH range 2--6. The liberated aldoxime mixture is separated from a lueous layer and the remaining aqueous layer is extracted with a non-polar or- a chlorinated solvent such as hexane, benzene, chloroform or the like. The organic layer and separated aldoxime mixture are combined, washed with water and dried over anhydrous sodium sulfate. The solvent is then completely removed by distillation and aldc::ime mixture obtained is reacted with noetic anhydride. phosphorus pentoxide. p-toluene sulfonic arid or the like to produce gera-nyl nitrile. Geranyl nirrile of the formula 1 is purifle I by steam distillation or hydro distillation of aqueous mixture at a pH 7-12. The upper oily layer of geranyl nitrile is separate from the alueous part. Fure geranyl nitrile is a mixture dis-and tans- isomers in the ratio ls as determined by GL. It has a fresh lemony odour and follws. physical constants; to~ lour less oil. BP1Sp 135-4 VJ E'1" "..5", tJDCC I + T-5 f analysed for C10H1511 , The invention is described further with reference to examples given below. These examples should not be coneture as to rstrict the scope of the invention. Example 1 Preaparation of citral aldexime the intermediate for t he synthe- SIS of geranyl nitirl from lemen grass oil: To a solution of lemon grass oil 015 ml (65 citral content) in 100 ml of 50% methanol is added an aqueous solution (50%) of hydroxylamine hydrochloride (79g, 1M) and the mixture stirred vigorously at room temperature. A 50% solution of sodium hydroxide is slowly added to the above mixture while stirring without raising the temperature till a pH of 7.5-8 is attained. After etirring for further 20 minutes the emulsion is diluted with water and extracted with exedmle of hexane. The upper organic layer is discarded and to the squeous solution is added dilate hydrochloric acid 10% till pH of 8.0 is obtained. At this pH an only layer begins to separate from the solution. The upper sily layer is separated in a separating funnel and rest of rhe aqueous portion is extracted with 2X?0 ml chloroform. The oily layer and the chloroform extracts are combined together washed free o± acid and dried over anhydrous calcium chloride. The solution i: concentrated in vacuo to furnish It.' nil of aldcxime mixture. Example 2 Conversion of intermediate sidozimes to gerany nitrile of formla 1 Aldexime mixture obtained as above ( 16 ml ) is alded t acetic anhydride ('110ml, 1 . 1M ' slowly with stirring as the temperature of the mixture rises. The mixture is then refluxed for 30 minutes on an oil bath and the progress of the reaction monifored by the gle. After the completion of the reaction 117 of sodium carbonate in 50." ml of water is a alded to the reaction mixture. The pure product of formula 1 is obtained by hydrodistillation/steam distillation of the above solution. Geranyl nitrile of formula 1 , a colourless oil which separates as an upper oily layer. It has fresh strong lemony odour yields (135 gm, 95%). We Claim: 1. A process for the preparation of geranyl nitrile (3,7-di methyl-2,6-octadienoic acid nitrile) of the formula 1 from lemon grass oil, which comprises: reacting lemon grass oil with hydroxylamine hydrochloride at pH in the range of 7-12 in a polar medium in presence of alkali solution (50% sodium hydroxide), stirring the mixture to obtain aldoximes, separating the resulting aldoximes from unreacted oil by known methods, dehydrating aldoxime mixtures with a dehydrating agent followed by hydro distillation or steam distillation to obtain the pure product. 2. A process as claimed in claim 1 where in the oximation of lemon grass oil is effected with hydroxylamine hydrochloride in a polar medium selected from ethanol, methanol, water or their mixtures. 3. A process as claimed in claims 1-2 wherein the separation of unreacted oil from oximes is effected in a non-polar or chlorinated solvent selected from hexane, benzene, chloroform. 4. A process as claimed in claims 1-3, wherein the aldoximes mixture is separated from the aqueous solution by acidification with a mineral acid such as hydrochloric acid or sulfuric acid. 5. A process as claimed in claims 1 to 4 where in the conversion of intermediate aldoxime mixture to geranyl nitrile is effected by dehydrating agents selected from acetic anhydride, phosphorous-pent oxide, p-toluene sulfonic acid. 6. A process for the preparation of geranyl nitrile (3,7-dimethyl-2,6-octadienoic acid nitrile) of the formula 1 from lemon grass oil shown in the drawing accompanying the specification substantially as herein described with reference to the examples.

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664-del-1996-correspondence-others.pdf

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664-del-1996-description (complete).pdf

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