FR2597094A1 - PROCESS FOR THE PREPARATION OF (+) - 13-NORFARANAL - Google Patents

Abstract

THE PRESENT INVENTION RELATES TO A PROCESS FOR THE PREPARATION OF () -13-NORFARANAL OF FORMULA 1 BELOW (CF DRAWING IN BOPI) THE PRODUCT CONSTITUTES THE TRACING PHEROMONE OF THE PHARAOH'S ANT.

Description

The present invention relates to a novel process for

  preparation of (+) - 13-norfaranal, which is

  the tracer pheromone of Pharaoh's ant.

  Pharaoh's ant is the most difficult to control pests in humans' environment. The ant of Pharaoh hides his nest in the walls of the apartments and there, the queens who

  breed conservation, propagation and rapid reproduction can hardly be dyed by conventional insecticides.

  Recently, compounds having a juvenile hormone effect have been successfully used in the control of the Pharaoh ant (eg methoprene). Pharaoh ants carry food

  treated with methoprene in their anthill and this inhibits the laying of queens.

  Pharaoh's ant travels 20 to 20 meters in length to forage for food, and ants mark these pathways with a special attracting material - the so-called "tracer" pheromone - which is characteristic of this species. The (+) - faranal is the most active component of this pheromone tracer of the Pharaoh ant and this compound causes the worker ants to leave the anthill and track at a concentration of 1 pg / cm only. This compound can be used effectively to control Pharaoh's ant

  when associated with juveniles.

  According to Hoyama et al. Z-Naturwissenschaften 70, 469 (1983)], the (+) - 13orfaranal having a simpler structure than the (+) - faranal, exerts a very strong tracer effect on the working ants of Pharaoh and this effect is almost as high. than that of (+) - faranal. So, the

  (+) - 13-norfaranal can therefore also be used to control the ant when associated with juveniles.

  (+) - 13-norfaranal has not yet been prepared in pure form until now. A single synthesis is described in the prior art (T. Koyama, M. Matsubara, K. Ogura, IEM Bruggemann, A. Vrielink: Naturwissenschaften 70, 469 (1983)], which results in the formation of a mixture of mixtures. 60 (+) - 13-norfaranal and its diastereoisomer having a configuration (3R, 4R). Geraniol is used as the starting material, phosphorylation is carried out, and the resulting geranyl phosphate is then coupled with ) -3-methyl-3-pentenylpyrophosphate using a purified synthetase enzyme system extracted from porcine liver This reaction gives (4R) - (2E, 6E) pyrophosphate in a low yield 3,4,7,11-tetramethyl-2,6,10-dodecatrien-ol, the product thus obtained is hydrolysed with a system of enzyme phosphatase and the (4R) - (2E, 6E) -3,4,7 11-tetra-methyl-2,6,10-dodecatrien-1-ol is oxidized with activated manganese oxide (4R) - (2E, 6E) -3,4,7,11-tetramethyl-2,6 , 10dodécatriènal thus obtained is reduced with a system of four akis (triphenylphosphite) palladium and tributyltin hydride in a 40:60 mixture of (3S, 4R) (E) -3,4,7,11-tetramethyl-6,10-dodecadienal and (3R) , 4R) (E) -3,4,7,11-t, 6,10-tramethyl-dodecadienal These two

components are not separated.

  The object of the present invention is to overcome the disadvantages of the known method and to provide an easy process for the preparation of the

(+) -13-norfaranal.

  According to the present invention, there is provided a process for the preparation of (+) - (3S, 4R) -3,4,7,11-tetramethyl-6,10-dodecadienal - ((+) 13-norfaranal)] of the formula (I) CrHO (1) which comprises forming an anion from the compound of formula (II)

O 0)

  (Ii) II with a strong base; the reaction of the anion thus obtained with a compound of the general formula (III) X (III) III (wherein X represents a chlorine, bromine, iodine, methanesulphonyloxy or p-toluenesulphonyloxy group), the esterification of the formula (IV) II IV thus obtained; treating the compound of general formula (V)

OH

  (V) v) V thus obtained (where R is a straight or branched chain alkyl group having 1 to 6 carbon atoms) with an agent capable of protecting the hydroxy group; the reduction of the compound of general formula (VI) VI I.ooa M'I) e (VI) VI CooR thus obtained with a metal hydride (o R is as defined above and R2 is methoxymethyl, ethoxyethyl or 2- tetrahydropyranyl); the reaction of the compound of general formula (VII) ## STR2 ## thus obtained (where R 2 is as defined above) with a halogenating or acylating agent; reducing the compound of general formula (VIII) k. (VIII) VIII thus obtained (wherein R and X are as defined above); hydrolysis of the compound of general formula (IX) (IX) IX thus obtained (where R is as defined above); and oxyeation of the compound of formula (X) (X)

  thus obtained in (+) - 13-norfaranal of formula (I).

  The present invention is based on the finding that the (+) - 13-norfaranal of formula (I) can be readily prepared in pure form from the readily available optically active compound of Formula (II) CS Chen, Y. Fujimoto, G. Girdaukas, CJ Sih: J. Am. Chem. Soc. 104, 7297 (1982) 2. During the first step of the synthesis starting from the (S) -4-methyltetrahydro-2H-pyran-2-one of formula (II), an anion is formed with a strong base (preferably with lithium diethylamide prepared from diethylamine and butyllithium, the anion thus formed is reacted without isolating it with a compound of the general formula (III) (wherein X is a chlorine, bromine, iodine, a mesyloxy, tosyloxy), preferably with the readily available geranyl bromide of general formula (III) (where X is a bromine atom), P. Gosselin, G. Madman F. Roussac: L-Synthesis 877, (1984)] The reaction is carried out at low temperature, preferably between -78 and -30 ° C. The compound of formula (IV) thus formed and contaminated with 6 C of its diastereoisomer (3S, 4S) is isolated by extraction from the reaction mixture. ) and purify it

by column chromatography.

  The compound of formula (IV) is converted into an ester of general formula (V) (where R 1 is an alkyl group

  straight or branched chain having 1 to 6 carbon atoms).

  It is preferred to form a methyl ester in methanol with trimethylamine. The ester of general formula (V) thus obtained is isolated, if desired, and then converted into a compound of general formula (VI) (where R is as defined above and R 2 is a methoxymethyl group, ethoxyethyl or 2-tetrahydropyranyl). This reaction is carried out according to a known method in

  itself, for example by reaction of the compound of the general formula (V) with methylchloromethyl ether to give a compound of the general formula (VI), wherein R1 is a methyl group and R2 is a methoxymethyl group.

  The compound of the general formula (VI) is reduced with a metal hydride (preferably with lithium tetrahydrido aluminate) in an anhydrous aprotic solvent (preferably in anhydrous tetrahydrofuran) to provide the compound of the general formula (VII) (

R2 is as defined above).

  The compound of general formula (VII) is isolated and converted into a compound of general formula (VIII) by methods known per se (where X and R are as defined above). It is preferable to proceed by using mesyl chloride and to prepare a mesylate of the general formula (VIII) (where R is as defined above, preferably a methoxymethyl group and X is a mesyloxy group). The compound thus obtained is reduced with a metal hydride (preferably lithium tetrahydrido aluminate) in an anhydrous aprotic solvent (preferably anhydrous tetrahydrofuran) to provide a compound of the general formula (IX) (where R is as defined

upper).

  The compound of general formula (IX) is isolated, after which the protecting group is removed by acid catalyzed hydrolysis - preferably with 0.1 to 0.01M methanolic hydrochloric acid. The compound of general formula (X) thus obtained is isolated and oxidized with a

  known oxidizing agent (preferably pyridinium dichromate). The desired compound of formula (I), ((+) - 13-norfaranal) is isolated from the reaction mixture with an isomer purity of 94-95%.

  The present invention is further illustrated

  using the following non-limiting examples.

EXAMPLE 1

  (-) - (3R, 4S) - (E) -4-Methyl-3- (3,7-dimethyl-2,6-octadienyl) tetrahydro-2H-pyran-2-one (compound of Formula IV) A solution of 1.2 g (1.7 ml, 16.7 mmol) of diethylamine and 15 ml of anhydrous tetrahydrofuran are charged with 12.4 ml (16.7 mmol) of a hexane solution of n-butyllithium at a temperature of less than -10 C and the mixture is stirred at 10 C for half an hour under an argon atmosphere. The mixture is cooled to a temperature of between -70 ° C. and -78 ° C. and at this temperature,

  a solution of 1.9 g (16.7 mmol) of (S) -4-methyl-tetrahydro-2H-pyran-2-one (compound of formula II) and 3 ml of anhydrous tetrahydrofuran is added dropwise .

  The reaction mixture is stirred at -78 ° C. for one hour, then a solution of 3.62 g (3.04 ml, 16.7 mmol) of geranyl bromide (compound of general formula III, X = Br) and of 2 ml of anhydrous hexamethylphosphoric acid triamide is added, the mixture is stirred at -78 ° C. for

  one hour and let stand at -30 C overnight.

  The reaction mixture is supplemented with 10 ml of water and 50 ml of ether, the ethereal phase is separated, the aqueous layer is extracted with 50 ml of ether and the combined ethereal solutions are washed successively with ml of hydrochloric acid. 5% and 10 ml of a saturated solution of sodium chloride and dried over magnesium sulfate. The solvent is removed under vacuum on a water bath and the residue is purified by low pressure column chromatography (Kieselgel 60HR, a 10: 1 mixture).

hexane and acetone).

  2.6 g of the desired compound are thus collected,

  with a yield of 63%, in the form of a colorless oil.

- 525

  Zoc7 = 5.2; Z-c 751 = -6.9 (c = 2.7, chloroform).

D 56

  TLC: Rf = 0.57 (hexane - acetone 5: 2).

  cG: Rt = 11.83 (SP 2100, 30m x 0.25mm, 160-260C, C [minute, N2, major component (IV);

94.1%

  isomer 3S, 4S: Rt = 11.64 minutes, 5.9%.

  IR (film): 1730 (CO), 1660 (C = C), 1450, 1380, 1270, 1200, -1 1140, 1100, 1070 cm -1 NMR for H (CDCl3): 1.09 (3H, d, J = 6 Hz, CH3), 1.4 1.95 (12H, m, 3CH3), CH2, CH), 2.05 (6H, m, 3CH2), 2.4 (1H, m, CH), 4, (2H, br, CH 2 -O), 5.09 (2H, m,

(2 CH = C).

  NMR for C (CDCl3): 16.23, 17.67, 20.65, 25.71 (4CH3), 20.50, 27.67 (2CH2), 2984 (CH), 30.95, 39.89 ( CH2), 48.26 (CH), 67.54 (O-CH2), 120.63, 124, 17, 131.31,

137.76 (4-C =), 173.75 (-COO).

  MS: m / z 250 (37) ZM +., 207 (18), 194 (3), 181 (30),

  137 (23), 136 (23), 127 (19), 114 (100, 109) (26),

99 (39), 69 (74).

EXAMPLE 2

  (2R, 1'S) - (E) -2- (Methyl-3-hydroxy-1-methyl-propyl) -5,9-dimethyl-4,8-decadienoate (V: R = CH 3) A mixture of 5 ml of triethylamine and 15 ml

  anhydrous methanol is added with 1.9 g (7.6 mmol) of (3R, 4S) - (E) -4-methyl-3- (3,7-dimethyl-2,6-octadienyl) tetrahydro-2H-pyran -one (IV). The reaction mixture is stirred for 18 hours. The solvent is distilled off under vacuum and the residue is purified by column chromatography (Kieselgel 60HR, a 10: 1 mixture of hexane and acetone).

  1.69 g of the desired compound are thus obtained in the form of a colorless oil with a yield of 79% TLC: Rf = 0.48 (hexane-acetone 5: 2)

  IR (film): 3380 (OH), 1730 (CO), 1660 (C-C), 1440, 1380, 1185, 1150, 1100, 1050 cm1. NMR for H (CDCl3): 0.95 (3H, d, J = 6Hz, CH3), 1.4 (1.95H, m, CH2, CH), 1.6 (6H, brs, 2). CH3), 1.66 (3H, s, CH3), 3.63 (2H, t, J = 6Hz, OCH2), 5.06 (2H, m, 2CH = C).

  MS: m / z 282 (10) -M + 7,250 (6), 239 (10), 207 (16), 195

  (11), 181 (24), 145 (13), 134 (20), 113 (22), 108

  (31), 96 (19), 93 (20), 81 (29), 79 (16), 69 (100),

(22), 43 (12), 41 (63).

EXAMPLE 3

  (2R, 1'S) - (E) -5,9-Dimethyl-2. 1-methyl-3- (methoxy-methoxy). 35:

: D: 3

  methyl 2 propyl7-4,8-decadienoate (VI: R = CH3: R2 =

CH2-OCH 3).

  Method A 1.62 g (5.74 mmol) of methyl (2R, lS ') - (E) -2- (3-hydroxy-1-methylpropyl) -5,9-dimethyl-4,8-decadienoate ( V: R = CH 3) is dissolved in 10 ml of dimethoxymethane, then added with 0.1 g (1.15 mmol) of lithium bromide and 0.1 g (0.06 mmol) of p-toluenesulphonic acid and the mixture is stirred at room temperature for 45 minutes. The reaction mixture is evaporated under vacuum in a water bath, the residue is dissolved in 50 ml of ether, the ethereal solution is washed with 5 ml of saturated sodium carbonate solution, 5 ml of water and 5 ml of water. 1 ml of saturated sodium chloride solution, dried and the ether is distilled off in vacuo. The residue is purified by column chromatography (Kieselgel HR, a mixture of hexane and ether). 0.9 g of the desired compound are thus obtained in the form of a colorless oil.

with a yield of 48%.

  Method B 0.81 g (2.87 mmol) of the compound V (R = CH 3) and 0.3 g (0.41 ml, 1.3 mmol) of triethylamine are dissolved in 8 ml of anhydrous ether and then added 0.69 g (8.6 mmol) of methylchloromethyl ether and the mixture was stirred at room temperature for 8 hours. The reaction mixture is treated with 50 ml of ether; the mixture is washed with 5 ml of 5% hydrochloric acid; 1 ml of saturated sodium bicarbonate solution, 5 ml of saturated sodium chloride solution and dried. The solvent is distilled off. The residue is purified according to the procedure of Example 1. Yield

0.68 g (73%).

  TLC: Rf = 0.52 (hexane - acetone 10: 1) GC: Rt = 14.70 minutes Main product (VI: R1 = CH3, R2 = CH2-O-CH3): 95% Isomer 2S, 1'S: Rt = 14.57 minutes, 5% IR (film): 1730 (CO), 1660 (C = C), 1440, 1200, 1160, 1120,

1040 cm1.

  NMR for H (CDCl3): 0.95 (3H, d, J = 6Hz, CH3), 1.2-1.8 (3H, m, CH2, CH), 1.59 (6H, brs, 2CH3) ), 1.67 (3H, s, CH3), 1.9 2.4 (7H, m, 3CH2, CH), 3.34 (3H, s, OCH3), 3.55 (2H, t, J = 7 Hz, CH 2 -O), 3.63 (3H, s, OCH 3), 4.68 (2H, s,

  O-CH 2 -O), 5.06 (2H, m, CH = C).

  MS: m / z 326 (20) [M 7, 294 (12), 281 (10), 265 (4), 263

  (5), 249 (10), 225 (7), 195 (24), 181 (7), 157 (8), 149 (17), 135 (24), 69 (88), 55 (17), 45 (100), 41

(55).

EXAMPLE 4

  (-) - (2R, S) - (E) -5,9-Dimethyl-2- [1-methyl- (3) -methoxymethoxy) -propyl-4, 8-decadien-1-ol (VII: R = A suspension of 0.17 g (4.5 mmol) of lithium (III) tetrahydridoaluminate and 7 ml of anhydrous tetrahydrofuran is charged with 0.7 g (2.14 mmol) of (2 R, methyl S- (E) -5,9-dimethyl-2-yl-methyl-3- (methoxymethoxy) 1 2 propyl, -4,8-decadienoate (VI: R = CH3, R = -CH2-OCH3); in 3 ml of anhydrous tetrahydrofuran. The reaction mixture is stirred at room temperature for one hour, decomposed by the addition of 2 ml of water, 1 ml of 5% hydrochloric acid and the mixture is extracted with 60 ml of ether in three portions. The combined ether solutions are washed with 10 ml of saturated sodium hydrogen carbonate solution and 10 ml of saturated sodium chloride solution, dried and the solvent is distilled off in vacuo. 0.54 g of the desired compound is thus obtained in the form of a colorless oil.

with a yield of 85%.

22,224 (32

  -7D2 = -1.7; 546 = 2.0 (c = 3.2, CHCl3) TLC: Rf = 0.48 (hexane - ethyl acetate 10: 5) Rf = 0.50 (hexane - acetone 5: 2) IR (film): 3420 (OH), 1660 (C = C), 1460, 1380, 1160, 1120, 1040 cm -1 and IR (film): 3420 (OH), 1660 (C = C), 1460, 1380, 1160, 1120, -1 1040 cm -1 NMR for H (CDCl 3): 0.94 (3H, d, J = 6 Hz, CH 3), 1.4 1.9 (4H, m, CH 2, 2 CH), 1.61 (6H, s); broad, 2CH3), 1.68 (3H, s, CH3), 1.9-2.4 (6H, m, 3CH2), 3.29 (3H, s, OCH3), 3.46 (2H, d, J = 6 Hz, CH 2 -O), 3.52 (2H, t, J = 6Hz, CH 2 -O), 4.50 (2H, s, O-CH 2 -O), 5.09 (2H, m). , 2CH = C), MS: m / z 298 (1) Z-M + 7,280 (3) fM-H207, 266 (3), 235 (20),

  205 (3), 123 (19), 111 (21), 85 (51), 81 (47), 69

(94), 55 (24), 45 (100), 41 (51).

EXAMPLE 5

  (+) - (3S, 4R) - (E) -3,5,11-Trimethyl-1- (methoxymethoxy) -42 (mesyloxymethyl) -6,10-dodecadiene (VIII; R = -CH2-OCH3,

2 3 '

X = OMesyl).

  A solution of 0.24 g (2.1 mmol) of mesyl chloride and 2 ml of anhydrous ether is added with a solution of 0.50 g (1.68 mmol) of (2R, S) - ( E) -5,9-diethyl-2-yl-1-methyl-3- (methoxymethoxy) -propyl-4,8-decadiene-1-ol (VII: R = -CH2-OCH3) and 0.25 g (0); (35 ml, 2.5 mmol) of triethylamine in 5 ml of ether at 0 ° C. under cooling and stirring. The reaction mixture is stirred at room temperature for 2 hours, supplemented with 20 ml of ether and 5 ml of 5% hydrochloric acid, the ethereal phase is separated, washed with 5 ml of a saturated solution of chloride. of sodium, dried and evaporated under vacuum. 0.53 g of the desired compound is thus obtained in the form of an oil, with a yield of 84%. AJ = + 1.70; Zk7546 = + 1.9 (c = 5.22, CHCl3 TLC: Rf: 0.52 (2: 1 hexane ethyl acetate) IR (film): 1660 (C = C), 1460, 1380, 1350, 1200 , 1170, 1150, 1100, 1050, 1030, 960, 940, 820 cm NMR for 1H (CCl4): 0.92 (3H, d, J = 6 Hz, CH3), 1.57 (6H, m). , 2 CH 3), 1.64 (3H, s, CH 3), 1.4 - 1.9 (4H, m, CH 2, 2 CH), 1.9 2.4 (6H, m, 3 CH 2), 2.86 ( 3H, m, CH 3 SQ 2), 3.25 (3H, s, OCH 3), 3.47 (2H, t, J = 6Hz, CH 2 -O), 4.04 (2H, d, J = 6Hz, CH 2 -O), 4, 46 (2H, s, O-CH 2),, 05 (2H, m, 2 CH = C) MS: m / z 344 (12) ZM-CH3-OH7, 331 (13) ), 280 (7), 248 (5),

  235 (20), 205 (5), 179 (10), 161 (8), 149 (16),

  (20), 123 (25), 111 (23), 109 (22), 107 (28), 85 (49), 81 (46), 69 (100), 67 (23), 55 (33),

(85), 41 (49).

EXAMPLE 6

  (-) - (3S, 4R) - (1E) -3,4,7,11-Tetramethyl-1- (methoxymethoxy) 6,10-dodecadiene (IX: R = -CH2-OCH3) A suspension of 2.209 g ( 5.52 mmol) of lithium tetrahydro-aluminate in 5 ml of anhydrous tetrahydrofuran, is added dropwise a solution of 0.52 g (1.38 mmol) of (3S, 4R) - (E) -3,7,11-trimethyl-1 (methoxymnethoxy) -4- (mesyloxymethyl) -6,10-dodecadiene (VIII: R = -CH2-OCH3, X = OMesyl) with stirring. The reaction mixture is heated to boiling for one hour, cooled to room temperature, supplemented with 2 ml of acetone and 2 ml of water. The mixture is diluted with ml of ether and extracted with 10 ml of 5% hydrochloric acid. The aqueous layer is extracted with a total of 20 ml of ether, the ethereal solutions are combined and washed with 10 ml of saturated sodium chloride solution, dried and the solvent is distilled under vacuum. 0.354 g of the desired compound is collected in the form of a colorless oil with a yield of 81%. 322 = -4, J546 - 5.4 (c = 4.63, CHCl3) TLC: Rf = 0.56 (hexane-acetone 5: 0.2) IR (film): 1660 (m.p. C = C), 1460, 1380, 1265, 1120, 1060, -11040 cm NMR for H (CCl4): 0.80 (3H, d, J = 6 Hz, CH3), 0.87 (3H, d, J = 6 Hz, CH 3), 1.4 - 1.9 (4H, m, CH 2, 2 CH), 1.58 (6H, brs, 2 CH 3), 1.64 (3H, s, CH 3), 2, 1 (6H, m, 3CH 2), 3.24 (3H, s, OCH 3), 3.45 (2H, t, J = 6Hz, CH 2 -O), 4.46 (2H, s, O-CH 2), O), 5.06 (2H, m, 2CH = C). MS: m / z 282 (7) (M7, 250 (9), 237 (13), 208 (10),

  177 (7), 163 (5), 137 (20), 113 (12), 109 (21), 99 (26), 95 (45), 83 (20), 81 (45), 69 (96) , 55

(27), 45 (100), 41 (53).

EXAMPLE 7

  (-) - (3S, 4R) - (E) -3,4,7,11-tetramethyl-6,10-dodecadien-1-ol 0.35 g (1.24 mmol) of (3S, 4R) - (E) -3,4,7,112 tetramethyl-1- (methoxymethoxy) -6,10-dodecadiene (IX: R = -CH2-OCH3) is dissolved in 5 ml of methanolic hydrochloric acid (0.05 mol / l) and the The solution is stirred at room temperature for 48 hours. The solvent is removed under vacuum and the residue is purified by column chromatography (Kieselgel 60HR, 10: 0.2 mixture of hexane and acetone). 0.183 g of the compound is thus obtained.

  desired in the form of a colorless oil, with a yield of 62%.

  D = -38, Z = -4.8 (c = 4.2, CHCl3) IR (film): 3350 (OH), 1660 (C = C), 1460, 1380, 1210, -11100, 1060 cm -1 NMR for 1H (CDCl 3): 0.84 (3H, d, J = 6 Hz, CH 3), 0.89 (3H, d, J = 6 Hz, CH 3), 1.4 - 1.9 (4H , m, CH 2, 2 CH), 1.59 (6H, 30 g, 2 CH 3), 1.68 (3H, s, CH 3), 2.03 (6H, m, 3 CH 2), 3.62 (2H, t , J = 6Hz, CH2-O), 5.10 (2H, m, 2CH = C) .13C NMR (CDCl3): 16.09, 16.76, 17.67, 25.71, (6CH3) , 26.71, 31.53 (2CH2), 33.73 (CH), 35.35 (CH2), 38.78 (CH), 39.9 (CH2),

  61.63 (OCH 2), 123.91, 124.44, 131.22, 135.32 (4-CH =).

  MS: m / z 238 (11) M + 1, 195 (12), 177 (4), 165 (4), 137

  (7), 123 (39), 109 (25), 99 (24), 95 (49), 83 (42),

  81 (37), 69 (100), 55 (41), 41 (48).

EXAMPLE 8

  (+) - (3S, 4R) - (E) -3,4,7,11-Tetramethyl-6,10-dodecadienal (I) [1 +] -13norfaranal] A solution of 0.106 g (0.45 mmol) of (3S, 4R) (E) -3,4,7,11-tetramethyl-6,10-dodecadien-1-ol (X) and ml of anhydrous dichloromethane are added with 0.216 g (0.58 mmol) of pyridinium dichromate. The reaction mixture is stirred at room temperature for 3 hours, filtered through a column packed with 8 g of silica salt, the column is washed with 30 ml of ether, the combined solutions are evaporated under vacuum and the residue is evaporated.

  is purified by low pressure column chromatography (Kieselgel 6OHR, a 10: 0.5 mixture of hexane and acetone). 0.071 g of the desired compound is obtained in the form of a colorless oil with a yield of 67%.

22 22

  R7D2 = +14.2, 46 = +15.8 (c = 2.56, CHCl3) TLC: Rf = 0.53 (hexane-acetone 5:02) IR (film): 2720, 1660 (C = C) , 1450, 1380, 1115, 1080, -1 1020 cm

  NMR for H (CDCl3): 0.83 (3H, d, J = 6Hz, CH3), 0.88 (3H, d, J = 6Hz, CH3), 1.4 - 1.9 (2H, m) , 2CH), 1.59 (6H, bs, 2CH3), 1.68 (3H, s, CH3), 2.01 (48H, m, 4 CH2), 5.09 (2H, m, 2CH = C 9.45 (1H, dd, CHO).

  NMR for 1C (CDCl3): 15.97, 16.09, 17.55, 17.67, 25.71 (5CH3), 26.62, 31.91 (2CH2), 32.0, 38.49 (2CH) ), 39.84, 47.42 (2CH2), 133.09, 124.29, 131.31, 135.9 (4 -C), 203.21 (-CHO).

  (O) TV '(001) 69' (M) 18 '(LT) 601' (EC) tZ1 '(S) LUT' (S) 6bl (S) SLI '/OH1-ZHD-7 (ZZ) C61 '["+ W7 (p) 9uZ z / u: ws Si

 6065Z

Claims (8)

  1.-Process for the preparation of (+) - (3S, 4R) 3,4,7,11-tetramethyl-6,10-dodecadienal Z (+) - 13-norfaranalL7 of formula (I) AT N - N CHO   Which comprises forming an anion from the compound of formula (II) (c) (i) II   with a strong base; the reaction of the anion thus obtained with a compound of general formula (III) (III)   III (wherein X is chlorine, bromine, iodine, methanesulfonyloxy or p-toluenesulfonyloxy) esterifying the compound of formula (IV) ## STR2 ## thus obtained; treating the compound of general formula (V) N N OH   thus obtained (where R 1 is a straight or branched chain alkyl group having 1 to 6 carbon atoms) with an agent capable of protecting the hydroxy group; reducing the compound of general formula (VI) COORO (VI)   VI CooR4 thus obtained with a metal hydride (o R1 is as defined above and R2 is methoxymethyl, 1-ethoxyethyl or 2-tetrahydropyranyl); reacting the compound of general formula (VII) ## STR2 ## thus obtained (where R is as defined above) with a halogenating or acylating agent; reducing the compound of general formula (VIII) : N E OR (VIII) VIII   thus obtained (wherein R2 and X are as defined above); the hydrolysis of the compound of general formula (IX) (IX) IX thus obtained (o R2 is as defined above); and oxidation of the compound of formula (X) O -; (X) X   thus obtained in (+) - 13-norfaranal of formula (I).   2. The process of claim 1 which comprises oxidizing the compound of formula (X) with pyridinium dichloride.   3. A process according to claim 1 or 2 which   comprises carrying out the hydrolysis of the compound of the general formula (IX) with methanolic hydrochloric acid.   4. A process according to any one of claims 1 to 3, which comprises reducing the compound of   general formula (VIII) (where X is a methanesulfonyloxy group) with lithium tetrahydridoaluminate.   5. A process as claimed in any one of claims 1 to 4, which comprises using a compound of the general formula (VIII) wherein X is a methanesulfonyloxy group for the preparation of the compound of the general formula (IX). 6. A process according to any one of claims 1 to 5, which comprises using a compound of   general formula (VII) where R is a methoxymethyl group for the preparation of the compound of general formula (VIII).   The process of any one of claims 1 to 6 which comprises using a compound   of general formula (VI) where R is a methyl group for   the preparation of the compound of general formula (VII).   8. A process as claimed in any one of claims 1 to 7 which comprises reducing the compound of general formula (VI) with lithium tetrahydridoaluminate.