CS226740B2 - Method of preparing (7e,9z)-alkadienol derivatives - Google Patents

Abstract

(7E,9Z)-alkadienol derivatives (I), <IMAGE> wherein R1 represents a lower alkyl group, and R2 represents a hydrogen atom or a lower acyl group are prepared by reacting a nonanal derivative (II), OHC-(CH2)7-CH2-OR2 (II> with an aliphatic alcohol halogenating the acetal (III) thus-obtained, <IMAGE> wherein R3 and R4 independently represent a lower alkyl group or together represent an ethylene group, treating the 2-halo-1,1-dialkoxynonane (IV) thus-obtained, <IMAGE> wherein X represents halogen, with a base treating the nonene derivative (V) thus-obtained, <IMAGE> with an acid, and reacting the nonenal (VI) thus-obtained, <IMAGE> with an alkyl-triphenylphosphonium halide (VII), <IMAGE> wherein X<(-)> represents a halide ion, in the presence of a base, in an apolar or dipolar solvent, under inert gas. This provides an economic process for the preparation of the compounds of the general formula (I) which produce a significantly strong stimulating reaction on male European grape vine moth.

Description

The invention relates to a process for the preparation of [7,9,9] -alkadienol derivatives of general formula (I)

H i

R ₁ -C = C-C = C - / CH _2/5 -CH ₂ -0-R ₂ / I /

H H H where

R 6 represents an ethyl group and

R ₂ represents a hydrogen atom or an acetyl group.

(7Е, 9Z) -dodecadienylacetate (I: R 1 x C ₂ H 1, R 2 = -COCH 3) is known to produce a significant potent stimulatory response to male European vine moths (Lobesia botrana).

The European grapevine is the largest vineyard bane in Central and Southern Europe. [7], 9Z] -dodecadienyl acetate is extracted from the ferinin of these insects (R.R. Ruser et al., Z. Naturforsch C.29, 781 (1974)). The compound is also synthesized and used in plant protection. The onset of swarming can also be indicated with these compounds. US Patent Specification No. 3, 845, 108; C. Discoins et al., C. R. Acad. Sci., Ser. D. 279,904 / 197-4G Bower et al., C.R. Acad. Sci., Ser. D. 280, 1469 (1975). Other derivatives of formula (I) have not yet been described.

- 3 226 740

Several procedures have been reported for the synthesis of (E, 9Z) -decodadienyl acetate. V. Roelofs et al. elaborated a synV 4 thesis comprising 11 reaction steps. They were based on bromoacetaldehyde diethyl acetal and suberic acid. Bromoacetaldehyde diethyl acetal was formed into triethyl phosphate phosphonate, which was subjected to acid hydrolysis, and the thus obtained formyl methyl phosphonate was converted into the corresponding imine derivative by cyclohexylamine. In another stage of the synthesis, methyl hydrooctadionate was prepared by reacting suberic acid with methanol, reacting with mercury (II) oxide and bromine, converting the methyl (7-bromoheptanoate) thus obtained into pyridine N-oxide to methyl- / 6 formylhexanoát / and the thus obtained methyl / 6-formylhexanoát / is reacted with an anion prepared from the above phosphonate with sodium hydride. Hdyrolyzou product in an acidic environment to obtain methyl ^t h ^yl - / ^{f orm-8-yl} - ^{7 /} E / ^T -OK X'noát ^{7 kt} allowed era! react with a phosphorane obtained by reacting trifenylpropyl phosphonium salts sodium / methylsulfonylmethylidem /. the thus obtained methyl-7 / 7E, 9Z / ^d to EKA enoát7 reduces ^{di hyd} r ^id em-Hton hHni.tým thus obtained / 7E, 9Z / -dodekadien-l-ol, is acylated with a mixture of acetic anhydride and pyridine to give the desired compound, which is of ^{a DdeI} storeoisomeru ^ 7 ⁷ E, 9 Z / - ^d of ^d EKA ^{di enyl p -acetate} u7 reparative gas chromatography This compound is formed in an amount of less than 20. This process is disadvantageous because a large number of reaction steps, expensive reagents and difficult preparative gas chromatography are required.

22В 740

In another method, J. N. Labovitz et al. (Tetrahedron Letters 1975, 4209) from 1-butyne. Reaction of this compound with methylmagnesium bromide gave 1-butinylmagHesium bromide which was reacted with acrolein. 1-Hepten-4-in-

The 3-ol thus obtained was heated with trimethyl orthoacetate to give a 4: 1 mixture of methyl 4 (Z) -nonen-6-ynoate 7 and methyl 4 (Z) -nonenone 6-ynoate). This mixture was reduced (without separation) with lithium aluminum hydride to give a mixture of 4 (E) - and 4 (Z) -nonen-6-in-1-ol. These compounds were converted with p-toluenesulfochloride to the corresponding tosylates, which were then converted to a mixture of 1-bromo-4 / E / -nonen-6-in and 1-bromo-4/2-nonen-6-in. The bromo derivatives were coupled with 3 - [(1-ethoxy) -ethoxy] propyl lithium in the presence of lithium tetrachloromethane, the product thus obtained was subjected to acid hydrolysis and 7 (E) -dodecen-9-in-1-ol was separated from the stereoisomer. crystallization. Pure alcohol was reacted with trimethylsilyl chloride and the silyl ether thus obtained was converted to (7E, 9Z) -dodecen-1-ol by reaction with bis (3-methyl-2-butyl) -borane and hydrolysis of the product thus obtained in acidic medium. (7E, 9Z) -Dodecen-1-ol was acylated with acetic anhydride to give (7E, 9Z) -dodecadienyl acetate. The main disadvantages of this method are reaction steps requiring special conditions and expensive reaction components (e.g. lithium aluminum hydride, dialkylborane, trimethylsilyl chloride).

According to another method, developed by E. Negishi et al

A. Abramovitch, β-octene-1-ol, subjected to the so-called acetylenic zipper reaction in the presence of 1,3-diaminopropane potassium salt. The 7-octin-1-ol thus obtained was acylated with acetic anhydride. »The acetate thus obtained was reacted with bis- / 3-methyl-

226 740

2-butyl-borane to give 8-acetoxy-1-octenyl-bis- (3-methyl-2-butyl) -borane which was reacted first with 1-butyne lithium salt, then with iodine, sodium acetate and peroxide hydrogen. The triple bond of the thus obtained 7 (E) -dodecen-9-yn-1-ol acetate was coupled by the addition of disiamylborane, the product was reacted first with acetic acid, then with hydrogen peroxide to give (7E, 9Z) -dodecadienylacetate. Synthesis is uneconomical because the starting materials and reagents (such as disiamylborane, alkyl lithium) are expensive.

According to another method published by C. Descoins et al. / Bul. Soc. Chim. France, 1977, 941), (7E, 9Z) -dodecadienyl acetate was synthesized from 1-cyclopropyl-2-pentin-1-ol. A complex of carbinol with carbonyleneballate formed into a complex which was then converted. to 1-bromo-3 (E) -octen-5-2'n with a mixture of hydrogen bromide and zinc bromide. The bromide thus obtained was reacted with a magnesium compound of 4-tetrahydropyranyloxybutyl chloride in the presence of copper salts. The 7 (E) -dodecen-9-in-1-ol tetrahydropyranyl ether thus obtained was hydrolyzed to 7 (E) -dodecen-9-in-1-ol in the presence of an acid catalyst. The compound was then reduced by catalytic hydrogenation to the (7E, 9Z) -dodecapphenoic compound obtained by acylating the reduced product.

According to another method of C. Descoins et al. was used as starting material of 1-hepten-4-in-3-ol. The compound is - reacted with triethyl orthoacetate to yield ethyl 74 / E / 6-nonene-Ion ^{/ 'kt} era red-forged. hydr ^id em. lithno-hliuitým *

226 740 The thus obtained 4 (E) -nonen-6-yn-ol is tosylated, the tosylate is reacted with lithium bromide to give 1-bromo-4- (E) -nonen-6-yne. kpuluje brominated compound with a magnesium compound of 1- / 1 / ethoxy / ^-e, ethoxy ^{/ b} -2- Rome ^th anus. Thus ^ Oz: Iskan 7 ^/ E ^/ -nonen- ⁶ - ^and NL-ol is acylated with acetic anhydride and acetate was reduced to give dialkylborane sežádaná compound.

The above methods of C. Descoins et al. they are uneconomical / because they require difficult accessible and expensive starting materials and reactants.

G. Cassani et al. has recently published a method for the preparation of (7E, 9Z) -dodecadienyl acetate (Tetrahedron Letters, 1980,3497). Starting from / 2E, 4Z / - heptadien-l-ol, which is acylated with acetyl acetate thus produced was coupled with a magnesium compound formed from a tetrahydropyranyl ether l-hydroxy-5-chloropentane ^surcharge tomnos ^those tetrachdorinědna ^ carbonate ^lit HNE ^h o. Tetrahydro -pyran ^{p y} leter / 7E, 9Z / -dodekadien-l-ol produced in the reaction was converted to / 7E, 9Z / -dodekadienylacetát the presence of a mixture of acetyl chloride and acetic acid. The method is uneconomical because the starting materials are very expensive.

The purpose of the invention is to provide a more economical process for the preparation of a compound of formula I having valuable biological effects, which can also be carried out more easily on an industrial scale.

The method of the compounds of the formula I is characterized in that the nonanal derivative of the formula II (II) is reacted.

0НС- / СН2 / 7 ^"СН 2 ^'0К 2 wherein is as defined above, 226,740 with an aliphatic alcohol having 1-2 carbon atoms, preferably an apolar solvent and a catalytic amount of an acid, thus obtained dialkoxynonííwy derivative of general formula III й ₃ -0 / III / CH- / CH _2/7 -CH ₂ -OR

0 ^R-Z wherein R ^ and R ^ are each independently a methyl group or together etljlenovou group, is reacted with a halogen, preferably in apvotickém solvent at a temperature in the range -10 to + 25 ° C ZAKT obtained 2-halo-l, The 1-dialkoxynonane derivative of the general formula IV

^X R ₃ -0-CH-CH-CH ₂ - / CH _2/5 -CH ₂ -OR ₂ / IV / X -O R ₄ wherein

226 740

R _2, R and R ^ are as defined above and X is halogen, is reacted with a base, nonenes obtained derivative of general formula V / V / R ^ -0 \

CH-CH = CH- / CH _2/5 -CH ₂ -OR ₂ /

r ₄ -0 where

R ₂ , R 1 and R 4 are as defined above, reacted with an acid obtained by the nonenal derivative of the general formula VI

OHC-C = C i / CH _2/5 -CH ₂ -OR ₂ / VI /

AND

H where

R ₂ has the abovementioned meaning, is reacted with alkyltrifenylfosfoniumhalogenidem VII / + / / VII

Ph ₃ P - CH ₂ -R ₁

X 'wherein the above meaning, and χ / - / denotes a halide ion, in the presence of a base in an apolar or dipolar solvent under an inert gas ^

226 740

The compounds of the formula II used as starting materials are known and can be prepared xx by known methods, for example by ozanolysis of the corresponding ethyl alcohol acyl derivative (V). Helfreich and V. SchlMfer: Ber. Dtch. Chem. Ges. Compounds of formula II wherein R ₂ is hydrogen can be prepared by hydrolyzing the derivatives prepared as described above.

The aliphatic alcohol used for the preparation of the dialkoxynonanoate derivatives of the general formula (III) may preferably be methanol or ethylene glycol. The reaction is preferably carried out in the presence of a catalytic amount of acid, in an apolar solvent / solvent. aromatic hydrocarbons. Excess aliphatic alcohol can also serve as the reaction medium. In this case, no additional solvent is needed. The obtained derivative of the general formula III need not be isolated.

The preparation of the 2-halo-1,1-dialkoxynonane derivative of the formula IV is preferably carried out in an aprotic solvent (e.g. halogenated hydrocarbon such as chloroform). Elemental bromine is preferably used as the halogenating agent.

The 2-halo-1,1-dialkoxynonane derivative of formula (IV) thus obtained is converted to a compound of formula (V) by a base. Sodium methylate is preferably used for this purpose. The reaction is carried out in a solvent.

Aliphatic alcohols or dimethylsulfoxide are preferably used as solvent.

The obtained compound of formula (V) is subjected to hydrolysis to obtain a derivative of formula (VI). The hydrolysis is carried out with an acid, preferably p-toluenesulfonic acid. Acetone is used as the reaction medium

The base used for the interaction of the compounds of formulas VI and VII is preferably (methylsulfinylmethyl) sodium, a target, potassium butylate or sodium bis-trimethylsilyl amide. The reaction is carried out in an aprotic solvent (e.g. benzene, dimethylformamide, dimethylsulfoxide). Works under

411226740 inert gas / argonem./ such as nitrogen or the reaction temperature is between ⁰ ° C and the boiling point te ^pl Ota extended ^p oužtě ^dL.

The compounds of formula I obtained can be separated from the reaction mixture by known methods (e.g. distillation.

The invention will be explained in detail in the following examples without limiting its scope.

Example 1

Preparation / _t 7E 9Z / -dodekadienylacetátu [/ 1 / R ¹ = C ₂ H _5, R ₂ = -C0CH ^_3-7

A. Preparation of 9-acetoxy-1-dimethoxynonanu [/ III /: R = ₂ -C0CH _3, R ₃ = R ₄ = CH ₃ _7

20.0 g (0.1 mol) of 9-acetoxynonanal

Dissolve in 150 ml of anhydrous methanol, add g of calcium chloride and allow the mixture to stand at room temperature for 10 hours. Excess methanol was distilled off in vacuo. The residual oily product is dissolved in 200 ml of ether, the ethereal solution is washed with water, dried over magnesium sulphate and the solvent is distilled off.

Yield 23.3 g (95%)

Rf = 0.65 (benzene-methanol 10: 1)

- lX Aialysis:

Pro. ^C 13 ^H 26 ° 4

226 740 (246.34) calculated C 63.38; 10.64% found:. 63.1 /> C, 10.1% H.

IC spectrum (Na.CC): 2900, 2850, 1740, 1460, 1380,. 1360, 1230 ^, 1110 ^ 1030 cm ^-1 .

¹ H-NMR ^s p ^e kt ^rum / ^CCl4 /: / fi 3 / 14H, ^ ^70/1, 92 / 3H, s,

COCH ³ // 3.15 / 6 ^ s, 2 OCH ³ /,

3.95 / 2H, t, J = 8Hz,

OCH 2], 4.2 (III, mc, CH-O).

B. Preparation of 9-acetoxy-2-bromo-1,1-dimethoxynonane

С / IV /: R 2 = -COCH _3, R 3 = R ₄ = CH3_7

24.6 g / 0.1 mole / of 9-acetoxy-1-dimethoxynonanu 7lll ^ / R 2 = -COCH 3, R 3 = R ₄ = CH3_7 was dissolved in 30 ml of anhydrous chloroform, cooled to a temperature in the range ^{d 0-3} ° C and ^added 'to the' btenzKnfro stirred ^and n ^{e extensible} mesh

16.8 g (5.6 ml, 0.105 mol / bromine) in 30 ml of anhydrous chloroform, taking care to keep the temperature of the mixture below ° C

The reaction mixture was stirred for another half hour. at a temperature between ⁰ and ^F 3rd ° ^ e ^of from ⁴⁰ ml ^DI ^ c ^ operation of any of ^Deh anhydrous methanol and poured into a solution of 15 g of the acetate. sodium in ¹³⁰ ml vod.y oc ^hl Azen ^s at 0 ° C. The mixture ^E is ^p Otom neutralized, the chloroformic phase is separated, the aqueous phase is extracted 2x with total 50 ml of chloroform. The organic extracts are combined, dried with magnesium sulfate, the solvent is distilled off and the residual oil β

14 226 740 is purified by column chromatography / silica gel 60; benzene-methanol 10: 2).

Yield: 24.5 / 76 / </

Rf = 0.7 (hexane-ethyl acetate 10: 2; 5)

IČspektrum / NaCI /: 1740, 1460, 1360, 1220, 1160, 1090, 1050, 940 cm ^"1 = H with ^p-INIRE ek ^t rum ^{/ CC1} ^ / <^ 1.35 ^{/ 12} H, mc, ⁶ CH ^2.0 (3H, s, COCH 3), 3.4 (6H). with,

OCH 3 /, 3.42 (1H, mc, CH), 4.0 (2H, i), J = 7 Hz, OCH ₂ /, 4.35 (1H, dl, J = 6 Hz, CH).

Hs ·. M ⁺ 326 ^, 324/1% /, m / ^e 295/16 / ^, 293 / 16L 213 / 22Д 170/5 / _? 153/177 »121/38 /, 95/13 /, 93/12 /, 89/48 /, 75 / НО /, 71/72 /, 61/14 /, 55 / U /, 47/37 /.

C. Preparation of 9-acetoxy-1,1-dimethoxy-2-nonene (R ¹ = -COCH 3 ^, R ³ = R ⁴ = CH ³ - 7)

To a suspension of 1.9 g (0.03 mol) of sodium methylate in 5 ml of anhydrous dimethylsulfoxide was added a solution of 6.5 g (0.02 mol) of 9-acetoxy-1-bromo-1,7-dimethoxynonane fyvf.

R2 = -C0CH _3, R ₃ = R ₄ = CH3_7 in 10 ml of anhydrous dimethylsulfoxide oc ^hl Azen ^eh about 5 ° ^ and ^provision is made, and ^{the pl} of TE and ^T ^ ⁷ reakš mixture.

zůstoto ^{d p} of ¹⁰ ° C. ^p Otom with a mixture ^{of 10} míctó mtout ^p s. same ^e temperature, poured into 20 ml of saturated sodium chloride having a ^d n oc ^{eh eh hl} Azen about 0 ° C and ex ^t ra U is ^H with ether.

The ether extract was washed successively with cold 10% HCl (10 ml), saturated sodium bicarbonate (10 ml) and water, dried (MgSO4) and distilled off the ether.

Yield: 4.1 g (84%)

Rf = 0.68 (hexane-ethyl acetate, 10: 1.5 ( ¹ H-4R (CH3) ₄ ): ^ 1.35 (8N, mc, 4 CHg), 2 (ZN, s, COCH-j) ,

2.1 / 2Н, mc, _CH2 /, 3.35 / 6Н, s, 2 OCH ₃ /, 4.0 / 2Н, t, J = 7 Hz /, 4.4 / 1Н, d, J = 6 Hz, НО /, 5-6 (2 N, m, CH = CH).

D. Preparation of 9-acetoxy-2 / E / -nonenalu // VI / FI ₂ = -COCH ₃ _7

To a solution of 10.0 g (0.041 mol) of 9-acetoxy-1,1-dimethoxy-2-nonene (vi): R ₂ = -COCH ₃ , R ₃ = R ₄ = CH ₃ in 50 ml of anhydrous acetone 0.1 g of p-toluenesulfonic acid is added and the solution is stirred for 10 minutes at a temperature below 5 ° C. The solvent was distilled off in vacuo, the residue was dissolved in ether and the wear solution was washed with water, saturated sodium bicarbonate solution, again, dried over magnesium sulfate and the solvent was distilled off in vacuo.

Yield: 6.66 g (82%)

Rf = 0.55 (hexane-ethyl acetate 10: 2.5)

- ΐΓAnalýza: 226 740 ° ^{с цН18} з / 198.25 / Calculated: 66.64% C, 9.15% H; found: 66.5% C, 9.0 / ° H.

IC with ^p ek ^t rum ^{/ l} NaCl ^{/ 1740, 16} 95, ¹⁶ 40, I ^380, I ^{360, 123} °, ^1140, 1090, '1040 960' cm ^-1.

syektrum ¹ H-NMR / CC1 ^{^:} TF 1,4 '/ 8 ^ m ^' ^ 4 CH ² 0 / 3H, s

C 0CH3 /, 2.3 / 2H, mc, CH2 /, 3.98 / 2H, t, J = 7 Hz, 0CH2 /, 6.0 / 1 H, d, J 3 _'2 = 16 Hz, Jx, 2 = 10 Hz, J4.2 = 1 Hz, H-2 /, 6.85 (1H, dt, ^J3 = ^{10 Hz} , ^J ' ³ 2 = ^{16 Hz} > ^{J3 1 = 1 H} z, ^H ' ^{3 /} ,

9.4 (1H, d, J = 8 Hz, CHO).

Hs: M + 198/2 /, m / e 137/5 /, 123/3 /, 109/3 /, 93/27 /, / 21 /, 73/27 /, 70/83 /, 67/56 /, 55 (45), 41 (100).

E. Preparation of (7E, 9Z) -dodecadienylacetate

27: R @ 1 H1, R @ ₂ = ^{--CH3 3-7}

A suspension of 18.3 g / 0.1 mole / of di-trimethylsilylamide solution and 43.2 g / 2.1 mol / trifenylpropylfosfoniuin DID ^{yo u} ^ / Vil / R ₁ = Cl ₃ CH ₂ ^-, i x = L / V 500 ml ^of anhydrous THF DEH ^of benzene was stirred for half an hour under argon at room temperature, then the mixture is boiled for 1 hour under reflux. It was then cooled to room temperature and a solution of 19.8 g / 0.1 mole / of 9-acetoxyi2- / E / I ^{// nonenal} in ^{the I / R} 2 = i ^C0CH37 in ⁵⁰ ml ^'of ezvodéh ^b b ^e n? ^woman .

-1 ^ 22В 740

The reaction mixture was stirred at room temperature for 10 hours and poured into ice water. The solution is extracted 3 times with a total of 50 ml of pentane, the extracts are combined and washed with 10% sulfuric acid solution, water, saturated sodium bicarbonate solution, again with water, dried with magnesium sulfate and the solvent is distilled off. The residue is taken up in 200 ml of pentane, the separated precipitate is filtered, the solvent is distilled off, and the residual oily product is purified by column chromatography (silica gel 60, benzene-methanol 10: 0.2).

Yield: 10.1 g (45%)

Rf = 0.9 / hexane-ethyl acetate 10: 2.5 / ·

According to gas chromatography and high pressure liquid chromatography, the purity of the product is greater than 98 µl; May contain less than 1% / 7Е, 9Е / isomer. Gas chromatography: Rt = 4.5 min / PYE UNICEM 105, 1 m

2.6 mm, 10 SE 54, Chromosorb W, t = 189 ° /.

Liquid chromatography: t R = 7 min (Du Pont 830, m, 3 mm, Parlisil 10, eluent: isooctane containing 2% methylene chloride).

- 1tfAnalysis:

226.74 for C 14 H 24-02 (224.33) calculated: C 74.95%, H 10.78%;

found: 74.8 ° C, 10.8% H.

IR spectrum (NaCl): 1730, 1640, 1440, 1380, 1360, 1230, 1030, 980 ^, 940 cm ^-1 .

¹ H-NMR ^s p ^e kt ^rum / CDC1_ ^/: Γθ, 99/3 ^ t, J = ^7, 5 Hz, CH /

1.35 (8H, mc, 4CH3), 2.04 (3H, s, COCH3),

2.15 (4H, mc, 2C4), 4.05 (2H, t, J = 6.5 Hz),

0CH2 /, 5.32 / 1H, dt, J _6, 7 = 8Hz, _J? >. ₈ = 11 Hz, Η-7 /,

5.60 (1H, dt, J9, ₁₀ = 14 Hz, J _{10 &gt; 11} = 7 Hz, H-10),

5.85 (1H, dd, J7 > 8 = ⁿ Hz, ^J 8.9 = ¹⁰ &lt; ⁵ &gt; Hz, Η-8),

6.20 (1H, m, J ₉ = 10 Hz, J ₉ = 10.5 Hz, J ₉ , 10 = 1 Hz, H-9).

Mass s ^p e ^kt rum: M ^{+ 22 4/2} 8 /, m / e ^{164/12 /,} I ^63/4 /, 149 / 3Д 137/7 /, 135/16/123/3 /, 122 / 8/121/23/109/6/108/18/107/16/105/3/97/3/96/20/95/45/94/24/93 / 36 /, 91/13 /, 83/8 /, '82 / 44 /, 81/36 /, 80/26 /, 79/67/77/19 /, 68/22 /, 27/100 /, 66 (8), 61 (7), 55 (39).

Example 2

Preparation of (7E.9Z) -dodecadienyl acetate // l / s R ¹ = C ₂ H ₅ , R ₂ = -COCH ^3- 7

A. Preparation of 9-acetoxynonanal-ethylene (? / II / R ₂ = -CQCH _3, R ₃ + R ₄ = -CH ₂ -CH ₂ t7

22B 740

A solution of 20.0 g / 0.1 mole / of 9-acetoyynonanalu, 6.9 g / 0.11 mole / of ethylene glycol and 0.2 g of p-toluenesulfonic acid in ¹ 5 ⁰ ml of anhydrous benzene is boiled for 3 he ^di n ^y Bank of equipped water separators ^y. The reaction mixture was brought to ¹⁰ ° C, washed with cold, saturated sodium bicarbonate solution and water, dried over magnesium sulfate, the solvent was distilled off and the residue was distilled in vacuo.

Yield: 20.0 g / 82 $ / Tt: ^128-130 ° C / ³⁹ Pa 99 Ič.s ^p EKT ^rum / NaCI ^/: 1740, 1460, 1435, 1360, 1230, ^{1120 cm-1} lO3O ^{1H - P} NMR with EKT ^rum / 14H, m ^ 7 CH ^2/1, 96 / 3Й ^ s

COCH 3 /, 3.8 (4H, mc, 200%),

3.95 (2H, t, J = 7Hz, OCH2 ₎ , 4.7 (1H, t, J = 5Hz, CH).

B. Preparation of 9-acetox-2-bromononanal-ethylene ketal

1 (IV): R ₂ = -uOCH ₃ , R ₃ + R ₄ = -C 11-2 -H 17

A solution of 24.4 g / 0.1 mole / of 9-eth ^{yl-acetdxynonanal} lenketalu in 30 ml of anhydrous chloroform was cohladí to a temperature between ^0-3 ° C and under cůazení ^PRIK and stirred and cold solution ^{of p} e.

16.8 g / 5.6 ml, 0.015 mole / bromine in 30 ml of anhydrous chloroform gives the ^p-OZO b ^y te ^pl OTA reaction mixture remained ^of a ^beta 3 'C. ^Of 3 m was stirred for l ^{h Pooh} Odin ^BC i ^t e ^pl of ^{I d} in the range of 0-3 ° ^{C, the} Otom is poured into a solution of 15 g of sodium acetate in 150 ml of water, cooled to 0 ^é ° C. ^R is in its capacity ^to neutoalazuje ^'p evným h ^yd ro ^g enuhličitanem sodným.Spodní chloroform phase was separated, the aqueous phase is washed with a total amount 2y' chlorofornm 50 ml,

The 226,740 extracts were combined and dried with magnesium sulfate. The solvent was distilled off and the residual oil was purified by low pressure column chromatography (silica gel 60, hexane-ethyl acetate 10: 1.5). Yield: 23.6 g (73%).

Rf = 0.75 (benzene-methanol 10: 2).

0.6 (hexane-ethyl acetate 10: 2.5) ·

IR (NaCl): 1740, 1550, 1460, 1360, 1230, 1140, 1100, 1030 cm ^{@ -1} .

¹ H ^{- nmr} pektrum / COC ^ / ^f l, 35 / 12H, m ^ 6 CH ^2/1, 96 / 3Н, COCH ^ /, 3.3 / 1 H, mc, CH /, 3.9 / 6H, mc, 30CH2], 4.8 (1H, d, J = 5 Hz, CH3)

C. Preparation of 9-ac ethoxy-2-nonenal-ethylene ketal R ² = -COCH 3 ^, R 2 + R ⁴ = -CH ² -CH ² 7

A solution of 6.46 g (0.02 mol). 9-Acetoxy-2-nk bromononenalethyl ^{e e} t ^and Ζΐν lu ^ / ^ ₂ = -000Η _3, R j + R ^ -Cl ^ ^-CH2- / in 10 ml of anhydrous dimethyl sulfoxide was added under cooling to a cold suspension of 1 7 g (0.03 mole) of sodium methylate in 5 ml of anhydrous dimethylsulfoxide, taking care not to raise the temperature of the mixture above 10 ° C. ^{N NU} reaction mixture was m ^{d d} c and ^crocheted ch ^{the LSI} 10 minutes, ^and is NaI with 10 ml of cold, saturated sodium chloride solution, and the mixture is shaken with 50 ml of ether. The ether phase was washed with cold 10% aqueous hydrochloric acid, water, saturated sodium bicarbonate, water again, dried over magnesium sulfate and the solvent was distilled off in vacuo.

Yield: 4.4 g (91%) · Rf: 0.65 (hexane-ethyl acetate 10: 2.5).

-2 $ 226,740 Spectrum / NaCI /: 1740, 1460, 1360, 1230½ 1140, 1040, 95Ο ^ ^"1 spectrum ^ - ^ / 0014 / ^ 1.35 / 811, mc, 4 CH ^2/1, 98 / 3H, s, COCH3S

3.8 (4H, mc, 20CH3), 3.95 (2H, t, J = 6 Hz, OC4), 4.9-6 (3H, mm, CH, CH = CH).

^H Môťová ^{E p} ektrum: M ^{+ 242/1%} ^ ^{m /} e ¹ 9 ^{8/2/17 0/5/1 57,777,} 137/41 /, 110/9/99/5/75 (89), 74/55 /, 73/64 /, 55/54 /, 43/100 /.

D. Preparation of 9-acetyl-27E7-nonenal (7vi) ^: R R -COCH ^

A solution of 24.2 g (0.1 mole) of 9-aethoxy-2-nonenal-ethylene ketal (R): R ^-COCC ^, Rj +R R4 = = Cg-CC ^H ^ and 0.2 g of p- toluenesulfonic acid in 100 ml of anhydrous acetone ηκ stirred for ¹⁰ minuted s ^tp 5 ° C. ^{R p} oz ou o ^Inhalants oddestHuje in ^vacuo, the residual oil was dissolved in 100 ml of cold ether. The ether solution was washed with water, saturated bicarbonate solution. sodium sulfate, again with water, dried with magnesium sulfate and solvent. distilled off in vacuo.

Yield: 17.8 g (9%). The compound is identical to the product obtained in Example 1 / B.

Е. Preparation of [7,9,9] -dodecadienylacetate (1/2 r ₂ = соау

22В 740

4.5 g (0.15 mol) of sodium hydride was added to 80 ml of anhydrous dimethylsulfoxide and the mixture was stirred at 70 ° C under argon for 1 hour. Then, it is cooled and a suspension of 44 g (0.1 mol) of triphenylpropylphosphonium iodide (III): X = 17 in 80 ml of anhydrous dimethylsulfoxide is added and the mixture is stirred for half an hour at 50 ° C. It is then decanted and a solution of 19.8 g (0.1 mol) of (9-acetoxy-2) -nonenal ((TL) - (-) -) is added in 10 ml of anhydrous dimethyl sulfide and the mixture is stirred for 4 dodines. at room temperature. it was then poured into ice water and extracted 4x eelkovým 400 cc of hexane. the organic phase seq) drawbars _from washed with water, 10% hydrochloric acid, again with water, dried over břečnatým solvent was distilled off and the residue Purification by column chromatography (silica gel 60, hexane-ethyl acetate 10: 1).

Yield: 7.18 g (32%), the compound is identical to the product obtained in Example 1 / E.

Example 3

Preparation of 9-acetoxy-2 (E) -nonanal

A. Preparation of 9-hydroxy-2-bromo-1,1-dimethoxynouan

4? Iv / í r ₂ = h, r ₃ = r ₄ = ch ₃ /

226 740

To a solution of 24.6 g / 0.1 mole / of 9-acetoxy-l-dimethoxynonanu / ^/ III /: R 2s ^C-OCH 3 ^/ in ⁴⁰ ml of anhydrous ^ dioroformu it was added dropwise a solution of 20.8 g / 7 ml 0.13 mol / bromine in 30 ml of anhydrous chloroform. The mixture was stirred for half an hour at room ^I, OC ^hl and ^DI to a temperature in the range from ^{I 0} to 3 ° C and ^add 40 mL of anhydrous methanol · The reaction mixture was poured into a cold solution of 14 g of sodium acetate in 130 ml of water, ^P O ^T OM neu r ^{t h} y ^l i.zuje ^{d g} ro u ^en-hlIčI tan.embodným. The chloroform phase is separated, the aqueous phase is extracted twice with a total of 50 ml of chloroform, the chloroform extracts are combined and dried with magnesium sulfate. The solvent was distilled off and the residual oil was purified by low pressure column chromatography (silica gel 60, benzene-methanol 10: 0.8).

Yield: 22.6 g (81%).

Rf = 0.55 (benzene-methanol 10: 2).

Analysis for C 3 ⁰ H23 _N ^B r / 283.21 / Calculated: 46.65% C, 8.18% H,

28.22% Br; found: 47.1 - C, 7.8% H, 27.0% Br. IS spectra ^µm (NaCl): 3350, 1460 ^, 1160 _from 960 cm ^-1 , spectrum ^X H-MNR (CCl 4) ^: 1.35 (12H, mc, 6 CH 2), 3.4 / 6H, s, 2 OCH ₃ /,

3.52 (2H, t, J = 6Hz, OCH2 ₎ . 4.35 (1H, d, J = 6H, _Z ).

B. Preparation of 9-hydroxy-l-dimethoxy-2-nonene / ^{A /} V / R ^ R ^ R ^ C ^

A cold solution of 28.3 grams / o, l mol / 9-hydroxy-2-bromo-l, ^1-n Timet onynonanu / ^{/ IV} /: ^R 2 = ^{H, R y,} with ^R 4 = CH ₃ / in 40 ml of anhydrous dimethylsulfoxide is added to a solution of 13.5 g (0.25 mol) of sodium methylate in 25 ml of anhydrous dimethylsulfoxide, and the temperature of the mixture is maintained below 5 ° C.

The mixture was stirred at 15 ° C for 10 minutes. It is then poured into 300 ml of saturated sodium chloride solution, extracted with 300 ml of ether, washed with 10 ml of hydrochloric acid solution, water, sodium bicarbonate, again with water, dried over magnesium sulfate and the solvent is distilled off in vacuo. column chromatography / silica gel 60, benzene-methanol 10: 0.4 / ·

Yield: 14.4 g (72%).

Analysis:

for СцН22 ^{0 3/202} »3 / Calculated: C 65.31%, H 10.96%; Found: C, 65.0; H, 11.1.

IR / NaCI /: 3300, 1460, 1360, 1120, 1040 cm ^1st

¹ H-NMR / CC1 ₄ / <1.35 T / 8Н, mc, 4 _CH2 /, 2.1 / 2Н, mc, CH ₂

3.15 / 6N, s, 2 OCH ₃ /, 3.5 / 2N, mc, OCH ₂ /, 4.55 / 1N, d, J = 6Hz, СН / 5-6 / 2N, m, CH = CH /.

C. Preparation of 9-hydroxynonanalu (/ TL / ·. B = ₂ a7

A solution of 20.2 grams / 0.1 mol · / 9-hydroxy-1-dimethoxynonenu ^? V / R ₂ SH, and 0.2 g of p-toluenesulfonic acid in 100 ml of anhydrous acetone was stirred for 6 min at The solvent was distilled off in vacuo, the residue was dissolved in 100 ml of ether, the ether solution was washed with water, 5% sodium bicarbonate solution, again with water, dried over magnesium sulfate and the solvent was distilled off in vacuo.

Yield: 14.7 g (94%).

Bf = 0.3 (benzene-methanol 10: 1.5)

Analysis: 226.740 pro (156.22) calculated: 69.19% C, 10.33% H Found: 69.0% C, 10.1% H

Spectrum / НаС1 / 3350, 1690, 1620, 1460, 1420, 1250, 1120, 1030 ^{cm-1 1} H spectrum NMfi / 001: ^ 1.4 / 8Н, mc, CH /, 2.3 / 2Н mc , CHg /, 2.5 / 1Н, m, can be exchanged for deuterium, ОН /, 3.45 / 2Н, t, J = 6 Hz, 0CH2 /, 6.0 / 1Н, dd, J32 = 16 0e, ^J 1.2 ^{= 1} ° ^Hz J 4.2 = 1 Hz, Н-2 /, 6.85 / 1Н, dt, J ₃ , ₄ = 10 Hz, J ₁ = 10 Hz, J _{3> 1} = 2 Hz, Н- 3 /, 9.4 (1 N, d, J = 6 Hz, N / N).

D. Preparation of 9-acetoxyl-2 (E) -nonphenal ((VL): R ₂ = -COCH ₃ 7

1.56 g (0.01 mol) of 9-hydroxy-2 (E) -nonenal (VI):

R ₂ = H / is dissolved in 5 ml of anhydrous pyridine а к solution were added while stirring 1.12 grams / 0.011 moles / of acetic anhydride. The reaction mixture is stirred at room temperature for 1 hour, 10 ml of dichloromethane are added and the mixture is poured into 10 ml of ice water. The lower organic phase is separated, the aqueous phase is shaken with 10 ml of dichloromethane, the organic extracts are combined and washed with 5% aq. hydrochloric acid, water, 5% aqueous sodium bicarbonate solution, again water, dried with magnesium sulfate and the solvent distilled off in vacuo.

- 2 <Γ226 740 Yield: 1.8 g (91%) · The product is identical to the compound prepared in Example 1 / D.

Example 4

Preparation of 9-hydroxy-2 / E / -nonenalu VI ^ / R ₂ = H7

A. Preparation of 9-hydroxy-2-nonenal-ethyleinketalu // V / R ₂ = H, R ₃ + R ₄ = -CH ₂ -CH ₂ -7

To a solution of 13.5 g / 0.25 mole / of sodium methylate in 25 ml of anhydrous ^{di h methylstyrene} LSU Fox ^{l id} u ^ oc azenéta at 0 ° C with ^p HD ^and with vigorous stirring a solution of 28.1 grams / 0 1 mol / 9-hydroxybutyl bromnenenaeteyh ^y lenketalu IV // / R ₂ = H, R 3 + R _{4 «ACH2-CH2} A7 in 40 ml of anhydrous dimykhylsulfmxidu and provision is made that the temperature of the mixture. Ke and ^{L t} and ^{P d} by 5 ° C. ^P a ^t a mixture ^of OM with ^gro wishes to ¹ 5 ° C, stirred-for 10 minutes and poured into 300 ml of concentrated sodium chloride · Směs.se extracted with 200 ml of ether, the ether solution was washed with cold 10 / aqueous sodium chloride , water, a 5% aqueous solution of sodium hydrogencarbonate, again water, dried with magnesium sulfate, and the solvent was distilled off in vacuo. Yield: 18.4 g (92 $)

IR: (N ^and Cl) ^: 3350 ^, 1460, 1380; 1120, 1040, 940 ^{cm X} l ^ S ^ -NMR ktram / CCl ^ A ^ 1.35 / 8H, mc, CH 4 ^2/2, 1/2 ^ rn, CH2 /, 3.5 / 2H, t , J = 6 - Hz, 0CH ₂ /, 3.8 / 4H, mc, 2 0CH ₂ /, 4,9

6.1 (2H, m, CH = CH).

226770 Mass with ^p e ^kt rum: M + ^{200/4 /,} m ^/ e ¹⁸³ / 2Д ^{16 9/8} Д ^{1 56/3 /,} 110/27, 99/6/85/6 /, 67/42 (43/100).

B. Preparation of 9-hydroxy-2 (K) -nonenal (K) ·. K ₂ = h 7

A solution of 20.0 g (0.1 mol) of 9-hydroxy-2-nonenal-ethylene ^to ethanol was added. ^In (B, B) - (CH3) 3 and ^{0.2 g of} p-toluenesulfonic acid in 100 ml of anhydrous acetone was stirred at room temperature for 20 minutes. The solvent is distilled off in vacuo, the residue is dissolved in 100 ml of ether, the ether phase is washed with water, 5% aqueous sodium bicarbonate solution, again with water, dried with magnesium sulfate, the solvent is distilled off and the remaining product is purified by column chromatography.

Yield # 11.7 g (75%) The compound is identical to the product obtained in Example 3 / C.

Example 5

Preparation / 7E, 9Z / -dodekadienolu 4 ^ 11 ^ ⁵ -./^=(^ 2 ^»R 2 =? /

A. Preparation 1.l-dimethoxy-9-hydroxy-3-nonene / ⁷ / ^{R 2} = H, R ₃ = R ₄ = CH ^j /

To a solution of 13.5 g (0.25 mol) of sodium methylate in 25 ml of anhydrous dimethylsulfoxide was added under stirring and cooling.

28.3 g / mu l mol / l-dimethoxy-2-bromo-9-hydroxynonanu f / l / t R ^ C ^ R ^ R ^ CC and this mixture was increased ^to 15 ° C. ^{N NU} reaction mixture was allowed to stand for 10 minutes and poured into 300 ml-saturated

- 2 · 7226 740 sodium chloride solution. It is then extracted 3 times with a total of 400 ml of ether, the extract is washed with 20 ml of cold aqueous / hydrogen chloride solution, saturated sodium bicarbonate solution and water, dried over magnesium sulfate and the solvent is distilled off. The residue can be used for the next reaction step without purification.

IR spectrum (NaCl): 3360, 2880, 1630, 1460, 1440, 1350, 1110, 1040, 960 cm ^-1 .

¹ H-NMR spectrum (CCl ₄ ): δ 1.35 (8 N, m), 2.1 (2 N, m), 2.4 (1 N, s, can be exchanged for DgO), 3.15 (6 N), s /, 3.5 / 2N, m /,

4.55 (1H, d, J = 5 Hz), 5.35 (2H, m).

O

B. Preparation of 9-hydroxy-2-nonenal // VI / R ₂ = h7

Dissolve 20.2 g (0.1 mol) of 1,1-dimethoxy-9-hydroxy-3-nonene in 100 ml of anhydrous acetone, add 0.2 g of p-toluenesulphonic acid and allow the mixture to stand for 20 minutes at a temperature of rooms. The solvent was distilled off and the residue was dissolved in 100 ml of ether. The ether solution was washed with water, 5% aqueous bicarbonate solution, again with water and dried over magnesium sulfate. The solvent was distilled off and the residue was dried under reduced pressure (13.332 Pa) in a water bath at 40 ° C.

Yield: 14.7 g (94%).

Rf = 0.3 (benzene-methanol 4: 0.8).

- 20 226 740

3300, 2900, 2850, 1680, 1620, 1440, 1260, / 8N, m /, 2.3 / 2H, m /, 2.35 / 1N, s, D ₂ ° / » ³ > ⁵⁵ / ^2Н » ^J = ^{7 Hz} / > ^{6 &gt};

Ič. spectrum (IIIaCl)

730 cm ” ^{X. 1} H-NMR spectrum (CCl ₄ ): [1,4] can be changed to dxdxt, Jd = 18 Hz, Jd = 11 Hz, Jt = 2 Hz, ^7 / 1N, dxd, Jd = 18 Hz,

Jd = 8 Hz /, 9.4 (1N, d, Jd = 8 Hz).

Analysis:

(156.22) for C ₉ H ₁₆ O ₂ calculated: 69.19% C, 10.33% H Found: 69.00% C, 10.10% H

C. Preparation of (7E, 9Z) -dodecadienol [1]: = C ₂ H ₅ , R ₂ = H ₇

К suspension of 86.4 g mol / trifenylpropylfosfoniumjodidu VII / R @ ₂ = C H-7 in 900 ml of anhydrous benzene was added to 36.6 g / 0.2 mole / of bis-amide and the mixture was stirred for half an hour at room temperature. It is then refluxed for 1 hour, cooled to room temperature and a solution of 15.6 g (0.11 mol) of 9-hydroxy-2-nonenal in 50 ml of anhydrous benzene is added dropwise. The reaction mixture was stirred for 8 hours and poured onto ice. The organic phase is separated, the aqueous phase is extracted 3 times with a total of 600 ml of pentane. The organic phases are combined, shaken three times with a total of 60 ml of a 10% aqueous hydrochloric acid solution, washed with concentrated sodium bicarbonate solution and water, dried over magnesium sulphate and the solvent is distilled off in vacuo.

226 740 in 400 ml of pentane, the separated triphenylphosphine oxide is filtered off and the mother liquor is evaporated in vacuo. The residue was purified by column chromatography. (Silica gel G, benzene-methanol 10: 0.2). Yield: 7.4 g / 41 $> /

Rf = 0.6 (benzene-methanol 0.8).

IR spectrum (NaCl): 3300, 2900, 2850, 1650, 1460, 1050, 980, 940 cm @ ^-1 .

_lH NMR-spectrum / CCI / _4: JTo, 99 / 3H, t, J = 7 Hz /, 1.3 / 10Н, m /

2.1 / 4H, m / _r 2.9 / lH, s, can be exchanged with D? O / 3.48 _t / 2H, t, J = 6 Hz /, 5.1 to 6.4 / 4Н, m /.

Analysis:

for ^θΐ2 Η 22 ° / 182.30 / Calculated: 79.06% C 12.77% H? Found:% C, 79.00;% H, 12.72.

Claims (6)

1 »A process for the preparation of (7,9,9-alkadienol derivatives of the general formula (I)) No. R-C = CC = C- / CH ₉ / - ~ CH _{about -0-R} ¹ I i | z 5 z Í H H H (I) where R 6 represents an ethyl group / R ₂ represents hydrogen atom or acetyl group, characterized by reacting nonanalový derivative II OCH- (CH ₂ ) ₇ -CH ₂ -OR ₂ (II) wherein R ₂ is as defined above with an aliphatic alcohol having 1-2 carbon atoms preferably in an apolar solvent and a catalytic amount of an acid, thus obtained dialkoxy-nonane derivatives of formula III CH / CH _2/7 -CH ₂ -OR ₄ r wherein ^Z -0 / III / - 3И226 740 R and R are independently a methyl group or together an ethylene group, NEC ^hook REA ^g OVA ^{T H} and ^L by ^{g ,,} ene with výh.od.ou pJPaMc va ^ ^p ^ m maiden ou ^št EDL. e, ^when the te ^{pl I} at ^pH in the range -10 to + 5 ° C for ^{2, kt} of the zils ^to Aný A 2-hologen-1,1-dialkoxynonane derivative of the formula IV (IV). R.-O ' ³ \ CH-CH-CH 2 / CH _{2/5 2} -CH2-0R R.-O where R2, R1 and R1 are to be reacted with a base, the obtained nonene derivative of the general meaning as defined above and X is halogen, of formula V R_-0 ³ \ CH-CH = CH- / CH _2/5 -CH ₂ -OR ₂ / V / wherein R ₄ -0 R2, R3 and R1 are as defined above, reacted with an acid obtained by the nonenal derivative of the general formula VI HI. 0HC-C- / CH _{2/5 -CH2} -0R2 and / VI / - 312.kde R 'is as defined above, 2, J 226 226 740 is reacted with an alkyl triphenylphosphonium halide. of formula VII M ' Ph? P-CH 2 -R 7 (VII) where R1 is as defined above and x (-) denotes a halide ion, in the presence of a base, in an apolar or dipolar solvent under an inert gas. 226 740 2. Process according to claim 1, characterized in that methanol or ethylene glycol is used as the aliphatic alcohol. 3. A process according to claim 1 wherein the compound of formula III is reacted with elemental bromine in chloroform or a chlorinated hydrocarbon. 4. A process according to claim 1 wherein the compound of formula IV is reacted with sodium methylate or potassium butylate as the base. 5. The process of claim 1 wherein the compound of formula (V) is reacted in an acotto with a p-toluenesulfonic acid. ‘ 6. A process according to claim 1, wherein the compound of formula VI is converted with a triphenylphosphonium iodide into a compound of formula I.