CS200416B1 - Vicinal alkoxyhalogenderivatives of aliphaticaromatic ethers with effect of juvenile hormone and process for preparing them - Google Patents

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to violar alkenyl halogendered derivatives of aliphatic-aroomatic ethers having the action of juvenile hormone (JH), and to a process for their preparation or their use.

A number of substances that imitate the action of one of its own so-called metamorphic hormones in the insect organism are currently known. · Substances with this effect, called juvenoids, are applied to insects in a period susceptible to JH. Using the selectivity of the effect of hitherto synthesized juvenoids, the aforementioned deviation from the normal development mechanism can be used to control harmful insect species causing both economic and human health damage.

The substances whose preparation and use are the subject of the present invention are novel analogues of JH with a predominant effect on insects of the family Pyrrheceridae and Pentatemidae.

SUMMARY OF THE INVENTION The present invention is directed to novel vioinal alkoxyhalogenates of aliphaticocaromatic ethers of the formula X, R ^F F; XC-CH (OR 6) - (CH 6) _and -C (R ⁶ Z ⁶ ) - C (R ⁵ Z ² ) - (CH 6) _b - CH (R ⁶ ) - O-OV-R ⁷ (I) in which> denotes

- symbol and oil number between 0 and 2,

- symbol b to the number 0 or 1,

- the symbol X is bromine or chlorine,

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2

- the symbols R, R methyl- or ethyl-ethyl,

- R ^{3 is} hydrogen, straight or branched chain alkyl of up to 6 carbon atoms, straight or branched alkoxyalkyl of up to 6 carbon atoms, araAkyl of up to 9 carbon atoms, haloalkyl, straight or branched chain of up to 6 carbon atoms, aoyl and straight or branched chain with a maximum of aa 6 carbon atoms

- the symbols R ⁴ , R ³ and hydrogen or methylacupine

- the symbol R ⁷ »hydrogen, alkyl and straight or branched chain of up to 4 carbon atoms, chlorine or bromine, nitroacid, alkylcarbonyl and straight or branched chain of up to 4 carbon atoms, alkenylcarbonyl and straight or branched chain of up to 4 carbon atoms, -hydroxyalkyl and straight or branched chains of up to 4 carbon atoms,

- the symbols Z 1 and Z ^{2 are} hydrogen or an appellation form a double bond or, if a a 2, then Z ^X represents heavily bromine or halogen and Z ² represents an alkoxy group of at most a and 6 carbon atoms ·

A process for the preparation of vioinal alkoxyhalogenated derivatives of aliphatickoaromatic ethers of formula (I), characterized in that the alkaliyl halide of formula (II), (R ^X R ² ) C CH - (CH 3) _and - C (R ⁴ Z ¹ ) - C 1 R ⁵ Z ² ) - (0 '- CH (R ⁶ ) - (XX) wherein R ^X , R ² , R ⁴ to R 2 (Z 2, Z ² , a, b) have the meaning given above and the aymbol denotes bromine or chlorine, and phenol of formula III,

HO R ⁷ (III) wherein R ^{7 is} as defined above to form an aliphatiacoaronatloether ether of formula IV, (R ¹ R ² ) C - CH - (0 ') and - 0 (R ⁴ Z ¹ ) - C (R ⁵ ^) ) - (0 ') h - CH (R ⁶ ) -0 ° < ¹⁷ >

wherein R ¹ , R ² , R ⁴ to R ⁷ , Z ¹ , Z ² , a, b have the meanings given above, which is a? - halogenoukelniaidene or H-halophthalimidene and compounds of the formula V,

HO - R ³ (V), where the symbol R ³ denotes the same in formula I, converts the monoalkoxyhalogen at a temperature of 0 ° C to 5 ° C and at a temperature of 15-25 ° C to a white (alkexyhalegene) derivative of the formula I ·

Reaction alkenylhalegenldu ebeenéhe vzeroe IIe fenelen ebeenéhe vzoree III occurs at a heat in the range of ED 20 de 80 ⁰ 0 preatředí apretlekéhe solvent, and preferably in the DL methylferaamidu and the presence of an alkaline agent, and preferably an anhydrous Kg NAV, KOH, CH ^ OR aebo RAH .

In the following, the invention is explained in more detail by way of examples, without and exclusively exemplifying them.

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Example 1: (7-Bromo-3,7-dimethyl-6-methoxy-2-octenyl) - (4-propionylphenyl) ether

Preparation of (3,7-dimethyl-2,6-ectadienyl) - (4-propionylphenyl) ether A solution of 1.5 g (0.01 mol) of p-hydroxypropiophenone in anhydrous dimethylformamide was first treated with 0.56 g of finely powdered KOH and dissolving 2.17 g of geranyl bromide. Reakění mixture was heated to 60 - 70 ⁰ 0 for 2 hours and then left at room temperature overnight. It was then diluted with water and extracted with diethyl ether. The ether layer was washed with 10% aqueous solution and KOH and water, dried over anhydrous MgSO 4 and evaporated under reduced pressure. The residue was chromatographed on silica gel with 8 wt.% Water (eluent> petroleumother containing up to 20 vol.% Diethyl ether). Chromatography yielded 1.71 g (60%) (3,7-diethyl-2,6-ectadienyl) - (4-propionylphenyl) ether (tl 160-2 ° C / 13.3 Pa) mp 29-31 ° C). Elemental analysis for (286) 1 calculated C 79.67%, H 9.15%; found C 79.80, H 9.06. MS spectrum (V 70 e) 1286 (M +), 151 (C _g H _u 0 _2), 150 (CGTT ^ Og), 121 (C ^ Og).

To a solution of 520 ng (0.0018 mol) of (3,7 - dimethyl - 2,6 - ektadienyl) - (4 -prepižaylfenyl) ether pattern IV, wherein A 2, B '0, R ^1, R ² and R ⁴ are methyl, R ^ and R ^ are H, R is - COCgHg and Z ¹ and Z ² together form a double bond in 5 mL of anhydrous methanol was under dry nitrogen was added at 0-5 ® 0534 mg (0.003 mole I - Bremsuccinimide (NBS). The reaction mixture was stirred at this temperature for a further 15 minutes and then diluted with water and extracted with diethyl ether. The ether layer was dried over anhydrous MgSO 4 and evaporated under reduced pressure. The residue was chromatographed on silica gel with 8 wt% water (eluent: petroleum ether containing up to 20% by weight of diethyl ether). Chromatography gave 690 mg (95%) (7-bromo-3,7-dimathyl-6-methoxy-2-ectenyl) Of (4-propionylphenyl) ether (t, 164 - 8? 3 / 13.3 Pa). Elemental analysis for Cg ^ gBrOO 39 (397) »Calculated: C, 60.45; H, 7.35; Br, 20.11. Found: C, 60.15; H, 7.22; Br, 20.46. MS spectrum (70oV) &gt; 396/8 (C11H18O5), 247/9 (Hg _0).

BrO), 150 (C 8 H 10 O 3), 121 (C 8 H 10 O), 93 (C 8 H 10 O).

Example 2 »(3,7-Dibromo-2,6-dimethexy-3,7-dimethyloctyl) - (4-propionylphenyl) ether

To a solution of 286 mg (0.001 mole) of (3,7-dimethyl-2,6-ectadienyl) - (4-propionylphenyl) ether in 2 ml of anhydrous methanol, under a dry nitrogen atmosphere, was added 356 mg (0.002) at 15-25 ° C. mol) DBS. The reaction mixture was stirred at this temperature for 1 hour and then diluted with water and extracted with diethyl ether. The ether layer was dried over anhydrous MgSO 4 and evaporated under reduced pressure. Chromatography of the residue on silica gel with 8% by weight of water (petroleum ether containing up to 20% by volume of diethyl ether) yielded 320 mg (78%) (3,7-pound-2,6-dimethexy-3,7-dimethyloctyl) (4-propionylphenyl) ether (tm 168-70 ° C / 13.3 Pa). Elemental analysis for C ₂₁ H ₃ BrBO _{4 (508} ), calculated 49.61%, 6.34% H, 31.40% Br) found 50.08% 0, 6.62% H, 31.31% Br . MS spectrum (70 s H, 506 (M +), NMR spectrum (CDCl 3, hexamethyldisiloxane internal standard): δ (ppm) 1 1.29 (s, 3H), 1.34 (s, 6H), 1.20 (t, 3H, J-7), 2.94 (q, 2H, J-7), 1.50-2.40 (m, 4H)

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3.92 (a, Η), 3.22 (β, 3Η), 3.26 (s, 3H), 4.32 (a, 2H), 4.67 (a, H), 6.96 (a ,

2H), 7.44 (a, 2H).

EXAMPLE 3 x - [(7-Diaethyl-6-hydroxy-2-octeaylexes) phenyl] propan-1-ol

From 2.86 g (0.01 mol) of (3,7-dinethal-2,6-octadienyl) -4 (4-propionylphenyl) ether, 50 ml of diaethyl-2,6-octadienyl) - (4-preplenylphenyl) of ether, n1 dl of methyl sulfoxide and 0.45 [mu] HgO, and 2.5 g of (65-) (7- game - 3,7-diaethyl-6-hydroxy-2) were prepared in the same experimental pedaines as in Example 1.

- octenyl) - (4-preponylphenyl) ether (b.p. 168-70 ° C / 13.3 Pa), calculated for 20% Br, 20.84% Br, found 20.67% Br. MS (70 eV) 1

380/2 i C ₁₉ H2 ₇ BrO ₃ ), 302 (, 231/3 (C 1 H 2 BrO)), 150 (C ₈ H ₂ O 3) IR infrared (5% mp in CCl 2) t V (C-0 ) 1688 «,

A solution of 930 g (0.0024 ael) of (7-brea-3,7-diaethyl-6-hydroxy-2-octenyl) - (4-preplenylphenyl) ether in 5 [mu] l of anhydrous diethyl ether was added dropwise at a temperature of 10-20 * 0 ea The reaction mixture was stirred at room temperature for 1 h and in the absence of atmospheric humidity to a suspension of 114 g of LiOH in 10 [mu] l of anhydrous diethyl ether. The reaction mixture was then heated at reflux for 30 minutes. Upon cooling in January and dilution of diethyl ether and decomposing unreacted ice hydride with stirring as well as precipitated aluminum hydroxide 10-20% scientific solution. The separated ether layer was washed with saturated HaCl solution, dried over anhydrous MgSO 4 and evaporated under reduced pressure. The obtained residue was then separated by eeveu column on silica gel with 8 haet% water (PE, containing up to 75% by volume of diethyl ether) to give 550 g (60%) of chreaatographically pure 1 - / (7-brea-3,7 diaethyl-6). - hydroxy - 2 - octeaylexylphenyl / propane - 1 - el. Elemental analysis for (385) »calculated 59.18% C, 7.58% H, 20.73% Br found 59.30%

0.80% H, 20.67% Br · IR (5% CCl 4 solution) (OH free) 3622, γ (OH bound) 3470,}} (CC) 1672, V (area) 1611 , 1588 and 1513 ca ^-1 . Example 4

Of the 383 g (0.001 aol) (7-brea-3,7-diaethyl-6-hydroxy-2-octenyl) - (4-preplenylphenyl) ether prepared according to Example 3, reaction with 1 g of oetevic anhydride was added at 0 14 g of anhydrous pyridine at room temperature obtained 150 g (35%) of (7-brea-3,7-diethyl-6-acetoxy-2-octenyl) (4-preplenylphenyl) ether. Elemental Analysis Found C, 50.29; H, 6.87; C, 59.04; H, 6.66.

Example 5

By the method described in Example 1, (7-brea-3,7-diaethyl-6-ieeprepexy-2-octenyl) (4-nitrophenyl) ether was prepared (CDCl 3 / TMS) ((J * (ppa) 1,09,1,12 (d, 6H, J-6Hs), 1,26,1,33 (β, 6H), 1,75 (ba, 3H), 1,9-2,5 (a, 2H), 3.4 - 4.0 (s, 2H), 4.63 (d, 2H, ^J CH> ⁶ H ^{5 H} *> · 5.53 <* ♦ · ^H + ^J H, V, ⁶ · ⁵ **), 6.95 (a, 2H, 9 Hs),

8.2 (a, 2H, _Jerthe - 9 Hs), (7-brea-3,7-diaethyl-6-hydroxy-2-octenyl) - (4-chlorophenyl) ether) IR (5% CCl 2) (OH free) 3611, ^ (OH bound) 3571,

200410 γ (CC) 1672, γ (aromatic) 1599, 1583 and 1495 ° «J ^_1 (7 - bromo - 3,7 - dimetbyl - 6 - isoproxy - 2 - oktemyl) - (4 - chlorophenyl) ether and» 23 _ 1,5208 »

V 9 9 (7-bromo-3,7-dimethyl-6- (2'-methoxy) ethoxy-2-octemyl) - (4-preplenylphenyl) ether} n ^ ²¹ »1.5230 f (7-bromo-3) 7-dimethyl-6-bezyloxy-2-octemyl) - (4-prepiemylphemyl) ether * _D ^23,5 - 1,5565 1 (7-bromo-3,7-dimethyl-6- (2-chloro) ethoxy-2 -) octemyl) - (4-prepimylphenyl) ether, n _D ²¹ 1.5345 i (7-bromo-3,7-dimethyl-6-methoxy-2-octemyl) - (4-methexycarbenylphenyl)

- ether) _η β ²³ 5 «f 1.5260 (7 - bromo - 6 - methoxy - 3,7 - dimethyloctyl) - (4 - ethylfeayl) ether FM _D ^21-1, 5071» (6 - bromo - 5 - methoxy - 6 - methyl - 2 - heptyl) - (4 - prepiemylphemyl) ether (b _d ²³ » ⁵ - 1,4884).

Example 6

Under the same reaction conditions as in Example 2, (3,7-dichloro-2,6) was obtained from (3,7-dimethyl-2,6-octadiemyl) - (4-prepiemylphemyl) ether and N-chlorosuccininide in anhydrous methanol. dimethoxy-3,7-dimothyloctyl) - (4-propionylphemyl) ether. Elemental analysis for ^C 21 ^H 32 ^G1 2 ° 4 ^ -19) «0% calculated 60.13,

7.69 <f> H, found 60.43 f> C, 7.52% H. MS spectrum (70 s) "404/6 (^ Ο Ο ^ ⁰³ ^ j

368/70 (B ^ C _{20 9 4} 10), 336/8 (Ο ^ Η ΟΙΟ ^. ^), 307/9 (Οχ Ο ^ ⁰¹ ^> ^{»151 (9} ° 11 ° 2 ^Η) ·

The biological activity of the compounds prepared according to the invention was tested on the basis of the insect juvenile hormone hectivity. The substances were applied topically in 1 ml of acetone at a dilution of 1 t 10, 10000, etc. and have freshly stripped pupae of beetles (Tenebrienidae) and freshly stripped larvae of the last Instar bug (Pyrrheeeridae and Pentatemidae). . Some of the results shown in Table 1 are expressed in standard units ID50, which will reduce the amount of micrograms per insect that causes the formation of intermediate forms between pupae and adults (beetles) under the above experimental conditions. or between larvae and despecea

Table 1

Examples of activities of the compounds prepared according to the invention in units per insect in topiotic application to insects of the family Pyrrheeeridae, Pentatemidae and Teaebrienidae

Substance

Dysdercus eingulatus

Qraphosema

Itálieum

Tenebrie molitor

METHYL ols-10,11 acid ester

- epoxy -3,7,11-trimethyl-trans trans -2,6-tridecadieneve (reference substance)

0.4

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(7-Bro--3,7-dimethyl-6-isopropoxy-2-octenyl) - (4-propionylphonyl) ether 0.01 1 8 (7-Bromo-3,7-dimethyl-6- * ethexyl-2-octenyl) - (4-propionylphenyl) ether 0.01 10 (7-bromo-3,7-dimethyl-6-ethoxy-2-octenyl) - (4-propionylphenyl) ether 1 20 May (7-Bromo-3,7-dimethyl-6-isopropoxy-2-octoayl) - (4-chlorophenyl) ether 5 10 1 - [(7-Bromo-3, 7-dimethyl-6-hydroxy-2-ocrenyloxy) phenyl] prepan-1-ol 0.1 50

DMΕ DMÍ I

Claims (2)

l.Vioinal alkoxyhalogenated derivatives of aliphatic-aronathioic ethers with the effect of juvenile hormone coated with formula I, R ¹ R ² X C - CH (OR ³ ) - (0¾) a - C (R ⁴ Z ¹ ) - C (R 4 Z ² ) - (CH 2) _b - CH (R ⁶ ) wherein * t - the symbol a denotes an oil number between 0 and 2, - the symbol S wetting 0 or 1, - symbol 2 wetting bromine or chlorine, 1 2 -symbols R, R soaks the methyl-or methyl group, - R ^{3 is} hydrogen, straight or branched chain alkyl of up to 6 carbon atoms, alkoxyalkyl and straight or branched chain of up to 6 carbon atoms, aralkyl of up to 9 carbon atoms, straight or branched chain alkyl of up to 6 carbon atoms, aeyl with straight or branched * chains * with a maximum of 6 carbon atoms - Ynbols R ⁴ , R ³ and R 6 denote hydrogen or methyl, -symbol R? denotes hydrogen, straight or branched chain alkyl of up to 4 carbon atoms, chlorine or bromine, nitro, straight or branched chain alkylcarbenyl of up to 4 carbon atoms, straight or branched chain alkoxycarbonyl of up to 4 carbon atoms, -hydroxyalkyl of straight chain or a branched chain e with a maximum of 4 carbon atoms, - the symbol Z ¹ and Z ² denotes hydrogen or together form a double bond or, if a »2, Z ¹ denotes also bromine or chlorine and Z ² denotes alkoxy groups having a maximum of 6 carbon atoms, 2. A process for the preparation of the vioinal alkoxyhalogenated derivatives of the aliphatic-aromatic ethers according to claim 1, characterized in that an alkoxyalhaleate of the formula II, (R ¹ R ² ) C-CH - (CHg) and - C (R ⁴ Z ¹ ) - C ^) - (CH) b - CH (R ⁶⁾ - 2 R (II) wherein R ^1, R ^2, R ⁴ to R ^6, Z ^1, Z ^2, a, b have the meanings výio above and the symbol X denotes bromine or chlorine, and phenol-coated formula III, HO R ⁷ (IXX) 200 wherein R ⁷ is as defined above to form an all-phthalocaromatic ether of general formula IV, (R ¹ R ² ) C-CH - (0 ') & - 0 (R ⁴ Z ¹ ) - C (R ⁵ Z ² ) - ( CH) b - CH (R ^s) - O - (O) - R ⁷ '(IV) wherein R ¹ , R ² , R ⁴ to R ⁷ , Z ¹ , Z ² , a, b are as defined above, with reaction and N-halosuccinimide, optionally N-halophtholimide and compounds of formula V, HO - S · ³ (V) wherein the symbol R ^ in most of the series 1 converts at a temperature ranging from 0 to 50 ° C to menealkoxyhalegene - and at a temperature of 15 to 25 ° C to a bis (alkexyhalogen) derivative of the formula 1 ,