CS252584B1 - Mixed succinic ester with 1- (2,2-dimethyl-2H-chromen-6-yl) -1-alkanol and 5,9,13-trimathyl-4,6-tatradecadien-3-ol, respectively. hydroxy-, 13-alkoxy- and 13-aralkoxycarbonylalkylcarboxy derivatives and processes for its preparation - Google Patents

Abstract

The essence of the solution is a mixed ester of succinic acid with 1-(2,2-dimethyl-2H-chromem-6-yl)-1- -alkanol and 5,9,13-trimethyl-4-6-tetradecadien- -3-ol, respectively its 13-hydroxy-, 13-alkoxy- and 13-aralkoxycarbonylalkylcarboxy derivative CO ,ch3 ch3 R1-CHo-co-ch2-CH2-CO-O-R2 The method of preparing a mixed ester of succinic acid consists in the reaction of the monoester derivative in the reaction with alcohol in the presence of a catalytic amount of 4-dimethylaminopyridine and dicyclohexylcarbodiimide in an environment of anhydrous diethyl ether at a temperature of 15 to 25 °C.

Description

The invention relates to a mixed ester of succinic acid with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-alkanol and 5,9,13-trimethyl-4,6-tetradecadien-3-ol, or its 13-hydroxy-, 13-alkoxy- and 13-aralkoxycarbonylalkylcarboxy derivative as a biologically active substance and a method for its preparation.

The compounds according to the invention are among the substances causing developmental deviation in insects in their resulting effect. Their specificity is that they contain in the molecule a part responsible for developmental deviation caused by the effect typical of juvenile hormone analogues and a part responsible for developmental deviation caused by the effect typical of precocene-type analogues.

The essence of the present invention is a mixed ester of succinic acid with 1-(2,2-dimethyl-2H-dimethyl-2H-chromen-6-yl)-1-alkanol and 5,9,13-trimethyl-4,6-tetradecadien-3-ol, or its 13-hydroxy-, 13-alkoxy- and 13-aralkoxycarbonylalkylcarboxy derivative of the general formula X

o -co -ch ₂ -ch ₂ -co-o -r ² where the symbol R ¹ denotes a straight or branched chain alkyl group with a maximum of 3 carbon atoms, the symbol R 2 denotes a group

CH- CH- CH- CH _K j 3 ,3,25

R -C-(CH ₂ ) ₃ -CH-CH ₂ -CH=CH-C=CH-CH ^CH 3 where the symbol R denotes hydrogen or a hydroxy group or a straight or branched chain alkoxy group with a maximum of 3 carbon atoms or the group -OR ⁴ , where the symbol R ⁴ denotes a group

-co - (ch ₂ ) ₂ -co -o —ch ₂

CH·,

CH,

2

The method for preparing a mixed ester of succinic acid of general formula I (R, R have the above meaning, R denotes hydrogen or a hydroxyl group or a straight or branched chain alkoxy group with a maximum of 3 carbon atoms) is characterized in that a monoester derivative of general formula II is reacted

o-co-ch ₂ -ch ₂ -cooh where the symbol R ¹ has the above meaning with an alcohol of general formula III ? ^H 3 CH, C,H _{c 3} 1 i ³ i ^{2 5} RC-(CH,),-CH-CH,-CH=CH-C=CH-CH-OH ^{2 3} I ²

CH ₃ CH ₃ (III) where the symbol R has the above meaning in the presence of an equimolar amount of dicyclohexylcarbodiimide and a catalytic amount of 4-diI methylaminopyridine in anhydrous diethyl ether at a temperature of 15 to 25 °C.

The method for preparing a mixed ester of succinic acid of general formula I (R , R 3 4 4 have the above-mentioned meaning, R denotes the group OR , where R has the above-mentioned meaning) is characterized in that a double molar amount of the monoester derivative of general formula XI, where the symbol R ¹ has the above-mentioned meaning, is reacted with an alcohol of general formula III, where R ³ denotes a hydroxy group in the presence of a double molar amount of dicyclohexylcarbodiimide and a catalytic amount of 4-dimethylaminopyridine in an environment of anhydrous diethyl ether at a temperature of 15 to 25 °C.

In the following, the invention is explained in more detail using exemplary embodiments, without being exclusively limited to these.

Example

A reaction mixture of 64 mg (0.2 mmol) of succinic acid monoester with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-propanol, 56 mg (0.2 mmol) of 5,9,13-trimethyl-13-methoxy-4,6-tetradecadien-3-ol and 41 mg (0.2 mmol) of dicyclohexylcarbodiimide in 5 ml of anhydrous diethyl ether was stirred at 15 to 25 °C for 2 hours in the presence of a catalytic amount of 4-dimethylaminopyridine and then left to stand overnight.

After filtering off N,N ¹ -dicyclohexylurea, the filtrate was washed successively with 5% aqueous hydrochloric acid solution, saturated sodium chloride solution. The ether layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was separated by column chromatography on silica gel with 8% by weight of water (eluent: petroleum ether containing up to 20% diethyl ether). 55 mg (47%) of the reaction product was obtained.

MS analysis: 582 (M ⁺ , C^H^Og) , 567 (C^H^Og) , 535 (C^H^Og) , 346 (C _2Q H ₂ gOg), 331 (C ₁₉ H ₂₃ O ₅ ), 303 <C ₁₇ H ₁₉ O ₅ ), 201 (C ₁₄ H _1? O), 185 (C^H^O) ;

iC analysis (CC1 ₄ ) : 2830 (ífgCHj in OCHj), 1740, 1729 (l/ C=O) , 1652, 1643 (VC=C) , 1615, 1494 ((Zarom.), 1392, 1378, 1365 «^CHg) cm ^-1 .

In the same way, a mixed ester of succinic acid with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-propanol and 5,9,13-trimethyl-4,6-tetradecadien-3-ol was prepared.

MS analysis: 552 346

185 (M ⁺ , C ₃₅ H ₅₂ O ₅ ), 486 (C _3Q H ₄ gO ₅ ) , 471 (C^H^Og) , 457 (C^H^Og) , ^(C 20 ^H 26°O5 ⁾ ' ^{331 (C} 19 ^H 23°5 ⁾ ' ^{318 <C} 18 ^H 22°5 ⁾ ' ^{303 <C} 17 ^H 19 ^O 5>' ^{201 (C} 14 ^H 17°>' ^(C 13 ^H 13 ^O) ' ¹⁰¹ < ^C 4 ^H 5°3»'

IR analysis (CC1 ₄ > : 1738 (γΟ=Ο) , 1652 , 1643 (RC=C) (J” _with CH ₃ ) , 1265 (^C-0 ester.) cm ³ .

1615, 1494 (Varom.), 1393, 1382, 1362,

Example 2

A reaction mixture of 64 mg (0.2 mmol) of succinic acid monoester with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-propanol, 27 mg (0.1 mmol) of 5,9,13-trimethyl-4,6-tetradecadien-3,13-ol and 41 mg (0.2 mmol) of dicyclohexylcarbodiimide in 5 ml of anhydrous diethyl ether was stirred at 15 to 25 °C for 2 hours in the presence of a catalytic amount of 4-dimethylaminopyridine and then left to stand overnight. After filtering off the N,N'-dicyclohexylurea, the filtrate was washed successively with 5% aqueous hydrochloric acid solution and saturated sodium chloride solution. The ether layer was dried over anhydrous sodium sulfate and then evaporated under reduced pressure. The residue was separated by column chromatography on silica gel with 8 wt. i. water (eluting with petroleum ether containing up to 20 vol. i. diethyl ether). 42 mg (48%) of the reaction product was obtained.

MS analysis: 652 (CjgH^Og) , 597 (C ₃₅ H _4g O _g ) , 581 (C ₃₅ H ₄₉ O _? ) , 346 (C ₂₀ H _2g O ₅ ) , 331 (C _lg H ₂₃ O ₅ ), ' 303 (C ₁₇ H ₁₉ O ₅ ), 201 (C ₁₄ H _1? O), 185 (C^Hj^O), 101 (C ₄ H ₅ O ₃ );

IC analysis (CC1 ₄ ): 1742, 1729 (Vc=O), 1651, 1643 (yC=C), 1614, 1494 (^arom.), 1375 <C^ ^ch 3> · 1266 (yC-0 in COOR) cm ^-1 .

Biological effects were monitored.

in termites:

I. influence on the development of soldiers and white soldiers, overall slowing down of development. Prorhinotermes simplex was used as a test organism (application on Whatman No. 1 chromatography paper, in acetone). To monitor the antijuvenilization effect, a high degree of determination of development to the soldier caste was first induced by using the juvenilization agent methoprene. The influence, i.e. reduction in the number of soldiers or complete prevention of their formation, or possibly the formation of 'transitional individuals between soldiers and larvae called intercastes, is then reported in the form of a fraction, where the numerator indicates the percentage of fully developed white soldiers formed, and the denominator indicates the percentage of intercastes formed.

Mixed ester of succinic acid with 1-(2,2-dimethyl-2H-octyl-6-yl)-1-propanol and 5,9,13-trimethyl-4,6-tetradecadiene-3,13-diol (0.2 wt. % in acetone): 0/0 after 11 days, 0/0 after 13 days, 0/0 after 15 days, 0/0 after 17 days, 0/0 after 19 days, 0/0 after 21 days.

Methoprene concentration (0.1 wt. % in acetone): 10/0 after 11 days, 30/0 after 13 days, 40/0 after 15 days, 60/0 after 17 days, 80/0 after 19 days, 80/0 after 21 days.

II. antifeedant effect.

Coptotermes formosanum was used as the test organism (application on Whatman No. 2 chromatography paper, in acetone). For the mixed ester of succinic acid with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-propanol and 5,9,13-trimethyl-4,6-tetradecadien-3-ol (1 wt. % in acetone): a reduction in feeding of termites of 84 % occurs compared to the control groups of termites. For the mixed ester of succinic acid with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-propanol and 5,9,13-trimethyl-13-methoxy-4,6-tetradecadien-3-ol (0.01 wt. % in acetone) a reduction in feeding of 67 % occurs compared to the control groups of termites.

For the mixed ester of succinic acid with 1-(2,2-dimethyl-2H-chromen-6-yl)-1-propanol with an alcohol of general formula III, where R ³ denotes the group -OR ⁴ (the symbols R ³ , R ⁴ have the above meaning) (0.1 wt. % in acetone), a reduction in voraciousness of 52% occurs compared to the control groups of termites.

The biological effects were also monitored in the beetle Tenebrio moltor. The activity was evaluated on the basis of inhibition of metamorphosis and is expressed in the amount of substance in micrograms per insect, which, upon topical application, causes the formation of intermediate forms: ID,- _n sample of the ^mixed ester of succinic acid according to the invention (R = ethyl group, R = methoxy group) = . 3 4 4 = 0.03: IDjq sample of the mixed ester according to the invention (R = ethyl group, R = OR , where R has the above meaning) = 1.

Claims (3)

SUBJECT OF THE INVENTION 1 2 A process for the preparation of a mixed succinic ester of the general formula I, wherein R and R 2 1 2 1. Mixed succinic ester with 1- (2,2-dimethyl-2H-chromen-6-yl) -1-alkanol and 5,9,13-trimethyl-4,6-tetradecadiene-3-ol or its 13-hydroxy-13-alkoxy and 13-aralkoxykarbonylalkylderivátem formula I, -O-CO-CH ₂ -CH ₂ -CO-OR ^of where R ¹ denotes a straight or branched chain alkyl group having a maximum of 3 carbon atoms, 2 R denotes a group CH CH CH CH _c 3 | 3 3 J2 5 R ₃ -C- (CH ₂ ) ₃ -CH-CH ₂ -CH = CH-C = CH-CHCH Where R is hydrogen or a hydroxy or straight or branched alkoxy group having a maximum of 3 carbon atoms or an -R (R) group, wherein R is (II) - CO - (CH ₂ ) ₂ - CO - O - CH C2 ^h 5 2. A process for the preparation of a mixed succinic ester of the formula I, wherein R and R are as defined above, R @ 1 denotes hydrogen or a hydroxyl group or a straight or branched chain alkoxy group of up to 3 carbon atoms, characterized by reacting the monoester a derivative of the general formula II o-co-ch ₂ -ch ₂ -co-oh wherein R ^d is as defined above with an alcohol of the general formula III CH, CH, CH, C H, _c 3,3 i ³ i ^{2 5} R -C- (CH ₂ ) ₃ -CH-CH ₂ -CH = CH-C-CH-CH-OH-CH ₃ wherein R is as defined above in the presence of an equimolar amount of dicyclohexylcarbodiimide and a catalytic amount of 4-dimethylaminopyridine at a temperature of 15 to 25 ° C. R &lt; 4 &gt; is as defined above, R is -ORR, wherein R is as defined above; characterized in that a double molar amount of a monoester derivative of formula (II), wherein R is as defined above, is reacted with an alcohol of formula III, wherein R is hydroxy in the presence of double molar amount of dicyclohexylcarbodiimide and catalytic amount of 4-dimethylaminopyridine in anhydrous diethyl ether at 15 to 25 ° C.