CS260904B1 - Ester-linked 2H-benzopyran derivatives as a biologically active substance and a process for their preparation - Google Patents

Abstract

The essence of the present solution are derivatives of 2H-benzopyran with an ester bond in the molecule of general formula I R3 where the symbol R1 denotes an alkyl group with a maximum of 3 carbon atoms; the symbol R2 denotes an alkyl group with a maximum of 19 carbon atoms, a haloalkyl group with a maximum of 4 carbon atoms, an oxoalkyl group with a maximum of 6 carbon atoms, a phenyl group, a phenyl group substituted with an alkyl with a maximum of 4 carbon atoms, a halogen (chlorine, bromine), a hydroxycarbonylalkyl group with a maximum of 6 carbon atoms; the symbols R2, R4 together form a double bond or independently of each other denote an alkoxy group with a maximum of 4 carbon atoms or chlorine or bromine. The method of preparing 2H-benzopyran derivatives with an ester bond in the molecule of general formula I consists in the reaction of a hydroxy compound of general formula II with an organic acid of general formula III OH R1 —CH p3 /11/ R2COOH /111/ in the presence of 4-dimethylaminopyridine and dicyclohexylcarbodiimide at a temperature of 10 to 20 °C, or by reaction with an organic acid chloride or anhydride in the presence of anhydrous pyridine at 20 to 60 °C.

Description

The present invention relates to 2H-benzopyran derivatives having an ester bond in a molecule having the properties of biologically active substances and a process for their preparation.

The compounds of the present invention cause developmental deviation in their effect on insects.

The present invention relates to 2H-benzopyran derivatives by an ester bond in the molecule

R ¹

AND

R = -COO-CH _n CH,

R ³ (1) wherein R represents an alkyl group having a maximum of 3 carbon atoms 2

R is alkyl of up to 19 carbon atoms, haloalkyl of up to 4 carbon atoms, oxoalkyl of up to 6 carbon atoms, phenyl, phenyl substituted with alkyl of up to 4 carbon atoms, halogen (chlorine, bromine), hydroxycarbonylalkyl of up to 6 carbon atoms, R together form a double bond or independently represent an alkoxy group having a maximum of 4 carbon atoms or chlorine or bromine.

A process for the preparation of 2H-benzopyran derivatives having an ester bond in a molecule of formula (I) is characterized by reacting a hydroxy compound of formula (II).

R ³ (11) with an organic acid of formula III

R ² COOH / 111 /

4) R to R are as defined above in the presence of 4-dimethylaminopyridine and dicyclohexylcarbodiimide at 10 to 20 ° C, respectively by reaction with an organic acid chloride or anhydride in the presence of anhydrous pyridine at 20 to 60 ° C.

In the following, the invention is explained in more detail by way of examples without being limited thereto.

Example 1

0.24 g (0.001 1 mol) 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran, 0.17 g (0.001 mol) decanoic acid, 0.22 g (0.001 1 mol) dicyclohexylcarbodiimide and 0 0.01 g (0.000 1 mol) of Ν, Ν-dimethylaminopyridine was stirred in 5 ml of anhydrous diethyl ether at 15-20 ° C for 2 hours. Everything was allowed to stand overnight at the same temperature. Then the reaction mixture was diluted with diethyl ether, filtered, and the filtrate was washed successively with 5% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. The ether layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was then separated by column chromatography on silica gel with 8 wt. % water (eluent: petroleum ether containing up to 20 vol% diethyl ether). 0.23 g (61%) of 2,2-dimethyl-6- (1-decanoyloxypropyl) -2H-benzopyran was obtained.

Elemental analysis was consistent with calculated values in the range = 0.3 i.

IC analysis / 4%, CC1 ₄ /: 1737 / VC = O /, 1644 / C nu /, 1615, 1494 Zvarom.Z, 1379, 1362 ZSgCHj / cm @ ^-1. MS analysis: ZC 372 ₂₄ H _{3 g} O ₃ Z 357 / C ₂₃ H ₃₃ C> ₃ /, 329 / C ₂₁ H ₂₉ O ₃ Z ₁₉ H ZC 306 _3Q O ₃ Z,

201 HC ₁₄ H _1? Mark, 189 / C ₁₂ H ₁₃ O ₂ Z, 185 ZC ₁₃ H ₁₃ OZ, 171 ZC 1 H 2 OZ. NMR analysis ZTMSZCDS1 ₃ , ppm / 8Z: 0.80Zt, 6HZCH ₃ CH ₂ CH + CH ₃ ZCH ₂ Z _g COO, 1.18 Z ₁₂ HZCH ₃ CH ₂ ZCH ₂ ZgCH ₂ , 1.34 / s, 6HZ, ZCH 2 C , 1.70 Zm, 4HZCH ₂ CH ₃ , 2.24 Zt, 2H / OCOCH ₂ , 5.54 / t, H / CHOCO, 5.55 Wt, H ₂ CH =, 6.27 / d, H 2 CH =, 6.68-7.06 Zm, 3HZ ArH.

They were prepared analogously to this procedure

2,2-dimethyl-6 '(1-chloroacetoxypropyl) -2H-benzopyran

IC analysis Z2% /: 1,762, 1,741 ZvC = OZ, 1,643 ZvC = CZ, 1,615, 1,494 Zvarom.Z, 1,387,

Ί 362 Z8 _with CH ₃ Z cm ¹ . MS analysis: 294Z6 CC ^ H ^ ClOjZ, 279Z81 _ZC15 H ₁₆ C1O _3/201 ZC ₁₄ H _1? Mark, 200 ^{/ C} 14 ^H 16 ^{O /} ' ^{185 / C} 13 ^H 13 ^{O /} ' ^{134 / C} 9 ^H 10 ^{O /}

2.2-Dimethyl 1-6- (5-Z 4-bromobenzoyloxy) propyl (J-2H-benzopyran)

IC analysis Z3% Z: 1,723 ZvC = OZ, 1,642 ZvC = CZ, 1,614, 1,592, 1,493 Welds /, 1,397,

379, 1 361 Z6 _with CH ₃ Zcm ^-1 . MS analysis: 400Z2 2i ^{7c H Br} 2 l 3 ° ^/ '358Z7 ZC _{2 () g} H ₃ BrO Z 306 CC ^ H ^ C ^ Z 201 CC ₁₄ H ₁₇ CC, CC ^ 183Z5 brooch, ZC 171. ₁₂ H _n OZ

2,2-Dimethyl-6- (5-Z-4-oxopentanoyloxy-propyl-2H-benzopyran)

IC analysis Z2% Z: 1726 asym./v C = OZ 1643 ZVČ = CZ, 1615, 1493, Zvarom.Z, 1375, 1362 Z8 _with CH ₃ ZCM ^_1. MS analysis: 316 CC ₁₉ H ₂₄ O ₄ /, 301 ZC _LG H ₂₁ O ₄ Z ZC 201 ₁₄ H _1? Mark, 185 ZC ₁₃ H ₁₃ O /, 171 ^{/ C} 12 ^H 11 ^{O /}

2,2-dimethyl-6-Z1-hexanoyloxypropyl-2H-benzopyran

IC analysis Z4% Z: 1,737 ZvOOZ, 1,643 ZvC = CZ, 1,614, 1,586, 1,496 Zvarom.Z, 1,384,

378, 1 361 Ac _with CH ₃ Zcm ^_1 . MS analysis: 316 7C2 () H2gO37, 301 ZC19H25O3Z, 201 / C14H17OZ, 200 ^{/ C} 14 ^H 16 ^{O /} ' ^{185 / C} 13 ^H 13 ^{O /} ' ^{115 / C} 6 ^H 11 ° 2 ^/ ' ⁷³ '' ^C 3 ^H 5 ^O 2 ^/

2,2'-Dimethyl-6 - [(1-benzoyloxypropyl) -2H-benzopyran

MS analysis: 322 ZM ⁺ Z, 307 ( ^c 20 ^H 19 ° 3 ^/ '201 ZCl 13 ^H 13 O 2 Z, 185 ^7c 13 ^H 13 ° / - 171 ZC 1 H 3 O 2 O),

105 ZC _? H ₅ O (77 ZC ₈ H ₈ ): IC analysis (2%, CCl ₄ Z: 1,723, 1,712 ZvC = OZ, 1,644, 1,652 ZvC = CZ,

614, 1 606, 1 586, 1 495, 1 452 Welding Z, 1,362, 1,378 1,270 ZvC-0 esterZcm ¹

2,2-Dimethyl-6- (1- (4-methylbenzoyloxy) propyl) -2H-benzopyran

MS analysis: 336 ZM ⁺ Z, 321 ( ^c 21 ^H) 21 ° 3 / ' ^{201 7C} 13 ^H 13 ° 2 ^' ^{185 7C} 13 ^H 13 ° ^{7, 171} ZC ₁₂ H _n OZ,

119 ZC _g H _? Mark, 91 ZC ₇ H _? OF; IR analysis Z2 «Z CC1 _4: 1721, 1712 ZVČ = OZ, 1642, 1652 ZVČ = CZ, 1614, 1580, 1494 Zvarom.Z, 1362, 1378 _g Ac CH ₃ Z, 1271 ^ZVČ-1 0 ester.Zem

Example 2

A mixture of 0.32 g (0.001 5 mol) of 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran, 0.14 g of anhydrous pyridine and 1 g of acetic anhydride was allowed to stand overnight at 10-20 ° C. . The reaction mixture was diluted with saturated sodium bicarbonate solution and extracted with diethyl ether. The dried ether layer residue was separated on a 8 wt. % water (eluent: petroleum ether containing up to 20 vol% diethyl ether). 0.29 g (74%) of 2,2-dimethyl-6- (1-acetoxypropyl) -2H-benzopyran was obtained. Elemental analysis was consistent with the calculated values in the range of + 0.3%. IR analysis (3%): 1738 (rC-O),

641 (vC-C), 1 614, 1 581, 1 491 (var./), 1 381, 1 370, 1 362/8 _with CH ₃ /, 1 238 (t'C-0 acetate / cm ')

MS analysis: 260 / C ₁₆ ^H 20 ° 3 ^{/ '24} 3 / ^C 15 ^H 17 ° 3 /' ^{200 / C} 14 ^H 16 ^{O /} ' ^{185 / C} 13 ^H 13 ^{O /} ' ^{171 / C} 12 ^H 11 ^{O /} '

115 (C ₈ H ₃₀ O), 91 (C 8 H ₁₀ O). NMR Analysis: 0.81 t / 3H / -CH ₂ CH ₃ 1.37 s / 3H / / CH _3/2 C 1 75 Q / H /

CH ₃ CH ₂ , 2.01 b / 3 H / CH ₃ O, 5.55 t / H / CHOCO, 5.57 d / H / CH ", 6.30 d / H / CH =, 6.70-0.8 m / 3H / ArH.

Example 3

A mixture of 0.22 g (0.001 mol) of 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran, 0.1 g of succinic anhydride and 87 mg of anhydrous pyridine was heated to 60 ° C for 7 hours and then allowed to stand overnight at 10-20 ° C. After the usual work-up, the reaction mixture was separated by column chromatography on silica gel with 8 wt. % water (eluent: petroleum ether containing up to 75% by volume of diethyl ether). 0.11 g (35%) of 2,2-dimethyl-6- [1- (3-carboxypropionyloxy) propyl] -2H-benzopyran was obtained. The elemental analysis was in accordance with the calculated values within the range of + 0.3 i. IR analysis (3%): 2668, 2 585 (vOH bond), 1739 (vC = O),

717 (vC = O acid dimer), 1.641, 1615 (vC = C), 1,597, 1,582, 1,492 (aromatic), 1,376,

362 / cm ² / cm ¹ . MS analysis: 318 / C _g H ₂₂ O _5/303 / C ₁₇ H _g O ₅ /, 218 / C ₁₄ H _g O ₂ /, 203 / C ₁₃ H ₁₅ O ₂ /, 185 / C ₁₃ H ₁₃ O (101 (C ₄ H ₅ O ₃ )). NMR Analysis: 0.81 / t, 3 H / CH ₃ CH ₂ 39 1 / s, 6H / / CH _3/2 C 1.74 / m, 2 H / CH ₃ CH _2, 2.62 / 4H / / CH _2/2 5.57 / t H / CHO 5.57 / d, H / CH, 6.29 / d, H / CH "6.69 to 7 with I9 / 311 / AVC.

Example 4

To a solution of 0.39 g (0.001 5 mol) 2,2-dimethyl-6- (1-acetoxypropyl) -2H-benzopyran in 5 mL anhydrous methanol was added 0.53 g at 0-5 ° C under a dry nitrogen atmosphere. (0.003 mol) of N-bromosuccinimide. The reaction mixture was stirred at this temperature for an additional 15 minutes, then diluted with water and extracted with diethyl ether. The ether layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was separated by column chromatography on silica gel with 8 wt. water (eluent: petroleum ether containing up to 20% by volume diethyl ether). Chromatography yielded 0.36 g (65%) of 2,2-dimethyl-3-bromo-4-methoxy-6- (1-acetocypropyl) -2H-benzopyran.

MS analysis: 372/70 / C _? H ₂₃ BrO ₄ /, 343/41 / C ₁₅ H _lg BrO ₄ /, 301/299 / C ₁₅ H _lg BrO ₂ /, 260 / C ₁₆ H _2t) O ₃ /, 245 / C ₁₅ H ₁₇ O ₃ / , 201, / C ₁₃ H ₁₃ O ₂ /, 185 / σ _{χ 3} Η _{χ 3} Ο /, 173 / C - HgO · ^, 161 / C ^ O /, 115 / C _g H _? /, / CgHjO /

Biological effects were observed in termites:

- influencing the development of soldiers and white soldiers, overall development retardation. '

Prorhinotermes simplex (application to Whatman # 1 chromatography paper in acetone) was used as the test organism. In laboratory colonies of test insects, the effect of a high degree of developmental determination on the military caste should first be induced by methoprene or other strong juvenilizing agents during the duration of the experiment, ie about 20 days. Antijuvenile agents then prevent the effect of metoprene or other juvenilizing agents, which, depending on the ratio of concentrations of both substances in the system to reduce the number of soldiers, or completely prevented the formation of soldiers, in many cases arise transitional individuals between soldiers and larvae. Influence is reported in the form of a fraction, where the numerator shows the percentage of fully developed white soldiers, while the denominator indicates the percentage of interkasts formed.

2,2-dimethyl-6- (1-acetoxypropyl) -2H-benzopyran (0.1%): 0/0 after 9 days, 0/0 after 12 days,

0/0 after 15 days, 0/0 after 20 days

2,2-dimethyl-6- (1-acetoxypropyl) -2H-benzopyran (0,1 i) + methoprene (0,1 *): 0/0 by days, 0/35 by 12 days, 5/35 by 15 days, 5/35 after 20 days

2.2-Dimethyl-6- (1-decanoyloxypropyl) -2H-benzopyran (0,1%) + methoprene (0,05%):

0/0 after 9 days, 0/0 after 12 days, 0/0 after 14 days, 0/0 after 16 days, 0/13 after 18 days, 0/13 after 20 days

2.2-dimethyl-6- (1-decanoyloxypropyl) -2H-benzopyran (0.1%): 0/0 after 9 days, 0/0 after 12 days, 0/0 after 14 days, 0/0 after 16 days, 0/0 after 18 days, 0/0 after 20 days

2.2-dimethyl-6-Q- (4-bromobenzoyloxy) propyl] -2H-benzopyran (0.1%): 0/0 after 9 days,

0/0 after 12 days, 0/0 after 14 days, 0/0 after 16 days, 0/0 after 18 days

2.2-Dimethyl-6- [1- (4-bromobenzoyloxy) propyl-2H-benzopyran (0.1%) + methoprene (0.05%):

0/0 after 9 days, 0/0 after 12 days, 0/0 after 14 days, 7/0 after 16 days 7/0 after 18 days

2.2-dimethyl-6-O- (4-oxopentanoyloxy) propyl] -2H-benzopyran (0.1%): 0/0 after 9 days,

0/0 after 12 days, 0/0 after 14 days, 0/0 after 16 days, 0/0 after 18 days

2.2-Dimethyl-6-ri- (4-oxopentanoyloxy) propyl] -2H-benzopyran (0.1%) + methoprene (0.05%):

0/0 after 9 days, 0/0 after 12 days, 7/7 after 14 days, 7/7 after 16 days, 7/7 after 18 days metrophem (0.1%): 0/0 after 9 days, 40 / 0 after 12 days, 53/0 after 15 days, 53/0 after 17 days

2.2-dimethyl-6- (1-chloroacetoxypropyl) -2H-benzopyran (0.2%): 0/0 after 9 days, 0/0 after 10 days, 0/33 after 13 days, 7/60 after 15 days, 7/80 after 17 days

2.2-dimethyl-6- (1-chloroacetoxypropyl) -2H-benzopyran (0.4%) + methoprene (0.1%): 0/0 after 9 days, 0/0 after 10 days, 0/13 after 13 days 0/20 after 15 days, 0/13 after 17 days metoprene (0.1%): 0/0 after 9 days, 0/0 after 10 days, 36/2 after 13 days, 40/13 after 15 days, 42/18 after 17 days

2.2-Dimethyl-6- 1- (4-methylbenzoyloxy) propyl] -2H-benzopyran (0.5%) + methoprene (0.1%):

0/0 after 10 days, 0/27 after 13 days, 0/47 after 16 days, 0/60 after 19 days, 0/60 after 22 days

2.2-dimethyl-6- (1-benzoyloxy) propyl-2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 after 10 days, 0/27 after 13 days, 0 / fepo 16 days, 0/53 after 19 days, 0/53 after 22 days metropren (0.1%): 0/0 after 10 days, 18/0 after 13 days, 23/3 after 16 days, 28/3 after 19 days days 28/3 after 22 days.

- antifeodant effects. Coptotermes formosanum (application to Whatman No. 2 chromatography paper in acetone) was used as the test organism. For a 1% solution of 2,2-dimethyl-6- (1-acetoxypropyl) -2H-benzepyropyran in acetone, termites reduce their corrosivity by 82% compared to the termite control group,

2.2-Dimethyl-6- (1-chloroacetoxypropyl) -2H-benzopyran o 78

2,2-dimethyl-6- [2- (4-methylbenzoyloxy) propyl] -2H-benzopyran by 79%.

For a 0.1% solution of 2,2-dimethyl-6- 1- (3-carboxypropionyloxy) propyl -2H-benzopyran in acetone, termites exhibit a reduction in fineness of 78% compared to the termite control group.

Biological effects in Dysdercus cingulatus (comparison with effects of precocene 2):

2,2-dimethyl-6- (1-decanoyloxypropyl) -2H-benzopyran: maximum precocene / antijuvenile effect at 10 g concentration precocene 2: maximum precocene / antijuvenile effect at 10 ¹ g concentration

The biological effect on Varroa jacobsoni Oudemans mites has been tested on bees near Vyšný

Slavkova. The data obtained are given in the table and compared with the reference substance.

Table

Substance Bees live Bees dead Varroa j alive dead (apostate) exceeded I (100 ^ 1) 40 30 2 43 surpassed II (100 pl) 47 3 8 40 compound ob. 98 2 0 33

the formula I ^{(R 1} = C2H5, R ² = (CH 2) _g CH _3,

4

R, R form a double bond) (12.5 µ x 11), contact application

Note: 50 bees were zigzagged at all times, on all Varroa j, otherwise 100 bees were zigzagged, Varroa on at least 30 bees. Contact application: acetone solution evaporator.

Claims (2)

OBJECT OF THE INVENTION CLAIMS 1. 2H-Benzopyran derivatives having an ester bond in a molecule of formula I R -COO-CH ^Z CH ₃ CH, / 1 / Wherein R is alkyl of up to 3 carbon atoms, R is alkyl of up to 3 carbon atoms 19 carbon atoms, haloalkyl of up to 4 carbon atoms, oxoalkyl of up to 6 carbon atoms, phenyl, phenyl substituted with alkyl of up to 4 carbon atoms, halogen, (preferably chlorine or bromine), hydroxycarbonylalkyl of up to 6 carbon atoms R together form a double bond or independently represents an alkoxy group having at most carbon atoms or chlorine or bromine. 2. Process for preparing derivatives of 2H-benzopyran ester linkage in the molecule of the formula I according to claim 1, wherein the symbols R ¹ to R ⁴ are as defined above, wherein the hydroxy compound is reacted of general formula II with an organic acid of formula III in the presence of 4-dimethylaminopyridine and dicyclohexylcarbodiimide at a temperature of 10 to 20 ° C, OH AND R CH, CH ₃ & CH R ² (11) ( ² cooh) (111), respectively, by reaction with the chloride or anhydride of an organic compound in the presence of anhydrous pyridine at 20 to 60 ° C, wherein the general formulas in formulas II and III have the meaning given in point 1.