CS252629B1 - Biologically active halogen-containing 2H-benzopyran derivatives per molecule and method for their preparation - Google Patents

Abstract

The essence of the solution is 2H-benzopyran derivatives containing halogen in the molecule of general formula I where R1 to R3 independently denote an alkyl group with a maximum of 3 carbon atoms, a phenyl group, a phenyl group substituted by a hydroxy group or an alkylcarbonyloxy group with a maximum of 4 carbon atoms in the alkyl, or 7 9 4 5 R and R together form a group =0, R and R denote a halogen or an alkoxy group with a maximum of 6 carbon atoms in such a way that if R4 denotes halogen, R5 denotes an alkoxy group and vice versa. The method of preparing 2H-benzopyran derivatives containing halogen of general formula I consists in the reaction of a 2H-benzopyran derivative of general formula I where the symbols R1 to R3 have the above-mentioned meaning, with an alkanol with a maximum of 6 carbon atoms in the alkyl and N-halosuccinimide at a temperature of 0 to 5 °C.

Description

The invention relates to halogen-containing 2H-benzopyran derivatives in a molecule and to a process for their preparation which appears to be biologically active substances.

The compounds of the present invention cause developmental deviation in insect effect.

The present invention provides halogen-containing 2H-benzopyran derivatives of the formula I.

where

3

R @ 1 to R @ 2 are, independently of one another, an alkyl group having a maximum of 3 carbon atoms, a phenyl group substituted with a hydroxy group or an alkylcarbonyloxy group

3 * with up to 4 carbon atoms in alkyl or R and R together form = O,

R ⁴ and R ⁵ denote halogen or an alkoxy group having a maximum of 6 carbon atoms in such a way that R 11 denotes halogen, R denotes alkoxy and vice versa.

Process for preparing halogen-containing 2H-benzopyran derivatives in a molecule is characterized in that the 2H-benzopyran derivative of the general formula II

where symbols r! to R ^ as defined above is reacted with an alkanol having a maximum of 6 carbon atoms in the alkyl and N-halosuccinimide at a temperature of 0 to 5 ° C.

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

Example

To a solution of 0.32 g (0.0015 mol) of 2,2-dimethyl-6-propionyl-2H-benzopyran in 5 ml of anhydrous methanol was added 0.53 g (0.003 mol) at 0-5 ° C under a dry nitrogen atmosphere. N-bromosuccinimide. The reaction mixture was stirred at this temperature for 15 minutes and then diluted with water and extracted with diethyl ether. The ethereal layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica gel with 8 wt. % water (eluent petroleum ether containing up to 20 vol% diethyl ether).

Chromatography gave 0.3 g (61%) of 2,2-dimethyl-3-bromo-3,4-dihydro-4-methoxy-6-propionyl-2H-benzopyran. IC analysis (CCl ₄ , 3%): 2823 (VC-H in OCH-j), 1686 (VC = O), 1607, 1591, 1491 (V arom.), 1460 (5 _and CH ₃ in OCH ₃ ), 1386, 1371 (δ ' _s CH ₃ ) cm ^-1 .

MS analysis: 326/8 / C ₁₅ H ₁₉ BrO ₃₎ 311/3 (C _g H ₁₄ BrO ₃₎ 297/9 (C ₁₃ H ₁₄ BRC> ₃₎ 265/7 (C ₁₂ H ₁₀ BrO ₂ ), 247 (C ₁₅ H ₁₉ O ₃ ), 231 (C ₁₄ H ₁₅ O ₃ >, 215 (C ₁₄ H ₁₅ O ₂ >, 201 <C ₁₃ H _n O ₂ ), 193 (C _n H ₁₃ O ₃₎ )

192 (C ₁₁ H ₁₂ O _3), 185 (C ₁₂ H _g O _2), 163 (C ^ Og), 73 (C ^ MgO), 57 (C = O).

NMR analysis (CDCl 3 / TMS), δ (ppm): 1.2 t (3H) CH ₃ CH ₂ CO, 1.49 s (3H), 1.60 s (3H) (CH ₃ Cl ₂ , 2.95 q (2H) ) CH _{3 CH,} 3.57 s (3H) OCH, 4.3 d (H), 4.7 d (H) CH, 6.86 to 7.92 m (3H) Ar.

In the same way he was ready

2,2-dimethyl-3-methoxy-3,4-dihydro-4-bromo-6- [dimethyl- (4-acetoxyphenyl)] - methyl-2H-benzopyran; iC analysis (CCl ₄ 3%): 2827 (in CH ₃ in OCH ₃ ), 1767, 1753 (in C = O), 1613, 1588, 1507,

1496 (in arom.), 1467 (δ CH, in OCH,), 1370, 1385 δ „CH,) cm ¹ . MS analysis: 446/8 as I S j (C ₂₃ H ₂₇ BrO ₄₎ 431/3 (C ₂₂ H ₂₄ BrO ₄₎ 404/6 (C ₂₁ H ₂₅ BrO _3), 389/91 (C-I ^ militates) 346/8 (C _1? H ₁₅ BrO ₃₎ 331/3 (C _g H ₁₂ BrO _3), 321 (C-HjjOj), 313 (C ^ H ^ Oj), 255 (C-goy) 135 (C 8 H 6), 73 (C 6 H 6). NMR analysis (CDCl 3 / TMS): 1.44 s, 1.56s (6H) (CH ₃ ) ₂ CO, 1.65s (6H) (C ₃ ) ₂ C-arom., 2.27s (3H) CH 3 COO, 3.43s (3H) OCg ₃ , 4.29d (H), CH-OCH 3, 4.67d (H), CHBr, J = 7.6, 6.69d (Η) arom. with heteroxy, J = 8.6, 6.90-7.05m (3H) aromatic condens. with heterocycle, 2H arom., 7.05-7.25m (3H) aromatic condens. with heterocycle, 2H arom.

and 2,2-dimethyl-3-methoxy-3,4-dihydro-4-bromo-6- [dimethyl- (4-hydroxyphenyl)] methyl-2H-benzopyran;

IC analysis (CCl ₄ , 3%): 3609.3527 (vOH), 2827 (vCH ₃ in OCH ₃ ), 1767, 1722 (in C = O), 1613, 1588, 1507, 1496 (in arom.), 1385, 1370 (6 _g CH _3> cm ^first MS analysis: 404/6 (C ^ H ^ militates) 389/91 (C _2Q H ₂₂ BrO ₃₎ 372/4 (C _{2 ()} H ₂₁ BrO ₂₎ 357/9 (C ₁₉ H ₁₈ BrO _2> 342/4 (C _g H ₁₅ BrO ₂₎ 294 IC HjgOj)

279 (C ₁₈ H ₁₅ O _3), 264 (C _1? H ₁₂ O _3), 263 (C ^ H ^ Oj) 149/51 (^ HgBrO), 83 (C = O).

Biological effects were monitored:

for termites: it was found that the development of soldiers and white soldiers, the influence of castes and the resulting lack of self-sufficiency and colony destruction were found, as well as the 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 for the duration of the experiment, ie about 20 days, for the successful monitoring of the antijuvenile effect, the effect of a high degree of developmental determination on the military caste must first be induced by methoprene or other strong juvenilizing agent. Antijuvenile agents prevent the effect of metoprene or other strong juvenilizing agents, which, depending on the ratio of concentrations of both substances in the system, leads to a reduction in the number of soldiers, or the formation of soldiers is completely prevented. In many cases, transitional forms between soldiers and larvae, the so-called interkasta. 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-3-bromo-3,4-dihydro-4-methoxy-6-propionyl-2H-benzopyran (0.1 wt%) + methoprene (0.1 wt%): 0/0 after 9 days 0/0 after 10 days, 13/0 after 13 days, 13/53 after 15 days, 13/53 after 19 days

2,2-dimethyl-3-methoxy-3,4-dihydro-4-bromo-6- [dimethyl- (4-acetoxyphenyl) methyl] -2H-benzopyran (0.2 wt%): 0/0 to 12 days, 0/0 after 14 days, 0/0 after 16 days comparison with precocene effects:

methoprene (0.1 wt%) + precocene (0.1 wt%): 7/3 after 13 days, 37/3 after 15 days,

43/7 after 17 days, 43/20 after 21 days, 43/20 after 33 days methoprene (0.1 wt%): 0/0 after 9 days, 40/0 after 12 days, 53/0 after 15 days 53/0 after 17 days;

Antifeeding effects:

Coptotermes formosanum was used as a test organism (application to Whatman No. 2 chromatography paper in acetone). For 2,2-dimethyl-3-bromo-3,4-dihydro-4-methoxy-6-propionyl-2H-benzopyran (0.001 wt.%) In acetone, termites reduce the glutenity by 61% compared to termite control groups.

For .2,2-dimethyl-3-methoxy-3,4-dihydro-4-bromo-6- [dimethyl- (4-acetoxyphenyl (methyl) -2H-benzopyran) (0.001 wt%) by 62%.

For 2,2-dimethyl-3-methoxy-3,4-dihydro-4-bromo-6- [dimethyl- (4-hydroxyphenyl) methyl [] - 2H-benzopyran (0.01 wt%) of 60

Claims (2)

SUBJECT OF THE INVENTION Biologically active 2H-benzopyran derivatives comprising in the molecule of the general formula I wherein 1 2 R and R are, independently of time, an alkyl group having a maximum of 3 carbon atoms, a phenyl group, a phenyl group substituted by a hydroxy group or an alkylcarbonyloxy group 2 3 with a maximum of 4 carbon atoms in the alkyl, or R and R together form = O, 4 5 R and R are halogen or alkoxy of up to 6 carbon atoms such that When R is halogen, R is alkoxy and vice versa. t 2. A process for the preparation of halogen-containing 2H-benzopyran derivatives in the molecule of formula (I) according to claim 1, which comprises reacting a 2H-benzopyran derivative of formula (II) wherein: R @ 1 to R @ 2 are as defined above, with an alkanol having a maximum of 6 carbon atoms in the alkyl and N-halosuccinimide at a temperature of 0 to 5 ° C.