CS252601B1 - 2h-benzopyran's biologically efficient derivatives and method of their preparation - Google Patents

Description

The present invention relates to 2H-benzopyran derivatives and processes for their preparation which appear to be biologically active substances.

Physiological effects other than those that cause juvenile hormones and their natural and synthetic analogues in the life cycle of insects should be exploited to combat insect pests. This includes, but is not limited to, an anti-hormonal effect, such as an anti-immuno-hormonal effect (W. S. Bowers, T. Ohta, J. S. Cleere, P. A. Marsella, Science 193,

542 (1976), K. Slama, Acta entomol. 75, 65, 1978), on juvenile hormone antagonist activity (GB staal, CA Henrick, BJ Bergot, CD Cerf, JP Hdwards, SJ Krame, Regulation of Insect Development and Behavior, Karpacz, 1980), further on avicidal, sterilizing activity , interference effect in embryogenesis (A. Dorn, Regulation of Insect Development and Behavior, Karpacz, 1980, GB Staal. Ent. Expt. and Appl. 31, 15, 1982) and the like.

Several types of compounds with the above biological properties have been prepared synthetically (W. S. Bowers, Proc. Pontifical Academy of Science 41, 129, 1977), F. Camps,

J. Coli, A. Messenguer, J. M. Moreto, M. A. Pericas, Tetrahedron Letters' 3091 (1979), J. Heterocyclic Chem. 17, 207 (1980), G. T. Brooks, A. F. Hammett, R. C. Jennings, A. P. Ottridge, G. Ei Pratt, Proo. British Crop Protection Conference, Vol. I, 273, 1979, D. M. Soderlund, A. Messeguer, W. S. Bowers, J. Agric. Food Chem. 28, 724 (1980); R. C. Jennings, A.

P. Ottridge, Chem. Commun. 920, 1979, T. Ohta, W. S. Bowers, Chem. Pharm. Bull., 25, 788 (1977).

Substances which cause developmental deviation in their effect in harmful insects in one of the above-mentioned areas and thus promise practical application in this context include the 2-H benzopyran derivatives according to the invention. The biological properties of some of them are enhanced by the relative availability and relatively low cost of the raw materials used.

The present invention provides derivatives

2H-benzopyran of formula I

(I) r ³ wherein R ³ and R ^{3 are} each independently hydrogen, alkyl of up to 3 carbon atoms, alkenyl or alkylidene of up to 5 carbon atoms, alkoxy of up to 4 carbon atoms, alkoxyalkoxy of up to 4 carbon atoms, alkoxycarbonyl of up to 4 carbon atoms in alkyl, hydroxy, phenyl, phenyl substituted with alkyl of up to 4 carbon atoms, alkylcarbonyloxy of up to 4 carbon atoms in alkyl or hydroxy,

Or R and R together form = O, = NOR, where R is hydrogen, alkyl of up to 8 carbon atoms, = NOCOR, wherein R is alkyl of up to 19 carbon atoms, wherein R ⁴ is hydrogen, hydroxy , alkoxy having a maximum of 4 carbon atoms.

The present invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives of formula (I), characterized in that sodium or potassium phenolate of formula (II) is reacted.

R ³ where R ³ to R ⁴ are as defined above, M denotes sodium or potassium, with 3-bromo-3-methyl-1-butine in anhydrous dimethylformamide at 60 to 70 ° C for 2 hours and then at at a temperature of 15-25 ° C for 12 hours to give the ether of formula III

R ³ ✓ CH,

I ³

0 — C-C = CH (III)

CH ₃ wherein R ³ to R ⁴ are as defined above and is heated in Ν, Ν-diethylaniline or Ν, Ν-dimethylaniline to reflux for 3-4 hours to give the 2H-benzopyran derivative of the general formula IV

(IV) wherein R ³ and R ⁴ are as defined above.

The present invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives of formula I wherein R ¹ , R ⁴ are as defined above, R ² is hydroxy, R ³ is hydrogen, wherein compound IV, wherein R ¹ , R ⁴ R ² and R ³ form = O, react with lithium aluminum hydride in anhydrous diethyl ether.

The present invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives of the formula I wherein R ¹ , R ⁴ are as defined above, R ² and R ^{3 are} alkylidene,

Wherein R is hydrogen, R is hydrogen, under catalysis with para-toluenesulfonic acid in benzene to reflux.

The invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives

Wherein R, R are as defined above, R and R form = NOR, wherein

14

R is as defined above, wherein Compound IV wherein R, R are as defined above

3, R and R form a = O group, react with hydroxylamine hydrochloride in the presence of sodium hydroxide in 96% ethanol, and then optionally react with sodium hydride and an alkyl halide wherein the alkyl is a straight or branched chain of at most

With carbon compounds optionally with XCOR compounds wherein R ° denotes straight and branched chain alkyl of up to 19 carbon atoms, X denotes chlorine or bromine.

The present invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives of the general formula I, wherein R, is as defined above, R znač is OR ?, where R? has

14 as defined above, R denotes hydrogen wherein Compound IV, wherein R, R, and R are as defined above

3, R is hydroxy, R is hydrogen, reacts at -10 ° C with phosphorus tribromide in the presence of anhydrous pyridine and then with sodium alkanolate, where the alkyl is a straight or branched chain of up to 4 carbon atoms, optionally with alkoxyalkanolate sodium, wherein the alkoxyalkyl is a straight or branched chain of up to 4 carbon atoms at a temperature of 15 to 25 ° C.

The invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives

In formula (I) wherein R, R are as defined above, R is OR wherein R is a group

14

-CH (CH ₃ ) OC ₂ H ₅ , where R is hydrogen, wherein compound IV, wherein R, R are as defined above, R 1 is hydroxy, R 1 is hydrogen, is reacted with ethyl vinyl ether to catalyze para-acid toluene sulfone at a temperature of 10 to 20 ° C.

The present invention further provides a process for the preparation of biologically active 2H-benzopyran derivatives of formula I wherein R1 is phenyl substituted by C1-4 alkyl having 4 to 4 carbon atoms, R @ ^{1 to} R @ 2 are as defined above, wherein R is denotes phenyl substituted by hydroxy, until R1 is as defined above, reacted with an organic acid chloride having a total carbon number of up to 5 in the presence of anhydrous potassium carbonate or an organic acid anhydride with a total carbon number of up to 5 in the presence of pyridine at 10-20 ° C.

The invention is further illustrated by the following examples without being limited thereto.

He did

To a solution of 1.5 g (0.01 mol) of 4-hydroxypropiophenone in 10 ml of anhydrous dimethylformamide was first added 0.56 g (0.01 mol) of powdered potassium hydroxide and, after dissolution, 1.47 g (0.01 mol) 3-bromo-3-methyl-1-butyne.

The reaction mixture was heated at 60-70 ° C for 2 hours and then allowed to stand overnight at 15-20 ° C. After dilution with water, it was extracted with diethyl ether. The ether layer residue dried over anhydrous magnesium sulfate was separated by chromatography on a silica gel (60-120 yum) column with 8 wt. A mixture of petroleum ether-diethyl ether and a maximum of 20% by volume diethyl ether was used as eluent.

Chromatographically pure 4- (1,1-dimethyl-2-propynyloxy) propiophenone (mp 76-78 ° C) (1.1 g? 0.005 mol) was then dissolved in 10 ml of Ν, Ν-diethylaniline and heated under reflux. with a reflux condenser for 3 to 4 hours.

The reaction mixture was then diluted with diethyl ether, washed with 2N H ₂ SO ₄ , water and saturated brine. After drying of the ether layer and evaporation of diethyl ether, the residue was purified by column chromatography on silica gel (eluent of diethyl ether-diethyl ether with a maximum of 20% by volume of diethyl ether) with a final total yield of 51% 2,2-dimethyl-6-propionyl-2H-benzopyran (bt 138). -141 ° C).

* · ****

4- (1,1-Dimethyl-2-propynyloxy) propiophenone: elemental analysis was consistent with the calculated values in the range of - 0.3%. IR analysis (3%, CCl2): 3307 (pC = CH), 2110 (1C = C), 1687 (VC = O) _/ 1600, 1576, 1505 (Varom.), 1384, 1366 (d _with CH) ₃ g) cm ^-1 . MS analysis: 216 (C ₁₄ H ₂ O _g)

201 (C ₁₃ H ₁₃ O ₂ ), 187 (C ₁₂ H ₁₁ O ₂ ), 159 (C ₁₃ H ₁₃ O ₂ ), 150 (C ₉ H ₁₃ O ₂ ), 121 (C ₁₃ H ₁₃ O ₂ ), 93 (C 0 H 12 O), 67 (C 8 H 11). NMR analysis (CDCl ₃ / TMS), ppm (delta): 1.15 t (3H) CH ₃ CH ₂ , 1.45 s (3H), 1.66 s (3H) (CH ₃ ) ₂ C,

2.57 s (H) C = CH, 2.92 q (2H) CH ₂ CH _3, 6.98 to 7.92 m (4H) Ar.

2,2-dimethyl-6-propionyl-2H-benzopyran: elemental analysis was in agreement with the calculated values. φ 0.3%, IR analysis (3%): 1685 (4 C = O 1, 1642 (V C = C), 1604, 1571, 1488, 1432 (Varom.), 1385, 1379, 1368, 1364 (tf _with CH) cm cm ^-1 MS analysis: 216 (C ₁₁ H ₁₁ O ₂ ), 201 (C ₁₃ H ₁₃ O ₂ ), 187 (C ₁₂ H ₁₁ O ₂ ), 159 (C ₁₁ H ₁₁ O 2), 144 (C ₁₁ H ₁₃ O ₂ ), 115 (C ₁₃ H ₁₃ O ₂ ) C (H ₃ O), 91 (0 → 0).

1.16 t (3H) CH ₃ CH ₂ , 1.40s (6H) (CH ₃ > ₂ C, 2.86 q (2H) CH ₃ CH ₂ , 5.64 d (H) CH =, 6.36 (H) d, CH = 6.80 to

7.75 m (3 H) ar.

In the same way they were prepared:

4- (1,1-dimethyl-2-propynyloxy) benzophenone and 2,2-dimethyl-6-benzoyl-2H-benzopyran therefrom

1,1-dimethyl-1- (4-phenylmethyl) phenoxy-2-propyne and 2,2-dimethyl-6-benzyl-2H-benzopyran therefrom

4- [Dimethyl-4- (1,1-dimethyl-2-propinoxy) phenyl] methylphenol and 2,2-dimethyl-6- [dlmethyl- (4-hydroxyphenyl)] methyl-2H-benzopyran methyl ester 4- ( 1,1-dimethyl-2-propynyloxy) benzoic acid and 2,2-dimethyl-6-methoxycarbonyl-2H-benzopyran

2-hydroxy-4- (1,1-dimethyl-2-propinoxypropiophenone and 2,2-dimethyl-5-hydroxy-6-propionyl-2H-benzopyran)

2-methoxy-4- (1,1-dimethyl-2-propinoxy) propiophenone and therefrom 2,2-dimethyl-5-methoxy-6-propionyl-2H-benzopyran.

Analytical data:

4- (1, l-dimethyl-2-propinoxy) benzophenone: MS analysis: 264 ^(c JGH ₃ MgO _2), 249 (C ₃₇ H ₃₃ O _2),

198 (C ₁₀ H ₁₃ O ₂ ), 159 (C ₁₁ H ₁₁ O), 149 (C ₉ H ₈ Cl 2), 121 (C ₉ H ₈ O ₃ ), 105 (C 6 O 10), 77 (C 0 H)

2,2-dimethyl-6-benzoyl-2H-benzopyran: IR analysis (4%): 1662 ([deg.] C. = O), 1643 (MC = C), 1602, 1577, 1496, 1489, 1447 (arom.), 1386, 1367 (</ _s CH ₃ ) cm ^-1 . MS analysis 264 (C ₁₇ H ₁₃ O ₂ ), 249 '(C ₁₇ H ₁₃ O ₂ ), 163 (C ₁₀ H ₁₁ O ₂ ), 134 (C ₉ H ₁₀ O), 120 (Οθ 13θΟ), 106 (C ₇ H ₈ O) 77 (CGH _5>

1.1-dimethyl-1- (4-phenylmethyl) phenoxy-2-propyne: IR analysis (4%): 3312 (JC = CH), 3294 (VC = CH asoc.), 2920, 2845 (1) CH ₂ ), 1613, 1586, 1513, 1498 (\) arom.), 1381, 1365 (<ΗθΗ ₃ ) cm ^-1 . MS analysis: 250 (C ₁₈ H _g O), 235 (Ο _{17 Η} χ5 Ο), 184 (C ₁₃ H ₁₂ O), 159 (C ^ JO), 106 (C ₇ HgO), 91 (C ₇ H ₇ >,

77 (CgHg), 67 (C _{5 H?)}

2.2-dimethyl-6-benzyl-2H-benzopyran: IR analysis (4%): 1640 ([nu] C-C), 1605, 1582, 1509,

1494, 1456 (V arom.), 1384, 1362 (J _with CH ₃ ) cm ^-1 . MS analysis: 250 (C ₁₈ H ₁₈ O), 235 (C ₁₇ H ₁₅ O), 144 (C ₁₀ H ₆ O), 115 (C ₉ H ₃ O), 91 (C ₇ H ₇ ), 77 (C ₉ H ₅ ). NMR analysis: 1.37 s (6H), (CH ₃ > ₂ C, 3.84 s (2H) Ar-CH ₂ -Ar, 5.54 d (H) CH =, 6.26 d (H) CH = 6.68-7.23 m (8H), arom.

4- [dimethyl- (1,1-dimethyl-2-propynyloxy) phenyl] methylphenol: IC analysis (3%): 3305 (vC = CH), 1612, 1595, 1511, 1493 (9 arom.), 1383, 1363 , 1360 (<Γ _θ ΟΗ ₃ ) cm ^-1 . MS analysis: 294 (C2QH22O2), 279 (C19HlgO2) 228 ^<C 15 ^H 16 ° _2> ^{<213 (c} i3 i4 ^H ° ^{2) '77 <C} 6 ^H 5>' 67 (^ 0)

2,2-dimethyl-6- [dimethyl- (4-hydroxyphenyl)] methyl-2H-benzopyran: IR analysis (3%): 3609 (9 OH), 3410 (V OH bond), 1640 (9 C = C) ), 1613, 1595, 1512, 1493 (9 arom.), 1383, 1368, 1360 ((£ _s CH ₃ ) cm ^-1 . MS analysis: 294 (C ₂₀ H ₂₂ O ₂ ), 279 (C ₁₉ H _{1 g).} O _2), 263 _(g C _g H O), 135 (C _g H ₁₁ O). NMR analysis: 1.37 s (6H) _{(CH3) 2} C, 1.56 s (6H) Ar-C (CH 2), - Ar, 4.97 s (H) OH 4- (1,1-dimethyl-2-propynyloxy) benzoic acid methyl ester: MS analysis 218 (C 1 H 6 H 2 O 3), 203 (C ₁₂ H ₁₁ O _3), 187 (C ₁₂ H ₁₁ O _2), 159 ICJ ^ O), 152 (C ₈ H _g O _3), 121 (C ₇ H ₅ O ₂₎ 93 (0 ^ 0), 67 (d). IR analysis (3%) 3300 (9 = CH), 2837 (9C-H _OCH3), 1721 (9 C = O ester.), 1608, 1577, 1489,

1442 (9 arom.), 1463 (J CH in OCH), 1383, 1368 (d CH, gem.), 1288, 1273 (9 C-O ester) cm ^-1 .

2,2-dimethyl-6-methoxycarbonyl-2H-benzopyran: IR analysis (3%): 1724 (7C = O) ester.), 1643 (9C = C), 1610, 1581, 1493 (9arom.), 1384 , 1368 (J _with CH ₃ gem.), 1289, 1275 (9C-O ester.) Cm ^-1 . MS analysis: 218 (C ₁₃ H ₁₄ O _3), 203 (C ₁₂ H _U O _3), 187 (C ^ H ^ p, 159 (C ^ H ^), 144 (Ci ΗθΟ) 115 (C _g H ₃ O)

2-propionyl-5- (1,1-dimethyl-2-propinoxy) phenol: IR analysis (4%): 3310 (7 C = CH), 3292 (VC = CH asoc.), 2950 (7 OH chelate), 2117 (7C = C), 1637 (VC = O chelate), 1583, 1503 (7 arom.), 1377, 1369 (cm ^@ _{3 with} CH3) cm ^@ -1. MS analysis: 232 (C14HlgO3), 217 (Ο13Ηχ3Ο3), 203 (C? H. ^^ 199 ^(C 13 ^H 11 ° 2>^'175 (C11 ^H 110 _2), 166 (C _g H ₁₀ O ₃₎ 135 _(C? H ₅ O _3). NMR analysis: 1.22 t (3H) CHjCHj, 1.71 s (6H) _{(CH3) 2} C, 2.65 s (H) C = CH, 2.94 q (2H) CH ₃ CH _{2 (} 6.65 d (H), Ar, 6.78 s (H) Ar, 7.65 d (H) Ar

2,2-dimethyl-5-hydroxy-6-propionyl-2H-benzopyran: IR analysis (4%): 2940 (7 OH chelate), 1643 (90 = 0, 1628 (9 C = O chelate), 1613, 1582, 1489 (9 arom.), 1392, 1379, 1364 (<1CH ₃ ) cm ^-1 MS analysis: 232 (C ₁₃ H ₁₅ O ₃ ), 217 (Ο ₁₃ Η _{χ 3} Ο ₃ ), 203 (Ο ₁₂ Η _1χ) Ο ₃ ), 199 (C ₁₃ H _n O ₂ ), 160 (C _g H ₄ O ₃ ),

NMR analysis: 1.17 t (3H) CH 3 CH 3. 1.40 s (6 H) (CH 3), C, 2.88 q (2H) CH, CH 3, 5.53 d (H) CH =, 6.29 d (H), Ar, 6.70 d (H) CH =, 7.50 d (H), Ar, 13.05 s (H) OH

2-methoxy-4- (1,1-dimethyl-2-propinoxy) propiophenone: IR analysis (4%): 3307 (7C = CH),

3289 (7 CSCH Asoc.), 2839 (v CH of _OCH3>, 2120 (VC = C), 1675 (7 C = O), 1603, 1576, 1498 (7 arom.),

1466 (dCH, vOCH,), 1384, 1365 (</ CH,), 1268 (9 C-0 in Ar-OCH,), 1038 (9C-0 in OCH,) cm ^-1 and 3 3 S 3 3 3

2,2-dimethyl-5-methoxy-6-propionyl-2H-benzopyran: IR analysis (4%): 2842 (7 CH in OCH3), 1674 (9C = O), 1642 (VC = C), 1612 , 1597, 1570, 1495 (V arom.), 1466 (J _ag vOCHj _CH3), 1384,

1360 _(CI CH _3), 1286, 1272 (C-9 in ArOCHj 0), 1020 (C-0 9 OCHjIcm in ^{the first}

Example 2

A solution of 0.32 g (0.0015 mol) of 2,2-dimethyl-6-propionyl-2H-benzopyran in 5 ml of anhydrous diethyl ether was added dropwise to a suspension of 40 mg of hydride at 10-20 ° C with stirring and in the absence of atmospheric humidity. of lithium aluminum in 10 ml of anhydrous diethyl ether.

The reaction mixture was then heated to reflux for 30 minutes. After cooling with ice and water and diluting with diethyl ether, unreacted ice water, precipitated aluminum hydroxide, with 10% aqueous H ₂ SO 4 solution was decomposed with stirring.

The separated ether layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The obtained residue was then separated by column chromatography on silica gel with 8 wt. % water (eluent petroleum ether-diethyl ether containing up to 50% by volume diethyl ether) to give 0.28 g (86%) of chromatographically pure 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran.

Elemental analysis was in agreement with the calculated values in the range of - 0.3%. IR ana252601 lysis (4%) i 3618 (gOH), 3480 (in OH bond), 1640 (VC = O), 1614, 1580, 1491 (line), 1375, 1361 (<< _s CH ₃ ) cm ^-1 . MS analysis: 218 ( ^C 14 H ₁₈ O ₂ ), 203 (C ₁₃ H ₁₅ O ₂ ), 200 (C ₁₄ H ₁₆ O), 189 (C ₁₂ H ₁₃ O ₂ ), 185 (C ₁₃ H ₁₃ O). NMR analysis: 0.66 t (3H) CH 3 CH 3, 1.39 s (6 H) (CH 3 J 3 C, 1.72 m (2H) CH 3 CH 3, 4.46 t (H) CHOH, 5.57 d (H) CH =, 6.30 d (H) CH =, 6.71-7.03 m (3H) ArH.

Example 3

To a solution of 0.11 g (0.0005 mol) of 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran in 5 ml of ethyl vinyl ether was added a catalytic amount of para-toluenesulfonic acid and then stirred at 15 to 20 ° C. 20 ° C for 30 minutes. After diluting the reaction mixture with 10% aqueous NaHCO 3, extracting the mixture with diethyl ether, drying and evaporating the ether layer, the residue was chromatographed on a 8 wt. % water eluting with petroleum ether containing up to 20 vol% diethyl ether.

Chromatographic homogeneous fractions gave, after combining and evaporating the eluent, 0.1 g (69%).

2,2-dimethyl-6- [1- (1-ethoxy) ethoxy] propyl-2H-benzopyran. Elemental analysis was in agreement with the calculated values in the range of - 0.3%. IR analysis (3%): 1640 (9 C = C), 1612, 1579,

1489 (v arom.), 1394, 1384, 1376, 1361 (/,.0^) cm ^-1.

MS analysis: 290 (C ₁₈ H _{2 g} 0 _3), 275 (C _1? H ₂₃ O _3), 217 (C ₁₄ H ₁₇ O _2), 201 (C ₁₄ H ₁₇ O), 189 (C ₁₂ H ₁₃ O ₂ ),

73 (C ₄ H _g O) 45 (C ₂ H ₅ O).

Example 4

To a solution of 0.11 g (0.0005 mol) of 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran in 15 ml of petroleum ether was added dropwise a solution of 0, with stirring at -10 ° C in the absence of atmospheric humidity. 4 g (0.015 mol) of phosphorus tribromide in 10 ml of petroleum ether. Then the reaction mixture was poured on ice with water, the petroleum ether layer was separated and washed with saturated aqueous NaHCO 3 solution and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was dissolved in 5 ml of anhydrous methanol.

A solution of 11 mg of sodium in 5 ml of anhydrous methanol was added with stirring at 10 to 20 ° C. After standing for one hour, water was carefully added to the reaction mixture and the reaction product was extracted with diethyl ether.

The washed, dried and evaporated ether layer was separated on 8 wt. % Water by column chromatography (eluting with petroleum ether containing up to 20% by volume diethyl ether). 0.05 g (42%) of 2,2-dimethyl-6- (1-methoxypropyl) -2H-benzopyran was obtained. Elemental analysis was consistent with the calculated values in the range of - 0.3%.

IR analysis (4%): 2824 (EF CH vOCHj), 1651, 1643 (VC = C), 1614, 1591, 1490 (V arom.), 1465 (TI _as CH _3), 1384, 1374, 1361 (J. _with CH ₃ ) cm ^-1 . MS analysis: 232 _(Ο χ5 Η 2θ Ο _2), 217 (C ^ _Hj? O _2), 203 (C ₁₃ H ₁₅ O _2), 185 (C ₁₃ H ₁₃ O), 171 (C ₁₂ H ₁₁ O) .

NMR analysis: 0.80 t (3H) CH ₃ CH ₂ , 1.36 s (6H). (CH ₃ ) ₂ C, 1.64 m (2H) CH ₃ CH ₂ , 3.15 s (3 H) OCH ₃ , 3.86 t (H) CHOCH ₃ , 5.57 d (H) CH =, 6 32 d (H) CH =, 6.87-7.01 m (3U) ArH.

Example 5

A mixture of 0.44 g (0.0015 mol) of 2,2-dimethyl-6- [dimethyl- (4-hydroxyphenyl)] methyl-2H-benzopyran, 0.14 g of anhydrous pyridine and 1 g of acetic anhydride was left at 10- 20 ° C overnight. Then the reaction mixture was diluted with saturated NaHCO 3 solution and extracted with diethyl ether. The dried ether layer residue was separated on an 8 wt. % water (eluent petroleum ether containing up to 20 vol% diethyl ether).

0.38 g (75%) of 2,2-dimethyl-6- [dimethyl- (4-acetoxyphenyl)] methyl-2H-benzopyran was obtained. Elemental analysis was consistent with the calculated values in the range of - 0.3%. IC analysis (4%): 1768, 1757 (V C = O), 1642 (γ C = C), 1607, 1506, 1494 (var.), 1384, 1369, 1362 (<f _with CH ₃ ), 1210 (V C) -O ester.) Cm ^-1 .

MS analysis: 336 (C ₂₂ H ₂₄ O _3), 321 _(Ο 2χ Η ₂₁ Ο _3), 279 (C ₁₉ H _g O)), 263 (C _g H _g O), 144 (0 _1θ Η _θ Ο) , 115 (C 8 H 10). NMR analysis: 1.36 s (6H), (Cg ₃ ) ₂ C, 1.59 s (6H) Ar (CH ₃ ) ₂ C-Ar, 2.23 s (3H), CH 3 COO, 5.54 d (H) CH =, 6.25 d (H) CH =, 6.63-7.31 m (7H) ArH.

Example 6

A solution of 0.21 g (0.001 mol) of 2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran in anhydrous benzene was heated to reflux for 20 minutes in the presence of 1 mg of para-toluenesulfonic acid. After benzene was distilled off under reduced pressure, the residue was diluted with saturated NaHCO 3 solution and extracted with diethyl ether.

Chromatography of the residue of the dried ether layer on an 8 wt. % water (petroleum ether eluent containing up to 10 vol% diethyl ether) gave 0.14 g (70%) of 2,2-dimethyl-6- (1-propenyl) -2H-benzopyran.

Elemental analysis was consistent with the calculated values in the range of - 0.3%. IR analysis (4%): 1652, 1643 (VC = C), 1611, 1507, 1491 (V arom.), 1383, 1369, 1362 (<T _{S CH3)} cm ^-1.

MS analysis: 200 (C ₁₄ H _g O), 185 (C? H? O), 115 (C _g H ₃ O) 91 (C _g H ₃ O) NMR Analysis: 1.41 s (6H), (CH ₃ ) ₂ C, 1.82 d (3H) CH ₃ CH =, 5.56 d (H), CH =, 6.30 ιη (Η), ' ₍ αΗ = 6.68-7.06 m) (3 H) ArH.

Example 7

To a solution of 0.84 g (0.004 mol) of 2,2-dimethyl-6-propionyl-2H-benzopyran in 20 ml of 96% ethanol was added 0.37 g of finely powdered sodium hydroxide with stirring at 15-20 ° C and after dissolution 1.9 g of hydroxylamine hydrochloride. Everything was allowed to stand at this temperature overnight.

Then, most of the ethanol was removed from the reaction mixture by vacuum distillation and the residue was partitioned between a saturated solution of NaHCO ₃ in water and diethyl ether. After washing, drying and evaporation of the ether layer, the residue was separated by column chromatography on silica gel with 8 wt. % water (eluent petroleum ether containing up to 50 vol% diethyl ether). 0.65 g (70%) of 2,2-dimethyl-6- (1-hydroxyiminopropyl) -2H-benzopyran was obtained (mp 117-119 ° C).

Elemental analysis was in accordance with calculated values in the range of 0.3% ·. IR analysis (3%): 3598 (OH), 3 * 290, 3240 (V OH dimer, trimmer), 1641 (VC = N + OC = C), 1607, 1574, 1494 (V arom), 1383, 1375, 1362 (cfgCHg), 947 (V NO) cm ^-1 . MS analysis: 231 (Ο ₁₄ Η ₁ ΝΟ ΝΟ ₂ ), 216 (C ₁₃ H ₁₄ NO ₂ >, 170 (C ₁ H ₆ NO), 144 ( _{θ 1θ θ θ,} ), 116 (C ₈ H ₃ O). : 1.11 t (3H) CH ₃ CH ₂ , 1.40 s (6H) (CH ₃ ) ₂ C,

2.74 q (2H) CH ₃ CH ₂ , 5.59 d (H) CH =, 6.33 d (H) CH =, 6.75-7.36 m (3H) ArH, 8.93, 8 88 bs (H) = NOH.

Example 8

To a solution of 0.11 g (0.0005 mol) of 2,2-dimethyl-6- (1-hydroxyiminopropyl) -2H-benzopyran in 5 ml of anhydrous dimethylformamide was added 12 mg of sodium hydride with stirring at 15-20 ° C. After gas evolution had ceased, 71 mg of methyl iodide was added to the reaction mixture at the same temperature and allowed to stand overnight. After diluting the reaction mixture with water and extracting with diethyl ether, the residue of the washed and dried ether layer was further separated by column chromatography (silica gel with 8 wt% water, eluent petroleum ether containing up to 20 vol% diethyl ether).

0.07 g (57%) of 2,2-dimethyl-6- (1-methoxyiminopropyl) -2H-benzopyran was obtained. Elemental analysis was in accordance with the calculated values in the range of 0.3%. IR Analysis: 2819 (rfgC-H in OCH 3), 1643, 1651 (V C = C), 1614, 1494 (V arom.), 1465 (J _and CH _{3 in} OCH ₃ ), 1382, 1362, 1367 (</ _S CH ₃₎ ) cm ¹ . MS analysis: 245 (C ₁₅ H NO _{2 g),} 230 (C ₁₄ H NO _{2 g),} 170 (C-HgNO) 144 _{(0 1 () Η} θ 0).

Γ '

NMR analysis: 0.97 t (3H) CH ₃ CH ₂ C = N, 1.29 s (6H) (CH ₃ ) ₂ C, 2.59 q (2H) CH ₃ CH ₂ C = N, 3.8 s (3H) = NOCH ₃ , 5.47 d (H) CH =, 6.24 d (H) CH =, 6.65-7.27 m (3H), ArH.

Example 9

To a solution prepared from 0.11 g (0.0005 mol) of 2,2-dimethyl-6- (1-hydroxyiminopropyl) -2H-benzopyran, 12 mg of sodium hydride and 5 ml of anhydrous dimethylformamide was stirred at a temperature of 83 mg of octanoic acid chloride was added at 15-25 ° C and allowed to stand at the same temperature overnight. The reaction mixture was diluted with water and extracted with diethyl ether.

The residue of the washed and dried ether layer was further separated by column chromatography on silica gel with 8 wt. % water (eluent: petroleum ether containing up to 30 vol% diethyl ether). 0.1 g (56%) of 2,2-dimethyl-6- (1-octanoyloxyiminopropyl) -2H-benzopyran was obtained.

The elemental analysis was in agreement with the calculated values even in the range of 0.3%. XC analysis (4%): 1759 ([nu] C-O), 1644, 1653 ([nu] C-C), 1613 ([nu] C-N), 1613, 1596, 1496 (arom.), 1377,

1367 (tf _with CH ₃ ) cm ^-1 .

MS analysis: 357 (C ₂₂ H ₃₁ NO _3), 342 (C ₂₁ H _{2 g} NO _3), 231 (C ₁₄ H _1? NO _2), 216 (C ₁₃ H ₁₄ NO _2), 201 ^(C 12 ^H 11 ^NO 2 ^{) 170} ( ^{c 11 H} aNO), 144 (C ₆ H ₁₆ O). NMR analysis: 0.82 t (3 H) (CH ₃ ) CH ₂ ) _g , 1.11 t (3 H) CH ₃ CH _{2 (} C = N, 1.25 m) 10 H) (CH 2 CH 3), 2.44 t (2H) CH ₃ CH ₂ CO, 2.73 q) 2H) CH ₃ CH ₂ C = N, 5.60 d (H)

CH =, 6.33 d (H) CH =, 6.76-7.50 m (2H) ArH.

Examples of biological effects: were investigated for termites:

- influencing the development of soldiers and white soldiers, overall slowdown in development. Prorhinotermes simplex (Whatman # 1 chromatography paper, in acetone) was used as the test organism. In laboratory colonies of non-test insects for the duration of the experiment, ie approx. 20 days, the effect of a high degree of developmental determination on the military caste must first be induced by a methoprene or other strong juvenilizing agent to successfully monitor the antijuvenile effect. Antijuvenile agents then prevent the effect of metoprene or other strong juvenilizing agents, which, depending on the ratio of concentrations of both substances in the system, reduce the number of soldiers, or the formation of soldiers is completely prevented. In many cases, transitional individuals between soldiers and larvae, so-called intercaasts. 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-hydroxypropyl) -2H-benzopyran (0.1%): 0/0 after 9 days, 0/0 after 12 days, 0/0 after 20 days

2.2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 after 9 days, 0/35 after 12 days, 5/40 after 20 days

2.2-Dimethyl-6- (1-hydroxyiminopropyl) -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-hydroxyiminopropyl) -2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 after 9 days, 25/0 after 12 days, 25/10 after 15 days , 25/15 after 20 days

2.2-dimethyl-6-propionyl-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-propionyl-2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 after 9 days, 0/35 after 12 days, 5/35 after 15 days, 10/40 after 20 days

2.2-Dimethyl-5-methoxy-6-propionyl-2H-benzopyran (0.1%) + methoprene (Ό, 5%): 0/0 ρο 9 days, 0/0 ρο 20 days

2.2-Dimethyl-5-hydroxy-6-propionyl-2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 ρο 9 days, 0/0 ρο 20 days

2,2-dimethyl-6- (1-propenyl) -2H-benzopyran (0,4%) + methoprene (0,1% ϊ: 0/0 ρο 10 days),

7/7 ρο 13 days, 20/13 ρο 16 days, 27/33 ρο 19 days metroprene (0.1%): 0/0 ρο 10 days, 18/0 ρο 13 days, 23/3 ρο 16 days, 28 / 3 ρο 19 days

2.2-dimethyl-6- (1-octanoyloxyiminopropyl) -2H-benzopyran (0.2%): 0/0 after 9 days, 0/0 after 13 days, 0/0 after 17 days

2.2-dimethyl-6- (1-octanoyloxyiminopropyl) -2H-benzopyran (0.2%) + methoprene (0.7%): 0/0 after 9 days, 0/7 after 13 days, 0/20 after 15 days , 0/20 after 17 days

2,2 ”dimethyl-6- (1-methoxypropyl) -2H-benzopyran- (0,2%): 0/0 after 9 days, 0/0 after 13 days,

0/0 after 15 days, 0/0 after 17 days

2.2-dimethyl-6- (1-methoxypropyl) -2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 after 9 days,

0/27 after 13 days, 13/47 * after 15 days, 13/73 after 17 days

2.2-Dimethyl-6- (1-methoxyiminopropyl) -2H-benzopyran (0.2%): 0/0 after 9 days, 0/0 after 17 days

2.2-dimethyl-6- (1-methoxyiminopropyl) -2H-benzopyran (0.2%) + methoprene (0.1%): 0/0 after 9 days, 7/13 after 13 days, 7/53 after 15 days , 7/67 after 17 days

2.2-Dimethyl-6- [1- (1-ethoxy) ethoxy] propyl-2H-benzopyran (0.2%): 0/0 after 9 days, 0/0 after 17 days

2,2-Dimethyl-6- (1-ethoxy) ethoxy] propyl-2H-benzopyran (0,1%) + methoprene (0,1%):

0/0 after 9 days, 0/13 after 13 days, 0/47 after 15 days, 0/47 after 17 days

2,2-dimethyl-6-methoxycarbonyl-2H-benzopyran (0,2%): 0/0 after 9 days, 0/0 after 17 days

2.2-dimethyl-6-methoxycarbonyl-2H-benzopyran (0.1%) + methoprene (0.1%): 0/0 after 9 days,

0/0 after 10 days, 0/7 after 13 days, 0/7 after 15 days, 0/13 after 17 days

- Antifeedant effects.

Coptotermes formosanum (application to Whatman # 2 chromatography paper in acetone) was used as the test organism. For 2,2-dimethyl-6- (1-methoxypropal) -2H-benzopyran (0.1%) in acetone, termites reduce 69% of voraciousness for 2,2-dimethyl-6- [1- (1-ethoxy) ethoxy] propyl-2H-benzopyran (1%) by 66%

- (1-methoxyiminopropyl) -2H-benzopyran (0.1%) by 37% for 2,2-dimethyl-6- (1-octanoyloxyiminopropyl) -2H-benzopyran (1%) by 42% for 2,2-dimethyl -6- (1-propenyl) -2H-benzopyran (0.01%) by 100% for 2,2-dimethyl-6-propionyl-2H-benzopyran (1%) by 83% for 2,2-dimethyl-6 - (1-hydroxypropyl) -2H-benzopyran (1%) by 76% for 2,2-dimethyl-6- [dimethyl- (4-hydroxyphenyl) methyl-2H-benzopyran (1%) by 99,5% for 2 2-dimethyl-6- [dimethyl- (4-acetoxyphenyl) methyl-2H-benzopyran (0.1%) by 94%.

In the bug Pyrrhocoris apterus: activity evaluated on the basis of inhibition of metamorphosis, expressed in micrograms per insect, inducing inter252601 10 mediated forms for topical application:

2,2-dimethyl-6-benzoyl-2H-benzopyran and 2,2-dimethyl-6-benzyl-2H-benzopyran and 2,2-dimethyl-6- (4-methylbenzoyl) -2H-benzopyran = 1

U Musea domestica (10) ig) freshly hatched imaginations:

for 2,2-dimethyl-6-propionyl-2H-benzopyran: reduction in egg hatching by 23%,

2,2-dimethyl-6- (1-hydroxypropyl) -2H-benzopyran and 2,2-dimethyl-6- (1-hydroxyimino-propyl) -2H-benzopyran o 11 for 2,2-dimethyl-5-hydroxy- 6-propionyl-2H-benzopyran by 40% compared to control experiments.

Claims (8)

SUBJECT OF THE INVENTION Biologically active 2H-benzopyran derivatives of the general formula I X 3 * wherein R to R are each independently hydrogen, alkyl of up to 3 carbon atoms, alkenyl or alkylidene of up to 5 carbon atoms, alkoxy of up to 4 carbon atoms, alkoxyalkoxy of up to 4 carbon atoms, alkoxycarbonyl of up to 4 carbon atoms in alkyl, hydroxy, phenyl, phenyl substituted with alkyl of up to 4 carbon atoms, alkylcarbonyloxy of up to 4 carbon atoms in alkyl, or hydroxy, 2 3 7 7 or R and R together form = O, = NOR where R is hydrogen, an alkyl group having at most g Q 4 carbon atoms, = NOCOR, where R is an alkyl group having a maximum of 19 carbon atoms and R ⁴ is hydrogen, hydroxy, alkoxy of up to 4 carbon atoms. 2. A method for preparing the biologically active derivatives of 2H-benzopyran of the formula I according to claim 1, wherein R ^1, R ⁴ are as defined above, ^R2 and ^R3 form = 0, characterized by reacting a sodium or potassium phenolate of the formula II R ³ where R ³ to R ⁴ are as defined above, M is sodium or potassium, with an equimolar amount of 3-bromo-3-methyl-1-butine in anhydrous dimethylformamide at 60 to 70 ° C for 2 hours and then at 15 to 20 ° C for 10 hours to give an ether of formula III (III) wherein R ⁴ , R ⁴ are as defined above, R ² and R ³ form a bond = 0 and this is heated in N, N-diethylaniline, optionally Ν, Ν-dimethylaniline to reflux for 3 to 4 hours. 3. A method for preparing the biologically active derivatives of 2H-benzopyran of the formula I according to claim 1, wherein R ⁴ and R ⁴ have the abovementioned meaning, R @ ² represents OH, R ³ is hydrogen, wherein the 2H-benzopyran derivative of formula IV wherein R ⁴ , R ⁴ are as defined above, R ² and R ³ form a bond = O, reacted with lithium aluminum hydride in anhydrous diethyl ether. 4. A process for the preparation of biologically active 2H-benzopyran derivatives of the general formula I according to claim 1 14 2 3 (1), wherein R, R are as defined above, R and R are alkylidene, characterized in that the 2H-benzopyran derivative of formula (IV), wherein R, R is as defined above, 2 3 R is hydroxy, R is hydrogen, heated to reflux with catalysis of paratoluenesulfonic acid in benzene. 5. A process for the preparation of biologically active 2H-benzopyran derivatives of the general formula I according to item 1, wherein R ⁴ , R ⁴ are as defined above, R ² and R ³ form a bond = NO ² , wherein R ² is as defined above. wherein the 2H-benzopyran derivative of formula IV wherein R ⁴ , R ⁴ is as defined above, R ² and R ³ form a bond = O, reacted with hydroxylamine hydrochloride in the presence of sodium hydroxide in 96% ethanol, then reacting the resulting compound optionally with sodium hydride and an alkyl halide wherein the alkyl is equal to or branched chain of up to 4 carbon atoms, optionally with XCOR compounds, wherein R represents both straight and branched chain alkyl of up to 19 carbon atoms, X represents chlorine or bromine. 6. A process for the preparation of biologically active 2H-benzopyran derivatives of the general formula I according to item 1, wherein R 1 is as defined above, represents an OR? R is hydrogen, characterized in that the 2H-benzopyran derivative of the general formula IV, wherein R ⁴ , R ⁴ are as defined above, R ² is hydroxy, R ³ is hydrogen, is left at -10 ° C to react with phosphorus tribromide in the presence of anhydrous pyridine and then with sodium alkanolate, where alkyl is straight or branched chain of up to 4 carbon atoms, optionally with sodium alkoxyalkanolate, where alkoxyalkyl is straight or branched chain of up to 4 carbon atoms, at 15 to 25 ° C. 7. A process for the preparation of biologically active 2H-benzopyran derivatives of the general formula I according to claim 1 1 4 2 7 7 point 1, wherein R, R are as defined above, R is OR, where R is -CH (CH 2) OC 4 H 8, where R ³ is hydrogen, characterized in that the 2H-benzopyran derivative of the general formula of formula IV wherein R ⁴ , R ⁴ are as defined above, R ² is hydroxy, R ³ is hydrogen is reacted with ethyl vinyl ether under catalysis of para-toluenesulfonic acid at a temperature of 10 to 20 ° C. 8. A process for the preparation of biologically active 2H-benzopyran derivatives of the general formula I according to claim 1, wherein R ^{@ 4} denotes a phenyl group substituted by an alkylcarbonyloxy group having up to 4 carbon atoms in the alkyl and R ^{@ 2} to R ^{@ 4.} a benzopyran derivative of the formula IV, wherein R ⁴ is a hydroxy-substituted phenyl group and R ² to R ⁴ are as defined above, with an organic acid chloride having a total carbon number of up to 5 in the presence of anhydrous potassium carbonate or an organic acid anhydride with a total carbon number in a molecule of at most 5 in the presence of anhydrous pyridine at a temperature of 10 to 20 ° C.