RU2015139C1 - Method of synthesis of substituted 2,5-dibenzoyl-1,4-dioxines - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: product: 2,5-dibenzoyl-1,4-dioxines of the general formula

, where R₁=H - H, R₂=C₆H₄OCH_3-n (I); R₁=OCH₃, R₂=CCl₃ (II); R₁=OC₂H₅, R₂=C₆H₄OCH_3-n (III). Reagent 1: dichloroacetone of formula II: n-R₁C₆H₄CCHCl₂. Reagent 2: aldehyde of formula III,

. Reaction conditions: process is carried out at 0-15 C in the medium of tert.-C₄H₉OH in the presence of tert.-С₄H₉OK at molar ratio of components 1:1:(1-2). EFFECT: improved method of synthesis.

Description

(I) где R₁ = H, R₂ = C₆H₄OCH_3-p; R₁ = OCH₃,
R₂ = CCl₃, R₁ = OC₂H₅, R₂ = С₆Н₄ОСН_3-р.The invention relates to a method for producing new 1,4-dioxins of the general formula I

(I) where R ₁ = H, R ₂ = C ₆ H ₄ OCH _3-p ; R ₁ = OCH ₃ ,
R ₂ = CCl ₃ , R ₁ = OC ₂ H ₅ , R ₂ = C ₆ H ₄ OCH _3-p .

 The dioxin structure of which suggests their biological activity and the possibility of using them in medicine.

Known processes for preparing the unsubstituted 1,4-dioxin action system MgI / Mg / B ₂ O at symmetrical tetrahlordioksan [I], dehydrohalogenation of trans-2,5-dihlordioksana in quinoline at ²²⁰ M [2], and by hydrolyzing 2,5- dimethoxydioxane [3].

 There is also known a method for producing 2,5-dimethyl-1,4-dioxin from trans-2,5-bis- (iodomethyl) -1,4-dioxane [4].

 In these methods, unsubstituted 4,4-dioxin and 2,5-dimethyl-1,4-dioxin are obtained from 1,4-dioxane derivatives. These methods require the use of expensive reagents or high temperatures.

 A known method of producing tetraphenyl-1,4-dioxin by condensation of benzoin with methanol, followed by heating the adduct to boiling in acetic anhydride [5].

 The aim of the invention is to develop an affordable method for producing substituted 2,5-dibenzoyl-1,4-dioxins, which cannot be obtained by known methods.

This goal is achieved by the interaction of the corresponding dichloroacetophenes with the corresponding aldehydes in the presence of tert-C ₄ H ₉ OK in t-C ₄ H ₉ OH medium.

The process is as follows. To a mixture of equimolar amounts of the appropriate aldehyde dihloratsetofena and under stirring at 0-15 ^{° C} in an atmosphere of dry argon was slowly added a previously prepared by reacting K tert-C ₄ H ₉ OH solution of tert-C ₄ H ₉ OK in tert-C ₄ H ₉ HE. The mixture was kept at room temperature for another 20 hours. Tert-C ₄ H ₉ OH was removed on a rotary evaporator. An aqueous NaCl solution and sulfuric ether are added to the residue. The part which is not dissolved after thorough shaking is filtered off, washed with distilled water and sulfuric ether. The crystals corresponding to compounds (I-III) are dried in air.

The structure of dioxin (1) is proved by X-ray diffraction analysis (diffractometer "ENRAF-NONIUS CAD-4", 856 reflections with F ² ≥ 3σ, direct method, OLS in the anisotropic approximation, H atoms were detected from difference series of electron density, R = 0.052). The structure of substituted 2,5-dibenzoyldioxins (I-III) is proved on the basis of elemental analysis, 1 H-NMR spectra (Varian T-60 device, 60 MHz operating frequency, TMS internal standard), IR spectra (UR-20 device).

The optimal ratio of dichloroacetophenic reagents: aldehyde: tert-C ₄ H ₉ OK = 1: 1: (1-2).

When using t = C ₄ H ₉ OK in an amount of more than 2 mol, there is the possibility of competing reactions.

The optimal temperature interval by adding a solution of tert-C ₄ H ₉ OK in tert-C ₄ H ₉ OH 0-15 ^o C. At a temperature above 15 ^{° C} may flow competing reactions.

 PRI me R 1. Obtaining 2,5-di (4-methoxyphenyl) -3,6-dibenzoyl-1,4-dioxin (1). The ratio of reagents is 1: 1: 2.

A solution of 3.0 g (0.0384 mol) in 80 mL K tert-C ₄ H ₉ OH are added under stirring in an argon atmosphere at a temperature of 0-15 ^{° C} to a mixture of 5.2 g (0.0384 mole) of anisaldehyde, 7.25 g (0.0384 mol) of dichloroacetophenone. The reaction mixture was kept at room temperature for another 20 hours. T = C ₄ H ₉ OH on a rotary evaporator. 30 ml of an aqueous solution of NaCl and 30 ml of sulfuric ether are added to the residue. Shake well. The insoluble portion is filtered off, washed with water and ether. The crystals are dried in air. Get 5.8 g (60%) with so pl. 194.5-195.5 ^about .

Found,%: C 75.40; H 5.01; C ₃₈ H ₂₄ O ₆ .

 Calculated,%: C 76.17; H 4.80.

): 1,331 (3) (С=С). Конформация гетероцикла плоская.IR spectrum (ν, cm ^-1 , paste in petroleum jelly): 1610 (С = С), 1673 (С = О). PMR spectrum (δ, ppm, CDCl ₃ ): 3.62, 3.63, two overlapping with (2CH ₃ O), 6.31-7.87 m (2 C ₆ H ₄ , 2C ₆ H ₅ ) X-ray analysis data (bond length,

): 1,331 (3) (C = C). The conformation of the heterocycle is flat.

 PRI me R 2. Obtaining 2,5-di (4-methoxybenzoyl) -3,6-bis- (trichloromethyl) -1,4-dioxin (III).

 The ratio of reagents is 1: 1: 1.5.

Compound (II) is obtained analogously to compound (I) in example 1. Yield 52%, mp. 126.5-128.5 ^about S.

Found,%: C 7.67; H 2.59; Cl 30.02
C ₂₄ H ₁₄ Cl ₆ O ₆ .

 Calculated,%: C 47.17; H 2.30; Cl 34.81.

 IR spectrum (ν, cm-1, paste in petroleum jelly): 1600 (С = С), 1660 (С = О).

1 H-NMR spectrum (δ, ppm, CDCl ₃ ): 3.50 s (CH ₃ O), 6.66; 7.56 sq doublets (C (O) C ₆ H ₄ ).

 PRI me R 3. Obtaining 2,5-di (4-ethoxyphenyl) -3,6-di (4-methoxybenzoyl) -1,4-dioxin (III).

 Reagent ratio: 1: 1: 1.

Compound (III) is obtained analogously to compounds (I) and (II) in example 1. Yield 54%. Mp 208-210 ^about C.

 Found,%: C 71.31; H, 5.48.

C ₃₆ H ₃₈ O ₈ .

 Calculated,%: C 72.97; H, 5.41.

IR spectrum (ν, cm ^-1 , paste in petroleum jelly): 1609 (С = С), 1672 (С = О).

1 H-NMR spectrum (δ, ppm, CDCl ₃ ): 1.40 tr (CH ₃ ), 3.66 s (CH ₃ O), 4.00 q (CH ₂ ) 6.56; 6.66 sq doublets (C ₆ H ₄ ), 7.16; 7.77 sq. Doublets (C (O) -C ₆ H ₄ ).

 Thus, this method allows the synthesis of new substituted 2,5-dibenzoyl-1,4-dioxins from the available starting compounds, which can be used in medicine.

Claims (1)

METHOD FOR PRODUCING SUBSTITUTED 2,5-DIBENZOYL-1,4-DIOXINS of the general formula
R

,
where R ₁ is H and R ₂ is C ₆ H ₄ OCH _3-n ;
R ₁ —OCH ₃ and R ₂ —CCl ₃
or R ₁ —OC ₂ H ₅ and R ₂ —C ₆ H ₄ OCH _3-n ,
characterized in that dichloroacetophenone of the general formula
nR ₁ C ₆ H

CHCl ₂ ,
where R ₁ has the indicated meanings,
subjected to interaction with the aldehyde of the General formula
R ₂ C

,
where R ₂ has the indicated meanings,
in the presence of potassium tert-butylate at a molar ratio of components 1: 1: 1 - 2, respectively, and the process is carried out at 0 - 15 ^o C in a medium of tert-butyl alcohol.