RU2269505C1 - Method of preparing macrocycles with alternate alka-1z,5z-diene fragments - Google Patents

Abstract

FIELD: organic synthesis.

SUBSTANCE: invention proposes synthesis of novel macrocycles with alternate alka-1Z,5Z-diene fragments having general formula 1:

where R represents (CH₂)₄, (CH₂)₅, or (CH₂)₆ and n = 3-5, which synthesis comprises reaction of α,ω-diallenes of general formula =•=-R-=•=, wherein R is as above, with ethylmagnesium bromide and magnesium powder at molar ratio 10:(10-14):(5-7), respectively, in presence of titanacene dichloride (Cp₂TiCl₂) catalyst used in amount 0.3-0.7 mmol per 1 mole α,ω-diallene. Reaction proceeds in tetrahydrofurane under nitrogen atmosphere at ambient temperature during 8-12 h. Macrocycles may find use in synthesis of biologically active compounds as well as in perfume industry.

EFFECT: expanded synthetic possibilities in macrocycle chemistry.

1 tbl, 11 ex

Description

The present invention relates to methods for producing new unsaturated cyclooligomeric hydrocarbons, and specifically to a method for producing macrocycles with alternating alka-1Z, 5Z-diene fragments of the general formula (1):

где R=(CH₂)₄, (CH₂)₅, (CH₂)₆; n=3-5

where R = (CH ₂ ) ₄ , (CH ₂ ) ₅ , (CH ₂ ) ₆ ; n = 3-5

The proposed compounds can be used in the synthesis of biologically active preparations for medicine and animal husbandry, as well as the perfume industry.

The known method (G.A. Tolstikov, U.M. Dzhemilev, S.S. Shavanov. On the issue of obtaining cyclotetramers of butadiene on complex nickel catalysts // Izv. AN SSSR, Ser. Chem., 1975, No. 11, C. 2624) obtaining cyclooligomers of butadiene (2-4) under the action of low-valent Ni complexes stabilized by triphenylphosphite in the presence of disubstituted acetylene according to the scheme:

The known method does not allow to obtain macrocycles (1) with alternating alka-1Z, 5Z-diene fragments.

A known method (UMDzhemilev, VAD'yakonov, LOKhaflzova, AGIbragimov. Cyclo- and carbomagnesiation of 1,2-dienes catalyzed by Zr complexes // Tetrahedron, 2004, V.60, p.1287) to obtain linear dimers of 1,2-dienes ( 5) with cis-disubstituted double bonds by the reaction of terminal allens (R- = • =) with ethylmagnesium bromide (EtMgBr) in the presence of magnesium (Mg, powder) and a titanocene dichloride catalyst (Cp ₂ TiCl ₂ ) followed by hydrolysis of the reaction mass according to the scheme:

In a known manner, macrocycles (1) with alternating alka-1Z, 5Z-diene fragments cannot be obtained.

Thus, in the literature there is no information on the stereoselective preparation of macrocycles (1) with alternating alka-1Z, 5Z-diene fragments.

A new method is proposed for producing macrocycles (1) with alternating alka-1Z, 5Z-diene fragments.

The essence of the method consists in the interaction of α, ω-diallenes of the general formula = • = -R- = • =, where R = (CH ₂ ) ₄ , (CH ₂ ) ₅ , (CH ₂ ) ₆ , with ethyl magnesium bromide (EtMgBr) and magnesium (Mg, powder), taken in the ratio = • = -R- = • =: EtMgBrMg = 10: (10-14) :( 5-7) mmoles, preferably 10: 12: 6 mmoles, in the presence of a titanocene dichloride catalyst (Cp ₂ TiCl ₂ ), taken in an amount of 0.3-0.7 mmol with respect to α, ω-diallen, preferably 0.5 mmol, in an argon atmosphere at room temperature (~ 20 ° C) and normal pressure in tetrahydrofuran (THF ) with subsequent hydrolysis of the reaction mass. The reaction time is 8-12 hours, preferably 10 hours. The total yield of macrocycles (1) with alternating alka-1Z, 5Z-diene fragments is 77-98%. The reaction proceeds according to the scheme:

R = (CH ₂ ) ₄ , (CH ₂ ) ₅ , (CH ₂ ) ₆ ; n = 3-5

Macrocycles (1) with alternating alka-1Z, 5Z-diene fragments are formed only with the participation of α, ω-diallenes (= • = -R- = • =), EtMgBr, and Cp ₂ TiCl ₂ catalyst. In the presence of other organomagnesium compounds (e.g., amides, alkoxides, magnesium acetylenides), other unsaturated compounds (olefins, acetylenes) or another catalyst (e.g., TiCl ₄ , FeCl ₃ , Fe (acac) ₃ , CoCl ₂ , PdCl ₂ , Pd ( acac) ₂ , NiCl ₂ , Ni (acac) ₂ , ZrCl ₄ ) target products (1) are not formed.

Carrying out this reaction in the presence of a catalyst Cp ₂ TiCl ₂ more than 7 mol.% In relation to α, ω-diallen does not lead to a significant increase in the yield of target products (1). The use of the catalyst Cp ₂ TiCl ₂ less than 3 mol% with respect to α, ω-diallen reduces the yield of macrocycles (1), which is possibly associated with a decrease in catalytically active centers in the reaction mass. The reactions were carried out at a temperature of ~ 20 ° C. At a higher temperature (for example, 40 ° C), there is no significant increase in the yield of the target products (1), and at a lower temperature (for example, 0 ° C), the reaction rate decreases.

A change in the ratio of the starting reagents in the direction of increasing the EtMgBr content with respect to the initial α, ω-diallen does not lead to a significant increase in the yield of the target products (1).

Reactions were carried out using tetrahydrofuran as a solvent. In other solvents (for example, aliphatic or aromatic), the reaction does not proceed.

Significant differences of the proposed method:

1. In the proposed method, α, ω-diallenes (= • = -R- = • =) are used as starting compounds, and in the known method, terminal allens (R- = • =).

The proposed method has the following advantages:

1. The method allows to obtain with high stereoselectivity macrocycles (1) with alternating alka-1Z, 5Z-diene fragments, the synthesis of which is not described in the literature.

The method is illustrated by the following examples:

EXAMPLE 1. In a 50 ml glass reactor mounted on a magnetic stirrer, in an argon atmosphere, 12 mmoles of freshly prepared EtMgBr in THF, 6 mg-at. Mg (powder), at a temperature of -5 ° C, 10 mmol of 1,2,9,10-undecatetraene and 0.5 mmol of Cr ₂ TiCl ₂ are stirred for 10 hours at room temperature (~ 20 ° C), the reaction mass is hydrolyzed 5- 8% HCl solution. Get macrocycles with alternating undeca-1Z, 5Z-diene fragments (1) with a yield of 88%.

Spectral characteristics of macrocycles with alternating undeca-1Z, 5Z-diene fragments (1):

¹ H NMR spectrum (CDCl ₃ , δ, ppm) of cyclooligomeric undec-1,5-diene (6): 1.17-1.46 (m, CH ₂ at C ⁸ , C ⁹ , C ¹⁰ ), 1.75-2.20 ( m, CH ₂ at C ³ , C ⁴ , C ⁷ , C ¹¹ ), 5.20-5.40 (m, CH, olefin). ¹³ C NMR spectrum (CDCl ₃ , δ, ppm): 130.30 (C ¹ , C ⁶ ), 129.20 (C ² , C ⁵ ), 27.18 (C ³ , C ⁴ ), 27.34 (C ⁷ , C ¹¹ ), 29.66 (C ⁸ , C ⁹ , C ¹⁰ ). IR spectrum (ν, cm ^-1 ): 730, 910, 1360, 1460, 1630, 2840, 2920.

Other examples confirming the method are given in table 1.

Table 1 №№ Starting α, ω-diallen,
= • = -R- = • = Molar ratio
= • = -R- = • =: EtMgBrMg: Cp ₂ TiCl ₂ Reaction time, hour Yield (1),% one 2 3 four 5 one.

1,2,9,10-ундекатетраен

1,2,9,10-undecatatetraen 10: 12: 6: 0.5 10 88 2. - ″ - 10: 14: 6: 0.5 10 92 3. - ″ - 10: 10: 6: 0.5 10 81 four. - ″ - 10: 12: 6: 0.5 10 89 5. - ″ - 10: 12: 5: 0.5 10 83 6. - ″ - 10: 12: 5: 0.7 10 98 7. - ″ - 10: 12: 6: 0.3 10 77 8. - ″ - 10: 12: 6: 0.5 12 95 9. - ″ - 10: 12: 6: 0.5 8 79 10.

1,2,8,9-decatetraen 10: 12: 6: 0.5 10 90 eleven.

1,2,10,11-dodecatetraen 10: 12: 6: 0.5 10 85

Reactions were carried out at room temperature (~ 20-21 ° C) in THF. The number of alternating alka-1Z, 5Z-diene fragments in all experiments is n = 3-5.

Claims (1)

A method of obtaining macrocycles with alternating alka-1Z, 5Z-diene fragments of the general formula (1):

where R = (CH ₂ ) ₄ , (CH ₂ ) ₅ , (CH ₂ ) ₆ , n = 3-5 consisting in the fact that α, ω-diallenes of the general formula = • = -R- = • =, where R = (CH ₂ ) ₄ , (CH ₂ ) ₅ , (CH ₂ ) ₆ , interact with ethyl magnesium bromide (EtMgBr) and magnesium (powder) in a molar ratio = • -R- = • =: EtMgBr: Mg, equal to 10: (10-14) :( 5-7), in the presence of a titanacenedichloride catalyst (Cp ₂ TiCl ₂ ), taken in an amount of 0 , 3-0.7 mmol with respect to α, ω-diallen, in THF in an argon atmosphere at room temperature (~ 20 ° C) for 8-12 hours