RU2557553C1 - Method of obtaining cyclopropylmalonyl peroxide - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to field of chemistry of organic peroxides, namely to method of obtaining cyclopropylmalonyl peroxide (5,6-dioxospiro[2.4]heptane-4,7-dione), representative of class of diacylperoxides, which is widely applied in organic synthesis as selective oxidant. Method of obtaining cyclopropylmalonyl peroxide of formula 1

consists in the fact that cyclopropylmalonic ether is subjected to interaction with clathrate of hydrogen peroxide and carbamide in presence of methanesulphonic acid, with carrying out process with molar ratio cyclopropylmalonic ether : hydrogen peroxide (in form of clathrate of hydrogen peroxide and carbamide) : methanesulphonic acid 1:5-10:20-45 respectively. Process is carried out at room temperature (20-25°C) for 18-24 hours with output from 80 to 90 % of target product.

EFFECT: increase of target product output to 90% in comparison with prototype (77% counted per cyclopropylmalonic acid (II) and 66% counted per cyclopropylmalonic ether (III)), reduction of stages and time, which considerably simplifies the process.

Description

The present invention relates to the field of chemistry of organic peroxides, and specifically to a method for producing cyclopropylmalonyl peroxide (5,6-dioxospiro [2.4] heptane-4,7-dione), a representative of the class of diacyl peroxides, which is widely used in organic synthesis as a selective oxidizing agent.

At present, the possibilities of use and the demand for cyclopropyl malonyl peroxide have significantly increased. Methods have been discovered for stereoselective dihydroxylation of alkenes [(a) M. Schwarz, O. Reiser. // Metal or No Metal: That Is the Question! // Angew. Chem. Int. Ed., 2011, 50, 10495-10497. (b) J.C. Griffith, K.M. Jones, S. Picon, M.J. Rawling, B.M. Kariuki, M. Campbell, N.C.O. Tomkinson \\ Alkene Syn Dihydroxylation with Malonoyl Peroxides \\ J. Am. Chem. Soc, 2010, 132, 14409-14411. (c) S. Picon, M. Rawling, M. Campbell, N. C. O. Tomkinson \\ Alkene Dihydroxylation with Malonoyl Peroxides: Catalysis Using Fluorinated Alcohols \\ Org. Lett., 2012, 14, 6250-6253. (d) K.M. Jones, N.C.O. Tomkinson \\ Metal-Free Dihydroxylation of Alkenes using Cyclobutane Malonoyl Peroxide \\ J. Org. Chem., 2012, 77, 921-928. http://dx.doi.org/10.1021/jo202084w (e) M.J. Rawling, J.H. Rowley, M. Campbell, A.R. Kennedy, J.A. Parkinson, N.C.O. Tomkinson \\ Mechanistic insights into the malonoyl peroxide syn-dihydroxylation of alkenes \\ Chem. SW., 2014, 5, 1777. (f) M.J. Rawling, N.C.O. Tomkinson \\ Metal-free syn-dioxygenation of alkenes \\ Org. Biomol. Chem., 2013, 11, 1434-1440.] And arene hydroxylation [C. Yuan, Y. Liang, T. Hernandez, A. Berriochoa, K.N. Houk, D. Siegel \\ Metal-free oxidation of aromatic carbon-hydrogen bonds through a reverse-rebound mechanism \\ Nature, 2013, 499, 192- 196. DOI: 10.1038 / nature 12284].

The only method known in the literature is the production of cyclopropylmalonyl peroxide (5,6-dioxospiro [2.4] heptane-4,7-dione) (I) by reacting cyclopropylmalonic acid (II) with hydrogen peroxide clathrate and urea in methanesulfonic acid [J.C. Griffth, K.M. Jones, S. Picon, M.J. Rawling, V.M. Kariuki, M. Cambell, N.C.O. Tomkinson \\ Alkene Syn Dihydroxylation with Malonoyl Peroxides \\ J. Am. Chem. Soc., 2010, 132, 14409-14411]. According to this method, cyclopropyl malonic acid (35 mmol) is added to a mixture of hydrogen peroxide clathrate and carbamide (104 mmol) in methanesulfonic acid (30 ml, 462 mmol), after 18 hours the product is isolated in 77% yield based on cyclopropyl malonic acid (II). The molar ratio of the reactants cyclopropyl malonic acid: hydrogen peroxide (in the form of a clathrate of hydrogen peroxide and urea): methanesulfonic acid is 1: 2.97: 13.2, respectively. Cyclopropyl malonic acid (II) is preliminarily obtained through the steps of alkaline hydrolysis of cyclopropyl malonic ester (III) for 60 hours, acidification of the reaction mass, isolation and drying. Based on cyclopropyl malonate ether (III), the yield of cyclopropyl malonyl peroxide (I) was 66%. The disadvantage of this method is the low yield of the target product, multi-stage and the duration of the process, as well as the need for isolation and purification of intermediate products. The process proceeds as follows:

The objective of the present invention is to increase the yield of the target cyclopropyl malonyl peroxide (5,6-dioxospiro [2.4] heptane-4,7-dione) (I) and simplify the technology of its production.

The problem is achieved by the proposed method for producing cyclopropyl malonyl peroxide of the formula I:

by reacting cyclopropyl malonic ester (III) with hydrogen peroxide and urea clathrate in the presence of methanesulfonic acid at a molar ratio of cyclopropyl malon ester (III): hydrogen peroxide (in the form of hydrogen peroxide and urea clathrate): methanesulfonic acid 1: 5-10: 20-45, respectively . The process is carried out at room temperature (20-25 ° C) for 18-24 hours with a yield of 80 to 90% according to the following scheme:

Direct reaction of cyclopropyl malonic ester as a starting compound with hydrogen peroxide and urea clathrate in the presence of methanesulfonic acid and the process at a molar ratio of cyclopropyl malonic ester (III): hydrogen peroxide (in the form of hydrogen peroxide and urea clathrate): methanesulfonic acid 1: 5- 10: 20-45, respectively, allowed not only to simplify the process by reducing the stages of alkaline hydrolysis of cyclopropyl malonate (III), acidification of the reaction mass, isolation and shki tsiklopropilmalonovoy acid (II), but also significantly improve the yield.

It should be noted that the use of cyclopropylmalonic ester (III) directly rather than cyclopropylmalonic acid (II) as the starting compound to obtain the final product was not obvious, since when using, for example, cyclopentylmalonic ester malonyl peroxide is not formed at all (comparative example 5 ) Thus, the invention meets the criterion of "inventive step", since it was not possible to predict in advance that the reaction will be successful, while the yield of the target product will be quite high.

The invention is illustrated by the following examples.

Example 1

Hydrogen peroxide clathrate and urea clathrate (2.53 g, 26.90 mmol, 10 mol per mole of cyclopropyl malonic ester) was added with stirring to methanesulfonic acid (5.17 g, 3.49 ml, 53.80 mmol, 20 mol per mol of cyclopropyl malon ether), the mixture was stirred for 2 minutes. Cyclopropyl malone ether (0.50 g, 2.69 mmol) was added and the mixture was stirred for 24 hours. H ₂ O (30 ml) and ethyl acetate (30 ml) were added, the organic layer was separated, the aqueous was washed with ethyl acetate (4 × 30 ml). The combined organic layers were washed with water H ₂ O (2 × 10 ml), 5% aqueous NaHCO ₃ solution (2 × 10 ml) and again with water H ₂ O (2 × 10 ml), dried over MgSO ₄ . The solvent was removed in vacuo of a water-jet pump. White crystals of cyclopropyl malonyl peroxide were obtained in 80% yield (0.28 g, 2.15 mmol). Лpl. = 89-91 ° C. ¹ H NMR (300.13 MHz, CDCl ₃ , δ): 2.08 (s, 4H). ¹³ C NMR (75.48 MHz, CDCl ₃ , δ): 19.8, 23.6, 172.1.

Example 2

Hydrogen peroxide clathrate and urea clathrate (2.53 g, 26.90 mmol, 10 mol per mole of cyclopropyl malonic ester) was added with stirring to methanesulfonic acid (11.63 g, 7.86 ml, 121.05 mmol, 45 mol per mole of cyclopropyl malonic ether), and the mixture was stirred for 2 minutes. Cyclopropyl malone ether (0.50 g, 2.69 mmol) was added and the mixture was stirred for 24 hours. H ₂ O (30 ml) and ethyl acetate (30 ml) were added, the organic layer was separated, the aqueous was washed with ethyl acetate (4 × 30 ml). The combined organic layers were washed with water H ₂ O (2 × 10 ml), 5% aqueous NaHCO ₃ solution (2 × 10 ml) and again with water H ₂ O (2 × 10 ml), dried over MgSO ₄ . The solvent was removed in vacuo of a water-jet pump. White crystals of cyclopropyl malonyl peroxide were obtained in 88% yield (0.30 g, 2.37 mmol). Лpl. = 89-91 ° C. ¹ H NMR (300.13 MHz, CDCl ₃ , δ): 2.08 (s, 4H). ¹³ C NMR (75.48 MHz, CDCl ₃ , δ): 19.8, 23.6, 172.1.

Example 3

Hydrogen peroxide clathrate and urea clathrate (2.53 g, 26.90 mmol, 10 mol per mole of cyclopropyl malonic ester) was added with stirring to methanesulfonic acid (7.76 g, 5.24 ml, 80.70 mmol, 30 mol per mole of cyclopropyl malon ether), and the mixture was stirred for 2 minutes. Cyclopropyl malone ether (0.50 g, 2.69 mmol) was added and the mixture was stirred for 18 hours. H ₂ O (30 ml) and ethyl acetate (30 ml) were added, the organic layer was separated, the aqueous was washed with ethyl acetate (4 × 30 ml). The combined organic layers were washed with water H ₂ O (2 × 10 ml), 5% aqueous NaHCO ₃ solution (2 × 10 ml) and again with water H ₂ O (2 × 10 ml), dried over MgSO ₄ . The solvent was removed in vacuo of a water-jet pump. White crystals of cyclopropyl malonyl peroxide were obtained in 90% yield (0.31 g, 2.42 mmol). Лpl. = 89-91 ° C. ¹ H NMR (300.13 MHz, CDCl ₃ , δ): 2.08 (s, 4H). ¹³ C NMR (75.48 MHz, CDCl ₃ , δ): 19.8, 23.6, 172.1.

Example 4

To methanesulfonic acid (7.76 g, 5.24 ml, 80.70 mmol, 30 mol per mole of cyclopropyl malone ether), hydrogen peroxide clathrate and urea clathrate (1.27 g, 13.45 mmol, 5 mol per mole of cyclopropyl malone ether) were added with stirring, the mixture was stirred for 2 minutes. Cyclopropyl malone ether (0.50 g, 2.69 mmol) was added and the mixture was stirred for 24 hours. H ₂ O (30 ml) and ethyl acetate (30 ml) were added, the organic layer was separated, the aqueous was washed with ethyl acetate (4 × 30 ml). The combined organic layers were washed with water H ₂ O (2 × 10 ml), 5% aqueous NaHCO ₃ solution (2 × 10 ml) and again with water H ₂ O (2 × 10 ml), dried over MgSO ₄ . The solvent was removed in vacuo of a water-jet pump. White crystals of cyclopropyl malonyl peroxide were obtained in 84% yield (0.29 g, 2.26 mmol). Лpl. = 89-91 ° C. ¹ H NMR (300.13 MHz, CDCl ₃ , δ): 2.08 (s, 4H). ¹³ C NMR (75.48 MHz, CDCL ₃ , δ): 19.8, 23.6, 172.1.

Example 5. (Comparative)

To methanesulfonic acid (4.48 g, 3.02 ml, 46.60 mmol, 20 mol per mole of cyclopentyl malonic ester), hydrogen peroxide clathrate and urea clathrate (2.19 g, 23.30 mmol, 10 mol per mole of cyclopentyl malonic ether) were added with stirring, the mixture was stirred for 2 minutes. Cyclopentyl malone ether (0.50 g, 2.33 mmol) was added and the mixture was stirred for 24 hours. H ₂ O (30 ml) and ethyl acetate (30 ml) were added, the organic layer was separated, the aqueous was washed with ethyl acetate (4 × 30 ml). The combined organic layers were washed with water H ₂ O (2 × 10 ml), 5% aqueous NaHCO ₃ solution (2 × 10 ml) and again with water H ₂ O (2 × 10 ml), dried over MgSO ₄ . The solvent was removed in vacuo of a water-jet pump. 0.48 g of a clear oil was obtained. Analysis by H ¹ and C ¹³ NMR spectroscopy showed that the isolated oil was the starting cyclopentyl malone ether with a purity of 90%.

The technical result of the invention is to increase the yield of the target product up to 90%, in contrast to the prototype (77% based on cyclopropyl malonic acid (II) and 66% based on cyclopropyl malonic acid (III)), reducing stages and time, which greatly simplifies the process and makes it inexpensive and affordable for laboratory and industrial applications.

Claims (1)

A method of producing cyclopropylmalonyl peroxide of the formula:

consisting in the fact that cyclopropyl malonic ester is reacted with a clathrate of hydrogen peroxide and urea in the presence of methanesulfonic acid and the process is carried out with a molar ratio of cyclopropyl malonic ester: hydrogen peroxide (in the form of clathrate of hydrogen peroxide and urea): methanesulfonic acid 1: 5-10: 20- 45 respectively.