KR20100039554A - Oxidation method of benzylic alcohols with urea-hydrogen peroxide and catalytic magnesium bromide - Google Patents

Abstract

PURPOSE: A method for manufacturing benzaldehyde or benzyl ketone is provided to prepare benzaldehyde or benzyl ketone at a high yield using environment-friendly urea-hydrogen peroxide and a reaction instead of conventional toxic organic solvent and oxidizer. CONSTITUTION: A method for manufacturing benzaldehyde or benzyl ketone comprises a step for oxidizing a first benzyl alcohol or a second benzyl alcohol with urea-hydrogen peroxide catalytically using magnesium bromide (MgBr2) under an ionic liquid. The first benzyl alcohol is selected from PhCH2OH, p-CH3C6H4CH2OH, p-FC6H4CH2OH, p-ClC6H4CH2OH, p-BrC6H4CH2OH, p-H3COC6H4CH2OH, p-NO2C6H4CH2OH, p-CF3C6H4CH2OH, 1-naphthalenemethanol, p-HOC6H4CH2OH, and p-CNC6H4CH2OH.

Description

Oxidation Method of Benzylic Alcohols with Urea-Hydrogen Peroxide and Catalytic Magnesium Bromide

The present invention relates to a process for producing benzyl aldehyde or benzyl ketone by oxidizing primary benzyl alcohol or secondary benzyl alcohol.

Oxidation of alcohols to the corresponding aldehydes and ketones is one of the most basic conversions in organic synthesis. Usually, the oxidation of benzyl alcohol is known as chromium trioxide (VI) (Hajipour, AR; Mallakpour, SE; Khoee, S. Synlett 2000 , 740), nitric acid (Strazzolini, P .; Runcio, A, Eur. J. Org. Chem. 2003 526), Dimethylsulfoxide / HBr (Li, C .; Xu, Y .; Lu, M .; Zhao, Z .; Liu, L.;, Zhao Z .; Cui, Y. Zheng, P .; Ji ., X .; Gao, G Synlett 2002, 2041), and (hypervalent) compounds of hypervalent iodine (Surendra, K .; Krishnaveni, NS ; Reddy, MA; Nageswar, YVD;. Rao, KR J. Org Chem. 2003 , 68 , 2058).

In recent years, there has been a great need to replace conventional toxic oxidants with more environmentally friendly chemicals in organic reactions. Compared to other reagents, hydrogen peroxide is an inexpensive and readily available oxidizing agent, so it is regarded as the most preferable oxidizing agent in terms of the environment. Various methods have been reported for hydrogen peroxide to enhance the oxidation of benzyl alcohol. Representative examples include active agents such as sodium tungstate (Chhikara, BS; Chandra, R .; Tandon, V. Synlett 2005 , 872) or the strong acid HBr (Jiang, N .; Ragauskas, AJ Tetrahedron Lett. 2005 , 46 , 3323) . Hydrogen peroxide with activator is used to oxidize benzyl alcohol. However, the unstable nature of liquid hydrogen peroxide has limited its use in substantial oxidation reactions. In recent years, instead of unstable concentrated hydrogen peroxide, urea-hydrogen peroxide (UHP) has emerged as a stable substitute because of its practical properties such as high stability, high hydrogen peroxide content and easy accessibility (Gonsalves, AMR; Johnstone). , RAW; Pereira, MM; Shaw, J. J. Chem Res., Synop. 1991 , 208). Urea-hydrogen peroxide is the epoxidation of olefins (Fan, CL; Lee, WD; Teng, NW; Sun, YC; Chen, K. J. Org. Chem. 2003 , 68 , 9816), sulfide sulfide ) (Balicki, R. Synth Commun. 1999 , 29 , 2235), oxidation of aromatic aldehydes to benzoic acid (Heaney, H .; Newbold, AJ Tetrahedron Lett. 2001 , 42 , 6607), and It has been used in various organic reactions, including oxidative halogenation of arene (Zienlinska, A .; Skulski, L. Tetrahedron Lett. 2004 , 45 , 1087). But, rather, because of the high stability of the UHP, the oxidation reaction is hexafluoro-2-propanol (hexafluoro-2-propanol) ( Legros, J .; Crousse, B .; Bonnet-Delpon, D .; Begue, JP. Eur J. Org. Chem. 2002 , 3290), methyl trioxorhenium (MTO) (Adam, W .; Mitchell, CM; Angew. Chem. Int. Ed. Engl. 1996 , 35 , 533) and It had to be carried out in the presence of a strong active agent such as formic acid. In addition, these reactions usually require the use of large excess UHP molarity. In addition, in some cases, unusual electromagnetic radiation and solvent-free reaction techniques were required (Paul, S .; Nanda, P .; Gupta, R. Synlett , 2004 , 531; (15) Varma, RS; Naicker, KP). Org. Lett. 1999 , 1 , 189).

Although a huge number of conversions have already been reported using UHP enhancement, in our present knowledge, oxidation of benzyl alcohol to aldehydes or ketones has only been made so far in the presence of Amberlite IRA-120 acidic resins. Only one example has been reported (Bhati, N .; Sarma, K .; Goswami, A. Chem. Lett. 2008 , 37 , 496). However, the process produced only oxidized carbonyl group compounds as a minor product over the range of 17-32% and basically produced phenol as the major product.

On the other hand, over the past decades, ionic liquids have attracted much attention because of their excellent solvent properties and expensive solvent properties as well as environmentally friendly properties. Ionic liquids are attractive environmentally friendly materials that replace toxic volatile organic solvents.

Therefore, while the present inventors are studying the oxidation method of alcohol using more environmentally friendly materials, by using the catalytic amount of magnesium bromide in the ionic liquid, and using urea-hydrogen peroxide as the oxidizing agent, various benzyl alcohols can be effectively oxidized. The present invention has been completed by confirming that it can.

It is an object of the present invention to provide a method for oxidizing benzyl alcohol using environmentally friendly materials.

In order to solve the above problems, the present invention uses magnesium bromide (MgBr ₂ ) under an ionic liquid as a primary benzyl alcohol or secondary benzyl alcohol as urea-hydrogen peroxide (UHP). To oxidize to provide benzyl aldehyde or benzyl ketone.

In the following, the present invention more specifically presents the general use of UHP in the oxidation of substituted benzyl alcohols.

The present invention utilizes urea-hydrogen peroxide in the presence of a catalytic amount of magnesium bromide to efficiently oxidize primary and secondary benzyl alcohols to the corresponding aromatic aldehydes and ketones. The reaction mechanism of the present invention can be represented by the scheme shown in FIG.

In the method for preparing benzyl aldehyde or benzyl ketone of the present invention, the primary benzyl alcohol is PhCH ₂ OH, p -CH ₃ C ₆ H ₄ CH ₂ OH, p -FC ₆ H ₄ CH ₂ OH, p -ClC ₆ H ₄ CH ₂ OH, p -BrC ₆ H ₄ CH ₂ OH, p -H ₃ COC ₆ H ₄ CH ₂ OH, p -NO ₂ C ₆ H ₄ CH ₂ OH, p -CF ₃ C ₆ H ₄ CH ₂ Preferred is an alcohol selected from the group consisting of OH, 1-naphthalenemethanol, p- HOC ₆ H ₄ CH ₂ OH and p- CNC ₆ H ₄ CH ₂ OH, wherein the secondary benzyl alcohol is PhCH (OH) CH ₃ , p -CH ₃ C ₆ H ₄ CH (OH) CH ₃ , p -FC ₆ H ₄ CH (OH) CH ₃ , p -ClC ₆ H ₄ CH (OH) CH ₃ , p -BrC ₆ H ₄ CH (OH) CH ₃ , PhCH (OH) Et, PhCH (OH) Ph, PhCH (OH) COPh, PhCH (OH) COOMe, PhCH (OH) COOEt, p- NO ₂ C ₆ H ₄ CH (OH) CH ₃ , is _{p -HOC 6 H 4 CH (OH} ) CH 3 and _{p -CNC 6 H 4 CH (OH} ) of an alcohol selected from the group of CH ₃ are preferred.

In the method for preparing benzyl aldehyde or benzyl ketone of the present invention, the ionic liquid is 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim] BF ₄ ), 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim] BF ₄ ) , 1-ethyl-3-methylimidazolium methylsulfate ([emim] MS), 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] PF ₆ ), 1-butyl-3-methylimidazolium methylsulfate ([bmim] MS) and 1-hexyl It is preferred that it is an ionic liquid selected from the group consisting of -3-methylimidazolium hexafluorophosphate ([hmim] PF ₆ ).

In the method for preparing benzyl aldehyde or benzyl ketone of the present invention, the urea-hydrogen peroxide is preferably 20 to 100 parts by weight of hydrogen peroxide relative to 100 parts by weight of urea, and the magnesium bromide is 0.01 to 0.2 equivalents based on 1 equivalent of UHP. And benzyl alcohol is preferably 0.1 to 5 equivalents.

In the method for producing benzyl aldehyde or benzyl ketone of the present invention, the oxidation reaction of the benzyl alcohol is preferably reacted for 1 to 4 hours at 40 ~ 80 ℃.

In the method for producing benzyl aldehyde or benzyl ketone of the present invention, it is preferable to go through the step of producing pure benzyl aldehyde or benzyl ketone through the organic extraction and separation and purification process after the oxidation reaction.

The present inventors found that magnesium bromide (0.1 equivalent) of 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim] BF ₄ ) at 60 ° C. for 2-3 hours. The reaction of UHP (1.2 equiv) and benzyl alcohol in the presence confirmed that the only observable product in all cases provided the corresponding aldehyde or ketone. The oxidation was successfully carried out by the above procedure over a wide range of structurally diverse primary and secondary benzyl alcohols, giving the corresponding carbonyl group compounds (see Table 1).

In the oxidation of the benzyl alcohol of the present invention, the use of 0.1 equivalents of magnesium bromide yields the desired oxidation product in sufficiently high yields. In the absence of magnesium bromide no oxidation reaction is observed. For example, the inventors obtained much lower yields of magnesium bromide when using other metal halides such as magnesium chloride, magnesium iodide, cupric bromide, sodium bromide instead of MgBr ₂ .

Substituents which deplete electrons on the aromatic ring did not significantly affect the efficiency of the reaction. However, strong electron depriving groups such as nitro groups gave somewhat lower yields (see number 7 in Table 1). Primary benzyl alcohol did not undergo peroxidation under the present reaction conditions. Acid-sensitive methoxy and ester functional groups (see Nos. 6, 18 and 19 in Table 1) remained to a lesser extent at present reaction conditions. Oxidation of diphenylmethanol, benzoin, and α-hydroxy esters readily produced benzophenone, benzyl, and α-keto esters, respectively (see numbers 16, 17, 18, and 19 of Table 1). . However, the application of the present invention to aliphatic alcohols provided a complex reaction mixture. This reaction is probably due to the mechanism of action for the production of phenols in alcohol using previously known UHP and Amberlite IR-120 resins (Bhati, N .; Sarma, K .; Goswami, A. Chem. Lett. 2008 , 37 , 496). Similarly, after organo hydroperoxide reaction intermediate formation, it is estimated that carbonyl compounds were produced via dehydration of this intermediate.

In summary, the present invention using UHP in the presence of magnesium bromide in ionic liquids demonstrates a novel and efficient protocol for the oxidation of benzyl alcohol to carbonyl group compounds. Environmentally friendly procedures that avoid the use of toxic reagents and harmful organic solvents during this reaction are useful and practical alternatives to conventional methods for the oxidation of benzyl alcohol and enable wider applications.

As described above, the present invention can produce benzyl aldehyde or benzyl ketone in high yield while using environmentally friendly urea-hydrogen peroxide and reaction conditions instead of the conventional toxic organic solvent and oxidizing agent, and thus, in the conventional method for the oxidation of benzyl alcohol. It is a useful and practical alternative to this and broader applications are possible.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are only for illustrating the present invention, and the present invention is not limited to the following examples and may be changed to other embodiments equivalent to substitutions and equivalents without departing from the technical spirit of the present invention. Will be apparent to those of ordinary skill in the art.

Example 1 General Procedure

The general experimental procedure for the oxidation of benzyl alcohol is as follows.

Benzyl alcohol in 1 ml ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim] BF ₄ ; purchased from C-TRI Co.), at room temperature. MgBr ₂ (0.018 g, 0.1 mmol, Sigma-Aldrich Co.) in a solution of 1.0 mmol, Sigma-Aldrich Co.) and UHP (0.113 g, 1.2 mmol, hydrogen peroxide 36.2%, Sigma-Aldrich Co.). Purchase). The reaction mixture was mixed at 60 ° C. for 2-3 hours, and the reaction mixture was extracted with dichloromethane (2 × 5 mL). The bound dichloromethane was washed with saturated physiological saline (2 × 5 mL) and dried over anhydrous magnesium sulfate. After evaporation of the solvent, the residue was purified by flash column chromatography (SiO ₂ , hexane: ethyl acetate = 3: 1) to give pure carbonyl compound.

<Examples 2 to 20>

As the benzyl alcohol of Example 1, each alcohol described as the substrate of Table 1 was used. As a result, oxidation was successfully carried out by the above procedure over a wide range of structurally diverse primary and secondary benzyl alcohols to provide the corresponding carbonyl group compounds (Table 1). In addition, in all cases, the use of 0.1 equivalents of magnesium bromide achieves the desired oxidation product in sufficiently high yields. In the absence of magnesium bromide no oxidation reaction is observed. Substitution of MgBr ₂ by other metal halides such as magnesium chloride, magnesium iodide, cupric bromide, sodium bromide has resulted in much lower efficiency.

Oxidation of Benzyl Alcohol with UHP / MgBr ₂ entry temperament product time Yield (%) ^a One PhCH ₂ OH PhCOH 2 94 2 p -CH ₃ C ₆ H ₄ CH ₂ OH p -CH ₃ C ₆ H ₄ COH 2 92 3 p -FC ₆ H ₄ CH ₂ OH p -FC ₆ H ₄ COH 2 88 4 p -ClC ₆ H ₄ CH ₂ OH p -ClC ₆ H ₄ COH 2 87 5 p -BrC ₆ H ₄ CH ₂ OH p -BrC ₆ H ₄ COH 2 85 6 p -H ₃ COC ₆ H ₄ CH ₂ OH p -H ₃ COC ₆ H ₄ COH 2 91 7 p -NO ₂ C ₆ H ₄ CH ₂ OH p -NO ₂ C ₆ H ₄ COH 2 77 8 p -CF ₃ C ₆ H ₄ CH ₂ OH p -CF ₃ C ₆ H ₄ COH 2 76 9 1-naphthalenemethanol 1-naphthaldehyde 2 75 10 PhCH (OH) CH ₃ PhCOCH ₃ 2 91 11 p -CH ₃ C ₆ H ₄ CH (OH) CH ₃ p -CH ₃ C ₆ H ₄ COCH ₃ 2 90 12 p -FC ₆ H ₄ CH (OH) CH ₃ p -FC ₆ H ₄ COCH ₃ 3 85 13 p -ClC ₆ H ₄ CH (OH) CH ₃ p -ClC ₆ H ₄ COCH ₃ 3 84 14 p -BrC ₆ H ₄ CH (OH) CH ₃ p -BrC ₆ H ₄ COCH ₃ 3 84 15 PhCH (OH) Et PhCOEt 2 86 16 PhCH (OH) Ph PhCOPh 2 87 17 PhCH (OH) COPh PhCOCOPh 3 87 18 PhCH (OH) COOMe PhCOCOOMe 2 78 19 PhCH (OH) COOEt PhCOCOOEt 2 78

^a isolated Yield

1 is a schematic diagram showing a process for preparing a carbonyl group compound by oxidation of benzyl alcohol of the present invention.

Claims (8)

Benzyl aldehyde or benzyl ketone was formed by oxidizing primary benzyl alcohol or secondary benzyl alcohol with urea-hydrogen peroxide (UHP), catalytically using magnesium bromide (MgBr ₂ ) under an ionic liquid. How to make. The method of claim 1, wherein the primary benzyl alcohol is PhCH ₂ OH, p -CH ₃ C ₆ H ₄ CH ₂ OH, p -FC ₆ H ₄ CH ₂ OH, p -ClC ₆ H ₄ CH ₂ OH, p- BrC ₆ H ₄ CH ₂ OH, p -H ₃ COC ₆ H ₄ CH ₂ OH, p -NO ₂ C ₆ H ₄ CH ₂ OH, p -CF ₃ C ₆ H ₄ CH ₂ OH, 1-naphthalenemethanol, p- A process for producing benzyl aldehyde or benzyl ketone, characterized in that the alcohol is selected from the group consisting of HOC ₆ H ₄ CH ₂ OH and p -CNC ₆ H ₄ CH ₂ OH. The method of claim 1, wherein the secondary benzyl alcohol is PhCH (OH) CH ₃ , p -CH ₃ C ₆ H ₄ CH (OH) CH ₃ , p -FC ₆ H ₄ CH (OH) CH ₃ , p -ClC ₆ H ₄ CH (OH) CH ₃ , p -BrC ₆ H ₄ CH (OH) CH ₃ , PhCH (OH) Et, PhCH (OH) Ph, PhCH (OH) COPh, PhCH (OH) COOMe, PhCH (OH ) COOEt, p -NO ₂ C ₆ H ₄ CH (OH) CH ₃ , _{p -HOC 6 H 4 CH (OH} ) CH 3 and _{p -CNC 6 H 4 CH (OH} ) method for producing a benzyl aldehyde or ketone benzyl, characterized in that the alcohol is selected from the group of CH _3. The method of claim 1, wherein the ionic liquid is 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim] BF ₄ ), 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim] BF ₄ ), 1-ethyl-3-methylimidazolium methylsulfate ([emim] MS), 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] PF ₆ ), 1-butyl-3-methylimidazolium methylsulfate ([bmim] MS) and 1-hexyl-3-methylimidazolium hexafluorophosphate ([hmim ] PF ₆ ) A method for producing benzyl aldehyde or benzyl ketone, characterized in that the ionic liquid selected from the group consisting of. The method of claim 1, wherein the urea-hydrogen peroxide is 20 to 100 parts by weight of hydrogen peroxide relative to 100 parts by weight of urea. The method of claim 1, wherein the magnesium bromide is 0.01 to 0.2 equivalents and the benzyl alcohol is 0.1 to 5 equivalents based on 1 equivalent of UHP. The method of claim 1, wherein the benzyl alcohol is oxidized at 40 to 80 ° C. for 1 to 4 hours. The method for preparing benzyl aldehyde or benzyl ketone according to claim 1, wherein the step of preparing pure benzyl aldehyde or benzyl ketone through organic extraction and separation and purification after the oxidation is completed.

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