JP2014148494A - Novel hypervalent iodine compound possessing a 5-nitro-1,2-benziodoxol-3(1h)-one site - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel trivalent hypervalent iodine compound which exhibits excellent reactivity in an oxidation reaction using a trivalent hypervalent iodine compound and which enables easy removal and recovery of a byproduct monovalent iodine compound by an extraction operation.SOLUTION: Provided is a novel trivalent hypervalent iodine compound possessing a 5-nitro-1,2-benziodoxol-3(1H)-one. With this compound, it becomes possible to oxidize even a compound which cannot be oxidized with conventional trivalent hypervalent iodine compounds, and to remove and recover a byproduct monovalent iodine compound after completion of the oxidizing reaction by washing and extraction operations.

Description

  The present invention relates to a novel hypervalent iodine compound having a 5-nitro-1,2-benziodoxol-3- (1H) -one moiety, and is required in the field of organic synthesis and other fields. To be used in the reaction reagent.

The reaction of oxidizing a primary alcohol to an aldehyde and a secondary alcohol to a ketone is one of the most important reactions in organic synthesis. In the past, oxidizing agents using chromium oxide such as Jones reagent, Sarett reagent, Collins reagent, etc. Has been used. In this oxidation reaction from alcohol to aldehyde or ketone, active research has been conducted with the aim of developing a more efficient oxidation method, and many excellent methods have been developed one after another. For example, E.I. J. et al. Corey et al. Oxidize alcohol using pyridinium chlorochromate (hereinafter referred to as PCC) in dichloromethane to obtain aldehyde or ketone in high yield. E. J. et al. Corey et al. Oxidized decanol using pyridinium dichromate (hereinafter referred to as PDC) in dichloromethane to obtain decanal in a yield of 98% (Non-patent Documents 1 and 2). However, all of these oxidizers use highly toxic heavy metal oxides as oxidizers. In addition, after the reaction is completed, there is a problem that the operation of completely removing heavy metal by-products from the target product becomes complicated. In recent years, in a system using bis (acetoxy) iodobenzene which is a trivalent hypervalent iodine compound and a catalytic amount of 2,2,6,6-tetramethyl-1-piperidine 1-oxyl (hereinafter, TEMPO), It has been reported that hydroxyl groups of allyl alcohol and saccharides can be oxidized to aldehydes or ketones with high yield (Patent Document 1, Non-Patent Document 3). Moreover, trivalent hypervalent iodine compounds have low toxicity. Therefore, it has come to be widely used in organic synthetic chemistry as a useful oxidizing agent. Examples of trivalent hypervalent iodine compounds include bis (acetoxy) iodobenzene, 4-nitro- [bis (acetoxy)] iodobenzene, and bis (trifluoroacetoxy) iodobenzene having the following structure: Can do.

JP 2002-20322 A

E. J. et al. Corey, J .; W. Suggs, Tetrahedron Lett. 1975, 2647. E. J. et al. Corey, G.M. Schmidt, Tetrahedron Lett. 1979, 399. A. D. Mico, R.M. Margarita, L.M. Parlanti, A.M. Vescovi, G.M. Piancatelli, J.A. Org. Chem. 1997, 62, 6974.

  Conventional trivalent hypervalent iodine compounds are excellent oxidizing agents with low toxicity. However, since the reactivity of these trivalent hypervalent iodine compounds is generally low, it may not be applicable to the oxidation of secondary alcohols, or the yield may be low. In addition, the oxidation reaction using these trivalent hypervalent iodine compounds may involve complicated means such as chromatography in order to remove monovalent iodobenzene by-produced from the target product. There is a need for an oxidizing agent that has good reactivity and is easily post-treated.

  Thus, as a result of intensive studies, the inventors have completed the present invention. That is, the present invention relates to a novel hypervalent iodine compound (hereinafter referred to as Nobel-DIB) having a 5-nitro-1,2-benziodoxol-3- (1H) -one moiety represented by the structural formula (1). Is.

  An embodiment of the present invention will be described. When the compound of the present invention is used in an alcohol oxidation reaction, even a compound that could not be oxidized by a conventional trivalent hypervalent iodine compound can be oxidized. Moreover, the monovalent | monohydric 2-iodo-5-nitrobenzoic acid byproduced can be easily collect | recovered by washing | cleaning and extraction operation, and an after-treatment is easy. Note that Nobel-DIB is a novel compound not yet published in literature. Hereinafter, as a representative example of Nobel-DIB, a method for synthesizing 1-acetoxy-5-nitro-1,2-benziodoxol-3- (1H) -one represented by the structural formula (2) will be clarified. This is an example, and the present invention is not limited to this.

Nobel-DIB (2) is synthesized in two steps according to the following reaction formula.

  The first step is a step of obtaining 2-iodo-5-nitrobenzoic acid (B) by reacting 2-iodobenzoic acid (A) with sulfuric acid and nitric acid. Although reaction temperature is not limited as long as reaction can be advanced, For example, the range of room temperature to 140 degreeC is preferable. The reaction time varies depending on the reaction temperature, but is appropriately selected between 30 minutes and 12 hours.

  The second step is a step of obtaining Nobel-DIB (2) by reacting 2-iodo-5-nitrobenzoic acid (B) with acetic acid in the presence of 3-chloroperbenzoic acid (MCPBA). Although reaction temperature is not limited as long as reaction can be advanced, For example, the range of room temperature to 70 degreeC is preferable. The reaction time varies depending on the reaction temperature, but is appropriately selected between 3 hours and 72 hours.

  In the following, taking Nobel-DIB (2) as a representative example of the present invention, application to the oxidation reaction from alcohols to aldehydes or ketones is shown as a reference example, and oxidation of a conventional trivalent hypervalent iodine compound is performed. The usefulness of the present invention will be clarified by showing the application to the reaction as a comparative example.

The reaction proceeds according to the following reaction formula. That is, Nobel-DIB acts as an oxidizing agent and converts alcohols into aldehydes or ketones with high yield. Although reaction temperature is not limited as long as reaction can be advanced, For example, the range of -20 degreeC to 70 degreeC is preferable. The reaction time varies depending on the type of solvent used and the reaction temperature, but is appropriately selected between 30 minutes and 72 hours.

Reference example 1
To a solution of 122 mg (1 mmol) of 4-methylbenzyl alcohol in DMF (4 mL), 351 mg (1 mmol) of Nobel-DIB (2) was added and stirred at 65 ° C. for 12 hours. Next, 351 mg (1 mmol) of Nobel-DIB (2) was added, and the mixture was further stirred for 12 hours. After completion of the reaction, 10 mL of a saturated aqueous sodium hydrogen carbonate solution and 10 mL of a mixed solvent of hexane / ether = 2/1 were added to separate the layers. The organic layer was dried over sodium sulfate, and the organic layer was concentrated to obtain 117 mg of 4-methylbenzaldehyde (yield 97%, purity 98%).

Comparative Example 1-1
By using 322 mg (1 mmol) of bis (acetoxy) iodobenzene in place of Nobel-DIB (2), the same reaction operation as in Reference Example 1 was performed, and 19 mg of 4-methylbenzaldehyde was obtained by purification by silica gel column chromatography. (Yield 16%).

Comparative Example 1-2
By using 367 mg (1 mmol) of 4-nitro-bis (acetoxy) iodobenzene in place of Nobel-DIB (2), the same reaction operation as in Reference Example 1 was carried out and purified by silica gel column chromatography to obtain 4-methyl 42 mg of benzaldehyde was obtained (35% yield).

Reference example 2
To a solution of 143 mg (1 mmol) of 4-chlorobenzyl alcohol in DMF (4 mL), 351 mg (1 mmol) of Nobel-DIB (2) was added and stirred at 65 ° C. for 12 hours. Next, 351 mg (1 mmol) of Nobel-DIB (2) was added, and the mixture was further stirred for 12 hours. After completion of the reaction, 10 mL of a saturated aqueous sodium hydrogen carbonate solution and 10 mL of a mixed solvent of hexane / ether = 2/1 were added to separate the layers. The organic layer was dried over sodium sulfate, and the organic layer was concentrated to obtain 122 mg of 4-chlorobenzaldehyde (yield 87%, purity 86%).

Comparative Example 2-1
The same reaction operation as in Reference Example 2 was carried out using 322 mg (1 mmol) of bis (acetoxy) iodobenzene in place of Nobel-DIB (2), and purified by silica gel column chromatography to obtain 32 mg of 4-chlorobenzaldehyde. (Yield 23%).

Comparative Example 2-2
By using 367 mg (1 mmol) of 4-nitro-bis (acetoxy) iodobenzene in place of Nobel-DIB (2), the same reaction operation as in Reference Example 2 was carried out, followed by purification by silica gel column chromatography. 49 mg of benzaldehyde was obtained (35% yield).

Reference example 3
351 mg (1 mmol) of Nobel-DIB (2) was added to a DMF (4 mL) solution of 136 mg (1 mmol) of 1-phenyl-1-propanol and stirred at 65 ° C. for 12 hours. Next, 351 mg (1 mmol) of Nobel-DIB (2) was added, and the mixture was further stirred for 12 hours. After completion of the reaction, 10 mL of a saturated aqueous sodium hydrogen carbonate solution and 10 mL of a mixed solvent of hexane / ether = 2/1 were added to separate the layers. The organic layer was dried over sodium sulfate, and the organic layer was concentrated to obtain 117 mg of propiophenone (yield 87%, purity 86%).

Comparative Example 3-1
The same reaction operation as in Reference Example 3 was performed using 322 mg (1 mmol) of bis (acetoxy) iodobenzene instead of Nobel-DIB (2), and 27 mg of propiophenone was obtained by purification by silica gel column chromatography. (Yield 20%).

Comparative Example 3-2
Propiofenone is obtained by performing the same reaction operation as in Reference Example 3 using 367 mg (1 mmol) of 4-nitro-bis (acetoxy) iodobenzene instead of Nobel-DIB (2) and purifying by silica gel column chromatography. 42 mg was obtained (yield 31%).

Reference example 4
351 mg (1 mmol) of Nobel-DIB (2) was added to a DMF (4 mL) solution of 184 mg (1 mmol) of cyclododecanol, and the mixture was stirred at 65 ° C. for 12 hours. Next, 351 mg (1 mmol) of Nobel-DIB (2) was added, and the mixture was further stirred for 12 hours. After completion of the reaction, 10 mL of a saturated aqueous sodium hydrogen carbonate solution and 10 mL of a mixed solvent of hexane / ether = 2/1 were added to separate the layers. The organic layer was dried over sodium sulfate, and the organic layer was concentrated to obtain 146 mg of cyclododecanone (yield 90%, purity 95%).

Comparative Example 4-1
The same reaction operation as in Reference Example 4 was carried out using 322 mg (1 mmol) of bis (acetoxy) iodobenzene instead of Nobel-DIB (2) and purified by silica gel column chromatography, but only a trace amount of cyclododecanone was obtained. I couldn't.

Comparative Example 4-2
Cyclododecanone is obtained by performing the same reaction operation as in Reference Example 4 using 367 mg (1 mmol) of 4-nitro-bis (acetoxy) iodobenzene instead of Nobel-DIB (2) and purifying by silica gel column chromatography. 9 mg was obtained (yield 5%).

  As described above, when Nobel-DIB according to the present invention is used in an alcohol oxidation reaction, even a compound that could not be oxidized by a conventional trivalent hypervalent iodine compound can be oxidized. Moreover, the monovalent | monohydric 2-iodo-5-nitrobenzoic acid byproduced can be easily collect | recovered by washing | cleaning and extraction operation, and an after-treatment is easy.

  Next, the present invention will be described in more detail with reference to examples. This is for illustrative purposes and does not limit the present invention. It will be apparent to those skilled in the art that variations are possible within the scope of the invention.

Example 1
1-acetoxy-5-nitro-1,2-benziodoxol-3- (1H) -one (synthesis of Nobel-DIB (2))
To the flask, 1.24 g (5 mmol) of 2-iodobenzoic acid was added and cooled to 0 ° C. A mixed solution of 4 mL of nitric acid and 6 mL of sulfuric acid was slowly added dropwise, followed by stirring at room temperature for 30 minutes and further at 130 ° C. for 3 hours. 30 mL of ice water was added to the reaction solution brought to room temperature, and the deposited precipitate was filtered and dried under reduced pressure to obtain 2-iodo-5-nitrobenzoic acid corresponding to the precursor (B) (1.244 g, 85 %).

To the flask, 1.46 g (5 mmol) of 2-iodo-5-nitrobenzoic acid and then 30 mL of acetic acid were added and stirred until homogeneous. 1.59 g (6 mmol) of 3-chloroperbenzoic acid (purity 65%) was added and stirred at 65 ° C. for 48 hours. Cool the reaction to 0 ° C. and add ether. The deposited precipitate was filtered and dried under reduced pressure to obtain 1-acetoxy-5-nitro-1,2-benziodoxol-3- (1H) -one (Nobel-DIB (2)) ( 1.666 g, 95%). The physical properties of the obtained (Nobel-DIB (2)) are shown below.
Melting point: 175-179 ° C
IR (neat): 1697 (C = O), 1665 (C = O), 1525 (-NO 2), 1346 (-NO 2), cm -1;
¹ H-NMR (500 MHz, CDCl ₃ ): δ = 2.30 (s, 3H), 8.28 (d, J = 8.9 Hz, 1H), 8.71 (dd, J = 2.6 Hz, J = 2.5 Hz, 1H), 9.04 (d, J = 2.6 Hz, 1H).

  As described above, the novel hypervalent iodine compound (Nobel-DIB) having a 5-nitro-1,2-benziodoxol-3- (1H) -one moiety according to the present invention can be used for an oxidation reaction. it can. Hypervalent iodine compounds having a trivalent hypervalent state are widely used in organic synthetic chemistry as mild oxidants, but are not generally applicable to the oxidation of secondary alcohols because of their low reactivity. Or, the oxidation yield may be low. Further, in the oxidation reaction using these trivalent hypervalent iodine compounds, it is necessary to remove monovalent iodobenzene produced as a by-product from the target product, and this operation involves complicated means such as chromatography. These are listed as problems, and the solution is strongly desired. When Nobel-DIB according to the present invention is used in an oxidation reaction, even a compound that could not be oxidized by a conventional trivalent hypervalent iodine compound can be oxidized. Moreover, the monovalent | monohydric 2-iodo-5-nitrobenzoic acid byproduced can be easily collect | recovered by washing | cleaning and extraction operation, and an after-treatment is easy. As is clear from the reference examples and comparative examples, the oxidation reaction using Nobel-DIB according to the present invention is more reactive and easy to handle than the conventional method using a trivalent hypervalent iodine compound. is there.

Claims (1)

The following structural formula (1)

(In the formula, R ¹ , R ² and R ³ are each an independent hydrogen atom, methyl group, ethyl group, propyl group, iso-propyl group, butyl group, tert-butyl group, pentyl group, hexyl group, phenyl group. , Or a fluorine atom).