JPH0688961B2 - Nitron production method - Google Patents

Description

BACKGROUND OF THE INVENTION The present invention relates to a method for producing nitrone functional compounds (nitrones) including diaryl nitrones, dialkyl nitrones and alkyl aryl nitrones. More specifically, the present invention relates to a one-step process for producing nitrones in high yield without producing large amounts of by-products.

Certain diaryl nitrones are particularly useful in contrast-enhanced photolithography, as disclosed in US patent application Ser. No. 735,016 filed on May 17, 1985 by Griffing et al. (US Pat. No. 4,702,996),
US Patent Application No. 687,68 filed December 31, 1984
No. 1 (US Pat. No. 4,661,433), US Patent Application No. 675,918 filed on Nov. 28, 1984 (US Pat. No. 4,8
59,789, 4,990,665, 5,108,874), and
US Patent Application No. 675,91 filed November 28, 1984
No. 5 (US Pat. No. 4,677,049). All of the above patent applications are assigned to the same assignment as the present invention. According to the teachings of Griffing et al., The diaryl nitrones are described by Methodender Organischen Chemie-
Houben-Weyl, Volume 10, Part 4, 1
968, pages 315-416, Chemical Reviews 1 (64), Jan Hamer and Anthony M. Carso.
acaluso), Nitrones, pages 476-483.

Davis et al., Co-pending US Patent Application No. 7
86,937 (U.S. Pat. No. 4,709,107) (incorporated herein by reference) discloses an improved process for making nitrones. This method involves (a) reducing a nitro compound with zinc to form hydroxylamines and zinc oxide, then (b) dissolving almost all zinc oxide in a dilute acid solution and converting hydroxylamines into aldehydes. Reacting to form nitrones. Although such a method is suitable for many purposes, it would be desirable to have an alternative method for producing nitrones, especially one that requires only one step.

SUMMARY OF THE INVENTION An object of the present invention is to provide a one-step method for producing nitrones.

Another object of the present invention is to provide a method for producing nitrones that minimizes the formation of organic by-products.

Another object of the invention is that the nitro compound is preferentially reduced to hydroxylamines, which condense with aldehydes to give nitrones before hydroxylamine is overreduced or aldehyde reduction occurs. To provide a method for producing nitrones.

According to the above object, it comprises (a) at least one nitro compound, (b) at least one aldehyde, (c) hydrogen source, and (d) hydrogenation catalyst, the nitro compound having the general formula: NO _{2 a} R × _b [wherein R is an aromatic hydrocarbon group having 6 to 20 carbon atoms, X is a halogen, a cyano group, an aliphatic acyl group having 1 to 8 carbon atoms, or 1 to 1 carbon atoms] Selected from the group consisting of 8 alkyl and substituted alkyl groups, aryl and substituted aryl groups having 6 to 13 carbon atoms, and alkoxycarbonyl groups having 2 to 8 carbon atoms, and b is an integer from 0 to 3. , A equals 1 or 2] is provided.

DESCRIPTION OF THE INVENTION According to the present invention, by reacting a mixture comprising (a) at least one nitro compound, (b) at least one aldehyde, (c) a hydrogen source, and (d) a hydrogenation catalyst, A one-step manufacturing method for nitrones is provided. It was unexpected that this process of the invention could be carried out in a single step. I mean,
As is well known, aldehydes are almost rapidly reduced to alcohols under hydrogenation conditions. 1972 WA Benjamin, I
nc.), HOHouse, Modern Synthetic R
See eactions, 2nd edition, page 9.

The term "nitro compound" as used herein refers to a molecular species that is reduced in accordance with the present invention and includes nitroaromatic compounds having an aromatic nucleus of about 6 to about 30 carbon atoms. The following formula is preferable.

(NO _{2 a} R × _b (I) Here, R is an aromatic hydrocarbon group having 6 to 20 carbon atoms, X is a halogen, a cyano group, an aliphatic acyl group having 1 to 8 carbon atoms. , An alkyl group having 1 to 8 carbon atoms and a substituted alkyl group, an aryl group having 6 to 13 carbon atoms and a substituted aryl group, and an alkoxycarbonyl group having 2 to 8 carbon atoms, and b is 0 to 3 And a is equal to 1 or 2. Most preferred are nitrobenzene, p-ethoxynitrobenzene, p-nitroethylbenzoate, p-nitromethylbenzoate, p-nitrobutylbenzoate and p-nitroaethophenone. is there.

The term "nitro compound" also includes nitroalkanes of the formula:

(NO _{2 c} R ¹ (II) where R ¹ is an alkyl or substituted alkyl group having 1 to about 15 carbon atoms, and c is equal to 1 or 2. Examples of suitable nitroalkanes include nitromethane. , Nitroethane, 1-nitropropane, 2-nitropropane, 1-nitrobutane, 1-nitropentane, nitrocyclohexane, 3-nitro-2-methylpentane, 2-nitro-2
-Methyl pentane etc. Of course, formulas I and II also include bisnitro compounds.

The term "aldehyde" includes both alkyl and aryl aldehydes. The aryl aldehydes that can be used in the present invention have an aromatic nucleus of about 6 to about 30 carbon atoms, and the alkyl aldehydes have about 15 carbon atoms.
It has up to 4 alkyl skeletons. Preferred aryl aldehydes are of the formula:

Preferred alkyl aldehydes are of the formula

Here, Z is (R ⁵ _d Q-R ⁶ or R ⁷ , Q is a monovalent, divalent or trivalent substituent or linking group, R ² ,
Each of R ³ and R ⁵ independently has hydrogen and 1 to 8 carbon atoms.
An alkyl group or a substituted alkyl group having 6 to 13 carbon atoms, or an aromatic or substituted aromatic group having 6 to 13 carbon atoms, and R ⁴ is an aliphatic group having 1 to 15 carbon atoms or an alicyclic group. , R ⁶ is an aromatic group containing ⁶ to 13 carbon atoms, and R ⁷ is an aromatic heterocyclic group containing about 4 to about 20 carbon atoms (wherein the heteroatoms are oxygen, nitrogen and sulfur). Is at least one atom selected), and d
Is an integer from 0 to 2, m is equal to 1 or 2, q is equal to 0 or 1, and n is an integer from 0 to 4 As apparent from the formula III, in the aryl aldehyde, an aryl group and a carboxy group are combined. There may be conjugated carbon bonds between. The formula III and IV aldehydes also include bisaldehydes. (Where m is 2), the two aldehyde functional groups are then linked to the aromatic nucleus Z or the alkyl skeleton R ⁴ or to each other. Both R ² and R ³ are typically hydrogen or a methyl group.

The type of Q is not so important and the appropriate one will be apparent to those skilled in the art. Q becomes monovalent, divalent or trivalent depending on the value of d being 0, 1 or 2. Examples of suitable monovalent Q are fluorine, chlorine, bromine, iodine and 1 carbon atom.
There are ~ 6 alkyl groups, and 6-13 carbon atom-containing arule groups. Examples of divalent Q are oxygen, sulfur, carbonyl, alkylene and arylene. An example of a suitable trivalent Q is nitrogen. Halogen, oxygen, sulfur or nitrogen are preferred.

Other suitable nitro compounds and aldehydes will be apparent to those skilled in the art or can be ascertained without undue experimentation.

Although hydrogen source is usually a hydrogen gas (H _2), hydride (H ^-)
Any variation that utilizes another hydrogen source, such as, is within the scope of the invention as claimed.

The hydrogenation catalyst is usually a noble metal (including oxides thereof) such as platinum, palladium, ruthenium, iridium, rhodium, osmium, rhenium and the like. It is known that the rate of hydrogenation varies depending on the type of catalyst and metal used, including the support used. Generally carbon supported metals are preferred but other supports such as alumina and silica may be used. Platinum on charcoal is particularly preferred. Generally carbon supported catalysts are
Contains up to 35% by weight of noble metal. Precious metal concentration is 2
Most preferably, it is 10%. The ratio of starting material to catalyst is preferably in the range of about 100: 0.1 to 100: 5. Metal complexes, especially platinum complexes, may also be used in the practice of the invention. Other hydrogenation catalysts will be apparent to those skilled in the art or can be determined as appropriate without undue experimentation.

The process of the present invention is preferably carried out in a suitable organic solvent. Examples of such solvents are lower aliphatic alcohols such as methanol, ethanol, propanol, isopropanol, butanol and the like.
Other organic solvents that are miscible with water (such as acenitrile) are suitable, but methanol and ethanol are most preferred. The amount of organic solvent used can vary widely, but the preferred proportions range from about 1% to about 75% by weight of the reaction mixture.

Optionally, reaction (rate) modifiers may be used in the process of the present invention and are preferred. Reaction modifiers suitable for use in the present invention are well known in the art, such as the 1970 Annals of the NY Academy of Science.
S., 171, p. 266, by Rylander et al. Examples of suitable reaction modifiers include heterocyclic nitrogen compounds, phosphines, phosphites, sulfides, sulfoxides and the like. A more detailed description can be found in co-pending US Patent Application No. 762,358 (US Pat. No. 4,72,358).
No. 3,030) and the references cited therein. Dimethyl sulfoxide (DMSO) has been found to be particularly effective in the practice of the present invention. The amount of modifier used should correspond to the amount of metal catalyst used. The molar ratio of metal catalyst to modifier is preferably in the range of about 1: 0.5 to about 1: 5,
The range of 1: 1 to 1: 2 is most preferable. The weight ratio of starting material to modifier is usually in the range 100: 0.5 to 100: 7.5, but 100: 0.
A ratio of 5-100: 2 is preferred.

Appropriate acids may be used to accelerate the rate of condensation of hydroxylamines and aldehydes. This includes both mineral and organic acids. The most preferred acids are carboxylic acids such as hexanoic acid, formic acid, pentanoic acid, acetic acid, phenylacetic acid, propanoic acid, butanoic acid, with acetic acid being especially preferred. Other preferred acids include sulfonic acids such as methyl sulfonic acid, ethyl sulfonic acid, phenyl sulfonic acid, etc., mineral acids such as hydrochloric acid, phosphoric acid, sulfuric acid, sulfurous acid, nitric acid, Rohm and Hass Co.
Company) has a functionalized polymeric resin such as that marketed under the trademark Amberlyst XN-1005.

The process of the present invention is carried out by mixing the above materials in a suitable reaction vessel. Generally, the reaction can be carried out at a temperature from about -50 ° C to about 150 ° C, and from 0 ° C to about 100 ° C.
C is preferred, with room temperature to about 50 C being most preferred. The pressure may range from a low pressure of about 0.1 atm to a high pressure of about 100 atm or more, preferably the reaction is carried out at 30 psi to 75 psi, particularly preferably 40 psi to 50 psi.

Examples are illustrated below so that those skilled in the art can more easily carry out the present invention, but the present invention is not limited to these examples. All parts and percentages are by weight unless otherwise indicated.

(Example) In each of the following Examples 1 to 9, a compound represented by the following formula (α- (4-diethylaminophenyl) -N-phenylnitrone) was produced under various conditions.

(Example 1) Nitrobenzene 20 g (162 mmol), 4-diethylaminobenzaldehyde 23 g (130 mmol), acetic acid 15.6 g (2
60 mmol), 125 ml of absolute ethanol, 1 ml of dimethylsulfoxide, and 0.4 g of 5% platinum supported on charcoal.
It was placed in a liter Parr hydrogenator. Seal the reaction vessel, flush with hydrogen to clean, and 50 ps with hydrogen.
It was pressurized to i, shaken and vigorously stirred. Pressure is 40psi and 50
kept between psi. After consumption of 2 equivalents of hydrogen (about 5 hours), the reaction vessel was opened, flushed with nitrogen for washing, and the solution was filtered to remove the catalyst. The filtrate was diluted with 200 ml of water and neutralized with aqueous sodium bicarbonate solution. Extract the neutralized solution with methylene chloride (2 x 100 ml),
Combine the extracts with methylene chloride and the bicarbonate solution,
Wash with water and brine. The solution was dried over magnesium sulfate, filtered and the solvent was evaporated to give a reddish brown, semi-solid crude product. This crude product was converted to hot tetrahydrofuran.
It was dissolved in 200 ml, 250 ml of hexane was added at 60 ° C., cooled to room temperature, and the product was recrystallized. When this is filtered, the melting point is
15.5 g of a yellow crystalline product at 107 ° C. was obtained (yield 45
%).

Example 2 The procedure of Example 1 was repeated. However, 7.8 g of acetic acid (130
(Mmol) only. The reaction time was reduced to 3 hours and the yield increased to 69%. The melting point of the product was 108 ° C, indicating increased purity. When analyzed by HPLC (high pressure liquid chromatography), the purity of the product nitrone exceeded 98%. The proton NMR results were consistent with a nitrone sample obtained by known methods.

Example 3 The procedure of Example 2 was repeated. However, platinum oxide (0.15 g) was used as the catalyst. The reaction time was still 3 hours, but the product yield had dropped to 37%. Platinum thus supported on charcoal is preferable as a hydrogenation catalyst.

Example 4 The procedure of Example 2 was repeated. However, DMSO was not used as a reaction modifier. The reaction time was 1.2 hours and the product yield was 29%. Therefore, it is preferable to use the reaction modifier.

(Example 5) In order to confirm reproducibility, the procedure of Example 2 was repeated as it was. The yield of the product was 25.5 g and the yield was 73%.

Example 6 The procedure of Example 2 was repeated. However, the solvent is ethanol 13
5 ml and water 15 ml. Product yield 25.9g, 74% yield
Met. Therefore, it need not be absolute ethanol.

Example 7 The procedure of Example 2 was repeated. However, the solvent was methanol. The yield of the product was 28.3g and the yield was 81%. The melting point of the product is 110-112 ° C, λmax (nm) is 388,
And εmax was 41000.

Example 8 20 g (162 mmol) of nitrobenzene, 23 g (130 mmol) of 4-diethylaminobenzaldehyde, 150 ml of absolute ethanol, 1 ml of dimethyl sulfoxide, and 0.4 g of platinum supported on charcoal were hydrogenated in 1 liter of parr. I put it in the device. The reaction vessel was sealed, flushed with hydrogen, washed, pressurized to 50 psi with hydrogen, shaken and stirred vigorously. The pressure was kept between 40 and 50 psi. After consumption of 2 equivalents of hydrogen (3 hours), the vessel was flushed with nitrogen and washed, 15.6 g (260 mmol) of acetic acid was added, and the mixture was stirred at 0.
It went on for 3 hours. The reaction mixture was filtered, the filtrate diluted with 200 ml of water and neutralized with sodium bicarbonate solution. The neutralized solution was extracted with methylene chloride (2 x 100 ml), extracted with methylene chloride (2 x 100 ml) and the combined extracts were washed with methylene chloride, sodium bicarbonate solution, water and brine. The methylene chloride solution was dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator to give a reddish brown solid. The solid was recrystallized from a 1: 1 tetrahydrofuran / hexane solution to give a yellow crystalline product in a yield of 9.7 g (28%). Therefore it is preferred to include acetic acid in the initial reaction mixture.

Example 9 20 g (162 mmol) nitrobenzene, 1 ml dimethylsulfoxide, 150 ml ethanol and 0.2 g platinum on charcoal were placed in a 1 liter Parr hydrogenator. The mixture was H ₂ until 2 mol of hydrogen was consumed (1 hour).
Hydrogenated at 40-50 psi. The reaction vessel was flushed with nitrogen and washed to give 4-diethylaminobenzaldehyde (23 g, 130 mmol) and acetic acid (39 g, 650 mmol).
Was added to a solution of 50 ml of ethanol. The mixture was stirred at room temperature for 0.7 hours, filtered to remove the platinum catalyst, neutralized with aqueous sodium bicarbonate, extracted with methylene chloride and the extract concentrated to give the crude product. This crude product
Recrystallization from a 1: 1 tetrahydrofuran / hexane solution gave 18.7 g (yield 54%) of the product nitrone. Thus, according to the one-step nitrone manufacturing method of the present invention,
Higher yields are achieved under similar conditions of catalyst, solvent, temperature and pressure than the corresponding two-step process.

Claims (19)

[Claims] 1. A nitrone comprising reacting a mixture comprising: (a) at least one nitro compound, (b) at least one aldehyde, (c) a hydrogen source, and (d) a hydrogenation catalyst. Wherein the nitro compound has the general formula: (NO _{2 a} R × _b [wherein R is an aromatic hydrocarbon group having 6 to 20 carbon atoms, X is halogen, cyano] Group, aliphatic acyl group having 1 to 8 carbon atoms, alkyl group and substituted alkyl group having 1 to 8 carbon atoms, aryl and substituted aryl group having 6 to 13 carbon atoms, and alkoxy having 2 to 8 carbon atoms Selected from the group consisting of carbonyl groups, b is an integer from 0 to 3 and a is equal to 1 or 2]. 2. The nitro compound has the general formula: (NO _{2 c} R ^{1 where} R ¹ is an alkyl or substituted alkyl group having 1 to about 15 carbon atoms, and c is equal to 1 or 2. ] The method according to claim 1, which is a nitroalkane having 3. The method according to claim 1, wherein the aldehyde is an aromatic aldehyde having an aromatic nucleus of about 6 to 30 carbon atoms. 4. The aldehyde has the general formula: [In the formula, Z is (R ⁵ _d Q-R ⁶ or R ⁷ , Q is a monovalent, divalent or trivalent substituent or bonding group, R ² ,
R ³ and R ⁵ each independently represent hydrogen or a carbon atom of 1 to 8
An alkyl or substituted alkyl group containing 6 to 13 carbon atoms, or an aromatic or substituted aromatic group containing ⁶ to 13 carbon atoms, R ⁶ is an aromatic group containing ⁶ to 13 carbon atoms, and R ⁷ is An aromatic heterocyclic group containing about 4 to about 20 carbon atoms and having at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, d
Is an integer from 0 to 2, m is equal to 1 or 2, and n is an integer from 0 to 4]. 5. The aldehyde has the general formula: Wherein R ⁴ is an aliphatic or cycloaliphatic radical having 1 to 15 carbon atoms, m is equal to 1 or 2 and q is equal to 0 or 1. A method as claimed in claim 1 characterized. 6. The method according to claim 1, wherein the hydrogen source is hydrogen gas. 7. The method according to claim 1, wherein the hydrogenation catalyst is a noble metal. 8. The method of claim 7 wherein the noble metal is platinum. 9. The method of claim 1 wherein the reaction mixture further comprises an organic solvent. 10. The method according to claim 9, wherein the organic solvent is a lower aliphatic alcohol. 11. The organic solvent comprises about 1% by weight of the reaction mixture.
10. The method of claim 9 wherein the method is present in an amount of about 75% by weight. 12. A process according to claim 1, 6 or 9 characterized in that the reaction mixture further comprises a reaction modifier. 13. The method of claim 12 wherein the reaction mixture also contains an amount of acid effective to increase the condensation rate. 14. The method according to claim 1, wherein the reaction is carried out at a temperature of about −50 ° C. to about 150 ° C. 15. The method according to claim 9, wherein the reaction is carried out at a temperature of about 0 ° C. to about 100 ° C. 16. The method according to claim 13, wherein the reaction is carried out at a temperature from room temperature to about 50 ° C. 17. The method according to claim 12, wherein the reaction is carried out at a pressure of 0.1 atm to 100 atm. 18. The method according to claim 13, wherein the reaction is carried out at a pressure of 30 psi to 75 psi. 19. The method according to claim 16, wherein the reaction is carried out at a pressure of 40 psi to 50 psi.