Process for producing organic compound having nitroxide free radical

An organic compound having a nitroxide free radial of the formula (2) is prepared by reacting a cyclic secondary amine having a steric hindrance of the formula (1) with a peroxide in the presence of at least 1 part by weight of an organic compound having a cyano group per 1 part by weight of the cyclic secondary amine having the steric hindrance. In the formulae (1) and (2), T is a methylene group, an ethylene group, an oxygen atom or a methyleneoxy group; R is an alkyl group, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an acyl group an acyloxy group, an amino group, a hydroxyl group or a heterocyclic group; R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and each an alkyl group or an aryl group, or R.sup.1 and R.sup.2 and/or R.sup.3 and R.sup.4 together form a tetramethylene group or a pentamethylene group; and n is an integer of 0 to 6. ##STR1##

FIELD OF THE INVENTION
 The present invention relates to a process for preparing an organic
 compound having a nitroxide free radial of the formula (2):
 ##STR2##
 wherein T is a methylene group, an ethylene group, an oxygen atom or a
 methyleneoxy group; R is an alkyl group, an aralkyl group, an aryl group,
 a cycloalkyl group, an alkoxy group, an acyl group an acyloxy group, an
 amino group, a hydroxyl group or a heterocyclic group; R.sup.1, R.sup.2,
 R.sup.3 and R.sup.4 are the same or different and each an alkyl group or
 an aryl group, or R.sup.1 and R.sup.2 and/or R.sup.3 and R.sup.4 together
 form a tetramethylene group or a pentamethylene group; and n is an integer
 of 0 to 6. This compound will be referred to as the "nitroxide compound
 (2)".
 The nitroxide compound (2) is useful as a spin label or a spin probe used
 in the ESR spectrum analysis, a polymerization inhibitor for unsaturated
 compound, or a stabilizer of organic polymers against thermal
 decomposition and photochemical decomposition.
 BACKGROUND ART
 It is known that an organic compound having a nitroxide free radical such
 as the nitroxide compound (2) is prepared by oxidizing a secondary amine
 having a steric hindrance with a peroxide. That is, the nitroxide compound
 (2) can be prepared by oxidizing a cyclic secondary amine having a steric
 hindrance of the formula (1):
 ##STR3##
 wherein T, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n are the same as
 defined above with a peroxide.
 However, when 2,2,6,6-tetramethylpiperidine is used as a cyclic secondary
 amine (1) and it is oxidized to obtain
 2,2,6,6-tetramethylpiperidine-N-oxyl, industrially satisfactory results
 are not attained, for example, the yield of the desired product is low as
 understood from the result of Comparative Examples described below, and
 the reaction time is long.
 DISCLOSURE OF THE INVENTION
 One object of the present invention is to provide a process for preparing
 the nitroxide compound (2) by oxidizing the cyclic secondary amine (1)
 with a peroxide at a high yield in a short reaction time.
 The present inventors have made extensive study to solve the above
 problems. As a result, it has been found that the nitroxide compound (2)
 can be obtained at a high yield in a short reaction time, when the cyclic
 secondary amine (1) is reacted with the peroxide in the presence of at
 least 1 wt. part of an organic compound having a cyano group per 1 wt.
 part of the cyclic secondary amine (1), and the present invention has been
 completed.
 Accordingly, the present invention provides a process for preparing the
 nitroxide compound (2) comprising the step of reacting a cyclic secondary
 amine of the formula (1):
 ##STR4##
 with a peroxide in the presence of at least 1 wt. part of an organic
 compound having acyano group per 1 wt. part of the cyclic secondary amine
 (1).

EMBODIMENTS FOR CARRYING OUT THE INVENTION
 The present invention will be explained in detail.
 In the above formula (1), which represents the cyclic secondary amine used
 in the process of the present invention, T is a methylene group, an
 ethylene group, an oxygen atom or a methyleneoxy group; R is an alkyl
 group, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxy
 group, an acyl group an acyloxy group, an amino group, a hydroxyl group or
 a heterocyclic group; R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same
 or different and each an alkyl group or an aryl group, or R.sup.1 and
 R.sup.2 and/or R.sup.3 and R.sup.4 together form a tetramethylene group or
 a pentamethylene group; and n is an integer of 0 to 6.
 The alkyl group represented by R may be a linear or branched alkyl group
 having 1 to 6 carbon atoms. Specific examples of the alkyl group include a
 methyl group, an ethyl group, a n-propyl group, an isopropyl group, a
 n-butyl group, an isobutyl group, a n-pentyl group, an isopentyl group, a
 neopentyl group, a n-hexyl group, a 2-methylpentyl group, a 3-methylpentyl
 group, a neohexyl group, etc.
 The aralkyl group may be an aralkyl group having 7 to 15 carbon atoms.
 Specific examples of the aralkyl group include a benzyl group, a phenethyl
 group, a phenylpropyl group, a benzhydryl group, etc.
 Specific examples of the aryl group include a phenyl group, a tolyl group,
 a xylyl group, a naphthyl group, etc.
 The cycloalkyl group may be a cycloalkyl group having 3 to 8 carbon atoms.
 Specific examples of the cycloalkyl group include a cyclopropyl group, a
 cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl
 group, a cyclooctyl group, etc.
 Specific examples of the alkoxy group include alkyloxy groups (e.g. a
 methoxy group, an ethoxy group, a propoxy group, etc.), and aralkyloxy
 groups (e.g. a benzyloxy group, etc.) Specific examples of the acyl group
 include linear or branched lower alkanoyl groups having 1 to 6 carbon
 atoms (e.g. a formyl group, an acetyl group, a propionyl group, a butyryl
 group, a valeryl group, a pivaloyl group, a pentanoyl group, etc.) and
 aroyl groups (e.g. a benzoyl group, a toluoyl group, a xyloyl group, a
 naphthoyl group, etc.)
 Specific examples of the acyloxy group include alkanoyloxy gropus (e.g. an
 acetoxy group, a propionyloxy group, etc.) and aroyloxy groups (e.g. a
 benzoyloxy group, etc.)
 Specific examples of the heterocyclic group include a thienyl group, a
 pyrrolyl group, a pyranyl group, a thiopyranyl group, a pyridyl group, a
 thiazolyl group, an imidazolinyl group, a pyrimidinyl group, a triazinyl
 group, an indolyl group, a quinolyl group, a purinyl group, a
 benzothiazolyl group, etc.
 R in the formula substitutes a hydrogen atom on the ring of the cyclic
 secondary amine (1)
 Examples of the alkyl and aryl groups represented by R.sup.1, R.sup.2,
 R.sup.3 and R.sup.4 may be the same as those exemplified in connection
 with R. Preferably, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are methyl
 groups.
 Specific examples of the cyclic secondary amine (1) include
 2,2,5,5-tetramethylpyrrolidine; derivatives of
 2,2,5,5-tetramethylpyrrolidine which have a substituent such as an alkoxy
 group (e.g. a methoxy group, an ethoxy group, a propoxy group,
 abenzyloxygroup, etc.), anacyloxygroup (e.g. anacetoxy group, a
 propionyloxy group, a benzoyloxy group, etc.) or a hydroxyl group on the
 3-position of 2,2,5,5-tetramethylpyrrolidine;
 2,2,6,6-tetramethylpiperidine; derivatives of
 2,2,6,6-tetramethylpiperidine which have a substituent such as an alkoxy
 group (e.g. a methoxy group, an ethoxy group, a propoxy group, a benzyloxy
 group, etc.), an acyloxy group (e.g. an acetoxy group, a propionyloxy
 group, a benzoyloxy group, etc.) or a hydroxyl group on the 4-position of
 2,2,6,6-tetramethylpiperidine; derivatives of 4,4-dimethyloxazolidine such
 as 2,2,4,4-tetramethyloxazolidine, 2,4,4-trimethyl-2-phenyloxazolidine,
 4-aza-3,3-dimethyl-1-oxaspiro [4.5] decane, etc.;
 3,3,5,5-tetramethylmorpholine; derivatives of
 3,3,5,5-tetramethylmorpholine which have a substituent such as an alkyl
 group (e.g. a methyl group, etc.) on the 2-position of
 3,3,5,5-tetramethylmorpholine. The cyclic secondary amine (1) may not be
 limited to the above exemplified compounds.
 According to the process of the present invention, the nitroxide compound
 (2) corresponding to the above cyclic secondary amine (1) can be obtained.
 For example, 2,2,5,5-tetramethylpyrrolidine-N-oxyl and its derivatives are
 prepared from 2,2,5,5-tetramethylpyrrolidine and its derivatives,
 2,2,6,6-tetramethylpiperizine-N-oxyl and its derivatives are prepared from
 2,2,6,6-tetramethylpiperizine and its derivatives,
 4,4-dimethyloxazolidine-N-oxyl derivatives are prepared from
 4,4-dimethyloxazolidine derivatives, and
 3,3,5,5-tetramethylmorpholine-N-oxyl and its derivatives are prepared from
 3,3,5,5-tetramethylmorpholine and its derivatives.
 As the peroxide used in the process of the present invention, hydrogen
 peroxide and any organic peroxide such as hydroperoxide and peracids may
 be used. Among them, hydrogen peroxide is preferable from the viewpoint of
 costs and the reduction of the amount of wastes.
 When hydrogen peroxide is used, a 5-70 wt. % aqueous solution, preferably a
 20-50 wt. % aqueous solution of hydrogen peroxide is used. The amount of
 hydrogen peroxide is at least 1.5 moles, preferably from 1.6 to 3.5 moles
 per 1 mole of the cyclic secondary amine (1).
 In the process of the present invention, the reaction is carried out in the
 presence of at least 1 wt. parts, preferably 1.5 to 50 wt. parts, more
 preferably 2 to 30 wt. parts of an organic compound having a cyano group
 per 1 wt. parts of the cyclic secondary amine (1). More preferably, the
 reaction is carried out in the presence of at least 1.5 moles, preferably
 2 to 50 moles of the organic compound having the cyano group per 1 mole of
 the cyclic secondary amine group (1) in the above weight parts range.
 The organic compound having the cyano group is not limited except those
 having a polymerizable double bond in the molecule such as acrylonitrile.
 Preferable examples of the organic compound having the cyano group include
 aliphatic nitrites (e.g. acetonitrile, propionitrile, butyronitrile,
 valeronitrile, capronitrile, etc.) and aromatic nitrites (e.g.
 benzonitrile, tolunitrile, etc.)
 When hydrogen peroxide is used in the form of an aqueous solution, the
 organic compound having the cyano group is preferably a water-soluble one,
 particularly preferably an acetonitrile and/or propionitrile.
 The process of the present invention may be carried out in a solvent. The
 solvent is suitably selected depending on the kinds of the cyclic
 secondary amine (1), the organic compound having the cyano group and the
 nitroxide compound (2), and preferably selected from solvents which are
 good solvents for the cyclic secondary amine (1) and the nitroxide
 compound (2), and miscible with the organic compound having the cyano
 group. Examples of the solvent include water, alcohols (e.g. methanol,
 ethanol, propanol, butanol, isopropanol, etc.), aromatic hydrocarbons
 (e.g. benzene, toluene, xylene, mesitylene, etc.), ethers (e.g. diethyl
 ether, diisopropyl ether, tetrahydrofuran, etc.) and so on. Preferred
 solvents are those which are not oxidized with the nitroxide compound (2),
 for example, water, the aromatic hydrocarbons, the ethers, etc.
 The solvent may not be used when the amount of the organic compound having
 the cyano group is at least 2.5 wt. parts, preferably at least 3 wt. parts
 per 1 wt. parts of the cyclic secondary amine (1), since the organic
 compound having the cyano group serves as a solvent in the process of the
 present invention.
 A catalyst may be used in the process of the present invention. The
 catalyst may be one that is used in a known process for preparing a
 compound having a nitroxide free radical by oxidizing a corresponding
 secondary amine having a steric hindrance with a peroxide. Preferred
 examples of the catalyst are compounds comprising metal elements of the 6
 Group of the 18 Groups Periodic Table, for example, tungsten, molybdenum,
 etc. Specific examples of the tungsten compound include tungstic acid,
 phosphortungstic acid, paratungstic acid, and their alkali metal salts
 (e.g. sodium salts, potassium salts) or ammonium salts. Specific examples
 of the molybdenum compounds include molybdic acid, molybdenum oxide,
 molybdenum carbonyl and their alkali metal salts (e.g. sodium salts,
 potassium salts) or ammonium salts). Specific examples include ammonium
 paratungstate, sodium tungstate, phosphortungstic acid, sodium molybdate,
 molybdenum trioxide, molybdenum hexacarbonyl, etc.
 The amount of the catalyst is usually from 0.001 to 0.1 wt. %, preferably
 from 0.01 to 0.05 wt. % of the weight of the cyclic secondary amine (1).
 The procedure of the process according to the present invention will be
 explained. For example, the peroxide is added to the mixture of the cyclic
 secondary amine (1) and the organic compound having the cyano group while
 stirring to react the cyclic secondary amine and the peroxide.
 The reaction temperature is usually from 0 to 75.degree. C., preferably
 from 40 to 65.degree. C.
 The nitroxide compound (2) can be prepared at ahigher yield by the above
 manner in which the reaction proceeds while the peroxide is added,
 although the cyclic secondary amine (1), the organic compound having the
 cyano group and the peroxide are mixed and reacted at the above
 temperature while stirring.
 The addition time of the peroxide is not limited, and usually from 1 to 10
 hours, preferably from 3 to 6 hours. After the addition of the peroxide,
 the reaction mixture is maintained at the above temperature for 1 to 10
 hours to complete the reaction.
 After the completion of the reaction, the nitroxide compound (2) may be
 isolated from the reaction mixture by a suitable combination of unit
 procedures such as concentration, extraction, distillation,
 recrystallization, etc.
 EXAMPLES
 The present invention will be illustrated by the Examples, which do not
 limit the present invention in any way.
 Example 1
 In a 100 ml reactor, 2,2,6,6-tetramethylpiperidine (4.3 g), acetonitrile
 (38.6 g) and ammonium paratungstate (0.21 g) were charged, and 35% aqueous
 hydrogen peroxide (8.8 g) was dropwise added to the mixture over 3 hours
 while stirring and maintaining the temperature at 50 to 51.degree. C.,
 followed by further reaction while stirring at the same temperature for 3
 hours. After the completion of the reaction, the reaction mixture was
 analyzed with gas chromatography. The yield of
 2,2,6,6-tetramethylpiperidine-1-oxyl was 93.5% (based on
 2,2,6,6-tetramethylpiperidine).
 Example 2
 A reaction was carried out in the same manner as in Example 1 except that a
 half of acetonitrile (19.3 g) was replaced by tetrahydrofuran (19.3 g). As
 a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 92.3%
 (based on 2,2,6,6-tetramethylpiperidine).
 Example 3
 In a 100 ml reactor, 2,2,6,6-tetramethylpiperidine (8.5 g), acetonitrile
 (25.5 g) and ammonium paratungstate (0.42 g) were charged, and 35% aqueous
 hydrogen peroxide (17.5 g) was dropwise added to the mixture over 3 hours
 while stirring and maintaining the temperature at 50 to 51.degree. C.,
 followed by further reaction while stirring at the same temperature for 3
 hours. After the completion of the reaction, the reaction mixture was
 analyzed with gas chromatography. The yield of
 2,2,6,6-tetramethylpiperidine-1-oxyl was 90.1% (based on
 2,2,6,6-tetramethylpiperidine).
 Example 4
 In a 100 ml reactor, 2,2,6,6-tetramethylpiperidine (8.5 g), acetonitrile
 (12.8 g), methanol (12.8 g) and ammonium paratungstate (0.42 g) were
 charged, and 35% aqueous hydrogen peroxide (17.5 g) was dropwise added to
 the mixture over 3 hours while stirring and maintaining the temperature at
 50 to 51.degree. C., followed by further reaction while stirring at the
 same temperature for 3 hours. After the completion of the reaction, the
 reaction mixture was analyzed with gas chromatography. The yield of
 2,2,6,6-tetramethylpiperidine-1-oxyl was 71.2% (based on
 2,2,6,6-tetramethylpiperidine).
 Example 5
 A reaction was carried out in the same manner as in Example 3 except that
 no ammonium paratungstate was used. As a result, the yield of
 2,2,6,6-tetramethylpiperidine-1-oxyl was 94.4% (based on
 2,2,6,6-tetramethylpiperidine).
 Example 6
 A reaction was carried out in the same manner as in Example 5 except that
 the amount of hydrogen peroxide was changed to 11.7 g and the addition
 time of hydrogen peroxide was changed to 2 hours. As a result, the yield
 of 2,2,6,6-tetramethylpiperidine-1-oxyl was 93.1% (based on
 2,2,6,6-tetramethylpiperidine).
 Comparative Example 1
 A reaction was carried out in the same manner as in Example 1 except that
 the amount of acetonitrile was changed to 2.5 g and methanol (36.1 g) was
 used. As a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was
 52.0% (based on 2,2,6,6-tetramethylpiperidine).
 Comparative Example 2
 A reaction was carried out in the same manner as in Example 1 except that
 tetrahydrofuran (38.6 g) was used in place of acetonitrile (38.6 g), and
 the reaction was continued for 10 hours while stirring after the
 completion of the addition of hydrogen peroxide. As a result, the yield of
 2,2,6,6-tetramethylpiperidine-1-oxyl was 38.5% (based on
 2,2,6,6-tetramethylpiperidine).
 The conditions and the results of Examples and Comparative Examples are
 summarized in the following Table.
 TABLE 1
 TMPPR 35% H.sub.2 O.sub.2 CH.sub.3 CN Solvent Catalyst Yield
 g (mole) g (mole) g (mole) g g %
 Ex. 1 4.3(0.03) 8.8(0.09) 38.6(0.94) 0 0.21 93.5
 C. Ex. 1 4.3(0.03) 8.8(0.09) 2.5(0.47) CH.sub.3 OH 0.21 52.0
 36.1
 Ex. 2 4.3(0.03) 8.8(0.09) 19.3(0.47) THF 0.21 92.3
 19.3
 C. Ex. 2 4.3(0.03) 8.8(0.09) 0 THF 0.21 38.5
 38.6
 Ex. 3 8.5(0.06) 17.5(0.18) 25.5(0.62) 0 0.42 90.1
 Ex. 4 8.5(0.06) 17.5(0.18) 12.8(0.31) CH.sub.3 OH 0.42 71.2
 12.8
 Ex. 5 8.5(0.06) 17.5(0.18) 25.5(0.62) 0 0 94.4
 Ex. 6 8.5(0.06) 11.7(0.12) 25.5(0.62) 0 0 93.1