JP4993116B2 - Amino group silylation method - Google Patents

Description

  The present invention relates to a method for silylating an amino group.

  Compounds containing an amino group protected with a silyl group are useful as synthetic intermediates for pharmaceuticals and agricultural chemicals, paint additives, and polymer modifiers.

  As a method for silylating an amino group, a method of reacting an amino group-containing compound with a chlorosilane compound is known. However, the silylation reaction of an amino group using a chlorosilane compound is less reactive than the silylation reaction of a hydroxy group, and the silylation reaction of an amino group using a chlorosilane compound having a particularly bulky group is Since the reaction rate is very slow, the production takes a long time and has a problem of low yield. For example, it has been reported that the silylation reaction of an amino group using t-butyldimethylchlorosilane is difficult (Non-patent document 1: PROTECTIVE GROUPS in ORGANIC SYNTHESIS p. 77).

PROTECTIVE GROUPS IN ORGANIC SYNTHESIS p. 77

  The present invention has been made in view of the above circumstances, and an object thereof is to provide an amino group silylation method which has a high reaction rate and can be carried out industrially.

As a result of intensive studies to achieve the above object, the present inventors have found that the following general formula (1)
R ¹ R ² NH (1)
(Wherein R ¹ and R ² are a hydrogen atom or a substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms. Alternatively, R ¹ and R ² are bonded to each other and bonded to each other) And may form a ring having 2 to 20 carbon atoms.)
The amino group of the amino group-containing compound represented by the following general formula (2)
R ³ R ⁴ R ⁵ SiCl (2)
(In the formula, R ³ , R ⁴ and R ⁵ are a hydrogen atom, a chlorine atom, or a substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms, and R ³ and R ⁴ , R ³ and R ^5, or R ⁴ and R ⁵ may be bonded to each other to form a ring having 2 to 20 carbon atoms together with the silicon atom to which they are bonded.
In the method of silylation with the chlorosilane compound represented by the above, it was found that by using a sulfonic acid compound or a salt thereof as a catalyst, the silylation reaction can be performed efficiently, and the present invention has been completed. is there.

  Accordingly, the present invention is characterized in that a sulfonic acid compound or a salt thereof is used as a catalyst in the method of silylating the amino group of the amino group-containing compound of the above formula (1) with the chlorosilane compound of the formula (2). A method for silylation of an amino group is provided.

  ADVANTAGE OF THE INVENTION According to this invention, the compound containing the amino group protected by the silyl group useful as a synthetic intermediate of pharmaceuticals and agricultural chemicals, a coating additive, and a polymer modifier can be manufactured efficiently.

The amino group silylation method of the present invention is to silylate an amino group of an amino group-containing compound of the following general formula (1) with a chlorosilane compound of the following general formula (2).
R ¹ R ² NH (1)
(Wherein R ¹ and R ² are a hydrogen atom or a substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms. Alternatively, R ¹ and R ² are bonded to each other and bonded to each other) And may form a ring having 2 to 20 carbon atoms, particularly 3 to 10 carbon atoms.)
R ³ R ⁴ R ⁵ SiCl (2)
(In the formula, R ³ , R ⁴ and R ⁵ are a hydrogen atom, a chlorine atom, or a substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms, and R ³ and R ⁴ , R ³ and R ^5, or R ⁴ and R ⁵ may be bonded to each other to form a ring having 2 to 20 carbon atoms, particularly 3 to 10 carbon atoms, together with the silicon atom to which they are bonded.

  Here, examples of the substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms include linear, branched or cyclic alkyl groups, alkenyl groups, aryl groups, aralkyl groups, and the like. As monovalent hydrocarbon groups, one or more hydrogen atoms of these unsubstituted monovalent hydrocarbon groups are substituted with halogen atoms such as fluorine atoms, chlorine atoms, cyano groups, acryloxy groups, methacryloxy groups, acetoxy groups, and the like. Things can be mentioned.

  In this case, specific examples of the amino group-containing compound of the above formula (1) include ammonia, methylamine, ethylamine, propylamine, isopropylamine, allylamine, butylamine, pentylamine, hexylamine, octylamine, 2-ethylhexylamine. , Benzylamine, cyclopentylamine, cyclohexylamine, ethylenediamine, diethylenetriamine, triethylenetetramine, 1,6-diaminohexane, aniline, toluidine, xylidine, naphthylamine, xylylenediamine, dimethylamine, diethylamine, dipropylamine, diisopropylamine, diallylamine , Dibutylamine, dipentylamine, dioctylamine, di (2-ethylhexyl) amine, ethyleneimine, pyrrolidine, piperi Emissions, piperazine, morpholine, imidazole, N- methylaniline, diphenylamine and the like.

  Specific examples of the chlorosilane compound of formula (2) include dimethylchlorosilane, trimethylchlorosilane, diethylchlorosilane, ethyldimethylchlorosilane, diethylmethylchlorosilane, triethylchlorosilane, vinyldimethylchlorosilane, tripropylchlorosilane, triisopropylchlorosilane, and tributylchlorosilane. , T-butyldimethylchlorosilane, di-t-butylmethylchlorosilane, tri-t-butylchlorosilane, triisobutylchlorosilane, trisec-butylchlorosilane, hexyldimethylchlorosilane, texyldimethylchlorosilane, octyldimethylchlorosilane, decyldimethylchlorosilane, octadecyldimethylchlorosilane , Cyclopentyldimethylchlorosilane, cyclohexyldi Tylchlorosilane, tricyclopentylchlorosilane, tricyclohexylchlorosilane, dimethylphenylchlorosilane, methyldiphenylchlorosilane, triphenylchlorosilane, t-butyldiphenylchlorosilane, di-t-butylphenylchlorosilane, styryldimethylchlorosilane, 2-cyanoethyldimethylchlorosilane, acetoxypropyldimethylchlorosilane 3-acryloxypropyldimethylchlorosilane, 3-methacryloxypropyldimethylchlorosilane, chloromethyldimethylchlorosilane, 3-chloropropyldimethylchlorosilane, 3,3,3-trifluoropropyldimethylchlorosilane, 3,3,4,4,5 , 5,6,6,6-nonafluorohexyldimethylchlorosilane, 3,3,4,4,5, , 6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyldimethylchlorosilane, dichlorosilane, methyldichlorosilane, dimethyldichlorosilane, ethyldichlorosilane, diethyldichlorosilane, vinyl Methyldichlorosilane, divinyldichlorosilane, propylmethyldichlorosilane, dibutyldichlorosilane, t-butylmethyldichlorosilane, di-t-butyldichlorosilane, diisobutyldichlorosilane, disec-butyldichlorosilane, hexylmethyldichlorosilane, texylmethyl Dichlorosilane, Octylmethyldichlorosilane, Decylmethyldichlorosilane, Octadecylmethyldichlorosilane, Cyclopentylmethyldichlorosilane, Cyclohexylmethyldichlorosilane, Dicyclope Nthyldichlorosilane, dicyclohexyldichlorosilane, methylphenyldichlorosilane, diphenyldichlorosilane, t-butylphenyldichlorosilane, styrylmethyldichlorosilane, 2-cyanoethylmethyldichlorosilane, acetoxypropylmethyldichlorosilane, 3-acryloxypropylmethyldichlorosilane , 3-methacryloxypropylmethyldichlorosilane, chloromethylmethyldichlorosilane, 3-chloropropylmethyldichlorosilane, 3,3,3-trifluoropropylmethyldichlorosilane, 3,3,4,4,5,5,6 , 6,6-Nonafluorohexylmethyldichlorosilane, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl Methyl dichloroshi , Trichlorosilane, methyltrichlorosilane, ethyltrichlorosilane, vinyltrichlorosilane, propyltrichlorosilane, isopropyltrichlorosilane, butyltrichlorosilane, t-butyltrichlorosilane, isobutyltrichlorosilane, sec-butyltrichlorosilane, hexyltrichlorosilane, textile Siltrichlorosilane, octyltrichlorosilane, decyltrichlorosilane, octadecyltrichlorosilane, cyclopentyltrichlorosilane, cyclohexyltrichlorosilane, phenyltrichlorosilane, styryltrichlorosilane, 2-cyanoethyltrichlorosilane, acetoxypropyltrichlorosilane, 3-acryloxypropyltrichlorosilane , 3-Methacryloxypropyltrichlorosilane Chloromethyltrichlorosilane, 3-chloropropyltrichlorosilane, 3,3,3-trifluoropropyltrichlorosilane, 3,3,4,4,5,5,6,6,6-nonafluorohexyltrichlorosilane, 3, 3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyltrichlorosilane, tetrachlorosilane, 1,2-bis (dimethylchloro Silyl) ethane, 1,2-bis (methyldichlorosilyl) ethane, 1,2-bis (trichlorosilyl) ethane, 1,6-bis (dimethylchlorosilyl) hexane, 1,6- (methyldichlorosilyl) hexane, 1,6-bis (trichlorosilyl) hexane, bis (dimethylchlorosilyl) norbornane, bis (methyldichlorosilyl) norbornane And bis (trichlorosilyl) norbornane and the like.

  Although the usage-amount of the chlorosilane compound of this invention is not specifically limited, From the point of reactivity and productivity, it is 0.1-4 in conversion of the silicon- chlorine bond of a chlorosilane compound with respect to 1 mol of amino groups of an amino group containing compound. A range of 0 mol, particularly 0.2 to 3.0 mol, is preferred.

  In the present invention, in the silylation reaction of the amino group-containing compound of the above formula (1), the amino group of the amino group-containing compound is silylated with a chlorosilane compound using a sulfonic acid compound or a salt thereof as a catalyst.

  Specific examples of the sulfonic acid compound include sulfuric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, dodecylbenzenesulfonic acid, trifluoromethanesulfonic acid, 1 1,2,2,2-tetrafluoroethanesulfonic acid, 1,1,2,2,2-pentafluoroethanesulfonic acid and the like. Examples of the salt include the ammonium salt, triethylamine salt, pyridine salt and the like of the sulfonic acid.

  The amount of the sulfonic acid compound or a salt thereof of the present invention is not particularly limited, but from the viewpoint of reactivity and productivity, 0.0001 to 0.1 mol, particularly 0, with respect to 1 mol of the amino group of the amino group-containing compound. A range of 0.001 to 0.05 mol is preferred.

  In the silylation reaction of the amino group-containing compound of the present invention, hydrogen chloride is produced as a by-product, which may be captured as a base of the amino group-containing compound itself represented by the above general formula (1). The compound may be captured as a base. As other amine compounds, in addition to the amino group-containing compound represented by the general formula (1), trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, pyridine, dimethylaminopyridine, dimethylaniline, methylimidazole, tetra Examples include methylethylenediamine and 1,8-diazabicyclo [5.4.0] undecene-7.

  Although the usage-amount of another amine compound is not specifically limited, From the point of reactivity and productivity, it is 0.3-10.0 mol with respect to 1 mol of amino groups of an amino group containing compound, Especially 0.5-5. A range of 0 mole is preferred.

  Although the reaction temperature of the said reaction is not specifically limited, 0-200 degreeC, Especially 10-180 degreeC is preferable.

  In addition, although the said reaction advances even without a solvent, a solvent can also be used. Solvents that can be used include hydrocarbon solvents such as pentane, hexane, cyclohexane, heptane, isooctane, benzene, toluene and xylene, ether solvents such as diethyl ether, tetrahydrofuran and dioxane, and ester solvents such as ethyl acetate and butyl acetate. And aprotic polar solvents such as acetonitrile and N, N-dimethylformamide, and chlorinated hydrocarbon solvents such as dichloromethane and chloroform. These solvents may be used alone or in a combination of two or more.

  After completion of the reaction, a hydrochloride of the amine compound is produced, which is filtered or added with water, aqueous sodium hydroxide, ethylenediamine, 1,8-diazabicyclo [5.4.0] undecene-7, It can be removed by a method such as separation. From the reaction solution from which the salt has been removed as described above, the target product can be recovered by an ordinary method such as distillation.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

[Example 1]
In a flask equipped with a stirrer, a reflux condenser, a dropping funnel and a thermometer, 38.6 g (0.2 mol) of triisopropylchlorosilane, 22.3 g (0.21 mol) of triethylamine, and 0.19 g of methanesulfonic acid (0. 002 mol) and heated to 80 ° C. After the internal temperature was stabilized, 12.0 g (0.21 mol) of allylamine was added dropwise over 1 hour, and the mixture was further stirred at that temperature for 3 hours. At this time, the mass ratio of triisopropylsilylallylamine as the target product to triisopropylchlorosilane as the raw material was 97: 3 by gas chromatography analysis.

[Comparative Example 1]
The reaction was performed in the same manner as in Example 1 except that methanesulfonic acid was not added. After completion of dropping, the mass ratio of triisopropylsilylallylamine as the target product to triisopropylchlorosilane as the raw material was 21:79 by gas chromatography analysis at the time of stirring for 3 hours.

[Example 2]
In a flask equipped with a stirrer, a reflux condenser, a dropping funnel and a thermometer, 30.1 g (0.2 mol) of t-butyldimethylchlorosilane, 30 ml of toluene, 0.19 g (0.002 mol) of methanesulfonic acid were charged. Heated to 70 ° C. After the internal temperature was stabilized, 32.2 g (0.44 mol) of diethylamine was added dropwise over 1 hour, and the mixture was further stirred at that temperature for 8 hours. At this time, the mass ratio of the target t-butyldimethylsilyldiethylamine and the raw material t-butyldimethylchlorosilane by gas chromatography analysis was 85:15.

[Comparative Example 2]
The reaction was performed in the same manner as in Example 2 except that methanesulfonic acid was not added. After the completion of dropping, the mass ratio of t-butyldimethylsilyldiethylamine as a target product and t-butyldimethylchlorosilane as a raw material was 3:97 by gas chromatography analysis at the time of stirring for 8 hours.

[Example 3]
A flask equipped with a stirrer, a reflux condenser, a dropping funnel and a thermometer was charged with 14.1 g (0.1 mol) of methylvinyldichlorosilane, 60 ml of toluene, and 0.19 g (0.002 mol) of methanesulfonic acid. Heated to ° C. After the internal temperature was stabilized, 30.7 g (0.42 mol) of diethylamine was added dropwise over 1 hour, and the mixture was further stirred at that temperature for 1 hour. At this time, the mass ratio of bis (diethylamino) methylvinylsilane, which is the target product, to diethylaminomethylvinylchlorosilane, which is the reaction intermediate, was 99.5: 0.5 by gas chromatography analysis.

[Comparative Example 3]
The reaction was performed in the same manner as in Example 3 except that methanesulfonic acid was not added. The mass ratio of the target product bis (diethylamino) methylvinylsilane to the reaction intermediate diethylaminomethylvinylchlorosilane was 23:77, as determined by gas chromatography analysis after stirring for 1 hour.

[Example 4]
In a flask equipped with a stirrer, a reflux condenser, a dropping funnel and a thermometer, 22.6 g (0.105 mol) of 1,2-bis (dimethylchlorosilyl) ethane, 22.3 g (0.22 mol) of triethylamine, trifluoro 0.3 g of romethanesulfonic acid and 60 ml of toluene were charged and heated to 100 ° C. After the internal temperature was stabilized, 9.3 g (0.1 mol) of aniline was added dropwise over 1 hour, and the mixture was further stirred at that temperature for 10 hours. At this point, 1-phenyl-2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane, which is the target product, and 1 which is a reaction intermediate are obtained by gas chromatography analysis. - phenylamino-3-chloro-1,1, 4, 4 - tetramethyl-1, 4 - mass ratio of the disilabutane was 91: 9.

[Comparative Example 4]
The reaction was performed in the same manner as in Example 4 except that trifluoromethanesulfonic acid was not added. 1-phenyl-2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane, which is the target product, as determined by gas chromatography analysis at the time of stirring for 10 hours after completion of the dropping; is a reaction intermediate 1-phenyl-amino-3-chloro-1,1, 4, 4 - tetramethyl-1, 4 - mass ratio of the disilabutane was eleven eighty-nine.

Claims (1)

The following general formula (1)
R ¹ R ² NH (1)
(Wherein R ¹ and R ² are a hydrogen atom or a substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms. Alternatively, R ¹ and R ² are bonded to each other and bonded to each other) And may form a ring having 2 to 20 carbon atoms.)
The amino group of the amino group-containing compound represented by the following general formula (2)
R ³ R ⁴ R ⁵ SiCl (2)
(In the formula, R ³ , R ⁴ and R ⁵ are a hydrogen atom, a chlorine atom, or a substituted or unsubstituted monovalent hydrocarbon group having 1 to 20 carbon atoms, and R ³ and R ⁴ , R ³ and R ^5, or R ⁴ and R ⁵ may be bonded to each other to form a ring having 2 to 20 carbon atoms together with the silicon atom to which they are bonded.
In the method of silylation with a chlorosilane compound represented by the formula (1), a sulfonic acid compound or a salt thereof is used as a catalyst.