JP2001247552A - Method of producing heterocyclic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of producing a benzoxazine derivative or a benzodiazine by a condensation and ring formation reaction not using an organic solvent having a fear of exerting a bad influence on environment. SOLUTION: This method of producing a compound of general formula (3) (Xs are each independently an inert substituent group; Ys are each independently an inert substituent group; m is an integer of 0-4; n is an integer of 0-5; Q is O when Z is OH and NH when Z is NH2) comprises reacting an aniline derivative of general formula (1) (X and m are each as shown in the general formula (3); Z is OH or NH2) with a benzaldehyde derivative of general formula (2) (Y and n are each as shown in the general formula (3)) in the presence of an ionic liquid. Z is OH or.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a benzoxazine derivative or benzodiazine useful as an intermediate for producing a medical or agricultural chemical or a functional substance.

[0002]

2. Description of the Related Art A method for synthesizing oxazolidine by condensing o-aminobenzyl alcohol or o-hydroxybenzylamine with aldehyde or ketone is described in J. Amer.
hem. Soc., 66, 1875 (1944)). According to this, o-aminobenzyl alcohol and an aldehyde or ketone are condensed under reflux in a benzene solvent to continuously remove water, and the reaction is carried out. Except in the case of an aldehyde or a specific ketone, glacial acetic acid is used as a catalyst. It is reported to be used as.

[0003]

SUMMARY OF THE INVENTION The present invention provides a reaction method which does not use an organic solvent which may adversely affect the environment by volatilizing or flowing out.

[0004]

Means for Solving the Problems The present inventor studied the reaction conditions under which the reaction proceeds smoothly without using an organic solvent in the above reaction. The inventors have found that it is not necessary to use the catalyst and it is not necessary to add a catalyst separately, and thus completed the present invention.

That is, the present invention provides a compound represented by the general formula (1)

[0006]

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Wherein X is an inert substituent, m is an integer of 0 to 4, and Z is OH or NH _2, and an aniline derivative represented by the general formula (2):

[0008]

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Wherein Y represents an inert substituent, and n represents an integer of 0 to 5. A benzaldehyde derivative represented by the following formula: 3)

[0010]

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(Wherein X, Y, m and n are the same as those in the general formula (1) or the general formula (2);
H represents O, and NH ₂ represents NH. )).

The general formula (1) used in the present invention,

[0013]

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The aniline derivative represented by the formula (wherein, X is independently an inert substituent, m is an integer of 0 to 4, and Z is OH or NH ₂ ) is not particularly limited. . X may form a divalent group by joining together, and may be a condensed ring, unsaturated carbon chain, saturated carbon chain, heterocondensed ring, unsaturated heterocyclic ring, saturated heterocyclic ring, An inert substituent may be bonded. The inert substituent is not particularly limited. A halogen (fluorine, chlorine, bromine or iodine) atom, an alkyl group which may have a substituent, a halogenated alkyl group which may have a substituent, an alkoxy group which may have a substituent, or a substituent Certain halogenated alkoxy groups and aryl groups can be exemplified. Examples of the aryl group include condensed carbocyclic compounds such as a phenyl group and a naphthyl group which may have a substituent, and condensed heterocyclic compounds such as a pyridyl group and a quinolyl group. Here, the substituent is not limited as long as it is an inert group.

The general formula (2) used in the present invention

[0016]

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(In the formula, Y is each independently an inert substituent, and n is an integer of 0 to 5.) The benzaldehyde derivative is not particularly limited. Examples of the inert substituent include a halogen (fluorine, chlorine, bromine or iodine) atom, an alkyl group which may have a substituent, a halogenated alkyl group which may have a substituent, and an alkoxy group which may have a substituent. Examples thereof include a halogenated alkoxy group which may have a group and a substituent, and an aryl group. Examples of the aryl group include condensed carbocyclic compounds such as a phenyl group and a naphthyl group which may have a substituent, and condensed heterocyclic compounds such as a pyridyl group and a quinolyl group. Here, the substituent is not limited as long as it is an inert group.

From the benzyl alcohol or aminobenzylamine represented by the general formula (1) and the benzaldehyde represented by the general formula (2), respectively, the following formulas (X, Y
Are each independently an inert substituent, m is an integer of 0 to 4,
n represents the integer of 0-5. ) Is obtained.

[0019]

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The method for producing benzoxazolidine or benzoaziridine of the present invention is characterized in that the reaction is carried out in the presence of an ionic liquid.

The ionic liquid used in the present invention (ionic liquor)
ids) is a salt composed entirely of organic cationic species and anionic species, is liquid at a temperature of about 100 ° C. or lower, and has substantially no vapor pressure near room temperature (25 ° C.) and has a high temperature (eg, about 300 ° C.) This refers to a substance that remains in a liquid state until). The ionic liquid serves as a solvent for organic compounds and inorganic compounds, and may itself be used as a catalyst for alkylation reactions, organic polymer polymerization reactions, oligomerization reactions, and the like, and as a solvent for extracting metals or organic substances.

The ionic liquid according to the present invention is a salt comprising a heterocyclic cation and an anionic species. As the heterocyclic cation,

[0023]

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Wherein R is independently an alkyl group.
Or an aryl group. n represents an integer. )
It is a cationic species. In the present specification, each of Im⁺(I
Midazolium cation), Py⁺(Pyridinium Kachio
N), bigN⁺(If n = 3, 1,5-diazabi
Cyclo [4,3,0] nonenium cation), bicy
U ⁺(When n = 5, 1,8-diazabicyclo [5,
4,0] -7-undecenium cation)
There is. As an alkyl group, it has about 1 to 22 carbon atoms.
Yes, preferably about 1 to 5
May be. For example, methyl group, ethyl group, n-pro
Pill group, isopropyl group, n-butyl group, n-pentyl
Group, n-hexyl group, benzyl group, etc.
Not limited to these. The carbon number (n) of the polymethylene group is 3
２２22, and 3 or 5 is particularly preferred. Ally
Substituted or unsubstituted phenyl, naphthyl
And the like.

Of these, Im⁺(Imidazoliumka
Thion), bigN⁺And bicyU ⁺Induction of Pyrimidine
Body cations are preferred, Im⁺In, R is different from each other
Disubstituted-imidazolium cations are more preferred.

The anion species according to the present invention include carboxylate represented by the general formula (4) and R'COO- (4) (wherein R 'represents an alkyl group or a fluoroalkyl group); equation _{(5), R'SO 3 - (} 5) (. wherein, R 'is an alkyl group, a fluoroalkyl group) alkane sulfonate represented by the general formula _{(6), (R'SO 2)} 2 A bisalkanesulfonylamide anion represented by N- (6) (wherein R 'represents an alkyl group or a fluoroalkyl group, or two R's are connected to each other to represent an alkylene group or a fluoroalkylene group) It is.

As the carboxylate represented by the general formula (4), R ′ has about 1 to 10 carbon atoms, and is acetate, propionate, trifluoroacetate (hereinafter, referred to as TA ⁻ ), pentafluoropropano. benzoate, heptafluoro butanoate (hereinafter, HB ^- called), etc. nonafluorobutyl pentanoate can be exemplified.

The alkane sulfonate represented by the general formula (5) is a carboxylate in which R 'has about 1 to 10 carbon atoms, and is methane sulfonate, ethane sulfonate, trifluoromethane sulfonate (hereinafter referred to as TfO).
^-That's right. ), Pentafluoroethanesulfonate,
2,2,2-trifluoroethanesulfonate, heptafluoropropanesulfonate, 2,2,3,3,3-
Pentafluoropropanesulfonate, nonafluorobutanesulfonate (hereinafter, Nfo ^-. Hereinafter), and others.

As the bisalkanesulfonylamide anion represented by the general formula (6), R ′ has 1 to 1 carbon atoms.
About 0, bis (trifluoromethanesulfonyl)
Amide (hereinafter, Tf ₂ N ^-. Called), bis (pentafluoroethane sulfonyl) amide, bis (heptafluoropropanesulfonyl) amide, bis (nonafluorobutanesulfonyl) amide, bis (undecafluoro-pentane sulfonyl) amide, ( Trifluoromethanesulfonyl) (pentafluoroethanesulfonyl) amide, (trifluoromethanesulfonyl) (heptafluoropropanesulfonyl) amide, (trifluoromethanesulfonyl) (nonafluorobutanesulfonyl) amide, bis (2,2,2-trifluoroethanesulfonyl) ) Amide, (trifluoromethanesulfonyl) (2,2,2-
Each anion such as trifluoroethanesulfonyl) amide,

[0030]

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(Wherein m represents an integer of 2 to 10).

[0032] Other, halogen (chlorine, bromine, iodine) ions, complex ions, for example, hexafluorophosphate (hereinafter, HP ^-. Hereinafter), tetrachloroaluminate, tetrafluoroborate (hereinafter, TB ^-. Hereinafter) such as Is mentioned.

As an example of the ionic liquid according to the present invention,
[1-Methyl-3-methyl Im⁺] [TfO^-], [1-
Methyl-3-methyl Im⁺] [Tf_TwoN^-], [1-Methyl
Le-3-methyl Im⁺] [TA^-], [1-ethyl-3-
Methyl Im⁺] [TfO^-], [1-ethyl-3-methyl]
Im⁺] [NfO^-], [1-ethyl-3-methyl I
m ⁺] [Tf_TwoN^-], [1-ethyl-3-methyl Im⁺]
[TA^-], [1-ethyl-3-methyl Im⁺] [H
B^-], [1-butyl-3-methyl Im⁺] [Tf
O^-], [1-butyl-3-methyl Im⁺] [Nf
O^-], [1-butyl-3-methyl Im⁺] [Tf
_TwoN^-], [1-butyl-3-methyl Im⁺] [TA^-],
[1-butyl-3-methyl Im⁺] [HB^-], [1-a
Sobutyl-3-methyl Im⁺] [Tf_TwoN^-], [1-me
Toxiethyl-3-methyl Im⁺] [TfO^-], [1-
Methoxyethyl-3-methyl Im⁺] [Tf_TwoN^-],
[1- (2,2,2-trifluoroethyl) -3-methyl]
Le Im⁺] [TfO^-], [1- (2,2,2-trifur
Oroethyl) -3-methyl Im⁺] [Tf_TwoN^-] [1-
Ethyl-3-ethyl Im⁺] [TfO^-], [1-ethyl
-3-ethyl Im⁺] [Tf_TwoN^-], [1-ethyl-3
-Methyl Im⁺] [TA^-], [1-butyl-3-ethyl]
Im⁺] [TfO^-], [1-butyl-3-ethyl I
m⁺] [NfO^-], [1-butyl-3-ethyl Im⁺]
[Tf_TwoN^-], [1-butyl-3-ethyl Im⁺] [T
A^-], [1-Ethyl-2,3-dimethyl Im⁺] [Tf
O^-], [1-Ethyl-2,3-dimethyl Im⁺] [Tf
_TwoN^-], [1-Ethyl-2,3-dimethyl Im⁺] [T
A^-], [1,2-Diethyl-3-methyl Im⁺] [Tf
O^-], [1,2-Diethyl-3-methyl Im⁺] [Tf
_TwoN^-], [1-ethyl-3,5-dimethyl Im⁺] [T
fO^-], [1-ethyl-3,5-dimethyl Im⁺] [T
f_TwoN^-], [1,3-diethyl-5-methyl Im⁺]
[TfO^-], [1,3-diethyl-5-methyl Im⁺]
[Tf_TwoN^-] And [N-methyl Py⁺] [Tf
O^-], [N-methyl Py⁺] [Tf_TwoN^-], [N-E
Chill Py⁺] [TfO^-], [N-ethyl Py⁺] [Tf
_TwoN^-], [N-propyl Py⁺] [TfO^-], [N-
Propyl Py⁺] [Tf_TwoN^-], [N-butyl Py⁺]
[TfO^-], [N-butyl Py⁺] [Tf_TwoN^-], [
N-pentyl Py⁺] [TfO^-], [N-pentyl P
y⁺] [Tf_TwoN^-], Etc. [5-methyl bicyN⁺] [T
fO^-], [5-methyl bicyN⁺] [Tf_TwoN^-],
[5-ethyl bicyN⁺] [TfO^-], [5-ethyl
bicyN⁺] [Tf_TwoN^-], [5-propyl bicy
N⁺] [TfO^-], [5-propyl bicyN⁺] [T
f_TwoN^-], [5-isopropyl bicyN⁺] [Tf
O^-], [5-isopropyl bicyN⁺] [Tf
_TwoN^-], [5-butyl bicyN⁺] [TfO ^-], [5
-Butyl biN⁺] [Tf_TwoN^-], [5-isobutyi]
Le bicyN⁺] [TfO^-], [5-isobutyl bic
yN⁺] [Tf_TwoN^-] And [8-methyl bicyU⁺]
[TfO^-], [8-methyl bicyN⁺] [Tf
_TwoN^-], [8-ethyl bicyU⁺] [TfO^-], [8
-Ethyl bicyU⁺] [Tf_TwoN^-], [8-propyl
bicyU⁺] [TfO^-], [8-propyl bicyU
⁺] [Tf_TwoN^-], [8-isopropyl bicyU⁺]
[TfO^-], [8-isopropyl bicyU⁺] [Tf
_TwoN^-], [8-butyl bicyU⁺] [TfO ^-], [8
-Butyl bicyU⁺] [Tf_TwoN^-], [8-isobutyi]
Le bicyU⁺] [TfO^-], [8-isobutyl bic
yU⁺] [Tf_TwoN^-] Etc. can be illustrated.

As the anion species, among the above, fluorocarboxylate, fluoroalkanesulfonate and bis (fluoroalkanesulfonyl) amide anion are preferable, and perfluoroalkanesulfonate and bis (perfluoroalkanesulfonyl) amide anion are more preferable.

Preferred as the ionic liquid of the present invention are dialkyl-substituted (or alkyl-dihalogenated) -imidazolium = perfluoroalkanesulfonate, dialkyl-substituted (or alkyl-dihalogenated) -imidazolium = bis Pyrimidine derivatives such as (perfluoroalkanesulfonyl) amide, dialkyl-substituted (or dihalogenated alkyl) -imidazolium = hexafluorophosphate, dialkyl-substituted (or dihalogenated alkyl) -imidazolium = tetrafluoroborate Examples thereof include perfluoroalkanesulfonate and pyrimidine derivative = bis (perfluoroalkanesulfonyl) amide, and it is more preferable to use trifluoromethanesulfonate as an anion. Here, the alkyl group has about 1 to 22 carbon atoms, preferably about 1 to 5 carbon atoms, and may have a branch in any case. For example, methyl group, ethyl group, n-
Examples include a propyl group, an isopropyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, and a benzyl group.

Particularly preferred examples of the ionic liquid of the present invention include [8-methyl bicy U ⁺ ].
[TfO ^-] [8-methyl-1,8-diazabicyclo [5,4,0] -7-Undeseniumu = trifluoromethanesulfonate], [8-ethyl bicyU ^+] [T
fO ^-] [8-ethyl-1,8-diazabicyclo [5,
[4,0] -7-undecenium trifluoromethanesulfonate], [5-ethylbicyN ⁺ ] [TfO ⁻ ]
[5-ethyl-1,5-diazabicyclo [4,3,0]
Nonenium trifluoromethanesulfonate], [1
-Ethyl-3-methyl Im ⁺ ] [TfO ⁻ ] [1-ethyl-3-methylimidazolium = trifluoromethanesulfonate].

The method for producing the ionic liquid of the present invention is not limited, but will be exemplified below. First, the heterocyclic compound is reacted with an alkylating agent to obtain a quaternary ammonium salt.
Typical examples of the alkylating agent include methyl chloride, ethyl chloride, methyl bromide, ethyl bromide, dimethyl sulfate, diethyl sulfate, and benzyl chloride, but other known alkylating agents can also be selected. In this case, since the obtained quaternary ammonium salt contains a halogen ion such as chlorine or a sulfate ion as a counter ion, an acid containing the desired anionic species, for example, trifluoromethanesulfonic acid or the like is added to add the anionic species. Can be ion-exchanged to a trifluoromethanesulfonic acid group. For example, an anion species exchange reaction from a halogen ion to a bis (perfluoroalkanesulfonyl) amide ion can be obtained by reacting lithium bis (trifluoromethanesulfonyl) amide in water. The exchange reaction to perfluoroalkanesulfonate can be performed by reacting potassium salt of perfluoroalkanesulfonic acid or the like. The anion species exchange reaction to a carboxylate ion or a perfluorocarboxylate ion can also be obtained by reacting each with a salt of sodium, potassium, silver or the like to separate a hardly soluble halogen metal salt. In addition, if an alkyl ester (for example, ethyl trifluoromethanesulfonate) of an acid (for example, trifluoromethanesulfonic acid) corresponding to an anionic species is used as an alkylating agent, an ionic liquid having trifluorosulfonate or the like as an anionic species is directly formed. can get.

The method of the present invention comprises the steps of preparing an aniline derivative represented by the general formula (1) and a aniline derivative represented by the general formula (2) in an ionic liquid, for example, 1-ethyl-3-methylimidazolium salt of trifluoromethanesulfonic acid. This is performed by adding a benzaldehyde derivative and maintaining the temperature at a predetermined value. Since water is generated as the reaction proceeds, it can be continuously distilled during the reaction, and a dehydrating agent can be added to the reaction system. You can also.
The reaction can be stirred or refluxed, and these measures can generally accelerate the reaction. In the method of the present invention, a catalyst such as an acid can be separately added, but is not usually required.

After completion of the reaction, when the ionic liquid and other reaction components are separated, the ionic liquid and the reactant can be separated by a separating funnel or the like, or the reactant is extracted with an organic solvent or the like. You can also. The collected ionic liquid can be purified by washing with an organic solvent or an aqueous solution, but the method of the present invention can be used again usually without further purification. On the other hand, the reaction product can be purified by the same method as in the ordinary post-treatment of the organic synthesis reaction.

In the method of the present invention, the ionic liquid may be used in any amount, but it may be used to such an extent that the reaction system is in a fluid state, and it is not always necessary that the whole is dissolved.

In the method of the present invention, one mole of the benzaldehyde derivative represented by the general formula (2) is involved in the condensation with respect to 1 mol of the aniline derivative represented by the general formula (1), and therefore, basically, it is involved. Although 1 mol may be used, about 0.5 to 10 mol is used, and about 1 to 2 mol is preferably adopted.

The reaction temperature varies depending on the combination of the aniline derivative represented by the general formula (1) and the benzaldehyde derivative represented by the general formula (2), but the reaction is carried out at a temperature higher than the freezing point of the reaction system and lower than the boiling point of the ionic liquid. . Usually, 0 to 200
C., preferably about 20 to 150.degree.
The pressure of the reaction system is set to about 0 to 10 PMa, and usually 0M
It may be carried out in the vicinity of Pa, and can be appropriately adjusted according to the boiling point of the reaction reagent.

Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited to these embodiments. Examples are shown below to exemplify that the condensation reaction according to the present invention can be applied to various compounds described in the present specification.

[0044]

EXAMPLES Preparation Example 1 Preparation of 8-ethyl-1,8-diazabicyclo [5,4,0] -7-undecenium trifluoromethanesulfonate 1,8-diazabicyclo [5,4,0] -7 - ethyl undecene 30.4 g (0.2 mol) trifluoromethanesulfonate _{(CF 3 SO 3 Et) 35.6g} (0.
2 mol) at room temperature, and the mixture was stirred for 2 hours. Thereafter, low-boiling substances were distilled off under reduced pressure in an oil bath at 70 ° C. for 2 hours to give a yield of 9%.
At 8%, 8-ethyl-1,8-diazabicyclo [5,4,
0] -7-undecenium trifluoromethanesulfonate was obtained.

Mp: 36-37 ° C. ¹ H-NMR (CDCl ₃ ): δ 1.28 (3H, t, J
= 7.32 Hz), 1.75-1.84 (8H, m)
2.15 (2H, m) 2.87 (2H, m) 3.55-
3.59 (2H, m) 3.60 (2H, q, J = 7.3
2 Hz) 3.68 (2H, m) ¹³ C NMR (CDCl ₃ ): δ 13.554, 19.9
59,22.841,25.937,28.069,2
8.475, 46.210, 48.855, 48.96
8, 55.080, 120.584 (q, J = 320.
^{4Hz), 165.966 19 F-NMR} (CDCl 3): δ83.37 (C 6 F 6 standard).

Elemental analysis: Calculated value (C ₁₂ H ₂₁ F ₃ N _{2)
SO 3: C, 43.63; H6.41} ; 8.48). Measurements (C, 43.43; H, 6.41; N, 8.5
0).

Preparation Example 2 Preparation of 8-methyl-1,8-diazabicyclo [5,4,0] -7-undecenium trifluoromethanesulfonate 1,8-diazabicyclo [5,4,0] -7- 16.4 g of methyl trifluoromethanesulfonate (CF ₃ SO ₃ Me) was added to 15.2 g (0.1 mol) of undecene.
1 mol) at room temperature, and the mixture was stirred for 2 hours. Then, a low-boiling substance was distilled off under reduced pressure for 2 hours in an oil bath at 70 ° C. to give a yield of 9%.
8-methyl-1,8-diazabicyclo [5,4,5%
0] -7-undecenium trifluoromethanesulfonate was obtained.

¹ H-NMR (CDCl ₃ ): δ 1.29
(3H, t, J = 7.14 Hz), 2.13-2.81
(4H, m), 3.07 (2H, t, J = 7.96H
z), 3.48 (6H, m), 3.79 (2H, t, J
= 7.69 Hz). ¹³ C NMR (CDCl ₃ ): δ 19.856, 22.1
32, 26.165, 28.649, 28.718, 4
1.203, 48.707, 48.847, 55.24
3, 120.459 (q, J = 320.4 Hz), 16
6.516 ¹⁹ F-NMR (CDCl ₃ ): δ 83.37 (C ₆ F ₆ standard).

Preparation Example 3 Preparation of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate 109 g (1 mol) of 1-methylimidazole and ethyltrifluoromethanesulfonate (CF ₃ SO ₃ Et) 1
After adding 78 g (1 mol) at room temperature and stirring for 2 hours,
The low-boiling substances were distilled off under reduced pressure in an oil bath at 70 ° C. for 2 hours to obtain 1-ethyl-3-methylimidazolium trifluoromethanesulfonate in a yield of 98%. Physical property data agreed with literature values.

Example 1 Synthesis of 4H, 2H-2- (phenyl) -3,1-benzoxazine 8-ethyl-1,8-diazabicyclo [5,4,0]-
246 mg of 2-aminobenzyl alcohol (1 g of 7-undecenium trifluoromethanesulfonate)
mmol) and 212 mg of benzaldehyde (2 mmol)
After l) was added and the mixture was stirred at room temperature for 30 minutes, the organic matter was extracted three times with 20 ml of diethyl ether, and the lower ionic liquid was recovered (recovered at 99% or more). The diethyl ether layer was dried over magnesium sulfate (MgSO ₄ ), and the product was isolated after distilling off diethyl ether (95% yield).

¹ H-NMR (CDCl ₃ ): δ4.95
(1H, d, J = 14.56 Hz), 5.35 (1H,
d, J = 14.56 Hz), 5.95 (1H, s),
6.70-7.60 (Ar-H). ¹³ C-NMR (CDCl ₃ ): δ 67.641, 85.
126, 116.879, 119.596, 121.9
51,124.831,126.371,127.24
7, 128.469, 128.890, 128.91
3,138.913,141.428,159.5. Calcd _{(C 14 H 13 NO: C} , 79.60;
H, 6.20; N, 6.63), found (C, 79.3).
5; H, 6.45; N, 6.70).

[0052]

[Table 1]

[Explanation of Table] Ionic liquid 1: 8-ethyl-1,8-diazabicyclo [5,4,0] -7-
Undecenium trifluoromethanesulfonate ionic liquid 2: 8-methyl-1,8-diazabicyclo [5,4,0] -7-
Undecenium = trifluoromethanesulfonate ionic liquid 3: 1-ethyl-3-methylimidazolium = trifluoromethanesulfonate ionic liquid 4: 1-ethyl-3-methyl-imidazolium = tetrafluoroborate ionic liquid 5: 1-butyl- 3-Methyl-imidazolium = hexafluorophosphate * mark: The recovered ionic liquid from the previous reaction was used.

The same reaction was performed using the recovered ionic liquid. The yield was 96% and the recovery of the ionic liquid was 97% (Example 1-2).

The same reaction was performed again using the ionic liquid recovered in the previous reaction. The yield was 97% and the recovery rate of the ionic liquid was 85% (Example 1-3).

[Examples 2 to 5] The ionic liquid was treated with 8-methyl-1,8-diazabicyclo [5,4,0] -7-undecenium trifluoromethanesulfonate, 1-ethyl-3-methyl-imidazolium = Trifluoromethanesulfonate, 1-ethyl-3-methyl-imidazolium tetrafluoroborate (Solvent Innovation
1-butyl-3-methyl-imidazolium =
Hexafluorophosphate (Solvent Innovation
And the same reaction as in Example 1 was carried out. Table 1 shows the results
Shown in

Example 6 Synthesis of 4H, 2H-2- (4'-fluorophenyl) -3,1-benzoxazine 1-ethyl-3-methylimidazolium = 2 in 780 mg (3 mmol) of trifluoromethanesulfonate −
246 mg (2 mmol) of aminobenzyl alcohol and 248 mg (2 mmol) of 4-fluorobenzaldehyde
After l) was added and the mixture was stirred at room temperature for 30 minutes, the organic matter was extracted three times with 20 ml of diethyl ether, and 763 mg (98% recovery) of the lower ionic liquid was recovered. The diethyl ether layer was dried over magnesium sulfate (MgSO ₄ ), and after distilling off diethyl ether, the product was isolated (yield 97%).

¹ H-NMR (CDCl ₃ ): δ 4.95
(1H, d, J = 14.55 Hz), 5.10 (1H,
d, J = 14.55 Hz), 5.57 (1H, s),
6.70-7.60 (Ar-H). ¹⁹ F-NMR (CDCl ₃ ): δ49.1 (1F,
m). Elemental analysis: calculated values (C ₁₄ H ₁₂ FNO: C, 73.35;
H, 5.28; N, 6.11), found (C, 72.9).
9; H, 5.01; N, 6.15).

Example 7 Synthesis of 4H, 2H-2- (4'-trifluoromethylphenyl) -3,1-benzoxazine In 1300 mg (5 mmol) of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate To 2
-615 mg (5 mmol) of aminobenzyl alcohol
And 870 mg of 4-trifluoromethylbenzaldehyde
(5 mmol), and the mixture was stirred at room temperature for 3 hours. Then, organic substances were extracted three times with 20 ml of diethyl ether.
1280 mg (98% recovery) of the lower ionic liquid was recovered. The diethyl ether layer was separated from magnesium sulfate (MgSO
_After drying in ₄ ) and distilling off diethyl ether, the product was isolated (yield 95%).

¹ H-NMR (CDCl ₃ ): δ 4.10.
(NH, bs), 4.94 (1H, d, J = 14.55)
Hz), 5.10 (1H, d, J = 14.55 Hz),
5.63 (1H, s), 6.70-7.70 (Ar-
H). ¹³ C-NMR (CDCl ₃ ): δ 67.40, 84.3
1,117.47,120.24,122.22,12
4.95, 125.40, 125.45, 125.5
0, 125.60, 126.90, 127.45, 13
1.00 (q), 140.93, 142.71. ¹⁹ F-NMR (CDCl ₃ ): δ 63.3 (3F,
s). Elemental analysis: calculated value (C ₁₅ H ₁₂ F ₃ NO: C, 64.5)
2; H, 4.33; N, 5.06), found (C, 6)
H, 4.76; N, 5.07).

Example 8 Synthesis of 4H, 2H-2- (phenyl) -5-chloro-3,1-benzoxazine 8-ethyl-1,8-diazabicyclo [5,4,0]-
7-undecenium 2-amino-5-chlorobenzyl alcohol in 1 g of trifluoromethanesulfonate
46 mg (2 mmol) and benzaldehyde 212 mg
(2 mmol) and stirred at room temperature for 30 minutes.
The organic substance was extracted three times using 20 ml of diethyl ether, and the lower ionic liquid was recovered (97% recovery). The diethyl ether layer was dried over magnesium sulfate (MgSO ₄ ), and the product was isolated after distilling off diethyl ether (96% yield).

¹ H-NMR (CDCl ₃ ): δ 4.10,
4.88 (1H, d, J = 14.84 Hz), 5.05
(1H, d, J = 14.84 Hz), 5.54 (1H,
s), 6.62-7.56 (Ar-H).

[Examples 9 to 10] As an ionic liquid, 8
-Methyl-1,8-diazabicyclo [5,4,0] -7
The same reaction as in Example 8 was carried out using -undecenium = trifluoromethanesulfonate or 1-ethyl-3-methylimidazolium = trifluoromethanesulfonate. Table 1 shows the results.

Embodiment 11 4H, 2H-2- (4'-
Synthesis of (fluorophenyl) -5-chloro-3,1-benzodiazine 246 mg (2 mmol) of 2-amino-5-chlorobenzyl alcohol in 780 mg of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate and 4
-248 mg (2 mmol) of fluorobenzaldehyde
After stirring at room temperature for 30 minutes, the organic matter was extracted three times with 20 ml of diethyl ether, and the lower ionic liquid was recovered (99% recovery). The diethyl ether layer was dried over magnesium sulfate (MgSO ₄ ) and the product was isolated after distilling off diethyl ether (yield 99).
%).

¹ H-NMR (CDCl ₃ ): δ 4.88
(1H, d, J = 14.83 Hz), 5.19 (1H,
d, J = 14.83 Hz), 5.54 (1H, s),
6.64-7.57 (Ar-H). ¹³ C-NMR (CDCl ₃ ): δ 67.729, 84.
462, 115.347, 115.635, 118.1
84, 123.385, 124.747, 127.37
3,128.172 (d, J = 8.3 Hz), 134.
590 (d, J = 3.15 Hz), 136,000, 1
39.500, 139.877, 164.593. ¹⁹ F-NMR (CDCl ₃ ): δ49.41 (1F,
m).

Example 12 Synthesis of 4H, 2H-2- (phenyl) -3,1-benzodiazine 8-ethyl-1,8-diazabicyclo [5,4,0]-
244 mg of 2-aminobenzylamine (2 mm) in 1 g of 7-undecenium trifluoromethanesulfonate
ol) and 212 mg (2 mmol) of benzaldehyde were added, and the mixture was stirred at room temperature for 30 minutes. Thereafter, organic substances were extracted three times with 20 ml of diethyl ether, and the lower ionic liquid was recovered (recovered at 99% or more). The diethyl ether layer was dried over magnesium sulfate (MgSO ₄ ), and the product was isolated after distilling off diethyl ether (yield 92).
%).

¹ H-NMR (CDCl ₃ ): δ 3.99
(1H, d, J = 16.75 Hz), 4.27 (1H,
d, J = 16.75 Hz), 5.24 (1H, s),
6.57-7.53 (Ar-H).

Examples 13 and 14 As ionic liquids,
8-methyl-1,8-diazabicyclo [5,4,0]-
The same reaction as in Example 12 was carried out using 7-undecenium trifluoromethanesulfonate or 1-ethyl-3-methylimidazolium trifluoromethanesulfonate. Table 1 shows the results.

Example 15 4H, 2H-2- (4'-
Synthesis of (fluorophenyl) -3,1-benzodiazine In 780 mg of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, 244 mg (2 mmol) of 2-aminobenzylamine and 248 mg (2 mmol) of 4-fluorobenzaldehyde were added, and room temperature was added. 3
After stirring for 0 minutes, the organic matter was extracted three times with 20 ml of diethyl ether, and the lower ionic liquid was recovered (94% or more recovery). The diethyl ether layer was dried over magnesium sulfate (MgSO ₄ ), and after distilling off diethyl ether, the product was isolated (yield 97%).

¹ H-NMR (CDCl ₃ ): δ3.98
(1H, d, J = 16.75 Hz), 4.26 (1H,
d, J = 16.75 Hz), 5.24 (1H, s),
6.59-7.53 (Ar-H). ¹³ C-NMR (CDCl ₃ ): δ 46.328, 68.
916, 114.975, 115.294, 115.5
78, 115.732 (d, J = 8.31 Hz), 11
8.230,121.064,126.090,12
7.175, 128.249 (d, J = 8.01H
z), 136.172, 139.664, 143.37
1. ¹⁹ F-NMR (CDCl ₃ ): δ 48.18 (1F,
m).

[0071]

According to the method of the present invention, an ionic liquid is used in place of an organic solvent, so that an organic solvent which may have an adverse effect on the environment by flowing to the outside is not used as a reaction medium. The desired benzoxazine or benzodiazine can be produced without adding a catalyst.

Claims (3)

[Claims] 1. A compound of the general formula (1) (In the formula, X is each independently an inert substituent, and m is 0 to
And Z represents OH or NH ₂ . ) And an aniline derivative represented by the general formula (2): (Wherein, Y is each independently an inert substituent, and n is 0 to
Represents an integer of 5. A) reacting a benzaldehyde derivative represented by the formula (3) in the presence of an ionic liquid. (Wherein, X, Y, m and n are the same as in the general formula (1) or the general formula (2), and Q is O, NH when Z is OH)
_In the case of ₂ , it represents NH. )). 2. The method for producing a heterocyclic compound according to claim 1, wherein the ionic liquid is dialkyl-substituted (or alkyl-dihalogenated) -imidazolium = perfluoroalkanesulfonate. 3. The method for producing a heterocyclic compound according to claim 1, wherein the ionic liquid is a pyrimidine derivative = perfluoroalkanesulfonate.