JPH06298746A - Production of cyclic imido ester - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an intermediate of pharmaceuticals, agrichemicals, etc., a modifier for a polymer, etc., in high yield and at a low cost by reacting a nitrile compound and aminoalcohol in the presence of rhodium complex catalyst. CONSTITUTION:The compound of formula II is obtained by reacting a compound of the formula RCN (R is 1-15C alkyl, 7-10C bicycloalkyl, phenylalkenyl, etc.) with a compound of formula I [(m) is 0-1; R<1> to R<6> are H, methyl, ethyl or propyl] in the presence of a rhodium complex catalyst of the formula RhX[Ph2P (CH2)nPPh2]Y [(n) is 3-6; X is H, halogen, PF6, ClO4, etc.; Y is norbornadiene, cyclooctadiene, etc.; Ph is phenyl] or a rhodium complex catalyst obtained by compounding a compound of the formula PhX(PPh3)3 with 0.5-2 times mole of Ph2P(CH2)3PPh2, etc., in an inert gas atmosphere or in hydrogen atmosphere at 0-250 deg.C. The solvent and catalyst can be reused.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a cyclic imidic acid ester which is useful as an intermediate for medicines, agricultural chemicals, dyes and the like, a modifier for polymers and an additive for adhesives. More specifically, 2 from nitrile compound and amino alcohol
The present invention relates to a new method for producing a cyclic imidate ester using a rhodium complex catalyst having a bidentate ligand.

[0002]

2. Description of the Related Art Conventionally, lithium has been used as a method for synthesizing a cyclic imidate ester from nitrile and amino alcohol.
A method is known in which metal ions such as calcium, zinc, cadmium, copper, manganese, iron, cobalt and nickel are used as catalysts (German Patent 2127776, 21).
58061, 2158615, 3224880, Lie
bigs Ann. Chem. 1974, 996-10.
09). In particular, Lewis acids (zinc, cadmium, etc.) are generally often used as a method for activating nitriles. However, good results have not been obtained when metal ions other than Lewis acids are used as catalysts. Further, these catalysts have problems in terms of recovery and reuse, and there is a problem in improving productivity per catalyst.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above problems by producing a cyclic imidic acid ester by a rhodium complex catalyst having a bidentate ligand.

[0004]

As a result of intensive studies to solve the above problems, the present invention has been completed. That is, the present invention provides the compound represented by the general formula (I) RCN ... (I) [wherein, R is (1) a C _{1 to} C ₅ alkyl group, and C ₁ to C _5
5 alkoxy group, N-alkyl substituted pyrrolyl group, thienyl group, furyl group or phenyl group (halogen atom,
C ₁ -C ₅ alkyl group or C ₁ -C ₅ alkoxy group) which may be substituted with C)
_{1 to} C ₁₅ alkyl group, (2) C _{7 to} C ₁₀ bicycloalkyl group (which may be substituted with C _{1 to} C ₅ alkyl group), (3) N-alkyl-substituted pyrrolyl group, thienyl group , Furyl group or phenyl group (halogen atom, C ₁
To C ₅ alkyl group or C _{1 to} C ₅ alkoxy group) or (4) halogen atom, C
It is substituted with ₁ -C ₅ alkyl group or an alkoxy group of C ₁ -C ₅ shows a phenyl alkenyl group. ] And a nitrile compound represented by

General formula (II)

[Chemical 3] [In the formula, m represents an integer of 0 or 1, and R ^{1 to} R ⁶ each independently represent a hydrogen atom, a methyl group, an ethyl group or a propyl group. ] With an amino alcohol represented by

General formula (III) RhX [Ph ₂ P (CH ₂ ) _n PPh ₂ ] Y (III) [In the formula, n is an integer of 3 to 6, X is a hydrogen atom, a halogen atom, PF ₆ , ClO ₄ , BF ₄ or CF ₃ SO ₃ ,
Y represents norbornadiene, cyclooctadiene or cyclooctatriene, and Ph represents a phenyl group. ] Or a rhodium complex catalyst represented by

General formula (IV) RhX (PPh ₃ ) ₃ (IV) [wherein X represents the same meaning as described above. ] To Ph ₂ P (C
H ₂ ) ₃ PPh ₂ , Ph ₂ P (CH ₂ ) ₄ PPh ₂ , P
h ₂ P (CH ₂ ) ₅ PPh ₂ or Ph ₂ P (CH
₂ ) General formula (V) characterized by reacting in the presence of a rhodium complex catalyst to which ₆ PPh ₂ is added in a 0.5-fold to 2-fold molar equivalent amount

[Chemical 4] [In the formula, R ^{1 to} R ⁶ and m have the same meanings as described above. ] The manufacturing method of the cyclic imide acid ester represented by these.

The present invention will be described in detail below. The following can be used as the nitrile compound of the general formula (I) which is a raw material used in the production method of the present invention. That is,
(1) R is a C ₁ -C ₅ alkyl group, a C ₁ -C ₅ alkoxy group, an N-alkyl-substituted pyrrolyl group, a thienyl group,
Furyl group or phenyl group (halogen atom, C _{1 to} C
₅ alkyl groups or C ₁ -C ₅ alkoxy groups) may be substituted with C ₁ -C ₁₅
A compound representing an alkyl group of, for example, acetonitrile, propionitrile, butyronitrile, capronitrile, dodecanitrile, trimethylacetonitrile, phenylacetonitrile, 2-thiopheneacetonitrile, 3-thiopheneacetonitrile, N-methyl-2-pyrroleacetonitrile, N-methyl- 3-pyrroleacetonitrile, 2-methylphenylacetonitrile, 3-methylphenylacetonitrile, 4-methylphenylacetonitrile, 2-fluorophenylacetonitrile, 3-fluorophenylacetonitrile, 4-fluorophenylacetonitrile, methoxyacetonitrile, etc.,

(2) R is a C _{7 to} C ₁₀ bicycloalkyl group (which may be substituted with a C _{1 to} C ₅ alkyl group)
A compound represented by, for example, norbornanecarbonitrile, (3) N-alkyl-substituted pyrrolyl group, thienyl group,
Furyl group or phenyl group (halogen atom, C _{1 to} C
₅ alkyl groups or C ₁ -C ₅ alkoxy groups may be substituted), such as N-methyl-
2-pyrrolecarbonitrile, N-methyl-3-pyrrolecarbonitrile, 2-thiophenecarbonitrile, 3
-Thiophenecarbonitrile, 2-cyanofuran, 3-
Cyanofuran, benzonitrile, 2-tolunitrile, 3
-Tolunitrile, 4-tolunitrile, 2-methoxybenzonitrile, 3-methoxybenzonitrile, 4-methoxybenzonitrile, 2-fluorobenzonitrile, 3-
(4) Halogen atom, C ₁ -C ₅ alkyl group or C ₁ -C ₅ alkoxy such as fluorobenzonitrile, 4-fluorobenzonitrile, 2-chlorobenzonitrile, 3-chlorobenzonitrile and 4-chlorobenzonitrile A compound representing a phenylalkenyl group which may be substituted with a group such as 4-chlorocinnamonitrile, 4
-Methylcinnamonitrile, 4-methoxycinnamonitrile, etc. are mentioned.

The amino alcohol of the general formula (II) which is the other raw material of the production method of the present invention is, for example, 2-aminoethanol, 2-amino-1-propanol, 2-amino-1-butanol or 2-amino. 2-Methyl-1-propanol, 3-amino-1-propanol, 3-amino-2,2-dimethyl-1-propanol, 3-amino-
1-Butanol, 3-amino-1-methyl-1-propanol, 3-amino-2-propanol and the like can be used.

In the method of the present invention, these nitrile compounds are reacted with or without an amino alcohol in the presence of a rhodium complex catalyst having a bidentate ligand, with or without a solvent of the general formula (V ) The cyclic imide acid ester shown by these is manufactured. Here, the rhodium complex used as a catalyst is a catalyst in which a negative, neutral or positive ligand is coordinated around a rhodium (Rh) atom and an ion and which is uniform in the reaction solution.

As a rhodium complex catalyst having a bidentate ligand
For example, RhCl [Ph₂ P (CH₂ )₃ PPh
₂ ] (2,5-norbornadiene), RhBr [Ph₂ 
P (CH₂ )₃ PPh₂ ] (2,5-norbornadier
), RhPF₆ [Ph₂ P (CH₂ )₃ PPh₂ ]
(2,5-norbornadiene), RhClO_Four [Ph₂ 
P (CH₂ )₃ PPh₂ ] (2,5-norbornadier
), RhBF_Four [Ph₂ P (CH₂ )₃ PPh₂ ]
(1,3,5-cyclooctatriene), RhBF_Four 
[Ph₂ P (CH₂ )₃ PPh₂ ] (1,5-Cyclo
Kutadiene), RhCF₃ SO₃ [Ph₂ P (CH₂ )
₃ PPh₂ ] (1,5-Cyclooctadiene), RhC
l [Ph₂ P (CH₂ )_Four PPh₂ ] (2,5-norvo
Lunadiene), RhBr [Ph₂ P (CH₂ )_Four PPh
₂ ] (2,5-norbornadiene), RhPF₆ [Ph
₂ P (CH₂ )_Four PPh₂ ] (2,5-norbornadier
), RhClO_Four [Ph₂ P (CH₂ )_Four PPh₂ ]
(2,5-norbornadiene), RhBF_Four [Ph₂ P
(CH₂ )_Four PPh₂ ] (1,3,5-Cyclooctato
Lien) RhBF_Four [Ph₂ P (CH₂ )_Four PPh₂ ]
(1,5-cyclooctadiene), RhCF₃ SO₃ 
[Ph₂ P (CH₂ )_Four PPh₂ ] (1,5-Cyclo
Kutadiene), RhCl [Ph₂ P (CH₂ )_Five PPh
₂ ] (2,5-norbornadiene), RhBr [Ph₂ 
P (CH₂ )_Five PPh₂ ] (2,5-norbornadier
), RhPF₆ [Ph₂ P (CH₂ )_Five PPh₂ ]
(2,5-norbornadiene), RhClO_Four [Ph₂ 
P (CH₂ )_Five PPh₂ ] (2,5-norbornadier
), RhBF_Four [Ph₂ P (CH₂ )_Five PPh₂ ]
(1,3,5-cyclooctatriene), RhBF_Four 
[Ph₂ P (CH₂ )_Five PPh₂ ] (1,5-Cyclo
Kutadiene), RhCF₃ SO₃ [Ph₂ P (CH₂ )
_Five PPh₂ ] (1,5-Cyclooctadiene), RhC
l [Ph₂ P (CH₂ )₆ PPh₂ ] (2,5-norvo
Lunadiene), RhBr [Ph₂ P (CH₂ )₆ PPh
₂ ] (2,5-norbornadiene), RhPF₆ [Ph
₂ P (CH₂ )₆ PPh₂ ] (2,5-norbornadier
), RhClO_Four [Ph₂ P (CH₂ )₆ PPh₂ ]
(2,5-norbornadiene), RhBF_Four [Ph₂ P
(CH₂ )₆ PPh₂ ] (1,3,5-Cyclooctato
Lien), RhBF_Four [Ph₂ P (CH₂ )₆ PPh
₂ ] (1,5-Cyclooctadiene), RhCF₃ SO
₃ [Ph₂ P (CH₂ )₆ PPh₂ ] (1,5-cyclo
Octadiene), etc., and also RhH (PPh₃ )₃ , R
hCl (PPh₃ )₃ , RhBr (PPh₃ )₃ There
Is RhCF₃ SO₃ (PPh₃ )₃ To Ph₂ P
(CH₂ )₃ PPh₂ , Ph₂ P (CH₂ )_Four PPh
₂ , Ph₂ P (CH₂ )_Five PPh₂ Or Ph₂ P
(CH₂ )₆ PPh₂ 0.5 to 2 times the molar equivalent
Those added may be mentioned.

The amount of the catalyst used is 0.001 to 50 mol%, preferably 0.01 to 50 mol% based on the starting amino alcohol.
It is 10 mol%. These catalysts are usually used alone, but two or more kinds may be used at the same time.

[Production Method] In the method of the present invention, a catalyst is added to the raw material amino alcohol and nitrile compound,
Heat reaction as a homogeneous system. The reaction is preferably performed under an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere or under a hydrogen atmosphere. The nitrile compound is used in an amount of 1 equivalent or more with respect to the amino alcohol, but it can also be used in excess (up to about 10 equivalents) as a solvent. When a solvent is used, a solvent inert to the reaction, for example, ethers such as tetrahydrofuran, dioxane, monoglyme, diglyme, triglyme and tetraglyme, aromatic hydrocarbons such as benzene, toluene, xylene and trimethylbenzene. , Dichloromethane, etc. are used.

The reaction conditions will differ depending on the nitrile compound used as the starting material, but generally the reaction temperature is 0 to 250 ° C, preferably room temperature to 180 ° C. When the reaction is carried out at a temperature above the boiling point of the raw material and the solvent, an autoclave is used so as to be a liquid phase reaction. The reaction time varies depending on the reaction temperature and cannot be generally stated, but it is generally several hours to hundreds of tens hours. After the reaction, if unreacted raw materials and solvent are used, the solvent is distilled (reduced pressure) and recovered, and then the target product is obtained by reduced pressure distillation, and if necessary, further purified by a conventional method to obtain a pure product. The target product can be obtained. The catalyst remaining after distillation under reduced pressure can be repeatedly used as it is in the next reaction. Further, after the reaction, a high boiling point solvent may be added, and if necessary, triphenylphosphine may be added to carry out distillation under reduced pressure to obtain a desired product, and the catalyst may be recovered in a solution state and repeatedly used in the reaction.

[0016]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to the scope of the following examples.

Example 1-1 A 0.1 L Schlenk tube was charged with a magnetic stirrer and purged with argon. Propionitrile 14.34 g, 2-aminoethanol 5.3 g and RhBF ₄ [Ph ₂ P (CH
₂ ) ₄ PPh ₂ ] (1,5-cyclooctadiene) 0.
25g was charged. The reaction was carried out for 5 hours with stirring under reflux of the solvent. The reaction solution was cooled to room temperature, and the crude reaction solution was quantitatively analyzed by gas chromatography. As a result, 2-ethyl-
2-oxazoline (boiling point 56-58 ° C / 100mmH
The yield of g) was 92.5%.

Example 1-2 The reaction crude liquid obtained in Example 1-1 was distilled under reduced pressure, and the remaining catalyst was recovered under an argon atmosphere. 14.34 g of propionitrile, 5.3 g of 2-aminoethanol and the recovered catalyst were added, and RhBF ₄ [Ph ₂ P was newly added.
0.01 g of (CH ₂ ) ₄ PPh ₂ ] (1,5-cyclooctadiene) was added and the reaction was carried out under the same conditions in a Schlenk tube of 0.03 l. As a result of quantitative analysis of the reaction crude liquid by gas chromatography, the yield of 2-ethyl-2-oxazoline (boiling point 56-58 ° C./100 mmHg) was 92.0%.

Example 2 A 0.1 L Schlenk tube was charged with a magnetic stirrer and purged with argon. Benzonitrile 8.5 g, 2-amino-1-
3.1 g of propanol and RhBF ₄ [Ph ₂ P (CH ₂
) ₄ PPh ₂ ] (1,5-cyclooctadiene) 0.
12g was charged. The reaction was carried out at a temperature of 120 ° C. for 7 hours while stirring. The Schlenk tube was cooled to room temperature, and the reaction crude liquid was quantitatively analyzed by gas chromatography.
Phenyl-4-methyl-2-oxazoline (boiling point 139
The yield at ˜145 ° C./10 mmHg) was 86.7%.

Example 3 A 0.1 L Schlenk tube was charged with a magnetic stirrer and purged with nitrogen, and 5.0 g of 3-thiopheneacetonitrile, 2.3 g of 2-amino-1-propanol and RhBF ₄ [Ph.
_{2 P (CH 2) 4 PPh} 2] (1,5- cyclooctadiene) 0. Were charged 10g. The reaction was carried out at a temperature of 140 ° C. for 6.5 hours with stirring. The autoclave was cooled to room temperature, and the crude reaction liquid was quantitatively analyzed by gas chromatography. As a result, the yield of 2- (3-thienylmethyl) -4-methyl-2-oxazoline (boiling point) was 84.0%. .

Example 4 A 0.1 l autoclave was charged with a magnetic stirrer and purged with argon. Propionitrile 11.7 g, 2-amino-1-propanol 5.3 g and RhBF ₄ [Ph ₂ P] were used.
(CH ₂ ) ₄ PPh ₂ ] (2,5-norbornadiene)
0.32g was charged. The reaction was carried out at a temperature of 140 ° C. for 4.5 hours while stirring. The autoclave was cooled to room temperature, and the reaction crude liquid was quantitatively analyzed by gas chromatography. As a result, the yield of 2-ethyl-4-methyl-2-oxazoline (boiling point 60 to 64 ° C / 100 mmHg) was 53.5.
%Met.

Example 5 A 0.1 L Schlenk tube was charged with a magnetic stirrer and purged with argon. Propionitrile 14.3 g, 2-aminoethanol 5.3 g, 1,6-bis (diphenylphosphinohexane). 0.15 g and RhCl (PPh ₃ ) ₃
0.32g was charged. The reaction was carried out for 5 hours with stirring under reflux of the solvent. As a result of quantitative analysis of the reaction crude liquid by gas chromatography, the yield of 2-ethyl-2-oxazoline (boiling point 56 to 58 ° C./100 mmHg) was 93.3%.

Example 6 A 0.1 l Schlenk tube was charged with a magnetic stirrer and purged with argon. Benzonitrile 8.5 g, 2-amino-1-
3.1 g of propanol and RhBF ₄ [Ph ₂ P (CH ₂
) ₄ PPh ₂ ] (1,5-cyclooctadiene) 0.
12g was charged. The reaction was carried out at a temperature of 120 ° C. for 7 hours while stirring. The Schlenk tube was cooled to room temperature, and the reaction crude liquid was quantitatively analyzed by gas chromatography.
Phenyl-4-methyl-2-oxazoline (boiling point 139
The yield at ˜145 ° C./10 mmHg) was 86.7%.

Example 7 A 0.1-liter autoclave was charged with a magnetic stirrer and purged with nitrogen to give 2-norbornanecarbonitrile (5.0 g, 3 g).
-Amino-1-propanol 3.0 g and RhPF _{6
[Ph 2 P (CH 2)} 3 PPh 2] (2,5- norbornadiene) 0. Was charged 40 g. The reaction was carried out at a temperature of 144 ° C. for 5.5 hours with stirring. The autoclave was cooled to room temperature, and the reaction crude liquid was quantitatively analyzed by gas chromatography. As a result, 2- (2-norbornyl) -5,6-
Dihydro-4H-1,3-oxazine (boiling point 122-1
The yield of 26 ° C./30 mmHg) was 90.3%.

Example 8 A magnetic stirrer was placed in a Schlenk tube of 0.03 l and purged with argon. 5.0 g of 2-cyanofuran, 3-amino-
3.6 g of 1-propanol, 0.09 g of 1,4-bis (diphenylphosphinobutane) and RhCl (PPh
₃ ) 0.22 g of ₃ was charged. The reaction was carried out for 90 hours while stirring at a temperature of 25 ° C. As a result of quantitative analysis of the reaction crude liquid by gas chromatography, 2- (2-furyl) -5,
6-dihydro-4H-1,3-oxazine (boiling point 119
The yield at ˜124 ° C./20 mmHg) was 84.7%.

[0026]

EFFECTS OF THE INVENTION According to the production method of the present invention, the production of by-products is suppressed, the cyclic imidate ester is obtained in good yield, the separation and production are easy, and the catalyst is stable in distillation and catalyst recovery. It is useful as a raw material for pharmaceuticals, agricultural chemicals, intermediates such as dyes, modifiers of polymers, adhesives, etc., because the activity hardly decreases after recovery and reuse, and the used solvent can be easily recovered and reused. A cyclic imidoester can be produced with good productivity and economy.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location C07D 265/10 407/04 307 7602-4C

Claims (1)

[Claims] 1. A compound represented by the general formula (I) RCN ... (I) wherein R is (1) a C ₁ -C ₅ alkyl group, and C ₁ -C
₅ alkoxy group, N-alkyl substituted pyrrolyl group, thienyl group, furyl group or phenyl group (halogen atom,
C ₁ -C ₅ alkyl group or C ₁ -C ₅ alkoxy group) which may be substituted with C)
_{1 to} C ₁₅ alkyl group, (2) C _{7 to} C ₁₀ bicycloalkyl group (which may be substituted with C _{1 to} C ₅ alkyl group), (3) N-alkyl-substituted pyrrolyl group, thienyl group , Furyl group or phenyl group (halogen atom, C ₁
To C ₅ alkyl group or C _{1 to} C ₅ alkoxy group) or (4) halogen atom, C
It is substituted with ₁ -C ₅ alkyl group or an alkoxy group of C ₁ -C ₅ shows a phenyl alkenyl group. ] And a nitrile compound represented by the general formula (II): [In the formula, m represents an integer of 0 or 1, and R ^{1 to} R ⁶ each independently represent a hydrogen atom, a methyl group, an ethyl group or a propyl group. Formula an amino alcohol represented _{by] (III) RhX [Ph 2} P (CH 2) n PPh 2] Y ··· (III) [ wherein, n an integer of 3-6, X is a hydrogen atom , Halogen atom, PF ₆ , ClO ₄ , BF ₄ or CF ₃ SO ₃ ,
Y represents norbornadiene, cyclooctadiene or cyclooctatriene, and Ph represents a phenyl group. Or a rhodium complex catalyst represented by the general formula (IV) RhX (PPh ₃ ) ₃ (IV) [wherein, X represents the same meaning as described above.] ] To Ph ₂ P (C
H ₂ ) ₃ PPh ₂ , Ph ₂ P (CH ₂ ) ₄ PPh ₂ , P
h ₂ P (CH ₂ ) ₅ PPh ₂ or Ph ₂ P (CH
₂ ) ₆ PPh ₂ is reacted in the presence of a rhodium complex catalyst in which 0.5 to 2 molar equivalents have been added to react with the general formula (V) [In the formula, R ^{1 to} R ⁶ and m have the same meanings as described above. ] The manufacturing method of the cyclic imide acid ester represented by these.