JP4277352B2 - Carbamate production method - Google Patents

Description

【００８０】
【発明の効果】
本発明により、触媒活性の低下や副生物の生成などにより、目的物の収率が低下すると共にその分離精製が困難になるという問題を起こすことなく、アリールカルバメートとアルコールをエステル交換反応させて、対応するカルバメートを収率よく工業的に製造することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a corresponding carbamate with high yield by transesterifying an aryl carbamate and an alcohol. Carbamate is a useful compound having a wide range of uses as a medical pesticide and its synthetic raw material, as well as fine chemicals and its synthetic raw material.
[0002]
[Prior art]
As a method for producing a carbamate by transesterification, a method of reacting a lower aliphatic carbamate and an alcohol in the presence of an alkyl titanate (Japanese Patent Laid-Open No. 53-73520), a reaction of pentachlorophenyl carbamate and an aromatic alcohol in the presence of a base. A method of reacting a carbamate and an aliphatic alcohol in the presence of a thallium compound or a tin compound (Japanese Patent Laid-Open No. 57-82360), a carbamate of a high boiling alcohol and a lower alcohol. A method for producing a carbamate of a lower alcohol by reacting at a high temperature in the presence of a catalyst (Japanese Patent Laid-Open No. 64-11016) is known.
[0003]
However, in order to industrially produce the corresponding carbamate in high yield by transesterifying the aryl carbamate and alcohol, the yield of the target product is reduced due to a decrease in catalytic activity and the formation of by-products, and the separation thereof. The problem that purification becomes difficult arises, and there are still points to be improved.
[0004]
[Problems to be solved by the invention]
In the present invention, without causing the problem that the yield of the target product decreases and the separation and purification becomes difficult due to the decrease in the catalytic activity and the generation of by-products, the aryl carbamate and the alcohol are transesterified, It is an object of the present invention to provide a method capable of industrially producing a corresponding carbamate with a high yield.
[0005]
[Means for Solving the Problems]
As a result of intensive studies to solve the above problems, the present inventors have unexpectedly found that the water in the reaction raw material liquid has a great influence and completed the present invention. That is, an object of the present invention is to contain an aryl carbamate (I), an alcohol (II) and a catalyst in producing a corresponding carbamate by transesterifying the aryl carbamate (I) and the alcohol (II) in the presence of a catalyst. To 1 mole of aryl carbamate (I)More than zeroThis is solved by a method for producing carbamate, which comprises using a reaction raw material liquid containing aryl carbamate (I), alcohol (II) and a catalyst containing 0.25 mol or less of water.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
Aryl carbamate (I) used as a raw material in the present invention,
R¹NHCOOR²
(Wherein R¹Represents a hydrogen atom, an alkyl group, an aralkyl group, an aryl group or a heterocyclic group;²Represents an aryl group. Is a compound represented by the formula:
[0007]
In addition, the alcohol (II) used as another raw material in the present invention is:
R^ThreeOH
(Wherein R^ThreeRepresents an alkyl group, an aralkyl group, an aryl group or a heterocyclic group. However, R^ThreeR is an aryl group, R²And R^ThreeIs different. And a compound represented by the formula:
[0008]
In the present invention, aryl carbamate (I) and alcohol (II) are transesterified in the presence of a catalyst,
R¹NHCOOR^Three
(Wherein R¹, R^ThreeIs the same as described above. The corresponding carbamate represented by the formula
[0009]
In the present invention, a reaction raw material solution containing aryl carbamate (I), alcohol (II) and a catalyst is prepared by transesterifying aryl carbamate (I) and alcohol (II) in the presence of a catalyst to produce the corresponding carbamate. To 1 mol of aryl carbamate (I) as raw material (preparation)More than zero0.25 mol or less (that is, 0.25 mol or less exceeding 0), preferablyMore than zeroA reaction raw material liquid containing aryl carbamate (I), alcohol (II) and a catalyst containing 0.23 mol or less (that is, 0.23 mol or less exceeding 0) is used. During the reaction, the water in the reaction solution is maintained in this range, and the transesterification reaction is performed. If the water content is not controlled, it is not preferable because not only the yield of the target product is reduced but also the separation and purification becomes difficult due to the reduction of the catalytic activity and the generation of by-products such as urea derivatives.
[0010]
The reaction raw material liquid (containing aryl carbamate (I), alcohol (II) and catalyst) having a controlled water content as described above comprises aryl carbamate (I), alcohol (II) and catalyst (and further if necessary). The reaction solvent) can be obtained by distilling or drying each of them separately and then mixing them. In this case, distillation or drying may be carried out only for necessary ones as long as the water content of the reaction raw material liquid can be controlled within the above range. In addition, the reaction raw material liquid whose water content is controlled is prepared by mixing aryl carbamate (I) and alcohol (II) (adding a reaction solvent if necessary) and distilling the mixed liquid before the reaction. It can also be obtained by mixing the catalyst after drying. At this time, if necessary, the catalyst may be separately dried. In these methods, distillation and drying may be used in combination.
[0011]
The distillation of the alcohol (II) is not particularly limited as long as the water content of the reaction raw material liquid can be controlled within the above range, and is carried out by a usual method. Alcohol (II) is dried by molecular sieves (3A, 4A, 5A, etc.), silica gel, magnesium sulfate, calcium sulfate, sodium sulfate, potassium carbonate, magnesium oxide, calcium oxide, calcium hydroxide, calcium hydride, metal It is carried out by treating the alcohol with at least one desiccant or dehydrating agent selected from magnesium, metallic sodium and the like. The atmosphere during the distillation or drying is not particularly limited as long as the water content of the reaction raw material liquid can be controlled within the above range, but is preferably a dry inert gas (nitrogen gas, argon gas, etc.) atmosphere. The distilled or dried alcohol (II) is preferably placed in a dry inert gas atmosphere.
[0012]
The distillation of the aryl carbamate (I) is not particularly limited as long as the water content of the reaction raw material liquid can be controlled within the above range, and the pressure, the apparatus and the like are not particularly limited, and are performed by ordinary distillation at 100 ° C. or lower. The atmosphere during the distillation is not particularly limited as long as the water content of the reaction raw material liquid can be controlled within the above range, but is preferably a dry inert gas atmosphere. The aryl carbamate (I) is dried at 100 ° C. or lower under reduced pressure, in a dry inert gas atmosphere or in a dry inert gas stream. The distilled or dried aryl carbamate (I) is preferably placed in a dry inert gas atmosphere.
[0013]
When the catalyst is solid at room temperature, the catalyst is heated at 100 to 200 ° C. under a flow of dry inert gas, or at 50 to 200 ° C. under a reduced pressure of 1 to 300 torr. Is done by. When the catalyst is liquid at room temperature, the catalyst is distilled or dried in the same manner as the alcohol (II). This distillation and drying can be used together. The dried catalyst is preferably placed in a dry inert gas atmosphere.
[0014]
In the aryl carbamate (I), R¹Examples of the alkyl group represented by: methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cycloheptyl Preferred examples include C 1-20 alkyl groups (including isomers) such as a group and a cyclooctyl group. If possible, this alkyl group may contain an unsaturated bond (carbon-carbon double bond, etc.) and / or a hetero atom (nitrogen atom, oxygen atom, sulfur atom, etc.) inside the carbon chain. Further, the carbon chain may form a ring structure (which may contain the heteroatom). When the carbon chain contains a nitrogen atom, an alkyl group having 1 to 15 carbon atoms, an aralkyl group having 7 to 15 carbon atoms, or an aryl group having 6 to 14 carbon atoms can be used as a substituent on the nitrogen atom. There are.
[0015]
The alkyl group further includes an alkoxy group having 1 to 15 carbon atoms (methoxy group, ethoxy group, propoxy group, butoxy group, etc.), a thioalkoxy group having 1 to 15 carbon atoms (thiomethoxy group, thioethoxy group, etc.), carbon number 6-14 aryloxy groups (phenoxy group, etc.), C6-C14 arylthiooxy groups (thiophenoxy group, etc.), C2-C15 alkoxycarbonyl groups (methoxycarbonyl group, ethoxycarbonyl group, etc.), C2-C15 acyl group (acetyl group, benzoyl group, etc.), C2-C15 dialkylamino group (dimethylamino group, diethylamino group, etc.), hetero atom (nitrogen atom, oxygen atom, sulfur atom, etc.) At least one C2-C15 heterocyclic group (pyridyl group, furyl group, etc.), nitro group, cyano group, hydroxyl group, and halogen Child (fluorine atom, chlorine atom, bromine atom, etc.) at least one selected from such as a substituent group.
[0016]
These substituents that the alkyl group may have include various isomers. If possible, these substituents contain an unsaturated bond (carbon-carbon double bond, etc.) and / or a hetero atom (nitrogen atom, oxygen atom, sulfur atom, etc.) inside the carbon chain of the alkyl moiety. You may go out. In addition, the alkyl portion may form a ring structure (which may contain the heteroatom), and may further contain one or more substituents that the alkyl group may have. When a nitrogen atom is contained inside the carbon chain of the alkyl portion of these substituents, one other substituent is present on the nitrogen atom as described above.
[0017]
In the aryl carbamate (I), R¹Preferred examples of the aralkyl group represented by the formula include aralkyl groups having 7 to 20 carbon atoms (including isomers) such as benzyl group, phenethyl group, phenylpropyl group, and phenylbutyl group. This aralkyl group may contain an unsaturated bond (carbon-carbon double bond etc.) and / or a hetero atom (nitrogen atom, oxygen atom, sulfur atom etc.) inside the carbon chain of the alkyl part. When the alkyl chain contains a nitrogen atom inside the carbon chain, one other substituent is present on the nitrogen atom as described above.
[0018]
The aralkyl group further includes an alkyl group having 1 to 15 carbon atoms (methyl group, ethyl group, propyl group, butyl group, etc.), an aralkyl group having 7 to 15 carbon atoms (benzyl group, phenethyl group, etc.), and 6 carbon atoms. ~ 14 aryl groups (phenyl group, naphthyl group, etc.), R¹As the substituent which the alkyl group as may have, one or more substituents may be present on the aromatic ring, R¹The alkyl group may have one or more substituents similar to the substituents that the alkyl group may have.
[0019]
These substituents that the aralkyl group may have include various isomers. And these substituents may contain an unsaturated bond (carbon-carbon double bond etc.) and / or a hetero atom (a nitrogen atom, an oxygen atom, a sulfur atom, etc.) inside the carbon chain of the alkyl part. In addition, the alkyl portion may form a ring structure (which may contain the heteroatom), and may further contain one or more substituents that the alkyl group may have. However, when a nitrogen atom is contained inside the carbon chain of the alkyl portion, one other substituent is present on the nitrogen atom as described above.
[0020]
In the aryl carbamate (I), R¹Preferred examples of the aryl group represented by the formula include aryl groups having 6 to 14 carbon atoms (including isomers) such as a phenyl group, a naphthyl group, and an anthranyl group.
The aryl group further includes an alkyl group having 1 to 15 carbon atoms (methyl group, ethyl group, propyl group, butyl group, etc.), an aralkyl group having 7 to 15 carbon atoms (benzyl group, phenethyl group, etc.), carbon Substituents for aryl groups (phenyl group, naphthyl group, etc.) of formulas 6-14, R¹The alkyl group as may have one or more substituents similar to the substituents that the alkyl group may have.
[0021]
These substituents that the aryl group may have include various isomers. And these substituents may contain an unsaturated bond (carbon-carbon double bond etc.) and / or a hetero atom (a nitrogen atom, an oxygen atom, a sulfur atom, etc.) inside the carbon chain of the alkyl part. In addition, the alkyl portion may form a ring structure (which may contain the heteroatom), and may further contain one or more substituents that the alkyl group may have. However, when a nitrogen atom is contained inside the carbon chain of the alkyl portion, one other substituent is present on the nitrogen atom as described above.
[0022]
Examples of the aryl group having a substituent include a tolyl group, a xylyl group, a biphenylyl group, a methoxyphenyl group, a chlorophenyl group, a bromophenyl group, a nitrophenyl group, a hydroxyphenyl group, a cyanophenyl group, and a dimethylaminophenyl group. It is done.
[0023]
In the aryl carbamate (I), R¹As the heterocyclic group represented by the formula, pyridyl group, pyridazinyl group, quinolyl group, isoquinolyl group, pyrimidinyl group, indolyl group, pyrazolyl group, imidazolyl group, benzimidazolyl group, triazolyl group, tetrazolyl group, oxazolyl group, benzoxazolyl group Heteroatoms such as ruthel group, thiazolyl group, benzothiazolyl group, thiadiazolyl group, isoxazolyl group, furyl group, benzofuryl group, tetrahydrofuryl group, thienyl group, benzthienyl group, tetrahydrothienyl group, tetrahydropyranyl group, N-substituted piperidinyl group Preferred examples include C 2-10 heterocyclic groups (including isomers) containing at least one nitrogen atom, oxygen atom, sulfur atom and the like.
[0024]
The heterocyclic group further includes R¹And may have one or more substituents similar to the substituents that the alkyl group, aralkyl group and aryl group may have. These substituents include isomers, and may contain an unsaturated bond and / or a hetero atom inside the carbon chain of the alkyl moiety as described above. Further, it may form a ring structure, and may further contain one or more substituents that the alkyl group may have. When the alkyl chain contains a nitrogen atom inside the carbon chain, one other substituent is present on the nitrogen atom as described above.
[0025]
In the aryl carbamate (I), R²Preferred examples of the aryl group represented by the formula include aryl groups having 6 to 14 carbon atoms (including isomers) such as a phenyl group, a naphthyl group, and an anthranyl group. These aryl groups further include alkyl groups having 1 to 15 carbon atoms (methyl group, ethyl group, propyl group, butyl group, etc.), R¹The aryl group as may have one or more of the same substituents.
[0026]
Examples of the aryl carbamate (I) include the following compounds. That is, R¹Examples of the aryl carbamate (I) in which is a hydrogen atom include phenyl carbamate.
[0027]
R¹Examples of the aryl carbamate (I) in which is an alkyl group include phenyl N-methyl carbamate, phenyl N-ethyl carbamate, phenyl N-propyl carbamate, phenyl N-butyl carbamate, and phenyl N-cyclohexyl carbamate. Furthermore, 4-nitrophenyl N-cyclohexyl carbamate, 4-phenoxyphenyl N-cyclohexyl carbamate, 4-acetylphenyl N-cyclohexyl carbamate, and the like can also be mentioned.
[0028]
R¹Examples of the aryl carbamate (I) in which is an aralkyl group include phenyl N-benzyl carbamate and phenyl N-1-phenethyl carbamate.
[0029]
R¹As aryl carbamate (I) in which is an aryl group, phenyl N-phenyl carbamate, phenyl N- (4-methylphenyl) carbamate, phenyl N- (2-chlorophenyl) carbamate, phenyl N- (4-nitrophenyl) carbamate , Phenyl N- (4-cyanophenyl) carbamate, phenyl N- (4-methoxyphenyl) carbamate, 1-naphthyl N- (4-chlorophenyl) carbamate, 1-naphthyl N- (4-methoxyphenyl) carbamate, etc. It is done.
[0030]
Furthermore, 4-methylphenyl N-phenyl carbamate, 4-fluorophenyl N-phenyl carbamate, 4-chlorophenyl N-phenyl carbamate, 4-nitrophenyl N-phenyl carbamate, 4-methoxyphenyl N-phenyl carbamate, R¹Are aryl carbamates (I) which are aryl groups.
[0031]
R¹Examples of the aryl carbamate (I) in which is a heterocyclic group include phenyl N- (2-pyridyl) carbamate, phenyl N- (4-pyridazinyl) carbamate, and phenyl N- (1-benzyl-4-piperidinyl) carbamate. And 4-nitrophenyl N- (4-pyridyl) carbamate and the like.
[0032]
In alcohol (II), R^ThreeAs the alkyl group, aralkyl group, aryl group and heterocyclic group represented by¹And the same alkyl groups, aralkyl groups, aryl groups and heterocyclic groups represented by However, R^ThreeR is an aryl group, R²A different aryl group is used. R^ThreeAn alkyl group, an aralkyl group, an aryl group, or a heterocyclic group represented by¹The alkyl group, aryl group, and heterocyclic group represented by may have one or more of the same substituents.
[0033]
Examples of the alcohol (II) include the following compounds.
That is, R^ThreeAlcohol (II) in which is an alkyl group includes methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-octanol, cyclopentanol, cyclohexanol, 2-chloroethanol, 2 -Methoxyethanol, 2-cyanoethanol, allyl alcohol, 2,3-epoxy-1-propanol and the like.
[0034]
R^ThreeExamples of alcohol (II) in which aralkyl is benzyl alcohol, 1-phenethyl alcohol, o-methylbenzyl alcohol, o-methoxybenzyl alcohol, o-chlorobenzyl alcohol, o-nitrobenzyl alcohol, o-cyanobenzyl alcohol, etc. Is mentioned.
[0035]
R^ThreeAlcohol (II) in which is an aryl group includes phenol, o-cresol, p-cresol, 2,4-xylenol, 4-trifluoromethylphenol, 4-methoxyphenol, 4-chlorophenol, 4-bromophenol, Examples include 4-nitrophenol, 4-cyanophenol, 4- (methylthio) phenol, 4-diethylaminophenol, 4-hydroxydiphenyl, 4-hydroxydiphenyl ether, 4-acetylphenol, catechol, and resorcin.
[0036]
R^ThreeExamples of alcohol (II) in which is a heterocyclic group include 2-hydroxypyridine, 3-hydroxypyridine, 4-hydroxypyridine, 4-hydroxypyrimidine, 4-hydroxyquinazoline, 2-hydroxyquinoline, 9-hydroxyxanthene, 5- Examples include hydroxyisoquinoline, tetrahydrofuran-3-ol, and 3-hydroxytetrahydrothiophene.
[0037]
The catalyst used in the present invention is not particularly limited as long as it promotes the transesterification reaction of aryl carbamate (I) and alcohol (II), and known catalysts can be used alone or in combination. Examples of such a catalyst include a metal compound selected from Group 1, Group 2, Group 7, Group 8, Group 9, Group 11, Group 12, Group 13, Group 14 and Group 15 of the periodic table, and 3 Preferred is a secondary amine.
[0038]
Examples of the Group 1 metal compounds include Group 1 metal carbonates (lithium carbonate, sodium carbonate, potassium carbonate, etc.), carboxylates (lithium acetate, sodium acetate, potassium acetate, lithium benzoate, sodium benzoate, benzoic acid). C1-C20 carboxylate such as potassium), bicarbonate (sodium bicarbonate, potassium bicarbonate, etc.), phosphate (tertiary lithium phosphate, tertiary sodium phosphate, tertiary potassium phosphate, etc.) ), Hydrogen phosphate (sodium hydrogen phosphate, potassium hydrogen phosphate, etc.), hydroxide (lithium hydroxide, sodium hydroxide, sodium hydroxide, etc.), alkoxide (lithium methoxide, sodium methoxide, potassium methoxide) , Sodium ethoxide, lithium phenoxide, sodium phenoxide, etc. Le or aryl alkoxide), and the like.
[0039]
Examples of the Group 2 metal compound include a Group 2 metal carbonate (magnesium carbonate, calcium carbonate, etc.) and a carboxylate salt (magnesium acetate, calcium acetate, magnesium benzoate, calcium benzoate, etc.). Acid salts), phosphates (tertiary magnesium phosphate, tribasic calcium phosphate, etc.), hydrogen phosphates (dibasic magnesium phosphate, dibasic calcium phosphate, etc.), hydroxides (magnesium hydroxide, calcium hydroxide, etc.) And alkoxide (alkyl or aryl alkoxide having 1 to 20 carbon atoms such as magnesium methoxide and magnesium ethoxide).
[0040]
Examples of the Group 7 metal compounds include Group 7 metal carboxylates (carboxylates having 1 to 20 carbon atoms such as manganese acetate (II) and manganese (III)), carbonates (manganese (II) carbonate, etc.) ), Phosphates (manganese phosphate (II) and the like), complexes (acetylacetonates such as manganese acetylacetonate (II) and manganese acetylacetonate (III)), and the like.
[0041]
Examples of the Group 8 metal compounds include Group 8 metal halides (iron (III) chloride, iron (III) bromide, ruthenium (III) chloride, ruthenium (III), etc.), nitrates (iron nitrate (III )), Carboxylates (carboxylates having 1 to 20 carbon atoms such as iron lactate (II), iron naphthenate), complexes (iron acetylacetonate (III), acetyl such as ruthenium acetylacetonate (III)) Acetonate).
[0042]
Examples of the group 9 metal compounds include group 9 metal halides (cobalt (II) chloride, cobalt (II) bromide, rhodium (III) chloride, iridium (IV) chloride, etc.), carbonates (cobalt carbonate (II )), Carboxylates (carboxylates having 1 to 20 carbon atoms such as cobalt acetate (II) and rhodium acetate (II)), complexes (cobalt acetylacetonate (II), cobalt acetylacetonate (III), Acetylacetonate such as rhodium acetylacetonate (III)).
[0043]
Examples of the Group 10 metal compounds include Group 10 metal halides (nickel (II) chloride, nickel (II) bromide, palladium (II) chloride, platinum (II) chloride), nitrates (nickel (II) nitrate). , Palladium nitrate (II), etc.), carbonates (nickel carbonate (II), etc.), carboxylates (nickel formate (II), nickel acetate (II), nickel 2-ethylhexanoate (II), palladium acetate (II) ) And the like (complex (acetylacetonate such as nickel acetylacetonate (II))) and the like.
[0044]
Examples of the Group 11 metal compounds include group 11 metal halides (copper chloride (II), copper bromide (II), silver chloride (I), gold chloride (III), etc.), nitrates (copper nitrate (II)). , Silver nitrate (I), etc.), carbonate (copper carbonate (II), silver carbonate (I), etc.), carboxylate (copper formate (II), copper acetate (II), pivalate copper (II), benzoic acid C1-C20 carboxylate such as copper (II), silver acetate (I), silver benzoate (I)), complex (acetylacetonate such as copper acetylacetonate (II)), alkoxide (copper methoxide) (C1-C20 alkoxide such as (II)) and the like.
[0045]
Examples of the group 12 metal compounds include group 12 metal halides (zinc chloride (II), zinc bromide (II), cadmium chloride (II), mercury chloride (II), etc.), nitrates (zinc nitrate (II)). , Cadmium nitrate (II), etc.), carbonates (zinc carbonate (II), cadmium carbonate (II), etc.), carboxylates (zinc acetate (II), zinc lactate (II), zinc benzoate (II), formic acid C1-C20 carboxylates such as cadmium (II), cadmium acetate (II), and cadmium stearate (II)), complexes (acetylacetonates such as zinc acetylacetonate (II)), and the like.
[0046]
Examples of the group 13 metal compound include group 13 metal halides (aluminum (III) chloride, aluminum bromide (III), gallium chloride (III), indium (III), etc.), nitrates (aluminum nitrate (III)). , Gallium nitrate (III), indium nitrate (III), etc.), carboxylates (carboxylates having 1 to 20 carbon atoms such as aluminum acetate (III), aluminum stearate (III)), complexes (aluminum acetylacetonate) Acetylacetonates such as (III)) and alkoxides (alkoxides having 1 to 20 carbon atoms such as aluminum ethoxide (III) and aluminum isopropoxide (III)).
[0047]
Examples of the Group 14 metal compounds include Group 14 metal halides (tin (II) chloride, tin (IV) chloride, lead (II), etc.), nitrates (lead nitrate (II), etc.), carbonates (carbonates). Lead (II), etc.), carboxylates (carboxylates having 1 to 20 carbon atoms such as tin (II) acetate, tin (IV) acetate, lead (II) acetate, lead (II) 2-ethylhexanoate) Etc.
[0048]
Examples of the Group 15 metal compounds include group 15 metal halides (antimony (III) chloride, antimony (IV) chloride, antimony (III) bromide, bismuth (III) chloride), nitrates (bismuth (III) nitrate). Etc.), carbonates (bismuth carbonate (III) etc.), carboxylates (carboxylates having 1 to 20 carbon atoms such as bismuth acetate (III) acetate and bismuth naphthenate (III)) and the like.
[0049]
Examples of the tertiary amine include trialkyl or triaralkylamine having 3 to 30 carbon atoms such as trimethylamine, dimethylethylamine, diethylmethylamine, triethylamine, tripropylamine, tributylamine, trihexylamine, tribenzylamine, N- C3-C20 cyclic amines such as methylpiperidine, 1-methylpyrrolidine, pyridine, pyridazine, pyrimidine, pyrazine, s-triazine, quinoline, isoquinoline, 1,8-diazabicyclo [5.4.0] -7-undecene Etc.
[0050]
The transesterification of aryl carbamate (I) and alcohol (II) uses, for example, a reaction raw material liquid (containing aryl carbamate (I), alcohol (II) and catalyst) whose water content is controlled as described above. The reaction is preferably carried out by reacting the aryl carbamate (I) with the alcohol (II) at a reaction temperature of −30 to 200 ° C., more preferably 0 to 150 ° C. to produce the corresponding carbamate (III). . When a metal compound selected from Group 7, Group 8, Group 9, Group 11, Group 12, Group 13, Group 14 and Group 15 of the periodic table is used as a catalyst, the reaction temperature is particularly preferably 0 to 100 ° C. preferable. The reaction pressure is not particularly limited, and may be any of pressurization, normal pressure, and reduced pressure. The reaction is preferably carried out with stirring, but is not particularly limited.
[0051]
In the transesterification reaction, the starting aryl carbamate (I) and alcohol (II) are 0.5 to 200 moles, more preferably 0.6 to 50 moles of alcohol (II) per mole of aryl carbamate (I). It is preferably used in a proportion of mol, especially 0.7 to 20 mol. Moreover, it is preferable that a catalyst is used in the ratio of 0.0001-0.5 mol with respect to 1 mol of aryl carbamate (I), Furthermore, 0.0002-0.2 mol.
[0052]
In the transesterification reaction, one or more reaction solvents can be used. In particular, when the entire reaction solution is solidified, it is preferable to use a reaction solvent in order to improve operability. When a reaction solvent is used, the reaction solvent is contained in the reaction raw material liquid. Therefore, the reaction solvent is distilled or dried as necessary so that the water in the reaction raw material liquid is in the above range. Are preferably used. The reaction solvent is distilled and dried in the same manner as the alcohol is distilled and dried. Distillation and drying may be performed in combination.
[0053]
The reaction solvent should be inert or low reactive to the starting aryl carbamate (I) or alcohol (II), the catalyst, and the target carbamate (III) produced corresponding to the starting material. There is no particular limitation. The amount of the reaction solvent used is preferably 0 to 50 parts by weight, more preferably 0 to 20 parts by weight, per 1 part by weight of the aryl carbamate (I).
[0054]
Examples of the reaction solvent include aliphatic hydrocarbons (preferably having 5 to 20 carbon atoms; pentane, hexane, heptane, octane, petroleum ether, cyclopentane, cyclohexane, cyclooctane, cyclododecane, ligroin, decalin, and lubricating oil. Etc.), aliphatic halogenated hydrocarbons (preferably having 1 to 20 carbon atoms; methylene chloride, chloroform, 1,2-dichloroethane, 1,2-dichloropropane, 1,4-dichlorobutane, etc.), aliphatic ether (Preferably those having 4 to 30 carbon atoms; diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, etc.) Aliphatic ketone (preferably having 3 to 15 carbon atoms; acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), aliphatic nitrile (preferably having 2 to 20 carbon atoms; acetonitrile, propionitrile, adiponitrile, etc.), aliphatic Amides (preferably having 3 to 20 carbon atoms; N, N-dimethylformamide, N, N-dimethylacetamide, etc.), aromatic hydrocarbons (preferably having 6 to 20 carbon atoms; benzene, toluene, xylene, ethylbenzene , Isopropylbenzene, n-butylbenzene, cyclohexylbenzene, tetralin, methylnaphthalene, etc.), aromatic halogenated hydrocarbons (preferably having 6 to 15 carbon atoms; chlorobenzene, o-dichlorobenzene, chloronaphthalene, etc.), aromatic Ether (preferably 7 to 7 carbon atoms) 0 compounds; anisole, diphenyl ether, etc.), aromatic nitriles (preferably those having 7-15 carbon atoms; benzonitrile, etc.), nitro compounds (preferably those having 1-15 carbon atoms; nitromethane, nitrobenzene, etc.), N -Methylpyrrolidinone, N, N-dimethylimidazolidinone, N, N, N ', N'-tetramethylurea, dimethyl sulfoxide and the like.
[0055]
After completion of the reaction, the produced carbamate (III) is separated by a conventional method. The separated carbamate (III) is further purified by recrystallization, distillation, sublimation, column chromatography or the like, if necessary.
[0056]
【Example】
Next, the present invention will be specifically described with reference to examples and comparative examples. In addition, the yield of carbamate (III) was calculated | required with respect to raw material aryl carbamate (I).
[0057]
Example 1
Phenyl N-phenylcarbamate (4.69 mmol) dried under reduced pressure (50 ° C., 5 torr), ethanol (41.9 mmol) with a water content of 0.86 wt%, and copper acetate (0 ° C., 5 torr) (0 ° C., 0 torr) .00938 mmol) was charged into a 5 ml glass closed reactor substituted with nitrogen gas, and the reaction was performed by heating and stirring at a bath temperature of 80 ° C. for 4 hours. The water content in the reaction raw material liquid ismaterialThe amount was 0.20 mol per 1 mol of aryl carbamate (phenyl N-phenyl carbamate). The moisture content was measured with a Karl Fischer moisture meter. When the reaction solution was analyzed by liquid chromatography after the reaction, the yield of ethyl N-phenylcarbamate was 89.4% and the yield of 1,3-diphenylurea was 2.4%.
[0058]
Comparative Example 1
The reaction and analysis were carried out in the same manner as in Example 1 except that ethanol was replaced with ethanol having a water content of 2.02% by weight (41.9 mmol). The water content in the reaction raw material liquid was 0.47 mol per 1 mol of the raw material aryl carbamate. As a result, the yield of ethyl N-phenylcarbamate was 53.8%, and the yield of 1,3-diphenylurea was 2.9%.
[0059]
Example 2
Reaction and analysis were performed in the same manner as in Example 1 except that copper acetate was replaced with copper nitrate trihydrate (0.00938 mmol). The water content in the reaction raw material liquid was 0.20 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of ethyl N-phenylcarbamate was 80.2% and the yield of 1,3-diphenylurea was 1.3%.
[0060]
Comparative Example 2
The reaction and analysis were carried out in the same manner as in Example 2 except that ethanol was replaced with ethanol having a water content of 2.02% by weight (41.9 mmol). The water content in the reaction raw material liquid was 0.47 mol per 1 mol of the raw material aryl carbamate. As a result, the yield of ethyl N-phenylcarbamate was 48.3% and the yield of 1,3-diphenylurea was 1.7%.
[0061]
Example 3
The reaction and analysis were carried out in the same manner as in Example 1 except that copper acetate was replaced with dried potassium carbonate (0.00938 mmol) in the same manner as in Example 1. The water content in the reaction raw material liquid was 0.20 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of ethyl N-phenylcarbamate was 82.5%, and the yield of 1,3-diphenylurea was 4.0%.
[0062]
Comparative Example 3
The reaction and analysis were carried out in the same manner as in Example 3 except that ethanol was replaced with ethanol having a water content of 2.02% by weight (41.9 mmol). The water content in the reaction raw material liquid was 0.47 mol per 1 mol of the raw material aryl carbamate. As a result, the yield of ethyl N-phenylcarbamate was 62.3%, and the yield of 1,3-diphenylurea was 13.6%.
[0063]
Example 4
The reaction and analysis were performed in the same manner as in Example 1 except that ethanol was replaced with isopropanol (41.9 mmol) having a water content of 0.14% by weight. The water content in the reaction raw material liquid was 0.04 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of 1-methylethyl N-phenylcarbamate was 85.1%, and the yield of 1,3-diphenylurea was 2.2%.
[0064]
Comparative Example 4
The reaction and analysis were conducted in the same manner as in Example 4 except that isopropanol (41.9 mmol) having a water content of 0.90% by weight was replaced. The water content in the reaction raw material liquid was 0.27 mol per 1 mol of the raw material aryl carbamate. As a result, the yield of 1-methylethyl N-phenylcarbamate was 62.0%, and the yield of 1,3-diphenylurea was 6.0%.
[0065]
Example 5
Reaction and analysis were performed in the same manner as in Example 4 except that copper acetate was replaced with copper nitrate trihydrate (0.00938 mmol). The water content in the reaction raw material liquid was 0.05 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of 1-methylethyl N-phenylcarbamate was 77.7%, and the yield of 1,3-diphenylurea was 1.1%.
[0066]
Comparative Example 5
The reaction and analysis were conducted in the same manner as in Example 5 except that isopropanol was replaced with isopropanol (41.9 mmol) having a water content of 0.90% by weight. The water content in the reaction raw material liquid was 0.28 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of 1-methylethyl N-phenylcarbamate was 35.6%, and the yield of 1,3-diphenylurea was 1.8%.
[0067]
Example 6
The reaction and analysis were performed in the same manner as in Example 4 except that copper acetate was replaced with dried potassium carbonate (0.00938 mmol) in the same manner as in Example 1. The water content in the reaction raw material liquid was 0.04 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of 1-methylethyl N-phenylcarbamate was 74.2%, and the yield of 1,3-diphenylurea was 1.6%.
[0068]
Comparative Example 6
The reaction and analysis were carried out in the same manner as in Example 6 except that isopropanol was replaced with isopropanol (41.9 mmol) having a water content of 0.90% by weight. The water content in the reaction raw material liquid was 0.28 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of 1-methylethyl N-phenylcarbamate was 58.2%, and the yield of 1,3-diphenylurea was 14.6%.
[0069]
Example 7
The reaction and analysis were performed in the same manner as in Example 1 except that ethanol was replaced with tert-butanol (41.9 mmol) having a water content of 0.02% by weight. The water content in the reaction raw material liquid was 0.01 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of tert-butyl N-phenylcarbamate was 74.9%, and the yield of 1,3-diphenylurea was 0.6%.
[0070]
Comparative Example 7
The reaction and analysis were performed in the same manner as in Example 7 except that tert-butanol was replaced with tert-butanol (41.9 mmol) having a water content of 0.75 wt%. The water content in the reaction raw material liquid was 0.28 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of tert-butyl N-phenylcarbamate was 7.4%, and the yield of 1,3-diphenylurea was 14.0%.
[0071]
Example 8
Reaction and analysis were performed in the same manner as in Example 7 except that copper acetate was replaced with copper nitrate trihydrate (0.00938 mmol). The water content in the reaction raw material liquid was 0.01 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of tert-butyl N-phenylcarbamate was 84.8%, and the yield of 1,3-diphenylurea was 0.7%.
[0072]
Comparative Example 8
The reaction and analysis were performed in the same manner as in Example 5 except that tert-butanol was replaced with tert-butanol (41.9 mmol) having a water content of 0.75 wt%. The water content in the reaction raw material liquid was 0.28 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of tert-butyl N-phenylcarbamate was 11.6%, and the yield of 1,3-diphenylurea was 11.3%.
[0073]
Example 9
Phenyl N-phenylcarbamate was replaced with phenyl N-cyclohexylcarbamate (4.69 mmol) dried in the same manner as in Example 1, and ethanol was replaced with benzyl alcohol (41.9 mmol) having a water content of 0.31 wt%. Reaction and analysis were conducted in the same manner as in Example 1. The water content in the reaction raw material liquid was 0.17 mol with respect to 1 mol of the raw material aryl carbamate (phenyl N-cyclohexyl carbamate). As a result, the yield of benzyl N-cyclohexyl carbamate was 87.6%.
[0074]
Comparative Example 9
The reaction and analysis were carried out in the same manner as in Example 9 except that benzyl alcohol was replaced with benzyl alcohol (41.9 mmol) having a water content of 0.64% by weight. The water content in the reaction raw material liquid was 0.35 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of benzyl N-cyclohexyl carbamate was 39.4%.
[0075]
Example 10
Reaction and analysis in the same manner as in Example 9, except that benzyl alcohol was replaced with benzyl alcohol (41.9 mmol) having a water content of 0.11% by weight and copper acetate was replaced with copper nitrate trihydrate (0.00938 mmol). Went. The water content in the reaction raw material liquid was 0.07 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of benzyl N-cyclohexyl carbamate was 92.7%.
[0076]
Comparative Example 10
The reaction and analysis were carried out in the same manner as in Example 10 except that benzyl alcohol was replaced with benzyl alcohol (41.9 mmol) having a water content of 0.64% by weight. The water content in the reaction raw material liquid was 0.35 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of benzyl N-cyclohexyl carbamate was 13.0%.
[0077]
Example 11
In addition to replacing ethanol with 4-bromophenol (41.9 mmol) having a water content of 0.01% by weight and copper acetate with 1,8-diazabicyclo [5.4.0] -7-undecene (0.375 mmol) Were reacted and analyzed in the same manner as in Example 1. The water content in the reaction raw material liquid was 0.01 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of phenyl N-cyclohexyl carbamate was 82.7%, and the yield of 1,3-diphenylurea was 1.5%.
[0078]
Comparative Example 11
The reaction and analysis were performed in the same manner as in Example 11 except that 0.08 g of water was further added to the reaction raw material liquid. The water content in the reaction raw material liquid was 0.96 mol with respect to 1 mol of the raw material aryl carbamate. As a result, the yield of phenyl N-cyclohexyl carbamate was 49.6%, and the yield of 1,3-diphenylurea was 20.2%.
The results of the above examples and comparative examples are shown in Table 1.
[0079]
[Table 1]

[0080]
【The invention's effect】
According to the present invention, the aryl carbamate and the alcohol are transesterified without causing the problem that the yield of the target product is reduced and the separation and purification is difficult due to the reduction of the catalytic activity and the generation of by-products. The corresponding carbamate can be industrially produced with good yield.

Claims (2)

In producing the corresponding carbamate by transesterifying the aryl carbamate (I) and the alcohol (II) in the presence of a catalyst, the aryl carbamate (I), the alcohol (II) and the reaction raw material liquid containing the catalyst are mixed with aryl. A carbamate characterized by using an aryl carbamate (I), an alcohol (II), and a reaction raw material liquid containing a catalyst, containing 0 to 0.25 mol or less of water with respect to 1 mol of carbamate (I). Manufacturing method. In producing the corresponding carbamate by transesterifying the aryl carbamate (I) and the alcohol (II) in the presence of a catalyst, the reaction mixture is charged with 1 mol of the aryl carbamate (I) and more than 0 to 0.25 mol. A method for producing a carbamate, comprising carrying out the reaction while containing the following water.