JPH08176091A - Production of acylisocyanate compounds - Google Patents

Abstract

PURPOSE: To obtain the subject compound little in byproducts and capable of being easily isolated in a high yield by heating a specific acylcarbamate compound in the presence of a basic substance and an acid halide at a low temperature. CONSTITUTION: An acyl carbamate of formula I [R<1> is 1-18C monovalent organic residue; n is an integer of 1-8; Z is hydrocarbon having a mol.wt. of 10-300, 6-14C aryl, heterocyclic compound; A is O, S; or when Z is directly bound to (-CON=C=O)n or (-CONHCOOR<1> )n , the bond terminal, C of Z does not have two or more H atoms] is mixed with (B) a basic substance and (C) an acid halide (e.g. thionyl chloride) and then heated to obtain an acyl isocyanate of formula II. The component B and the component C are preferably used in amounts of 0.5-30 equivalent and 0.5-3 equivalent, respectively, per equivalent of the component A.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for producing an acylisocyanate in which an atom bonded to an acyl carbon is a carbon which does not have oxygen, sulfur or hydrogen. The acyl isocyanates according to the present invention are extremely important as intermediates for producing medicines, agricultural chemicals, paints, electronic materials and the like.

[0002]

BACKGROUND OF THE INVENTION Acyl isocyanates have the property that they react easily with a very wide range of alcohols, amines, thiols, etc. without a catalyst.
It is an extremely useful compound as an intermediate for producing many compounds in the fields of electronic materials, plastics and the like.

As a typical method for synthesizing the above-mentioned acyl isocyanates, for example, a method in which an amide compound is reacted with oxalyl chloride is known (Spitiere et al.),
Journal of Organic Chemistry (J.
Org. Chem. ), P. 27, p. 3742 et seq., 1
962; ibid, Vol. 28, pp. 1805 and below, 1963.
Year; Vol. 30, Vol. 4, p. 306, pp. 1965).
When this method is applied to an aromatic amide compound, the target acylisocyanates can be obtained with a good yield, but when applied to an aliphatic amide compound, the yield is low except in specific cases. There was a problem.

Further, the above reaction has complicated steps of process control due to the existence of endothermic and exothermic steps, and the starting material is an amide having high reactivity with the acyl isocyanates of the product, and thus remains. There was a problem that side reaction with the starting material is likely to occur.

Further, West German Patent No. 228544 (1985) discloses a method for producing a benzoyl isocyanate by thermally decomposing a 1,1-diacyl-3,3-dialkylurea compound at around 220.degree. ing. This method has a problem in that high temperature is required for thermal decomposition, there is a high possibility of side reaction, and it is difficult to isolate the produced by-product. Moreover, there was no case where these methods were applied to the production of acyl isocyanates.

As a method for thermally decomposing a usual urethane compound R-NHCOOR to synthesize an isocyanate, for example, in JP-A-62-10053, heating an ω-alkoxycarbamoylalkyl (meth) acrylate or the like is used. A method for synthesizing .omega.-isocyanatoalkyl acrylate is disclosed, which is disclosed in JP-A-63-162662.
The publication discloses a method for producing isophorone diisocyanate by decomposing a urethane compound under heating without using phosgene. These are 200-450
There is a problem in that a high temperature of 0 ° C. and a condition of about 8 mmHg or less are required, an operation such as distillation under reduced pressure is required to suppress by-products due to thermal decomposition, and the apparatus becomes complicated.

[0007]

SUMMARY OF THE INVENTION In view of the above situation, the present invention is directed to a reaction that proceeds under mild conditions and a small number of side reactions.
Moreover, it aims at providing the manufacturing method of the acyl isocyanate which can isolate a product easily.

[0008]

The gist of the present invention is that a carbon atom bonded to a carbonyl carbon in a substituent to a carbonyl constituting an acyl group does not have oxygen, sulfur or hydrogen at least two. A basic substance and an acid halide are added to the acyl carbamate which is and heated to produce the corresponding acyl isocyanate. The present invention is described in detail below.

In the present invention, the acyl isocyanates can be represented by the following general formula (1), and the acyl carbamates can be represented by the following general formula (2).

[0010]

Embedded image

In the formula, R ¹ represents a monovalent organic residue having 1 to 18 carbon atoms, and n represents an integer of 1 to 8. Z is a substituted or unsubstituted, linear, branched or cyclic, saturated or unsaturated, hydrocarbon group having a molecular weight of 10 to 300; a substituted or unsubstituted aryl group having 6 to 14 carbon atoms or a substituted group Alternatively, it represents an unsubstituted heterocyclic compound group.
In another aspect of the invention Z represents a polymer based on acrylic polymers. A either represents O or S, or represents that Z is bonded directly (-CON = C = O) n or (-CONHCOOR ¹⁾ n. However, A is to represent that the Z is bound directly (-CON = C = O) n or (-CONHCOOR ¹⁾ n, the carbon of the binding end of the Z has two or more hydrogen Never. The reaction of the present invention can be represented by the following reaction formula (I).

[0012]

Embedded image

In the formula, R ¹ , Z, A and n are the same as defined above.
D represents a partial structure derived from an acid halide. In the above reaction, an acyl carbamate reacts with an acid halide in the presence of a basic substance to form a 6-membered ring transition state, which is thermally decomposed to an acyl isocyanate.

R ¹ represents a monovalent organic residue having 1 to 18 carbon atoms. Examples of such a group include an alkyl group, an aryl group, an aralkyl group, an alkynyl group, an alkenyl group, an alkaryl group, and the like, and an alkoxy group, an ester group, a thioalkoxy group, and an alkoxy group. Those substituted with an alkyl group, an aryloxy group, an alkoxyaryl group, an aryloxyalkyl group or the like;
Examples thereof include those substituted with a cyano group and the like.

Examples of Z are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.
-Alkyl groups such as butyl and t-butyl; alkynyl groups such as ethynyl, propenyl and butenyl; alkenyl groups such as ethenyl, propynyl and butynyl; aryl groups such as phenyl and naphthyl; heterocyclic compound groups such as furyl and pyrimidyl; These are an alkoxy group, an ester group, a thioalkoxy group, an alkoxyalkyl group, an aryloxy group,
Those substituted with an alkoxyaryl group, an aryloxyalkyl group or the like; and those substituted with a halogen, a nitro group, a cyano group or the like can be mentioned.

In addition to the above, Z represents a polymer mainly composed of an acrylic polymer. Examples of these include (meth) acrylate and alkyl (meth)
Examples thereof include acrylic polymers such as acrylates, but are not limited to acrylic polymers as long as they are commonly used as polymers.

The above A represents O or S. In addition to the above, in A, Z is directly (-CON = C = O) n or (-C
ONHCOOR ¹ ) n is represented. In this case, the carbon at the bond end of Z does not have more than one hydrogen.

The above n is an integer of 1-8. When Z is not a polymer, n is preferably 1 or 2, and when Z is a polymer, n is preferably 8.

Among the acyl carbamates represented by the general formula (2), the compound in which n is 1 is, for example, N
-Methacryloylethyl carbamate, N-benzoylethyl carbamate, Nt-butyroylethyl carbamate, N-2,6-difluorobenzoylethyl carbamate, N-cinnamoylethyl carbamate, N-
Trichloroacetylmethylcarbamate, N-4-methoxybenzoylethylcarbamate, N-naphthylcarbonylethylcarbamate, N-benzoylbutylcarbamate, N-methacryloyl-2-hexyloxyethylcarbamate, N-benzoylphenylcarbamate, N-methoxycarbonylmethylcarbamate , N-
Examples thereof include terephthaloyl ethyl carbamate.

Further, among the acyl carbamates represented by the general formula (2), those in which Z is a polymer include, for example, N-methacryloyl-2-hexyloxyethyl carbamate polymer in which n is 8. Can be mentioned.

The above-mentioned basic substance may be an organic base or an inorganic base, and is not particularly limited.
Guanidinium salt, tertiary amine, quaternary ammonium salt and the like are preferable, and in consideration of reactivity, guanidinium salt,
More preferred are quaternary ammonium salts.

Examples of the guanidinium salt include, for example:
Hexabutylguanidinium chloride, hexabutylguanidinium bromide, hexamethylguanidinium chloride, hexamethylguanidinium bromide and the like can be mentioned. These guanidinium salts are described in Synthesis, Volume 11, 904-90.
5, page 1983; can be synthesized according to German Patent No. 2718275.

Examples of the tertiary amine include triethylamine, tributylamine, dimethylaniline, pyridine, diazabicyclooctane, methyldicyclohexylamine and the like.

Examples of the above quaternary ammonium salt have a cation moiety of tetrabutylammonium, tetramethylammonium, tetraethylammonium, tetrahexylammonium, trimethylbenzylammonium, tetrapropylammonium, tetrahexylammonium, tetraoctylammonium and tetradecyl. Ammonium, tetrahexadecyl ammonium, triethylhexyl ammonium, 2-hydroxyethyl trimethyl ammonium, methyl trioctyl ammonium, cetyl trimethyl ammonium, 2-chloroethyl trimethyl ammonium, methylpyridinium, etc., the anion part is fluoride, bromide, chloride, Iodide, acetate, laurate, glycolate, benzoa Can salicylate, methanesulfonate, p- toluenesulfonate, dodecylbenzenesulfonate, triflate, nitrate, sulfate, there may be mentioned those such as consisting of methosulfate, and the like.

Examples of the above acid halides include thionyl chloride, oxalyl chloride, phosgene, its trimer, benzoyl chloride and the like.

In the method of the present invention, the compounding amount of the acid halide with respect to the acyl carbamate is preferably 0.5 to 3 equivalents, and more preferably 1 to 2 equivalents, relative to 1 equivalent of the acyl carbamate. In addition, the amount of the above-mentioned basic substance to be added per 1 equivalent of the acyl carbamate is 0.
5 to 30 equivalent% is preferable, and 1 to 15 equivalent% is more preferable.

The above-mentioned acyl carbamate, basic substance and acid halide may be reacted in a solution or without a solvent. The solvent is not particularly limited as long as it does not react with the product acylisocyanate, and examples thereof include hydrocarbon solvents such as hexane and heptane; aromatic solvents such as benzene and toluene; diethyl ether, dibutyl ether. , An ether solvent such as dioxane; a halogen solvent such as dichloroethane and dichlorobenzene; a ketone solvent such as methyl isobutyl ketone.

The reaction temperature is preferably 30 to 200 ° C, more preferably 80 to 130 ° C. When the temperature exceeds 200 ° C, the formed acyl isocyanates and the starting acylcarbamate are decomposed, and when the temperature is lower than 30 ° C, the reaction does not proceed sufficiently.

In the method of the present invention, the reactivity of the reaction product acylisocyanates with the starting acylcarbamates is low and the side reaction is small. Further, the acyl carbamate, the basic substance and the acid halide are heated to produce R ¹ Cl,
Since it is SO ₂ or the like and can be easily removed from the system, the reverse reaction of the above reaction formula (I) is suppressed. Therefore, the isolation of the acyl isocyanates does not require an operation such as distillation under reduced pressure at a high temperature, and the synthetic reaction of the acyl isocyanates can be carried out in one pot. The method of the present invention is suitable as an industrial production method because of the above characteristics.

The acyl isocyanates produced according to the present invention are extremely useful for producing many compounds in the technical fields of medicine, agricultural chemicals and polymers due to their excellent reactivity. For example, acetylisocyanate is used as a key intermediate in the production of triazolinones (J. Heterocyclic Chem., Vol. 27,
2017 page and below, 1990). Trichloroacetylisocyanate is widely used to form the carbamate component during the synthesis of antibiotics such as cefluoxime (CA 94 84147e). Further, t-butoxycarbonyl isocyanate, 2,2,2-trichloroethoxycarbonyl isocyanate, benzyloxycarbonyl isocyanate and the like are used for the production of other antibiotics.

As the drug, for example, a lipoxygenase inhibitor is synthesized from benzoyl isocyanate.
Substituted benzoyl isocyanates, such as 2,6-difluorobenzoyl isocyanate, are widely used in the manufacture of many urea benzoyl insecticides. Synthesis of protected amines directly from benzoyloxycarbonyl isocyanate has also been carried out (synthesis (S
No. 12, pp. 992 et seq., 198
8 years).

Further, methacryloyl isocyanate having an acyl isocyanate group and a polymerizable double bond in one molecule can react both functional groups independently, and various compounds can be synthesized. . The acylisocyanate group readily reacts with numerous types of alcohols, amines, thiols, etc. without a catalyst to give vinyl group-containing derivatives containing residues derived from the reacted active hydrogen-containing compound. The resulting vinyl group of the vinyl group-containing derivative exhibits almost the same reactivity as a normal (meth) acrylic monomer. Therefore, polymerization can be easily performed by a radical polymerization initiator, ultraviolet irradiation, etc., and the desired functional group bonded to the isocyanate group can be introduced into the polymer.

Also, the methacryl group of methacryloyl isocyanate can be copolymerized with various other monomers to give polyisocyanate. The isocyanate group of the resulting polyisocyanate maintains high reactivity, and is reacted with alcohol, amine, thiol, etc.,
It is also possible to introduce a residue derived from an active hydrogen compound. Since the range of selection of the residue derived from the above active hydrogen compound and the above-mentioned other copolymerizable monomer is large, a resin or the like having a resin characteristic value such as a glass transition temperature or a solubility parameter which meets the demand is produced. It will be possible.

Further, methacryloyl isocyanate is
It is possible to graft-copolymerize methacrylic groups to various polyfunctional active hydrogen-containing resins from low molecular weight to high molecular weight. These vinyl group-grafted resins can be cured with a radical polymerization initiator or the like, and can be used for improving a crosslinked coating film or the like.

[0035]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

Example 1 5 g (0.03) of N-methacryloylethyl carbamate
2 mol) and 12 g of toluene were mixed, 7.6 g (0.064 mol) of thionyl chloride was added thereto, and the mixture was heated with stirring at 88 ° C. To this, 0.5 g (2 mol%) of hexabutylguanidinium chloride (hereinafter CHBG) was added,
The heating and stirring were continued for 5.5 hours. 2250 cm by IR
The absorption peak of ^-1 was observed, and the formation of acyl isocyanates was confirmed. From the NMR measurement, it was found that methacryloyl isocyanate was obtained in a yield of 34%. The boiling point was 121 to 122 ° C. (760 mmHg).

Example 2 2 g (0.0104) of N-benzoylethyl carbamate
Mol) and 12 g of toluene were mixed, 2.5 g (0.0208 mol) of thionyl chloride was added thereto, and the mixture was heated and stirred at 90 ° C. Tetraammonium chloride 0.0
2 g (0.072 mol) was added and heating and stirring was continued for 3.3 hours. By IR, an absorption peak at 2250 cm ^-1 was observed, and formation of acyl isocyanates was confirmed. Methanol was added thereto to isolate it as an N-benzoylmethyl carbamate derivative, and it was confirmed that the yield of acyl isocyanates was 98%. The melting point was 118 ° C.

Examples 3 to 15 In the same manner as in Example 1, the acyl carbamates shown in Table 1,
Reaction was carried out with a combination of acid halide and basic substance to obtain corresponding acyl isocyanates. Table 1 shows the isolation method, yield, and boiling point at each pressure. CHBG in Table 1
Is hexabutylguanidinium chloride, TBAC is tetrabutylammonium chloride, TBAB is tetrabutylammonium bromide, and TBAF is tetrabutylammonium fluoride.

Example 16 Hexyloxyethyl carbamate 20 g, methyl methacrylate 20 g, ethylhexyl acrylate 20
g, azobisisobutyl nitrile (AIB
A mixture in which 0.6 g of N) was dissolved was added dropwise to 90 g of butyl acetate heated to 100 ° C. over 1.5 hours. After that, by continuing heating and stirring for 1.5 hours,
Polymer 1 having a molecular weight of 3000 was obtained. This polymer 1 was used as an acyl carbamate and reacted with the combination of the acid halide and the basic substance shown in Table 1 to obtain the corresponding acyl isocyanate group-containing acrylic polymer. The results are shown in Table 1.

[0040]

[Table 1]

[0041]

INDUSTRIAL APPLICABILITY According to the present invention, a method of heating an acyl carbamate at a low temperature in the presence of a basic substance and an acid halide makes it easy to isolate a product with a small amount of by-products, and a wide variety of products can be obtained. Acyl isocyanates can be manufactured industrially and safely.

Claims (6)

[Claims] 1. A basic substance for acyl carbamate in which an atom bonded to a carbonyl carbon in a substituent for carbonyl constituting an acyl group is oxygen, sulfur, or carbon not having two or more hydrogens. And a method for producing an acylisocyanate, which comprises adding an acid halide and heating. 2. The acyl isocyanate according to claim 1, wherein the acyl isocyanate is represented by the following general formula (1) and the acyl carbamate is represented by the following general formula (2). Manufacturing method. Embedded image In the formula, R ¹ represents a monovalent organic residue having 1 to 18 carbon atoms, and n represents an integer of 1 to 8. Z is a substituted or unsubstituted, linear, branched or cyclic, saturated or unsaturated, hydrocarbon group having a molecular weight of 10 to 300; a substituted or unsubstituted aryl group having 6 to 14 carbon atoms or a substituted group Alternatively, it represents an unsubstituted heterocyclic compound group. A represents O or S, or Z is directly (-CON = C = O).
Represents being bonded to n or (-CONHCOOR ¹ ) n. However, A and Z are directly (-CON = C =
To represent that it is bound with O) n or (-CONHCOOR ¹⁾ n, the carbon of the binding end of Z may never have two or more hydrogen. 3. The method for producing an acylisocyanate according to claim 2, wherein Z is a polymer mainly composed of an acrylic polymer. 4. The method for producing an acylisocyanate according to claim 1, 2 or 3, wherein the basic substance is a guanidinium salt, a tertiary amine or a quaternary ammonium salt. 5. The method for producing an acyl isocyanate according to claim 1, 2, 3 or 4, wherein the acid halide is thionyl chloride, oxalyl chloride or phosgene. 6. The method for producing an acylisocyanate according to claim 2, 4 or 5, wherein Z-A is an isopropenyl group and n is 1.