EP1303493A1

EP1303493A1 - Method for the production of n,n'-carbonyldiazoles and azolide salts

Info

Publication number: EP1303493A1
Application number: EP01945342A
Authority: EP
Inventors: Johannes Scherer; Alexander Klausener; Robert Söllner
Original assignee: Bayer AG; Bayer Chemicals AG
Current assignee: Saltigo GmbH
Priority date: 2000-07-19
Filing date: 2001-07-06
Publication date: 2003-04-23
Also published as: US20020111497A1; WO2002018347A1; AU2001267587A1; DE10035011A1; US6774239B2; US20030013891A1; US6465658B2

Abstract

N,N'-Carbonyldiazoles are obtained in a particularly advantageous manner, whereby the corresponding azolide salt is reacted with phosgene in an aromatic or ethereal solvent. Said azolide salts are preferably produced by a novel method from an azole which is reacted with a compound of formula M'R?7 or MgR8¿Z' in the presence of a solvent.

Description

Process for the preparation of N.N'-carbάnyldiazoleπ and azolide salts

The present invention relates to improved processes for the preparation of N, N'-carbonyldiazoles by reacting azolide salts with phosgene and for the preparation of azolide salts,

It is already known in principle that N, N'-Ca bonyldiazole can be obtained if azoles are reacted with phosgene (see DE-AS 10 33 210, Chem. Ber. 96, 337 '4 (1963) and Org. Synth. Coll. Vol. IV, 201-204 (1968) and BP-A 692 476).

A disadvantage of all of these processes is that the adhesion of the azole used is used as a scavenger for the hydrogen chloride formed and therefore only a maximum of 50% of the azole used can be converted into the desired carbonyldiazole. This is a serious disadvantage since azoles are expensive products and therefore a large azole consumption causes high manufacturing costs. Furthermore, some of the azole hydrochlorides are obtained as a sticky precipitate which is difficult to separate from the carbonyldiazole prepared. Finally, the azole hydrochloride formed as a by-product has to be disposed of, which causes additional costs.

The process for the synthesis of KN'-carboπyldiimidazole according to US Pat. No. 4,965,366 attempts to circumvent these disadvantages, in which imidazole is reacted with chlorotrimethylsilane to trimethylsilylimidazole in a first reaction step. In order to capture the hydrogen chloride, an amine (for example l ₃ 2-diaminoethane) is added, the hydrochloride of which is filtered off and either fed to the amine as it is recovered or disposed of. The trimethylsilylimidazoi formed in the reaction must still be purified by distillation before the further reaction. In the next step, the trimethylsiliridazole is reacted with phosgene. Here, chlorotrimethylsilane is formed again, which can be used again in the reaction after purification. A disadvantage of this method are the many stages of synthesis and purification as well as the chlorotrimethylsilane, which is difficult to handle due to its hygroscopic and corrosive properties.A total of three auxiliaries are to be used for this N, N'-carbonyldiimidazole synthesis, namely, chlorotrimethylsilane, 1,2-diaminoethane and sodium hydroxide solution. In addition, the amine, the imidazole and the solvent required for the trimethylsilylimidazole synthesis have to be dried in a complex manner.

A process for the preparation of N, N'-carbonyldiazoles of the formula (I) has now been

In the

X ¹ , X ² and X ³ each independently represent CR ¹ or nitrogen, where R ^{1 is} hydrogen or Ci-Cg-alkyl and

R2 stands for hydrogen

or

X ^{2 has} the meaning given above and

X ¹ and X ^{3 are} CR ¹ , the R ¹ on X ^{1 being} hydrogen or C _r C ₆ alkyl, and the R ¹ on X ³ together with ² forming a —CH CHCH-CH = CH bridge .

found, which is characterized in that azolide salts of the formula

in the

M® stands for an equivalent of an alkali or alkaline earth metal cation or a quaternary omurnion of the formula (TU)

[YR ³ 4 R5 Rψ TO, in the

Y for phosphorus or nitrogen and

R ³ , *, R. ⁵ and R ⁶ each independently represent CC ₂ o-alkyl, phenyl, benzyl or ethylbenzyl and

the other symbols have the meaning given for formula (I),

reacted with phosgene in an aromatic or an ether as a solvent.

In formulas (1) and (II), X and X ² are preferably, independently of one another, CH, N or CCH ₃ , X ³ for CH and R ² for hydrogen or X ¹ for CH, X ² for CH, N or CCH ₃ , and X ³ for CR ¹ , where R ¹ and R ² together form a -CH = CH-CH = CH bridge. In formula (II), M ^{Θ is} preferably one mole of lithium, sodium or potassium cations or Vi moles of magnesium cations or 1 mole of a quaternary onium ion of the formula (IH) with Y = phosphorus or nitrogen and R ³ = R ⁴ = R = < ⁵ - C Cg alkyl, or R ³ - R ⁴ - R ⁵ = C _r C ₆ alkyl and R ⁶ - C ₄ -C ₂₀ alkyl, phenyl, benzyl or ethyl. In particular, ^φ stands for 1 mole of lithium, sodium or potassium cations.

Sodium or potassium imidazolide or the corresponding -1,2,4-triazolides, -pyrazolides or -benzimidazolides are particularly preferably used and N, N'-carbonyl-diimidazαl, N, N'-carbonyl-di (1,2,4- triazole) _s N, N'-carborryl-dipyrazole or NJST-carbonyl-dibenzimidazole.

In the process according to the invention, for example, 0.25 to 0.60 mol of phosgene can be used per 1 mol of azolide salt of the formula (II). This amount is preferably 0.45 to 0.55 mlJ

Aromatic solvents such as benzene, toluene, xylenes, monochlorobenzene, dichlorobenzenes and trichlorobenzenes and ethers such as acyolisclϊe and cyclic mono- and oligoethers, for example diethyl ether, diisopropyl ether, methyl tert-butyl ether, dibmyl ether, ethylene glycol dimethyl ether, diethylene glycol triethylene glycol, are suitable as solvents ethyl ether, tetrahydrofuran, 2-methyl-tetrahydrofuraτi and dioxane. Mixtures of these solvents can also be used. Preferred are 2-methyl-tetrahydrofuran and aromatic solvents, in particular benzene, toluene, xylenes, monochlorobenzene, dichlorobenzenes and mixtures of these solvents. The preferred solvents can be easily dried, e.g. by azeotropic distillation. A water content of the solvent of less than 0J% is preferred.

The process according to the invention can be carried out, for example, at temperatures in the range from 10 to 120 ° C. Temperatures in the range from 20 to 100 ° C. are preferred, in particular from 40 to 100 ° C. The Rcak tion temperature at least so high that the N, N-carbonyldiazole of formula (I) does not precipitate during the reaction.

Azolide salts of the formula (II) are, for example, according to I A. Chem. Soc. 102, 4182 or EP-A 352 352. However, these processes are cumbersome and complex because either reagents that are difficult to handle (e.g. sodium hydride or butyllithium) are required or the azolide salt has to be isolated and purified. However, a particularly favorable process for the preparation of azolide salts of the formula (ΪI) has also been found, the details of which are described below. Azolide salts of the formula (II) which have been prepared by the process according to the invention for the preparation of azolide salts of the formula (II) are preferably used in the process according to the invention for the preparation of N, N'-carbonyl-diazoles of the formula (I). This has e.g. the advantage that the azolide salt of the formula (II) does not have to be isolated, but can be used in the form of the reaction mixture obtained in its preparation according to the invention, if appropriate after distilling off the solvent of the formula (Vü) present.

It is advantageous to carry out the process according to the invention for the preparation of N, N * carbonyldiazoles in the presence of a phase transfer catalyst. As phase transfer catalysts come e.g. those of the formulas (VIII) to (X) into question

[YR ⁴ RS 6] + Z- (VIII),

in which

R ³ , R ⁴ , R ⁵ and R ^{δ have} the meaning given for formula (III),

io each independently represents C _r C ₂ Q-alkyl, phenyl, benzyl or ethylbenzyl,

R ^{11 has} the same meaning as R ¹ ° regardless of ^l °,

R ¹⁰ and R ^{11 can} also together form a (-CH ₂ - _n - ^{bridge m} ^ n ^{= an} a zen number from 1 to 10,

Rl2 for N ^ ¹¹ , C _r C ₂₀ alkyl, phenyl, benzyl or ethylbenzyl and

Z- stands for Cl ", Br, I-, OH", HSO4-, BF ₄ "or PF ₆ ".

Azoles of the formula (TV) (see below) can also be used as phase transfer catalysts.

Based on one mole of azolide salt of formula (II), e.g. Use 0.0001 to 0.2 mol, preferably 0.001 to 0.02 mol, of a phase transfer catalyst,

In the production of N.N'-carbonyldiazoles according to the invention, a chloride of the formula is formed as the second reaction product

M-Cl- (XI) in which M + has the meaning given for formula (II). This chloride precipitates out during the production of N, N-carbonyldiazole. The present after the reaction the reaction mixture can be worked up, for example, ⁱ separates first the one n the chloride formed, for example by filtration or waste hebem of the liquid components and from the filtrate or the abgeheberten liquid ^¬ ness the hergestclte N, N'-carbonyldiazole isolated either by cooling to +40 to -70 ° C, preferably to +25 to -20 ° C, but not as 5 ° C above the solidification point of the solvent used, and filtering off the crystallizing product or the volatile Withdrawing or distilling off constituents, the product is thus obtained in solid form.

The production of N, N'-carbonyldiazoles according to the invention has the advantage that the entire azole or azolide salt used is available for the formation of N, N'-caxbonyldiazole and not half of it is converted into azole hydrochloride. The yields of N, N'-cafbonyldiazole are around twice as high as in the direct reaction of azoles with phosgene. Even if phosgene is used in substoichiometric amounts, a clean HN carbonyldiazole is obtained, since unreacted azolide salts, unlike azoles, are poorly soluble in the reaction mixture and, if they are present, together with the chloride of the formula (XI) from the reac _t be removed ionsgemisch. The accounts in the direct order ^¬ reduction of azole can with phosgene required precise stoichiometric metering of phosgene in the inventive method since Produktverun- Cleaners not occur with imumgesetztem azole starting material.

The present invention further relates to a process for the preparation of azolide salts of the formula (Iϊ), which is characterized in that an azole of the formula (IV)

I * ³ (IV),

R ^< in which the symbols used have the meaning given for formula (I),

with a compound of formula (V) or formula (VI)

M ⁷ (V) M SZ '(VI),

in which

M ^{1 represents} an equivalent of an alkali or alkaline earth metal, but not a quaternary onium ion of the formula (III),

R 7 is OR ', N (R ⁹⁾ ₂ or ^l / ₂ C0 _3, wherein

R ^{9 is} C _r C ₆ alkyl or phenyl,

R ⁸ for C _r C ₆ alkyl or phenyl,

and

Z 'represents CL Br or I,

reacted in a solvent.

In formula (IV), the symbols used preferably represent what is stated as preferred in formula (I). In formula (V), M 'preferably represents lithium, sodium or potassium and R ⁷ preferably OR ⁹ with R ⁹ - hydrogen or methyl.

In formula (VI), R ^{8 is} preferably methyl. Ethyl or phenyl and Z 'preferably for chlorine or bromine. The solvent can be, for example, one of the solvents mentioned above for carbonyldiazole synthesis or mixtures thereof with a solvent of the formula (VII)

MR? (VII)

in which R ^{7 has} the meaning given for formula (V), but cannot stand for ^I A CO ₃ .

If, after the azolide salt production, solvents of the formula (Vü) are present, these are distilled off before the reaction with phosgene to give N, N'-carbonyldiazoles of the formula (I).

In preferred embodiments of the process according to the invention for the preparation of azolide salts of the formula (II), lithium, sodium or potassium hydroxide is used as the compound of the formula (V) and water is used as a solvent in a mixture with chlorobenzene, toluene or xylene, and water which has been introduced and distilled is distilled azeotropically, or sodium methylate is used as the compound of formula (V) and methanol is used as a solvent in a mixture with chlorobenzene or xylene, and methanol which has been introduced and formed is distilled off.

The preferred embodiments of the process according to the invention for the preparation of azolide salts of the formula (II) are particularly advantageous over the processes known from the literature because the reaction mixtures which are then obtained and freed from water and methanol are added directly to the process for the preparation of N, N'-carbony] diazoles of the formula (I) and can do without the separation, work-up, purification and drying of the azolide salts of the formula (11). In addition, no expensive and no difficult-to-use reagents are generally required. Examples

example 1

274.4 g of imidazole were placed in 1000 g of chlorobenzene in a flask with a water separator. 320 g of a 50% strength by weight sodium hydroxide solution were added dropwise. Then water was removed until the distillate no longer separated into two phases. In this way, 231 ml of water was removed from the reaction mixture. Then 100 ml of chlorobenzene were distilled off, then the solid portions of the reaction mixture were separated by H filtration and dried. This gave 357.2 g of sodium imidazolide (99.2% of theory).

Example 2

180 g of sodium imidazolide (obtained according to Example 1) and 2 g of tributylhexadecylphosphonium bromide were placed in a flask in 1000 g of chlorobenzene dried by distillation. At a temperature of 75-80 ° C., 98 g of phosgene were introduced over the course of one hour. After the addition had ended, stirring was continued at 80 ° C. for 1 hour while passing through a vigorous stream of nitrogen. The present precipitate was filtered off at 80 ° C. and washed with 100 g of chlorobenzene from S0 ° C. The filtrate and washing liquid were combined and cooled to 20 ° C. The resulting precipitate was filtered off, washed with 100 g of dry chlorobenzene at 20 ° C. and dried at 60 ° C. in vacuo (50 mbar). 141.1 g of carbonyldiimidazole were obtained in the form of colorless crystals with a purity of 98.7%. This corresponds to a yield of 87.0% of theory.

Examples 3 to 8

The procedure was as in Example 2, but other phase transfer catalysts were used, details are shown in the following table.

Example 9

1200 g of chorbene and 272.4 g of imidazole were placed in a flask with a water separator. 320 g of 50% strength by weight sodium hydroxide solution were added dropwise. Water was removed until the distillate no longer separated into two phases. After 224 ml of water had been removed in this way, 100 ml of chlorobenzene were distilled off, then 2 g of tributylhexadecylphosphonium bromide were added and 202 g of phosgene were introduced at 80-85 ° C. in one hour. After the addition had ended, stirring was continued at 90 ° C. for 1 hour while passing through a vigorous stream of nitrogen. The precipitate then present was filtered off at 80 ° C. and washed with 90 g of chlorobenzene at 90 ° C. The filtrate and the washing liquid were combined and cooled to 0 ° C. The resulting precipitate was filtered off, washed with 200 g of dry chlorobenzene and dried at 60 ° C in a vacuum (50 mbar). 266 g of carbonyldiimidazole were obtained in the form of colorless crystals in a purity of 97.0%. This corresponded to a yield of 79.5% of theory. Example 10

272.4 g of imidazole were placed in 1400 g of chlorobenzene in a flask with an attached column and distillation bridge. For this purpose, 720 g of 30% methanolic sodium meihanolate solution were added dropwise and the methanol formed was distilled off. Then 300 ml of chlorobenzene were distilled off and 2 g of tributylhexadecylphosphonium bromide were added. 202 g of phosgene were introduced in the course of one hour at 80-90 ° C. After the addition had ended, stirring was continued for 1 hour at 90 ° C. while passing through a vigorous nitrogen stream. The precipitate present was then filtered off at 80 ° C. and treated with 200 g of chlorobenzene washed from 90 ° C. The filtrate and the washing liquid were combined and cooled to 0 ° C. The precipitate which formed was filtered off, washed with 200 g of dry chlorobenzene and dried at 60 ° C. in vacuo (250 ml). 5 g of carbonyldiimidazole with a purity of 97.4% were obtained in the form of colorless ^" crystals. This corresponded to a yield of 72.3% of theory.

Examples 11 to 15

It was experienced as in Example 1, but other azolide salts were used in an appropriate molar amount. Details are shown in the table below.

Example 16

286.0 g of imidazole were placed in 1200 g of chlorobenzene in a flask with a water separator, and 320 g of 50% strength aqueous sodium hydroxide solution were added. Then water was removed until the distillate no longer separated into two phases. After 224 ml of water had been removed 100 ml of chlorobenzene were distilled off. 202 g of phosgene were then introduced at 80-85 ° C. in one hour Nitrogen stream stirred at 90 ° C for 1 hour, the precipitate then filtered off at 80 ° C and washed with 200 g of chlorobenzene at 90 ° C. The filtrate and washing liquid were combined and cooled to 0 ° C. The resulting precipitate was filtered off, washed with 200 g of dry chlorobenzene and dried at 60 ° C in a vacuum (50 mbar). 290.6 g of Caτbonyl-diimidazole were thus obtained in the form of colorless crystals with a purity of 97%. This corresponded to a dent of 88% of theory.

Example 17

286.0 g of imidazole were placed in 1400 g of chlorobenzene in a flask with an attached column and distillation bridge. 720 g of 30% methanolic sodium methoxide solution were added dropwise. First, methanol was distilled off, then 300 ml of chlorobenzene. 202 g of phosgene were introduced primarily at 80-85 ° C. in one hour. When the addition was complete, stirring was continued for 1 hour at 90 ° C. while passing through a vigorous nitrogen stream, the precipitate present was then filtered off at 80 ° C. and washed with 90 g of chlorobenzene at 90 ° C. The filtrate and washing liquid were combined and cooled to 0 ° C. The precipitate which formed was filtered off, ^washed with 200 g of dry chlorobenzene at 20 ^° C. and dried at 60 ° C. in vacuo (SO mbar). Thus 278.3 g carbonvldnmida ^ ol were obtained in the form of colorless crystals and with a purity of 97 8%. This corresponded to a yield of 84.0% of theory.

Claims

claims

1, Process for the preparation of N, N'-carbonyldiazo of the formula

in the

X ¹ , X ² and X ³ each independently represent CR ¹ or nitrogen, where R ^{1 is} hydrogen or Ci-C _f j-Ai yl and

R ^{2 represents} hydrogen

or

χ2 has the above meaning and

X ¹ and X ^{3 are} CR ¹ , the R ¹ on X ^{1 being} hydrogen or C _j -C _ß- alkyl and the R ¹ on X ³ together with R ^{2 being} a -CH = CH-CH-CH- Forms a bridge,

characterized in that azolide salts of the formula

in the

® stands for an equivalent of an alkali or alkaline earth metal cation or a quaternary ion of the formula (ΪII)

Y for phosphorus or nitrogen and

R ³ , 4, R5 and R ⁶ each independently represent C ^ -C o-Al y !, phenyl, benzyl or ethylbenzyl and

the other symbols have the meaning given for formula (I),

reacted with phosgene in an aromatic or an ether as a solvent.

2. The method according to claim 1, characterized in that in the formulas (I) and (II)

I and X2 independently of one another for CH, N or CCH ₃ , X ³ for CH and 2 for hydrogen or X ¹ for CH, X ² for CH, N or CCH ₃ , and X ³ for CR ¹ , where R ¹ and R ² together form a -CH = CH-CH = CH bridge,

and in formula (II) M ⁺ for 1 mol of lithium, sodium or potassium cations or Vi mol of magnesium cations or 1 mol of a quaternary ammonium ion of the formula (III) with Y - phosphorus or nitrogen and R ³ - R4 = 5 _ = R6 ₌ C, -C ₈ alkyl or R ³ = ⁴ R ⁵ = C _r C ₆ alkyl and R ⁶ - C ₄ -C ₂ o-alkyl, phenyl. ctvyl or ethyl.

3. Process according to Claims 1 and 2, characterized in that 0.25 to 0.60 mol of phosgene is used per 1 mol of azolide salt of the formula (II).

4. Process according to Claims 1 to 3, characterized in that it is carried out at temperatures in the range from 10 to 120 ° C.

5. Process according to Claims 1 to 4, characterized in that it is carried out in the presence of a phase transfer catalyst.

6. Process according to Claims 1 to 5, characterized in that 0.0001 to 0.02 mol of a phase transfer catalyst is used per 1 mol of azolide salt of the formula (II).

7. Process according to Claims 1 to 6, characterized in that the reaction mixture present after the reaction is worked up, in which the chloride formed is first separated off and the N, N'-carbonyldiazole prepared is isolated from the reaction mixture which has been freed from chloride, in which cools to +40 to -70 ° C, but not lower than 5 ° C above the solidification point of the solvent used, and the product which crystallizes out is filtered off.

8. Process according to Claims 1 to 7, characterized in that the N, N'-carbonyldiazole prepared is isolated from the reaction mixture freed from chloride, in which the volatile constituents are stripped off or distilled off, and the product is thus obtained in solid form.

9. Process for the preparation of azolide salts of the formula (II)

in the

M ^{φ stands} for an equivalent of an alkali or alkaline earth metal cation or a quaternary onium ion of the formula (II)

[Y ^ R4 R5 6 ® (III), in the

Y for phosphorus or nitrogen and

R ³ ~ R ⁴ , R ⁵ and R ⁶ independently of one another each represent CC ₂ b-alkyl, phenyl benzyl or ethylbenzyl and

the other symbols have the meaning given in formula (I) in claim 1,

characterized in that an azole of the formula (IV)

in which the symbols used have the meaning given for formula (I).

with a compound of formula (V) or formula (VI) M'R ⁷ (V) MgR ⁸ Z '(VI),

in which

M * represents an equivalent of an alkali or alkaline earth metal, but not a quaternary onium aeon of the formula (II),

R ^{7 stands} for R ^, OR9, N (R ⁹ ) ₂ or '/ * C0 ₃ , where

R ^{9 represents} H \ C _r C ₆ alkyl or phenyl,

R ^s for C _r C ₆ alkyl or phenyl,

and

Z 'represents CJ, Br or I,

reacted in a solvent.

A method according to claim 9, characterized in that the solvent is aromatics or ethers or mixtures thereof with a solvent of the formula

HR ⁷ (VII)

is in which R ^{7 has} the meaning given in formula (V), but cannot stand for VΪ CO ^.