WO2000034288A1

WO2000034288A1 - Process for removal of cyanide from reactions producing 1,3 diones

Info

Publication number: WO2000034288A1
Application number: PCT/US1998/026015
Authority: WO
Inventors: Steven Arnold Dombchik; Kanu Maganbhai Patel
Original assignee: EI Du Pont de Nemours and Co
Current assignee: EIDP Inc
Priority date: 1998-12-08
Filing date: 1998-12-08
Publication date: 2000-06-15
Anticipated expiration: 2001-06-08
Also published as: AU1716799A

Abstract

This invention relates to a process using a peroxide source to remove cyanide from the acylated 1,3-dicarbonyl reaction products of formula (I) produced by the reaction of cyanide with precursors, or the reaction of cyanide moiety containing precursors. J is (J-1) or (J-2), Q is (Q-1) or (Q-2). All definitions are as defined in the application.

Description

TITLE PROCESS FOR REMOVAL OF CYANIDE FROM REACTIONS PRODUCING 1,3 DIONES BACKGROUND OF THE INVENTION This invention relates to a process for removing cyanide from reactions producing acylated 1,3-dicarbonyl compounds. More particularly, this invention relates to a process using a peroxide source and a base to remove cyanide from the acylated 1,3-dicarbonyl reaction products produced by the reaction of cyanide with precursors, or the reaction of cyanide moiety containing precursors. 2-(substituted benzoyl)-l,3-cyclohexane diones are known as herbicides. Processes for making such compounds are disclosed in for example, U.S. Patent nos. 4,946,981, and 5,006,158. Pyrazole-4-yl-benzoyl derivatives are disclosed in PCT WO 96/26206 and WO 95/04054. These compounds can be produced by rearrangement of an enol ester with cyanide source or prepared directly from 2(substituted)benzoyl cyanide and cyclohexane diones or pyrazoles. Since these methods of producing diones involve cyanide, the product always contains cyanide as an impurity.

The process of the present invention involves treatment of acylated 1,3-dicarbonyl products containing cyanide as an impurity with a peroxide source and a base. The product of this process contains less than about 0.1 ppm cyanide or an amount of cyanide which is non-detectable by calorimetric method, as described in Standard Methods for the

Examination of Water and Wastewater, American Health Association, A. E. Greenburg, L. S. Clesceri and A. D. Eaton, 1992 18^th edition, pp 4-24. U.S. Patent no. 3,835,047 describes rendering liquids containing cyanohydrins non-toxic by treatment with hydrogen peroxide. One skilled in the art would expect hydrogen peroxide to react with the cyanide in the acylated 1,3-dicarbonyl -producing reactions, but would also expect the hydrogen peroxide to modify the product, making it useless as a herbicide. In addition, one would not expect this reaction to require a large excess of hydrogen peroxide in order to effectively lower the level of cyanide. The surprising result, which is the subject of this invention, is that under the reaction conditions described herein, the cyanide content can be reduced to non-detectable levels with a large excess of hydrogen peroxide while preserving the integrity of the desirable herbicidal products.

EP 527,614 describes the removal of cyanide from tricarbonyl compounds using enzymes. Enzyme methods are often expensive and difficult to scale up. Therefore, there is a need for a method for effective removal of cyanide from dione reactions. SUMMARY OF THE INVENTION

This invention relates to a process for removing cyanide from a reaction product produced by the rearrangement of an enol ester catalyzed by a cyanide source or the reaction of an acyl-cyanide with a 1,3-diketone, wherein said removal is carried out in the presence of an effective amount of a peroxide source. Preferably this invention relates to removal of cyanide where the reaction product has the formula:

wherein J is

J-l J-2

Q is

Q-l Q-2

R¹ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio, C^-Cg haloalkylthio, halogen or cyano; R² is C_rC alkyl, C_rC haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio,

C₂-Cg haloalkylthio, halogen, cyano or nitro; or R¹ and R² are taken together to form -X¹-(CH )_t-X²-, optionally substituted with 1-4

CH₃; or R¹ and R² are taken together with the carbon to which they are attached to form C(=O) or C(=S); each R³ is independently Cj-C₄ alkyl; R⁴ and R⁵ are each independently H, C_j-C₆ alkyl, C_j-C6 haloalkyl, C_j-Cg alkoxy,

Cj-Cg haloalkoxy, S(O)_nR¹⁶, halogen, cyano or nitro; each R⁶ is independently halogen, Cj-C₄ alkoxy, Cι-C haloalkoxy, C_j- alkyl,

C_rC haloalkyl, C1-C3 alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano; R^6a is halogen, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₄ haloalkyl, C_rC₃ alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹⁴R¹⁵, nitro or cyano; R⁷ is H or M; each R⁸ is independently H, C_rC3 alkyl, C3-C alkenyl, C₃-C alkynyl, C1-C3 alkoxy, formyl, C₂-C₄ alkoxycarbonyl, -CH(C₁-C₃ alkoxy)₂, C_rC₃ alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH2CH2O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH₂OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C1-C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁴ is independently H or C C₄ alkyl; R¹⁵ is C_j-C₄ alkyl or Cj-C₄ alkoxy; or R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-, -CH2CH2CH₂CH₂,

-CH2CH₂CH2CH2CH2- or -CH₂CH₂OCH₂CH2-; each R¹⁶ is independently C C₄ alkyl or Cj-C₄ haloalkyl; X¹ and X² are independently O or S;

M is an alkali or alkaline earth metal; or M is HN(Cι-Cg alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; p is O, 1, 2, 3 or 4; r is 0, 1, 2, 3 or 4; t is 2 or 3; and w is 0, 1 or 2.

More preferably this invention relates to removing cyanide from reaction products where the product has the following chemical formula:

wherein Q is

Q-l Q-2

R¹ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio, C^-Cg haloalkylthio, halogen or cyano; R² is C_rC₄ alkyl, C_rC₄ haloalkyl, Cj-C₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio,

C2-C₆ haloalkylthio, halogen, cyano or nitro; or R¹ and R² are taken together to form -X¹-(CH₂)_t-X²-, optionally substituted with 1-4

CH₃; or R¹ and R² are taken together with the carbon to which they are attached to form C(=O) or C(=S); each R³ is independently Cj-C₄ alkyl; R⁴ and R⁵ are each independently H, C_j-Cg alkyl, C_j-Cg haloalkyl, Cι-C₆ alkoxy,

C_j-Cg haloalkoxy, S(O)_nR¹⁶, halogen, cyano or nitro; R⁷ is H or M; each R⁸ is independently H,

alkyl, C3-Q alkenyl, C3-C alkynyl, C_]-C₃ alkoxy, formyl, C2-C₄ alkoxycarbonyl, -CH(Cj-C3 alkoxy)2, C₁-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH2CH2O-,

-OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH2OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C1-C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, C_j-C₄ alkyl, Cj-C haloalkyl, Cι-C₄ alkoxy, Cj-C₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁶ is independently C C₄ alkyl or Cj-C₄ haloalkyl; X¹ and X² are independently O or S;

M is an alkali or alkaline earth metal; or M is HNCC_j-C^ alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3 or 4; t is 2 or 3; and w is 0, 1 or 2.

More preferably this invention relates to removing cyanide from reaction products where the product has the chemical formula:

or

or

This invention relates to a process for removing cyanide from a compound having the formula:

or

lb

wherein said removal is carried out in the presence of an effective amount of a peroxide source and wherein Q is

Q-l each R⁶ is independently halogen, Cι-C alkoxy, C_rC₄ haloalkoxy, C_j- alkyl, C_j-C haloalkyl, C₁-C3 alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano;

R^6a is halogen,

alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹ Rl5, nitro or cyano;

R⁷ is H or M; each R⁸ is independently H, C1-C3 alkyl, C3-C4 alkenyl, C₃-C₄ alkynyl, C_rC₃ alkoxy, formyl, C₂-C alkoxycarbonyl, -CH(C_rC3 alkoxy)₂, C1-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH2CH2O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; each R¹⁴ is independently H or C_j-C alkyl;

R¹⁵ is C_rC₄ alkyl or C_rC₄ alkoxy; or

R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂- , -CH₂CH₂CH₂CH₂CH₂- or -CH₂CH₂OCH₂CH₂-; each R¹⁶ is independently Cj-C₄ alkyl or C C₄ haloalkyl;

M is an alkali or alkaline earth metal; or M is HN(Cι-Cg alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; r is O, 1, 2, 3 or 4. This invention relates to a process for removing cyanide from a compound having the formula

lb

wherein said removal is carried out in the presence of an effective amount of a peroxide source and wherein

Q is

Q-2

each R⁶ is independently halogen, C C₄ alkoxy, C_j-C₄ haloalkoxy, C_j-C₄ alkyl,

Cj-C₄ haloalkyl,

alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano; R^6a is halogen, C_j- . alkoxy, C_j- haloalkoxy, C C₄ haloalkyl, C1-C3 alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹⁴R¹⁵, nitro or cyano; R⁷ is H or M; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH₂OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with CJ-C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, Cj-C₄ alkyl, Cj-C₄ haloalkyl, C C₄ alkoxy, C C₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁴ is independently H or C_rC₄ alkyl; R¹⁵ is Ci"C₄ alkyl or C C₄ alkoxy; or R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂-

, -CH₂CH₂CH₂CH₂CH2- or -CH2CH2OCH2CH2-; each R¹⁶ is independently C C₄ alkyl or C C₄ haloalkyl; M is an alkali or alkaline earth metal; or M is HN(Cι-C₆ alkyl^; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; r is O, 1, 2, 3 or 4. Preferably the process of cyanide removal is carried out under basic conditions with a molar excess of peroxide relative to cyanide, the peroxide source is selected from the group consisting of hydrogen peroxide, benzoyl peroxide, peracetic acid, or 1,1,1-trifluoromethyl peracetic acid, and the process is carried out at a temperature of about -10 to 60° C and a pressure of -10 to 10 bar. More preferably, the process of cyanide removal is carried with a ratio of cyanide to H2O2 of about 1:50 to about 1:200, and in the presence of a solvent selected from the group consisting of methanol, ethanol, acetonitrile, ethyl acetate, toluene and water.

DETAILS OF THE INVENTION

This invention relates to a process for removal of cyanide from acylated 1,3-dicarbonyl compounds produced by rearrangement of corresponding enol esters using a cyanide source or by the treatment of an acyl cyanide with a dione.

The type of compounds referred to as acylated 1,3-dicarbonyl compounds have the general formula 1 ,

wherein J is

J-l J-2 Q is

Q-l Q-2

R¹ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio, C₂-C6 haloalkylthio, halogen or cyano; R² is Cι-C₄ alkyl, Cj-C4 haloalkyl, Cj-C alkoxy, Cj- haloalkoxy, C_j-C₆ alkylthio,

C₂-Cg haloalkylthio, halogen, cyano or nitro; or R¹ and R² are taken together to form -X¹-(CH₂)_t-X²-, optionally substituted with 1-4

CH₃; or R¹ and R² are taken together with the carbon to which they are attached to form C(=O) or C(=S); each R³ is independently C C₄ alkyl; R⁴ and R⁵ are each independently H, Cj-Cg alkyl, C -Cg haloalkyl, C_j-C₆ alkoxy,

Cj-C₆ haloalkoxy, SCO^R¹⁶, halogen, cyano or nitro; each R⁶ is independently halogen, C_j- alkoxy, Cι-C₄ haloalkoxy, C_j-C₄ alkyl,

Cj-C₄ haloalkyl, C1-C3 alkoxycarbonyl, S O^R¹⁶, nitro or cyano; R^6a is halogen, Cj-Q alkoxy, Cj-C haloalkoxy, Cj-C₄ haloalkyl, C_j-C₃ alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹⁴R¹⁵, nitro or cyano; R⁷ is H or M; each R⁸ is independently H, C1-C3 alkyl, C3-C₄ alkenyl, C₃-C₄ alkynyl, C1-C3 alkoxy, formyl, C₂-C alkoxycarbonyl, -CH(C_]-C3 alkoxy)₂, C_j-C-3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH₂O-,

-OCH₂CH₂CH₂O-. -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH₂OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C1-C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, C C₄ alkyl, Cj-C₄ haloalkyl, C_rC alkoxy, C_rC₄ haloalkoxy, halogen, cyano or nitro; R¹ is H or C_rC₄ alkyl; each R¹⁴ is independently H or C_j-C₄ alkyl; R¹⁵ is C_j-C₄ alkyl or C_j-C alkoxy; or R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂-

, -CH₂CH₂CH₂CH₂CH₂- or -CH₂CH₂OCH₂CH₂-; each R¹⁶ is independently C_rC₄ alkyl or C_rC haloalkyl; X¹ and X² are independently O or S; M is an alkali or alkaline earth metal; or M is HN(Cι-C₆ alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3 or 4; t is 2 or 3; and w is 0, 1 or 2.

Procedures for producing compounds of Formula 1 are found in, for example, U.S. Patent nos. 5,006,158 and 4,695,673 and publications WO 97/01550A1, and WO 95/04054. All of the listed processes will produce acylated 1 ,3-dicarbonyl products contaminated with cyanide.

According to the present invention, a process is provided to remove cyanide impurity from Formula 1 compounds in a suitable solvent. By suitable solvent is meant a liquid wherein the reactants can be dissolved or suspended and the process proceeds. Suitable solvents include alcohols such as methanol, ethanol, isopropanol and the like, water, acetonitrile, tetrahydrofuran, dioxane, dimethylsulfoxide and NN-dimethyl formamide. The reaction temperature is typically from -25 °C to 100 °C. The reaction times are from 0.5 h to 24 h. The cyanide to peroxide ratio is 1 :500. Typically the pressure is from about -2 to +25 atm. Suitable bases include both organic bases such as trialkylamines and inorganic bases such as alkali metal alkoxides or hydroxides. The trialkylamines preferably have from 1-6, or more preferably 1-4 carbon atoms per alkyl group. A particularly preferable amine is triethylamine. The base is used in the amount of from about 1 to about 2 mol per mol of tricarbonyl compound, preferably 1.25 to 1.5 mol per mol. Suitable peroxide sources include, but are not limited to, aqueous hydrogen peroxide, peracetic acid, trifluoromethyl peracetic acid, m-chloroperbenzoic acid and the like. The preferred ratio of cyanide to peroxide is between 1 :25 to 1 :200. Preferably the peroxide should exceed the molar quantity of cyanide by at least 25 fold.

Preferably the peroxide source is 35% aqueous hydrogen peroxide. A preferred process to remove cyanide from Formula 1 is at temperatures from about -10 to 100 °C, reaction times of 0.5 to 6h, pressures of about one atmosphere, mole ratios of Formula 1 compounds to alkoxide or hydroxide is 1:1, the mole ratio of cyanide to peroxide is 1:200, and the solvent is methanol. Particularly preferred for achieving high yield of cyanide free compounds of Formula 1 is where the reaction temperature is from 0-25 °C, reaction time is 1-2 h, pressure is 1 atmosphere and the solvent is methanol. The alkoxide or hydroxide is typically added to a suspension of Formula 1 in solvent with mixing. The hydrogen peroxide can be added first to the reaction mixture followed by base or the base can be added before the hydrogen peroxide. The preferred process is to add base in a solvent followed by hydrogen peroxide. The reaction temperature is maintained during and after the addition is complete and until the reaction has gone to completion. Isolation of the cyanide free* product of Formula 1 can be accomplished by standard workup procedures such as filtration to obtain salts of compounds of Formula 1. The salt free compounds can be obtained by acidic workup using dilute hydrochloric acid or acetic acid. (*Cyanide determination for filtrate and product is by the calorimetric method previously described, levels under 0.1 ppm or non-detectable are defined as cyanide free.)

This invention further pertains to a process for making cyanide free preparations of compounds selected from Formula la (Formula 1 wherein J is J-l)

la

wherein Q is

Q-l Q-2

R¹ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio, C -Cg haloalkylthio, halogen or cyano; R² is C_rC alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, Cι-C₄ haloalkoxy, Cj-Cg alkylthio,

C -C^ haloalkylthio, halogen, cyano or nitro; or R¹ and R² are taken together to form -X¹-(CH₂)_t-X²-, optionally substituted with 1-4

CH₃; or R¹ and R² are taken together with the carbon to which they are attached to form C(=O) or C(=S); each R³ is independently Cj-C₄ alkyl; R⁴ and R⁵ are each independently H, -Cg alkyl, C_rC₆ haloalkyl, C_rC₆ alkoxy,

C_j-Cg haloalkoxy, S(O)_nR¹⁶, halogen, cyano or nitro; R⁷ is H or M; each R⁸ is independently H, C C3 alkyl, C3- alkenyl, C3-C₄ alkynyl, C1-C3 alkoxy, formyl, C₂-C alkoxycarbonyl, -CH(Cι-C₃ alkoxy)₂, C1-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH₂O-,

-OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or -CH₂CH OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C₁-C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, Ci-C alkyl, C C₄ haloalkyl, C_j-C₄ alkoxy, C C₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁶ is independently Cι-C₄ alkyl or C1-C₄ haloalkyl;

X¹ and X² are independently O or S;

M is an alkali or alkaline earth metal; or M is HN(C_j-C6 alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3 or 4; t is 2 or 3; and w is 0, 1 or 2.

Or more preferably this invention pertains to removing cyanide from mixtures containing compounds of formula 2a or 2b,

2a

or

2b

This invention further pertains to making cyanide-free preparations of compounds selected from formula lb (formula 1 wherein J is J-2),

lb wherein

Q is

Q-l Q-2

each R⁶ is independently halogen, C C₄ alkoxy, Cj-C₄ haloalkoxy, Cj-C₄ alkyl, C_j-C₄ haloalkyl, C₁-C3 alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano; R^6a is halogen, Cι-C₄ alkoxy, C_rC₄ haloalkoxy, C_rC₄ haloalkyl, -C3 alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹⁴R¹5, nitro or cyano; R⁷ is H or M; each R⁸ is independently H, C_rC₃ alkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl, C_rC₃ alkoxy, formyl, C₂-C alkoxycarbonyl, -CH(Cι-C₃ alkoxy)₂, C₁-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH₂O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH₂OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C₁-C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, Cj-C₄ alkyl, C1-C4 haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁴ is independently H or C C₄ alkyl;

R¹⁵ is C_j-C4 alkyl or Cι-C₄ alkoxy; or

R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH₂CH₂CH₂CH₂-, -CH2CH2CH₂CH₂CH₂- or -CH2CH2OCH2CH₂-; each R¹⁶ is independently Cj-C alkyl or C C₄ haloalkyl;

M is an alkali or alkaline earth metal; or M is HN(Cι-C₆ alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; r is O, 1, 2, 3 or 4. More preferably this invention relates to removal of cyanide from mixtures containing a compound of Formula 3.

Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. *H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets, dt = doublet of triplets, br s = broad singlet. HPLC is high pressure liquid chromatography. HPLC purity is area percentage.

Free cyanide was determined via a calorimetric method based upon the reaction of chloramine T with any cyanide present to form cyanogen chloride. The cyanogen chloride forms a red-blue color upon addition of a pyridine-barbituric acid reagent. The UV- visible spectra was recorded at or near 582 nm and cyanide content was calculated. EXAMPLE 1

2-r 2.3-dihvdro-5.8-dimethylspiror4H-l-benzothiopyran-4.2 '-π.31dioxolanl-6-vn carbonvn-3-hvdroxy-2-cyclohexen-l-one S,S-dioxide potassium salt A 100 mL round bottom flask was charged with 2-[(2,3-dihydro-5,8-dimethylspiro[4H- 1 -benzothiopyran-4,2'-[ 1 ,3]dioxolan]-6-yl) carbonyl]-3-hydroxy-2-cyclohexen- 1 -one S,S- dioxide triethylamine (2 g, 3.94 mmol, cyanide content 143 ppm) and methanol (12 mL). The mixture was stirred and 45% aqueous (aq) potassium hydroxide (0.6 g) was added. A clear solution resulted, then 35% aqueous hydrogen peroxide (0.2 g, 200 molar excess over [CN-] ) was added at once and within 5 min precipitate appeared. The mixture was stirred at room temperature for 2 h and the product was collected by filtration washed with methanol (twice with 6 mL, analysis of combined filtrate demonstrated [CN"] less than 0.1 ppm) and dried under vacuum at 50°C overnight to yield 1.7 g of white powder containing title compound m.p. >250°C, [CN"] <0.1 ppm. HPLC purity 82%, yield 97%. ^l H NMR DMSO- d₆: δ 1.75 (m,2H), 2 DM1.75 (m,2H), 2.08 (s,3H), 2.10 (m,4H), 2.40 (m,2H), 2.51 (s,3H), 3.12 (CH₃OH, 4-7%), 3.41 (m,2H), 4.12 (m,2H), 4.16 (m,2H), 6.77 (s,lH). Further examples are illustrated in Tables 1 and 2.

Table 1

(A) (B)

Table 2

(C) (B)

Claims

CLAIMS What is claimed is:

1. A process for removing cyanide from a reaction product produced by

(a) the reanangement of an enol ester catalyzed by a cyanide source or

(b) the reaction of an acyl-cyanide with a 1,3-diketone, wherein said removal is carried out in the presence of an effective amount of a peroxide source.

2. The process of Claim 1 wherein the reaction product has the formula:

wherein J is

J-l J-2

Q is

Q-l Q-2

R¹ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio, C2-Cg haloalkylthio, halogen or cyano; R² is C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC haloalkoxy, C_rC₆ alkylthio,

C2-C6 haloalkylthio, halogen, cyano or nitro; or R¹ and R² are taken together to form -X¹-(CH₂)_t-X²-, optionally substituted with 1-4

CH₃; or R¹ and R² are taken together with the carbon to which they are attached to form C(=O) or C(=S); each R³ is independently Cj-C₄ alkyl; R⁴ and R⁵ are each independently H, Cj-Cg alkyl,

haloalkyl, C_j-Cg alkoxy,

C_j-Cg haloalkoxy, S O^R¹⁶, halogen, cyano or nitro; each R⁶ is independently halogen, C_j-C₄ alkoxy, Cj- haloalkoxy, C_j- . alkyl,

C C₄ haloalkyl, C₁-C3 alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano; R^6a is halogen, Cj-C alkoxy, C_]-C₄ haloalkoxy, Cj- haloalkyl, C1-C3 alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹⁴R¹⁵, nitro or cyano;

R⁷ is H or M; each R⁸ is independently H, C₁-C3 alkyl, C₃-C₄ alkenyl, C₃-C alkynyl, Cj-C₃ alkoxy, formyl, C₂-C alkoxycarbonyl, -CH(Cι-C₃ alkoxy)₂, C_J-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH₂O-,

-OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; R¹⁰ is H, C_j-C₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH2CH₂OR¹ ; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C_j-C3 alkyl, halogen, cyano or nitro;

R¹¹ is H, Cj-C alkyl, Cj-C₄ haloalkyl, Cj-C₄ alkoxy, C C₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁴ is independently H or C_j-C₄ alkyl; R¹⁵ is C_rC₄ alkyl or C_rC₄ alkoxy; or

R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH2CH2CH2CH₂-, -CH₂CH₂CH₂CH₂CH2- or -CH₂CH₂OCH₂CH₂-; each R¹⁶ is independently Cj-C₄ alkyl or C C₄ haloalkyl; X¹ and X² are independently O or S; M is an alkali or alkaline earth metal; or M is HN(Cι-Cg alkyl^; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; p is O, 1, 2, 3 or 4; r is 0, 1, 2, 3 or 4; t is 2 or 3; and w is 0, 1 or 2.

3. The process of Claim 2 wherein the product has the following chemical formula:

la

wherein Q is

Q-l Q-2

R¹ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C_rC₆ alkylthio, C2-C6 haloalkylthio, halogen or cyano; R² is C_rC₄ alkyl, C C₄ haloalkyl, Cj-C alkoxy, C₁-C4 haloalkoxy, C_rC₆ alkylthio,

CH3; or R¹ and R² are taken together with the carbon to which they are attached to form C(=O) or C(=S); each R³ is independently C_}-C₄ alkyl; R⁴ and R⁵ are each independently H, C_rC₆ alkyl, C_rC₆ haloalkyl, C_j-Cg alkoxy,

C_j-C₆ haloalkoxy, S(O)_nR¹⁶, halogen, cyano or nitro; R⁷ is H or M; each R⁸ is independently H, Cj-C₃ alkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl, C1-C3 alkoxy, formyl, C2-C alkoxycarbonyl, -CH(Cj-C₃ alkoxy)₂, C1-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH₂O-,

-CH2CH2OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C₁-C3 alkyl, halogen, cyano or nitro;

R^{1 1} is H, C C alkyl, C C.₄ haloalkyl, C1-C4 alkoxy, C_j-0₄ haloalkoxy, halogen, cyano or nitro;

R¹² is H or C_rC₄ alkyl; each R¹⁶ is independently C_j-C₄ alkyl or C_j-C₄ haloalkyl;

X¹ and X² are independently O or S;

M is an alkali or alkaline earth metal; or M is HN(Cι-C₆ alkyl^; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3 or 4; t is 2 or 3; and w is 0, 1 or 2.

The process of Claim 2 wherein the product has the chemical formula:

The process of Claim 2 wherein the product has the chemical formula:

The process of Claim 2 wherein the product has the chemical formula:

lb wherein

Q is

Q-l Q-2

each R⁶ is independently halogen, C C₄ alkoxy, C_j-C₄ haloalkoxy, C C₄ alkyl, C C₄ haloalkyl, Cj-C₃ alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano;

R^6a is halogen, Cj-C₄ alkoxy, Cj-C₄ haloalkoxy, C C₄ haloalkyl, C_j-C₃ alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹⁴R¹⁵, nitro or cyano;

R⁷ is H or M; each R⁸ is independently H, C1-C3 alkyl, C3-C alkenyl, C3-C alkynyl, C1-C3 alkoxy, formyl, C₂-C₄ alkoxycarbonyl, -CH(C_]-C3 alkoxy)₂, Cj-C₃ alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH2O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃;

R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH₂OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C1-C3 alkyl, halogen, cyano or nitro;

R¹¹ is H, Cj-C₄ alkyl, Cι-C₄ haloalkyl, C_j-C₄ alkoxy, C₁-C4. haloalkoxy, halogen, cyano or nitro;

R¹² is H or C_rC₄ alkyl; each R¹⁴ is independently H or Cι-C alkyl;

R¹⁵ is C_j-C₄ alkyl or C_!-C₄ alkoxy; or

R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH₂CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂CH2- or -CH₂CH₂OCH₂CH₂-; each R¹⁶ is independently C₁-C₄ alkyl or C₁-C₄ haloalkyl;

M is an alkali or alkaline earth metal; or M is HN(Cι-C6 alkyl^; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; r is 0, 1, 2, 3 or 4;

7. The process of Claim 6 wherein the product has the chemical formula:

8. The process of Claim 1 wherein the reaction is carried out under basic conditions with a molar excess of peroxide relative to cyanide.

9. The process of Claim 1 wherein the peroxide source is selected from the group consisting of hydrogen peroxide, benzoyl peroxide, peracetic acid, or 1,1,1-trifluoromethyl peracetic acid.

10. The process of Claim 1 wherein said process is carried out at a temperature of about - 10 to 60° C and a pressure of - 10 to 10 bar.

11. The process of Claim 1 wherein the ratio of cyanide to H₂O2 is about 1 :50 to about 1:200.

12. The process of Claim 1 wherein said process is carried out in the presence of a solvent selected from the group consisting of methanol, ethanol, acetonitrile, ethyl acetate, toluene and water.

13. A process for removing cyanide from a compound having the formula:

wherein said removal is carried out in the presence of an effective amount of a peroxide source.

14. A process for removing cyanide from a compound having the formula:

lb

Q-l each R⁶ is independently halogen, Cι-C₄ alkoxy, C C₄ haloalkoxy, C_j-C₄ alkyl, Cj-C₄ haloalkyl, Cj-C3 alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano;

R^6a is halogen, C_]-C₄ alkoxy, C C₄ haloalkoxy, C C₄ haloalkyl, C₁-C3 alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹ R¹⁵, nitro or cyano;

R⁷ is H or M; each R⁸ is independently H, C₁-C3 alkyl, C3-C₄ alkenyl, C3-C₄ alkynyl, C₁-C3 alkoxy, formyl, C2-C₄ alkoxycarbonyl, -CH(Cι-C3 alkoxy)2, C₁-C3 alkylthio, C₂-C₄ alkylthioalkyl, cyano or halogen; or when two R⁸ are attached to the same carbon atom, then said R⁸ pair can be taken together to form -OCH₂CH₂O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃; each R¹⁴ is independently H or C C₄ alkyl;

R¹⁵ is C_rC₄ alkyl or C_rC₄ alkoxy; or

R¹⁴ and R^l5 can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH₂CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂CH₂- or -CH₂CH₂OCH₂CH₂-; each R¹⁶ is independently C C₄ alkyl or C haloalkyl;

M is an alkali or alkaline earth metal; or M is HN(Cι-C6 alkyl)3; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; r is O, 1, 2, 3 or 4.

15. A process for removing cyanide from a compound having the formula:

lb

Q is

Q-2

each R⁶ is independently halogen, Cι-C₄ alkoxy, C_j-C haloalkoxy, C C₄ alkyl,

C C₄ haloalkyl, C C-3 alkoxycarbonyl, S(O)_nR¹⁶, nitro or cyano; R^6a is halogen, Cj-C₄ alkoxy, C C haloalkoxy, C C₄ haloalkyl, C₁-C3 alkoxycarbonyl, S(O)_nR¹⁶, S(O)₂NR¹ R¹⁵, nitro or cyano; R⁷ is H or M; R¹⁰ is H, C_rC₄ alkyl, C_rC₄ haloalkyl, C₃-C₄ alkenyl, C₃-C₄ alkynyl or

-CH₂CH₂OR¹²; or R¹⁰ is phenyl or benzyl, each optionally substituted on the phenyl ring with C C3 alkyl, halogen, cyano or nitro; R^{1 1} is H, C_rC alkyl, C_rC4 haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, halogen, cyano or nitro; R¹² is H or C_rC₄ alkyl; each R¹⁴ is independently H or C1-C4 alkyl; R¹⁵ is C_rC alkyl or C_rC₄ alkoxy; or R¹⁴ and R¹⁵ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH₂CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂CH₂- or -CH₂CH₂OCH₂CH₂-; each R¹⁶ is independently C₁-C₄ alkyl or C_J-C4 haloalkyl; M is an alkali or alkaline earth metal; or M is HN(Cι-C6 alkyl)₃; m is 0, 1, 2 or 3; each n is independently 0, 1 or 2; r is O, 1, 2, 3 or 4.

16. The process of Claim 13, 14, or 15 wherein said process is carried out at a temperature of about -10 to 60° C and at a pressure of -10 to 10 bar.

17. The process of Claim 13, 14, or 15 wherein the ratio of cyanide to H₂O₂ is about 1 :50 to about 1:200.

18. The process of Claim 13, 14, or 15 wherein said process is carried out in the presence of a solvent selected from the group consisting of methanol, ethanol, acetonitrile, ethyl acetate, toluene and water.