GB1597377A - Process for preparing 2,2,6,6-tetrachloro or tetrabromo cyclohexanone - Google Patents

Description

(54) PROCESS FOR PREPARING 2,2,6,6,-TETRACHLORO OR TETRABROMO CYCLOHEXANONE (71) We, FISONS LIMITED, a British Company, of Fison House, 9 Grosvenor Street.

London WIX OAH, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: Case 2632 This invention relates to a process for preparing 2,2,6,6-tetrachlorocyclohexanone or 2,2,6,6-tetrabromocyclohexanone.

These two compounds have uses particularly as intermediates, e.g. in the production of pyrogallol or a salt thereof by hydrolysing either of them. We have now discovered a surprisingly useful process for preparing the compounds.

Accordingly, the invention provides a process for preparing 2,2,6,6tetrachlorocyclohexanone or 2,2,6,6-tetrabromocyclohexanone, which comprises reacting in the liquid phase, in the case of the production of 2,2,6,6-tetrachlorocyclohexanone, chlorine, and in the case of the production of 2,2,6,6-tetrabromocyclohexanone, bromine, with a cyclohexanone compound of formula

where each Y is the same or different and represents, in the case of the production of 2,2,6,6-tetrachlorocyclohexanone, an atom of hydrogen or chlorine, and in the case of the production of 2,2,6,6-tetrabromocyclohexanone, an atom of hydrogen or bromine, in the presence as catalyst of an organophosphorus compound of formula

where X represents an atom of chlorine or bromine; n is 0 or 1; and when n is 0, m is 0 or 2, Rl is alkyl of 1 to 10, e.g. 1 to 6, carbon atoms or phenyl, and R2 and R3 are the same or different and are hydrogen, alkyl of 1 to 10, e.g. 1 to 6, carbon atoms or phenyl; and when n is 1, m is 0, and R1, R2 and R3 are the same and each is

alkyl of 1 to 10, e.g. 1 to 6, carbon atoms or phenyl, or R1 is hydrogen and R2 and R3 are the same or different and each is alkyl of 1 to 10, e.g. 1 to 6, carbon atoms or phenyl; or a salt of such an organophosphorus compound.

This catalyst enables the reaction to be carried out readily and in high yield. It is particularly useful when the desired product of the reaction is to be hydrolysed to pyrogallol or a salt thereof, and especially when the pyrogallol or salt thereof is to be reacted with 2,2-dimethoxypropane and the 2,2-dimethyl-4-hydroxy-1,3-benzodioxole product reacted with methyl isocyanate to produce the pesticide bendiocarb, 2,2-dimethyl-1,3-benzodioxol- 4-yl methylcarbamate.

Any alkyl group in the catalyst is usually of 1-4 carbon atoms, particularly methyl, ethyl or n-butyl, though it may also be of 8 carbon atoms especially 2-ethylhexyl or n-octyl. When there is more than one alkyl group in the molecule, they are conveniently the same.

In a preferred embodiment, n is 1 and R1, R2 and R are each

i.e. the catalyst is hexamethylphosphoramide or a salt thereof.

The catalyst is preferably a tertiary phosphine, e.g. dimethylethylphosphine, tri-noctylphosphine or tri(2-ethylhexyl)-phosphine, or a salt thereof. In a preferred embodiment, the catalyst is tributylphosphine. References to tributylphosphine are to tri-nbutylphosphine. In another preferred embodiment, the catalyst is tributylphosphine or a salt thereof.

The catalyst may be a phosphine oxide, particularly a tertiary phosphine oxide.

In a preferred embodiment, the catalyst is triphenylphosphine or triphenylphosphine oxide.

In a particular embodiment, m is 0.

The catalyst may be provided as the organophosphorus compound itself or as a salt of this compound where a salt exists. Thus, the reaction may be carried out in the presence of acid salts of the catalysts. Suitable acids include both inorganic acids, such as Lewis acids (e.g.

boron trifluoride) or mineral acids e.g. hydrochloric or sulphuric acid, or organic acids, such as carboxylic acids containing up to 10 carbon atoms (e.g. acetic acid or propionic acid). The salt may be a quaternary phosphonium salt.

The nature of the acid portion of the salt is not particularly significant; it is the basic portion of the catalyst which is important. Moreover, copious quantities of hydrochloric or hydrobromic acid (depending on whether chlorine or bromine is used) are normally produced in the course of the reaction, so that a substantial portion of the catalyst is generally present as the hydrochloric or hydrobromic acid salt regardless of the particular ingredient used as source of the catalyst.

Preferably 2,2,6,6-tetrachlorocyclohexanone is prepared and the catalyst is provided in the form of the hydrochloric acid salt, e.g. tributylphosphine hydrochloride or triphenylphosphine hydrochloride. Conveniently hydrogen chloride gas is passed into tributylphosphine or triphenylphosphine in 2,2,6,6-tetrachlorocyclohexanone or carbon tetrachloride, and the salt formed used as catalyst in the chlorination to produce 2,2,6,6tetrachlorocyclohexanone.

The catalyst may be chlorinated or brominated during the course of the reaction, and the acid portion of the acid salt catalyst, particularly salts of organic acids, may be chlorinated or brominated during the course of the reaction. Thus, if the catalyst is provided as a phosphine (n is 0 in the formula above), it may well be chlorinated to and function as the dichloro derivative. For instance, tributylphosphine or triphenylphosphine may be converted to and function as Bu3PC12 or Ph3PC12 respectively. The catalyst may be provided as such a chlorinated or brominated derivative. In the case of chlorination with tributylphosphine or triphenylphosphine, however, this is not preferred since the dichloro derivatives tend to be unstable.

When the catalyst is provided as a phosphine (n is 0 in the formula above), it may well be oxidised during the course of the reaction to and function as a phosphine oxide (n is 1 in the formula above). For instance, if the catalyst is provided as tributylphosphine or triphenylphosphine or a salt of either, it may well be chlorinated to the corresponding dichloro derivative and then oxidised to the corresponding tributylphosphine oxide or triphenylphosphine oxide. The catalyst may be provided as such a phosphine oxide.

Preferably the catalyst is provided to the reaction mixture as an organophosphorus compound of formula II wherein m is 0 or a salt thereof.

Especially preferred is providing the catalyst to the reaction mixture as tributylphosphine or a salt thereof, triphenylphosphine or a salt thereof, tributylphosphine oxide or triphenylphosphine oxide. References to tributylphosphine oxide are to tri-nbutylphosphine oxide.

The catalyst may be a mixture of the organophosphorus compounds but this is not preferred.

The amount of catalyst is not critical, but generally its weight is at least 0.1%, preferably from 0.5 to 12%, of the weight of the cyclohexanone compound.

The compounds of formula I employed as starting materials in the process are either known compounds, or may be prepared by methods well known to those skilled in organic chemical synthesis for the preparation of analogous compounds.

The process is of particular interest for the production of 2,2,6,6tetrachlorocyclohexanone, so that the halogen involved is chlorine rather than bromine and Y represents an atom of hydrogen or chlorine rather than an atom of hydrogen or bromine.

The cyclohexanone compound is preferably cyclohexanone itself, though an intermediately halogenated compound can be employed. For instance, to produce 2,2,6,6tetrachlorocyclohexanone one can start from 2,2,6-trichlorocyclohexanone.

The reaction is preferably conducted in the presence of a solvent. Suitable solvents include saturated chlorinated hydrocarbons (e.g. aliphatic hydrocarbons containing 1 or 2 carbon atoms and 2-4 chlorine atoms, such. as carbon tetrachloride, methylene dichloride, 1,2-dichloroethane or tetrachloroethanes), saturated hydrocarbons (e.g. those containing 5-10 carbon atoms such as pentane, hexane, cyclohexane, octane or decane) or saturated carboxylic acids (e.g. saturated aliphatic carboxylic acids containing 2-5 carbon atoms, such as acetic acid, propionic acid or butanoic acid). In the production of 2,2,6,6tetrachlorocyclohexanone, 2,2,6-trichlorocyclohexanone may be employed as solvent.

Preferably, however, the solvent is molten desired product, e.g. 2,2,6,6tetrachlorocyclohexanone, itself. A mixture of solvents can be employed but this is not preferred.

In a preferred mode of operation, the halogen and cyclohexanone compound are fed to a reaction zone containing a solvent and the catalyst.

The reaction is usually conducted at a temperature within the range 60-160 C, preferably 75-110 C, e.g. 80-110"C. The reaction temperature is preferably below the boiling point of the solvent if a solvent is employed. When molten 2,2,6,6-tetrachlorocyclohexanone is employed as solvent, the minimum reaction temperature is its melting point as altered by the other materials present. The melting point of pure 2,2,6,6-tetrachlorocyclohexanone is 82-83"C.

When chlorinating cyclohexanone itself, the first 3 chlorine atoms may be introduced to the molecule, to produce 2,2,6-trichlorocyclohexanone, at a lower temperature, e.g. down to 20"C, but to introduce the fourth chlorine atom to produce 2,2,6,6tetrachlorocyclohexanone, the temperature is usually as discussed above.

In the present reaction, water is preferably avoided. The weight of water is preferably below 5% of the weight of the cyclohexanone compound.

The reaction is preferably carried out under substantially anhydrous conditions, i.e. less than 1%, preferably less than 0.5%, by weight of water being present based on the weight of the cyclohexanone compound.

Preferably, 2,2,6,6-tetrachlorocyclohexanone is prepared by reacting chlorine with cyclohexanone, in the liquid phase, under substantially anhydrous conditions, at a temperature of 60-160"C, in a process in which there is provided as catalyst for the reaction an organophosphorus compound of formula

phenyl ( m phenyl--, n pbenyl wherein n is 0 or 1; and when n is 0, m is 0 or 2 and when n is 1, m is 0; or a salt of such an organophosphorus compound.

The overall amount of chlorine or bromine employed is normally sufficient to convert all the cyclohexanone compound to desired product. When the reaction is conducted by feeding the halogen and cyclohexanone compound to a reaction zone containing a solvent and the catalyst, it is preferred, in order to minimise side reactions, that the amount of the halogen in contact with the cyclohexanone in the reaction zone be at all times at least the stoichiometric amount required to convert the cyclohexanone compound present to the desired product. For instance, starting from cyclohexanone there is preferably at least 4 moles of halogen fed per mole of cyclohexanone fed; desirably, 4-6 moles of halogen are fed while each mole of cyclohexanone is fed.

The desired product can be separated in conventional ways. It can be used without purification to produce pyrogallol or a salt thereof by hydrolysis, but the product can be purified if desired by conventional techniques e.g. by recrystallisation or sublimation. The hydrolysis is described for example in United Kingdom patent specification 1574413.

The invention is illustrated by the following Examples 1-8, 10 and 11. Example 9 illustrates the corresponding process without a catalyst. In the Examples, parts and percentages are by weight.

Example 1 45g of 2,2,6,6-tetrachlorocyclohexanone (TCCH) and 5g of tributylphosphine were charged to a 500 ml flask fitted with a mechanical stirrer, a thermometer, a water condenser and a chlorine inlet tube having a sinter outlet to the bottom of the flask. The flask was heated, and the melt at 85-900C was swept with nitrogen for 10 minutes. At 95-105"C, 276g of chlorine and 66g of cyclohexanone were charged to the flask continuously over 6.7 hours.

The mole ratio of chlorine to cyclohexanone was kept at 5.8 throughout the addition.

Chlorine was then added continuously at the same rate as it was before for 11/2 hours while maintaining the same temperature. 375 ml n-hexane were added to the reaction mixture, which was then heated to give a clear solution, weighing 464.1g. Cooling of the solution to 5"C precipitated crystals of TCCH, which were filtered off and dried. The yield of freshly formed TCCH (i.e. the TCCH over and above that charged initially to the flask) was 86.5%. Analysis showed that the TCCH was 99% pure.

Example 2 5.0g Triphenylphosphine were added to 60 mls CCl4 in a 250 mls flask fitted with a stirrer, condenser, thermometer, gas inlet tube below the liquid surface and cyclohexanone feed tube above the liquid surface. HCl gas equivalent to the triphenylphosphine was bubbled in at room temperature followed by a nitrogen purge while the mixture was heated to reflux.

Cl2 gas, 3.48 moles, and cyclohexanone, 0.695 mole, were then fed in at even rates over 4.25 hours, while the temperature of the reaction mixture rose from 70"-105"C. The cyclohexanone feed was then stopped and the Cl2 feed continued at the same rate for a further 1.5 hours. The resulting clear solution crystallised on cooling to 191.3g of a white solid containing 81% of TCCH (94.5% of theoretical yield).

Example containing 81% 3 As Example 1, but with 0.5g instead of 5.Og of triphenylphosphine. TCCH yield was 71.8%.

Example 4 As Example 3, but omitting HCl. TCCH yield was 59.3%.

Example 5 As Example 2, substituting 5.0g triphenylphosphine oxide for triphenylphosphine.

TCCH yield was 99%.

Example 6 As Example 5, but using 0.5g instead of 5.0g of triphenylphosphine oxide. TCCH yield was 68.7%.

Example 7 As Example 2 substituting 5g hexamethylphosphoramide for the triphenylphosphine.

TCCH yield was 91.2%.

Example 8 As Example 2 but omitting triphenylphosphine and HCl. TCCH yield was 4.6%.

Examples 9-11 Following the general procedure of Example 1, chlorine and cyclohexanone, in a mole ratio of 5:1, were fed into carbon tetrachloride as solvent containing either no catalyst or the catalyst listed in the table below in amount equal to 7% of the weight of total cycohexanone feed. The feed of chlorine and cyclohexanone was maintained for 4.3 hours, and in the case of the catalyst the feed of chlorine only was then continued at its same rate for another 1.5 hours. The results are shown in the following table: % TCCH in product TCCH At end of After post feed Example Catalyst % yield joint feed chlorination 9 None 7 10 Tributyl phosphine hydro chloride 95 49 78 11 Triphenyl phosphine 95 WHAT WE CLAIM IS: 1. A process for preparing 2,2,6,6-tetrachlorocyclohexanone or 2,2,6,6tetrabromocyclohexanone, which comprises reacting in the liquid phase, in the case of the production of 2,2,6,6-tetrachlorocyclohexanone, chlorine, and in the case of the production of 2,2,6,6-tetrabromocyclohexanone, bromine, with a cyclohexanone compound of formula

where each Y is the same or different and represents, in the case of the production of 2,2,6,6-tetrachlorocyclohexanone. an atom of hydrogen or chlorine, and in the case of the

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (14)

1. **WARNING** start of CLMS field may overlap end of DESC **.

   Example 5 As Example 2, substituting 5.0g triphenylphosphine oxide for triphenylphosphine.

   TCCH yield was 99%.

   Example 6 As Example 5, but using 0.5g instead of 5.0g of triphenylphosphine oxide. TCCH yield was 68.7%.

   Example 7 As Example 2 substituting 5g hexamethylphosphoramide for the triphenylphosphine.

   TCCH yield was 91.2%.

   Example 8 As Example 2 but omitting triphenylphosphine and HCl. TCCH yield was 4.6%.

   Examples 9-11 Following the general procedure of Example 1, chlorine and cyclohexanone, in a mole ratio of 5:1, were fed into carbon tetrachloride as solvent containing either no catalyst or the catalyst listed in the table below in amount equal to 7% of the weight of total cycohexanone feed. The feed of chlorine and cyclohexanone was maintained for 4.3 hours, and in the case of the catalyst the feed of chlorine only was then continued at its same rate for another 1.5 hours. The results are shown in the following table: % TCCH in product TCCH At end of After post feed Example Catalyst % yield joint feed chlorination

   9 None 7

   10 Tributyl phosphine hydro chloride 95 49 78

   11 Triphenyl phosphine 95 WHAT WE CLAIM IS: 1. A process for preparing 2,2,6,6-tetrachlorocyclohexanone or 2,2,6,6tetrabromocyclohexanone, which comprises reacting in the liquid phase, in the case of the production of 2,2,6,6-tetrachlorocyclohexanone, chlorine, and in the case of the production of 2,2,6,6-tetrabromocyclohexanone, bromine, with a cyclohexanone compound of formula

   where each Y is the same or different and represents, in the case of the production of 2,2,6,6-tetrachlorocyclohexanone. an atom of hydrogen or chlorine, and in the case of the

   production of 2,2,6,6-tetrabromocyclohexanone, an atom of hydrogen or bromine, in the presence as catalyst of an organophosphorus compound of formula

   where X represents an atom of chlorine or bromine; n is 0 or 1; and when n is 0, m isO or 2, R1 is alkyl of 1 to 10 carbon atoms or phenyl, and R2 and R3 are the same or different and are hydrogen, alkyl of 1 to 10 carbon atoms or phenyl; and when n is 1, m is 0, and R1, R2 and R3 are the same and each is

   alkyl of 1 to 10 carbon atoms or phenyl, or R1 is hydrogen and R2 and R3 are the same or different and each is alkyl of 1 to 10 carbon atoms or phenyl; or a salt of such an organophosphorus compound.
2. 2. A process according to claim 1 wherein each alkyl group in formula II is of 1-6 carbon atoms.
3. 3. A process according to claim 1 wherein n is 1 and Rl, R2 and R3 are each
4. 4. A process according to claim 1 wherein R1, R2 and R3 are each phenyl.
5. 5. A process according to claim 1 or 2 wherein m is 0.
6. 6. A process according to any one of the preceding claims wherein 2,2,6,6tetrachlorocyclohexanone is prepared.
7. 7. A process according to any one of the preceding claims wherein the cyclohexanone compound is cyclohexanone itself.
8. 8. A process according to any one of the preceding claims wherein the reaction is conducted at a temperature of 60-160"C.
9. 9. A process according to any one of the preceding claims wherein the reaction is conducted under substantially anhydrous conditions.
10. 10. A process for preparing 2,2,6,6-tetrachlorocyclohexanone, by reacting in the liquid phase, under substantially anhydrous conditions, at a temperature of 60-160"C, chlorine with cyclohexanone, in which process there is provided as catalyst for the reaction an organophosphorus compound of formula:

    phenyl (,Ci) phenylP (0) n phenyl/ V ) n wherein n is 0 or 1; and when n is 0, m is 0 or 2 and when n is 1, m is 0; or a salt of such an organophosphorus compound.
11. 11. A process for preparing 2,2,6,6-tetrachlorocyclohexanone or 2,2,6,6,tetrabromocyclohexanone catalytically, which process is performed substantially as described herein.
12. 12. A process for preparing 2,2,6,6-tetrachlorocyclohexanone or 2,2,6,6 tetrabromocyclohexanone catalytically, which process is performed substantially as described herein in any one of Examples 1-8, 10 and 11.
13. 13. 2,2,616-Tetrachlorocyclohexanone or 2,2,6,6-tetrabromocyclohexanone, when prepared by a process claimed in any one of the preceding claims.
14. 14. A process for preparing pyrogallol or a salt thereof, which process comprises hydrolysing 2,2,6,6-tetrachlorocyclohexanone or 2,2,6,6-tetrabromocyclohexanone, claimed in claim 13.