FORM 2
THE PATENTS ACT 1970
[39 OF 1970]
&
The Patents Rule, 2003
COMPLETE SPECIFICATION
[See Section 10 and Rule 13]
"CHEMICAL PROCESS"
SYNGENTA LIMITED, a British company of Fernhurst, Haslemere, Surrey GU27 3JE, United Kingdom,
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:-

The present invention relates to a process for extracting organic salts from aqueous solutions.

5 cyclohexanone is known to be used to extract certain organic material from aqueous media (see for example US 5801241 and US 4208280). An article by Ya. I. Korenman et al in the Russian Journal of Applied Chemistry, Vol. 71, No. 3 [1998], 532-534, discusses the extraction of phenol with cyclohexanone from aqueous salt solutions and indicates that the most efficient extraction is achieved at a pH of about 2.
10 According to the present invention, there is provided a process for extracting from aqueous solution the alkali metal or ammbmuni salt of a phenol, naphthol, anthrol or phenanthrol or the corresponding thiol, which comprises contacting an aqueous alkaline or neutral solution of the alkali metal or ammonium salt, in which is dissolved an alkali metal or ammonium fluoride, chloride, bromide, hydroxide, nitrate, nitrite, sulphate, sulphite, sulphide,
15 hiosulphite, phosphate, hydrogen phosphate, carbonate, bicarbonate; cyanate, cyanide, thiocyanate, borate, chlorate, chlorite, hypochlorite, perchlorate, chromate, dichromate or permanganate, with a partially water-miscible organic solvent so as to transfer aqueous solution of the alk ill metal or ammonium salt of the phenol, naphthol, anthrol or phenanthrol or corresponding thiol into the solvent whilst retaining separate aqueous and solvent phases, and
20 thereafter separating the solvent phase containing the alkali metal or ammonium salt and water from the t queous phase, the ratio of solvent to water in the separated solvent phase being from 0.5:1 to 10:1 w/w.
The choice of solvent is determined by its ability to extract sufficient of the aqueous ' solution of the alkali metal or ammonium salt of the phenol, naphthol, anthrol or phenanthrol or
25 corresponding thiol such that the ratio of solvent to water in the separated solvent phase is from 0.5:1 to 10:1 w/w, for example from 0.5:1 to 5:1 w/w and typically from 0.5:1 to 3:1 w/w.
The solvent:water ratio is readily determined by standard analytical techniques. Thus, the water content of the separated solvent phase can be measured using a Merrohm 784 KFP Titrino (supplied by Metrohm Ltd CH-9101 Herisau Switzerland) incorporating Hydranal-
30 Composite 5K and Hydranal-Ketosolver reagents. These reagents are supplied by Riedel-de Haen Labcrchemikalien GmbH and Co.KG, Postfach/PO Box 10 02 62, F-30918 Seelze,

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15

Germany. The salt content can be measured by a standard titratiqn with hydrochloric acid and the solvent content can then be calculated by difference.
Suitable solvents include those solvents which can dissolve from 5 to 50% w/w, for example from 5 to 30% w/w, of water. They include alcohols such as n-butanol and iso-butyl alcohol, ketones such as methyl ethyl ketone and cycloalkanones.
Suitable cycloalkanones include cyclopentanone, cyclohexanone and cycloheptanone and alkyl-stjibstituted cycloalkanones such as 2- and 3-methylcyclopentanone, 2,2- and 2,4-dimethylcyclopentanone, 2-, 3- and 4-methylcyclohexanone, 2,2- and 2,6-dimethylcyclohexanone, 2,2,6-trimethylcyciohexanone, 4-ethylcyclohexanone, 2-fert-butylcyclohexanone, 4-tert-butylcyclohexanone. Unsubstituted C5.7 cycloalkanones are preferred, especially unsubstituted cyclohexanone. The quantity of solvent used will normally be 1 to 8 moles, for example 1 to 6 moles, typically 4 moles, for each mole of the alkali metal or ammonium salt of the phenol, naphthol, anthrol or phenanthrol or corresponding thiol present.
i The phenol, naphthol, anthrol or phenanthrol or corresponding tfiiol may be any . unsubstituted or substituted phenol, thiophenol, 1- or 2-naphthol or thionaphthol, hydroxy- or mercap :oanthracene such as 1- or 2-hydroxyanthracene, or hydroxy- or mercaptophenanthrene such as 1-, 2-, 3-, 4- or 9-hydroxyphenanthrene.
Suitably it is a compound of the general formula (I):

20

(I)

wherein X is S or O and any one of Ri to R5 is H or a substituent stable to the conditions of the process or Rj and R2 or R2 and R3 join to form a fused ring system or stable group. Typically, X is S or O and any one of Ri to R5 is H," halo, alkyl, haloalkyl, alkoxyalkyl, alkoxy,
25 haloalkaxy, alkoxyalkoxy, alkylthio, haloalkylthio, cyano, nitro, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, phenyl, phenoxy or phenylalkyl, or Ri and R2 or R2 and R3 join to form a fused benzene ring or naphthalene ring system in which the benzene ring or
-3 -

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naphtlialene ring system optionally carries one or more of the single substituents defined for Ri to R5 abcve.
Alkyl moieties, including the alkyl moieties of haloalkyl, alkoxy, alkylthio, etc., usually contain from 1 to 6, typically from 1 to 4, carbon atoms in the form of straight or branched chains.
5 Examples are methyl, ethyl, n and wo-propyl, n-sec, iso- and tert-butyl, i-pentyl and n-hexyl.
Halo includes fluoro, chloro, bromo and iodo. Most commonly it is fluoro or chloro.
Haloalkyl is typically trifluoromethyl and haloalkoxy is typically trifluoromethoxy.
Alkylcarbonyl is typically acetyl and phenylalkyl is typically benzyl. Alkali metals include lithium, sodium and potassium. Sodium and potassium are preferred
10 for both the alkali metal salt of the phenol, etc., and the alkali metal fluoride, etc. Potassium is especially preferred.
The process of the invention is of particular interest for extracting alkali metal or ammoijuum salts of a compound of formula (I) where X is S or O (especially O), each of Ri to R5 is H or oi(ie of Ri to R5 is fluoro, chloro, bromo, Ci_4 alkyl, Q.4 alkoxy, trifluoro-methyl,
15 trifluoromethoxy, cyano or nitro or Ri and R2 or R2 and R3 join to form a fused benzene ring optionally carrying a substituent defined for R] to R5 above, and the others are H.
The process is of especial interest for extracting alkali metal salts of 2-cyanophenol and 3-hydrox ybenzotrifluoride.
The alkali metal or ammonium fluoride, chloride, bromide, hydroxide, nitrate, nitrite,
20 sulphate, sulphite, sulphide, thiosulphate, phosphate, hydrogen phosphate, carbonate, bicarbonate, cyanate, cyanide, thiocyanate, borate, chlorate, chlorite, hypochlorite, perchlorate, chromate, dichromate or permanganate, which is dissolved in the aqueous alkaline or neutral solution of the alkali metal or ammonium salt of the phenol, naphthol, anthrol or phenanthrol or corresponding thiol, is required to effect separation of the aqueous and organic phases and increase extraction
25 efficiency. Most suitably it is a sodium or potassium fluoride, chloride, sulphate or phosphate. The cation of the alkali metal or ammonium fluoride etc., may be the same as or different from the cation of the alkali metal or ammonium salt of the phenol, etc., but will often be the same. When a different cation is used, cation exchange may occur. For example, the potassium salt of the phenol, etc.,
30 may be extracted when potassium sulphate is used alongside the ammonium salt of the phenol, etc.

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The amount of alkali metal or ammonium fluoride, etc., used will normally be at least 0.5 mole, usually 1.0 mole, for each mole of the alkali metal or ammonium salt of the phenol, etc., present.
In one aspect of the present invention there is provided a process for extracting from
5 aqueous solution an alkali metal salt of 2-cyanophenol or 3-benzotrifluoride which comprises contacting an aqueous alkaline solution of the alkali metal salt, in which is dissolved an alkali metal halide, sulphate or phosphate, with a cycloalkanone, so as to transfer the metal salt into the cycloalkanone, and thereafter separating the cycloalkanone containing the metal salt from the aqueor s solution.
10 The aqueous solution of the alkali metal or ammonium salt of the phenol etc., may be prepared by treating the phenol, etc., with an alkali metal hydroxide in water with or without the alkali metal or ammonium fluoride, etc., present. If not present, it may be added afterwards. Alternatively, the alkali metal or ammonium salt of the phenol etc., may be pre-formed. In this case, the aqueous solution may be kept neutral or made alkaline by the addition of a base, such as
15 an alkali metal or ammonium hydroxide or carbonate.
The process of the invention is conveniently carried out by adding the organic solvent to the aqueous alkaline or neutral solution of the alkali metal or ammonium salt of the phenol, etc., contair ing the alkali metal or a ammonium fluoride etc., or vice versa, stirring or otherwise agitating the two-phase system until no further salt is extracted into the organic solvent phase and
20 separating the two phases. The extraction can be carried out effectively at atmospheric pressure and at a temperature of from 0°C to 90°C, normally from 15°C to 80°C, for example from 20°C to 70°C, especially from 50°C to 70°C, and typically at about 60°C. The optimum agitation time will depend on the quantity of solution to be extracted, the amount of solvent used to carry out the extract on, the temperature and the efficiency of agitation. For example, for small scale extractions
25 where about 0.03moles of the alkali metal or ammonium salt are extracted from about 0.3 moles of water, 30 minutes stirring at 60°C using 0.12 moles of solvent is usually sufficient to extract most of the alkali metal or ammonium salt.
The examples presented hereinafter show how the extraction can be done batch-wise but it will be apparent that it may also be done by continuous or counter-current extraction using
30 standard chemical processing techniques.

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2-Cyanophenol and 3-hydroxybenzotrifluoride are useful intermediates in the manufacture of, for instance, agrochemical products and are conveniently extracted as alkali metal or ammonium salts directly from the aqueous medium in which they are prepared.
The invention is illustrated by the following Examples in which:
5
g = grammes GC = gas chromatography
mol = moles °C = degrees centigrade
EXAMPLE 1
This example illustrates the extraction of the potassium salt of 3-hydroxybenzotrifluoride 10 from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
A solution of potassium hydroxide flake (2.05g at 95% strength, 0.03mol), potassium
fluoridp (1.65g, 0.03mol) and 3-hydroxybenzotrifluoride (4.8g, 0.03mol) in water (5.2g) was
stirred for one hour at 60°C. Cyclohexanone (11.5g, 0.12mol) was charged arid the solution was
stirred for a further 30 minutes at 60°C.
15 I The solution was transferred to a heated separating funnel where it was allowed to separate into two clear phases. The lower substantially aqueous phase was separated (4.5g), •followed by the upper substantially organic phase (18.91g). Qualitative GC analysis showed that
the cyclohexanone solution contained the potassium salt of 3-hydroxybenzotrifluoride in
approximately 77% recovery.
20 EXAMPLE 2
This example illustrates the extraction of the potassium
salt of 2-cyanophenol from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
A solution of potassium hydroxide flake (2.05g at. 95%
strength, 0.03mol), potassium fluoride (1.65g, 0.03mol) and 2-cyanophenol (3.5g, 0.03mol) in water (5.2g) was stirred for one
25 hour at 60°C. Cyclohexanone (11.5g, 0.12mol) was charged and the solution was stirred for a
further 30 minutes at 60°C.
The solution was transferred to a heated separating
funnel where it was allowed to separate into two clear phases. The lower substantially aqueous phase was separated (4.12g), followed by the upper substantially organic phase (17.02g). Qualitative GC analysis showed that
30 the cyclohexanone solution contained the potassium salt of 2-cyanophenol in approximately 63% recovery.

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EXAMPLE 3
This example further illustrates the extraction of the potassium salt of 2-cyanophenol from
an aque ous solution containing potassium fluoride into cyclohexanone at 60CC.
2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution
5 (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60CC. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
10 The lower substantially aqueous phase weighing 6.2g and the upper substantially organic phase weighing 21.6g were recovered.
The organic phase contained 27.7% water (by the Karl-Fischer titration) and 21.2% of the potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 97% of the salt had been extracted into the cyclohexanone.
15 The analytical method and calculation used is described below.
A sample of the extracted metal salt in solvent (~0.5g) was accurately weighed and dissolved in deionis;d water (50ml). A standardised 1% solution of potassium hydroxide (1 ml) was then added and the solution titrated with a 0.1M solution of hydrochloric acid. The results are calculated as follows.
20 Salt content (%) = (EP2-EP1) x C32 x C02
COO x100
EP1 volume of hydrochloric acid added to first endpoint
EP2 volume of hydrochloric acid added to second endpoint
25 COO sample weight
C02 molecular weight of salt
C32 strength correction factor for hydrochloric acid
where: EP1 = 0.82 ml; EP2 = 7.688 ml; COO = 0.5084 g; C02 = 157; C32 = 1 Salt content (%) =
6.868 x 1 x 157 = 21.2
0.5084 x 100
EXAMPLE 4
This example illustrates the extraction of the potassium salt of 3-cyanophenoI from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.

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3-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7gd>30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was
5 then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 6.3g and the upper substantially organic phase weighing 21.5g were recovered.
The organic phase contained 25.9% water (by the Karl-Fischer titration) and 20.5% of the
10 potassium salt of the 3-cyanophenol (by titration with hydrochloric acid), indicating that 94% of the sail; had been extracted into the cyclohexanone.
EXAMPLE 5
This example illustrates the extraction of the potassium salt of 4-cyanophenol from an
aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
15 4-Cyanophenol (3.8g@95% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then ad ded, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these
20 were separated at 60°C.
The lower substantially aqueous phase weighing 6.7g and the upper substantially organic phase weighing 21. 1g were recovered.
The organic phase contained 21.9% water (by the Karl-Fischer titration) and 23.0% of the potassium salt of the 4-cyanophenol (by titration with hydrochloric acid), indicating that >99% of
25 the salt had been extracted into the cyclohexanone.
EXAMPLE 6
This example illustrates the extraction of the potassium salt of 2-bromophenol from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
2-Bromophenol (5.3g@98% strength, 0.03mol), aqueous potassium hydroxide solution
30 6.7g<§ 30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mq>l) was added and stirred for a further 15 minutes. Cyclohexanone

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(11.8g,|0.120mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were farmed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 7.2g and the upper substantially organic phase weighing 22.9g were recovered.
5 The organic phase contained 24.6% water (by the Karl-Fischer titration) and 27.1 % of the potassium salt of the 2-bromophenol (by titration with hydrochloric acid), indicating that 98% of the salt] had been extracted into the cyclohexanone.
EXAMPLE 7
This example illustrates the extraction of the potassium salt of 3-bromophenol from an
10 aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
3-Bromophenol (5.3g@98% strength, 0.030mol), aqueous potassium hydroxide solution (6.7g(§)30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was
15 then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 6.0g and the upper substantially organic phase weighing 23.3g were recovered.
The organic phase contained 23.2% water (by the Karl-Fischer titration) and 27.6% of the
20 potassium salt of the 3-bromophenol (by titration with hydrochloric acid), indicating that >99% of ■ the sail had been extracted into the cyclohexanone.
EXAMPLE 8
This example illustrates the extraction of the potassium salt of 2-nitrophenol from an
aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
25 2-Nitrophenol (4.3g@98% strength, 0.03mol), aqueous potassium hydroxide solution(6.7g(3j>30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these
30 were separated at 60°C.
The lower substantially aqueous phase weighing 7.5g and the upper substantially organic phase weighing 21.0g were recovered.
The organic phase contained 20.5% water (by the Karl-Fischer titration) and 25.2% of the potassium salt of the 2-nitrophenol (by titration with hydrochloric acid), indicating that >99% of
35 the sal: had been extracted into the cyclohexanone.

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EXAMPLE 9
This example illustrates the extraction of the potassium salt of 1-naphthol from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
1-Naphthol (4.4g@99% strength, 0.03mol), aqueous potassium hydroxide solution
5 (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to
60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g,
0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was
then added, and the mixture stirred at 60°C for 30 minutes; Two layers were formed, and these
were separated at 60°C.
10 The lower substantially aqueous phase weighing 7.0g and the upper substantially organic phase weighing 22.7g were recovered.
The organic phase contained 21.9% water (by the Karl-Fischer titration) and 23.3% of the
potassium salt of the 1-naphthol (by titration with hydrochloric acid), indicating that 97% of the
salt had been extracted into the cyclohexanone.
15 EXAMPLE 10
This example illustrates the extraction of the potassium salt of l-bromo-2-naphthol from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
l-Bromo-2-naphthol (6.9g@97% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3 mol) were charged to a stirred tube and
20 heated to 60°C. The mixture was held at this temperature
for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 13.3g and the upper substantially organic
25 phase weighing 18.8g were recovered.
The organic phase contained 10.4% water (by the Karl-Fischer titration) and 14.8% of the potassium salt of the l-bromo-2-naphthol (by titration with hydrochloric acid), indicating that 36% of the J alt had been extracted into the cyclohexanone.

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EXAMPLE 11
This example illustrates the extraction of the potassium salt of 7-methoxy-2-naphthol from an aqufeous solution containing potassium fluoride into cyclohexanone at 60°C.
7-Methoxy-2-naphthol (5.4g@98% strength, 0.03mol), aqueous potassium hydroxide
5 solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride(1.8g, ().03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol)
was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
10 The lower substantially aqueous phase weighing 6.4g and the upper substantially organic phase weighing 23.7g were recovered.
The organic phase contained 25.8% water (by the Karl-Fischer titration) and 26.1% of the
potassium salt of the 7-methoxy-2-naphthol (by titration with hydrochloric acid), indicating that
97% of the salt had been extracted into the cyclohexanone.
15 EXAMPLE 12
This example illustrates the extraction of the potassium salt of 2-thionaphthol from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.
2-Thionaphthol (4.9g@98% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g(§30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to
20 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g,
0.03mcl) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 6.9g and the upper substantially organic
25 phase weighing 21.9g were recovered.
The organic phase contained 25.9% water (by the Karl-Fischer titration) and 20.0% of the potassi am salt of the 2-thionaphthol (by titration with hydrochloric acid), indicating that 74% of the salt had been extracted into the cyclohexanone.
EXAMPLE 13
30 This example illustrates the extraction of the potassium salt of 2-chlorobenzenethiol from an aqueous solution containing potassium fluoride into cyclohexanone at 60°C.

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2-Chlorobenzenethiol (4.4g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3ol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol)
5 was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C
The lower substantially aqueous phase weighing 6.5g, and the upper substantially organic phase weighing 22.3g were recovered.
The organic phase contained 31.8% water (by the Karl-Fischer titration) and 21.4% of the
10 potassium salt of the 2-chlorobenzenethiol (by titration with hydrochloric acid), indicating that 87% of the salt had been extracted into the cyclohexanone.
EXAMPLE 14
This example illustrates the extraction of the potassium salt of 2-cyanophenol from an aqueous solution containing potassium fluoride into n-butanol at 60°C.
15 2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g,
0.03mcl) was added and stirred for a further 15 minutes. n-Butanol (9.0g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were
20 separated at 60°C.
The lower substantially aqueous phase weighing 5.5g and the upper substantially organic phase weighing 19.5g were recovered.
The organic phase contained 36.3% water (by the Karl-Fischer titration) and 23.4% of the potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 97% of
25 the salt had been extracted into the n-butanol.

EXAMPLE 15

This example illustrates the extraction of the potassium salt of 2-cyanophenol from an aqueous solution containing potassium fluoride into methyl ethyl ketone at 60°C.
2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution
30 (6.7g (o>30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g,0.03mql) was added and stirred for a further 15 minutes. Methyl ethyl ketone

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(8.7g, 0.12mol) was men added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 4.8g and the upper substantially organic
phase weighing 19.6g were recovered.
5 The organic phase contained 42.9% water (by the Karl-Fischer titration) and 23.4% of the potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 97% of the sail had been extracted into the methyl ethyl ketone.

EXAMPLE 16
This example illustrates the extraction of the potassium salt of 2-cyanophenol from an
10 aqueous solution containing potassium fluoride into isobutyl alcohol at 60°C.
2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g(§J30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium fluoride (1.8g, 0.03mol) was added and stirred for a further
15 minutes.' Isobutyl alcohol (9.1g, 0.12mol) was 15 then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 5.9g and the upper substantially organic phase weighing 19.5g were recovered.
The organic phase contained 35.7% water (by the Karl-Fischer titration) and 23.0% of the
20 potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 95% of the salt) had been extracted into the isobutyl alcohol.
EXAMPLE 17
This example illustrates the extraction of the potassium salt of 2-cyanophenol from an
aqueous solution containing potassium phosphate into cyclohexanone at 60°C.
25 2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium phosphate (6.6g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these
30 were separated at 60°C.
The lower substantially aqueous phase weighing 12.5g and the upper substantially organic phase weighing 20.0g were recovered.

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The organic phase contained 26.3% water (by the Karl-Fischer titration) and 24.7% of the potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that >99% of the salt had been extracted into the cyclohexanone.
EXAMPLE 18
5 This example illustrates die extraction of the potassium salt of 2-cyanophenol from an aqueous solution containing potassium chloride into cyclohexanone at 60°C.
2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then potassium chloride (2.3g,
10 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 4.1g and the upper substantially organic phase Weighing 29.4g were recovered.
15 The organic phase contained 28.5% water (by the Karl-Fischer titration) and 14.0% of the potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 87% of the salt had been extracted into the cyclohexanone.
EXAMPLE 19
This example illustrates the extraction of the salt of 2-cyanophenol from an aqueous
20 solution containing sodium chloride into cyclohexanone at 60°C.
2-Cyanophenol (3.6g@99% strength, 0.03mol), aqueous potassium hydroxide solution (6.7g@30% w/w, 0.036 mol) and water (6g, 0.3mol) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then sodium chloride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added,
25 and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C.
The lower substantially aqueous phase weighing 0.6g and the upper substantially organic phase weighing 26.8 were recovered.
The organic phase contained 48.1% water (by the Karl-Fischer titration) and 17.2% of the
30 salt of tie 2-cyanophenol (by titration with hydrochloric acid), indicating that 98% of the salt had been extracted into the cyclohexanone.

WO 02/02464

PCT/GB01/02622

EXAMPLE 20
This example illustrates the extraction of the sodium salt of 2-cyanophenol from an aqueous solution containing sodium chloride into cyclohexanone at 60°C.
2-Cyanophenol (3.6g@99% strength, 0.03mol), sodium hydroxide (1.5g@97% strength,
5 0.036iaol) and water (9.5g) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then sodium chloride (1.8g, 0.03mol) was added and stirred for a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C far 30 minutes. Two layers were formed, and these were separated at 60°C. The lower substantially aqueous phase weighing 4.5g and the upper substantially organic phase
10 weighing 21.8g were recovered.
The organic phase contained 33.6% water (by the Karl-Fischer titration) and 20.8% of the sodium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 96% of the salt had been extracted into the cyclohexanone.
EXAMPLE 21
15 This example illustrates the extraction of the salt of 2-cyanophenol from an aqueous solution containing sodium chloride into cyclohexanone at 60°C.
2-Cyanophenol (3.6g@99% strength, 0.03mol), potassium carbonate (5.1g@98% strength, 0.036mol) and water (17.8g) were charged to a stirred tube and heated to 60°C. The mixture was held at this temperature for 1 hour, then sodium chloride (1.8g, 0.03mol) was added and stirred for
20 a further 15 minutes. Cyclohexanone (11.8g, 0.12mol) was then added, and the mixture stirred at 60°C for 30 minutes. Two layers were formed, and these were separated at 60°C. The lover substantially aqueous phase weighing 19.3g and the upper substantially organic phase weighing 19.0g were recovered.
The organic phase contained 34.5% water (by the Karl-Fischer titration) and 23.8% of the salt of
25 the 2-cyanophenol (by titration with hydrochloric acid), indicating that 96% of the salt had been extract 3d into the cyclohexanone.
EXAMPLE 22
This example illustrates the extraction of the potassium salt of 2-cyanophenol from an aqueous solution of the ammonium salt of 2-cyanophenol containing potassium sulphate into
30 cyclohexanone at 60°C.

WO 02/02464

PCT/GB01/02622

15^



2-Cyanophenol, ammonium salt, (5.2g@99%, 0.0375mol) was dissolved in water (30g) and potassium sulphate (4.8g@99%, 0.0275mol) added. The mixture was heated up to 60°C, and then cyclohexanone (14.8g, 0.15mol) was added. Agitation was maintained for a further 30 minute s and then discontinued. Two layers were formed, and these were separated at 60°C. The lower substantially aqueous phase weighing 32.8g and the upper substantially organic phase weighing 18.0g were recovered.
The organic phase contained 26.3% water (by the Karl-Fischer titration) and 22.8% of the potassium salt of the 2-cyanophenol (by titration with hydrochloric acid), indicating that 86.9% of the salt had been extracted into the cyclohexanone.
The aqueous layer was treated with base and a large amount of ammonia gas was given off. The organic layer was treated in the same way and no ammonia was detected. From this, and the similarity of behaviour when titrated, it was deduced that the potassium salt of 2-cyanophenol was extracted into the cyclohexanone leaving behind the more soluble ammonium sulphate.



We claim:
1. A process for extracting from aqueous solution the alkali metal 3r ammonium salt of a phenol, naphthol, anthrol or phenanthrol or the corresponding thiol, which comprises contacting an aqueous alkaline or neutral solution of the alkali metal or ammonium salt, in which is dissolved an alkali metal or ammonium fluoride, chloride, bromide, hydroxide, nitrate, nitrite, sulphate, sulphite, sulphide, thiosulphate, phosphate, hydrogen phosphate, carbonate, bicarbonate, cyanate, cyanide, thiocyanate, borate, chlorate, chorite, hypochlorite, perchlorate, chromate, dichromate or permanganate, with a partially water miscible organic solvent so as to transfer aqueous solution of the alkali metal or ammonium salt of the phenol, naphthol, janthrol or phenanthrol or corresponding thiol into the solvent whilst still retaining separate aqueous and solvent phases and thereafter separating the solvent phase containing the alkali metal or ammonium salt and water from the aqueous phase, the ratio of solvent to water in the separated solvent phase being from 0.5:1 to 10:1 wlw.
2. 2.A process as claimed in claim 1 wherein the ratio of solvent to water in the separated solvent phase is from 0.5:1 to 5:1 w/w.
3. A process as claimed in claim 1 wherein the ratio of solvent to water in the separated solvent phase is from 0.5:1 to 3:1 w/w.
4. A process as claimed in any one of claims 1 to 3 wherein the solvent is a cycloalkanone.
5. A process as claimed in any one of claims 1 to 3 wherein the solvent is cyclohexanone.

6. A process as claimed in any one of the preceding claims wherein the phenol, naphthol, anthrol or phenanthrol or the corresponding thiol is a compound of the general formula (I):


(I)

wherein X is S or O and any one of Rl to R5 is H, halo, alkyl, haloalkyl, alkoxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, alkylthio, haloalkylthio, cyano, nitro, amino alkylamino, dialkyamino, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, phenyl, phenoxy or phenylalkyl or Rl and R2 or R2 and R3 join to form a fused ring system or stable group.
A 7. process as claimed in claim 5 wherein Rl and R2 or R2 and R3 join to form a fused benzene ring or naphthalene ring system wherein the benzene ring or naphthalene ring system optionally carries one or more of the single substituents defined for Rl to R5 above.

8. A process as claimed in claim 5 wherein the compound of general formula (I) is 2-cyanopheno or 3-hydroxybenzotrifluoride.
9. A process as claimed in any one of the preceding claims wherein the amount of alkali metal or ammonium fluoride, chloride, bromide, hydroxide, nitrate, nitrite, sulphate, sulphite, sulphide, thiosulphate, phosphate, hydrogen phosphate, carbonate, bicarbonate, cyanate, cyanide, thiocyanate, borate, chlorate, chlorite, hypochlorite, perchlorate, chromate, dichromate or permanganate used is at least 0.5 mole for each

mole of the alkali metal or ammonium salt of the phenol, naphthol, anthrol or phenanthrol or the corresponding thiol present.
10. A process for extracting from aqueous solution an alkali metal salt of 2- cyanophenol or 3-benzotrifluoride which comprises contacting an aqueous alkaline solution of the alkali metal salt, wherein is dissolved an alkali metal halide, sulphate or phosphate, with a cycloalkanone, so as to transfer the metal salt into the cycloalkanone, and thereafter separating the cycloalkanone containing the metal salt from the aqueous solution.
11. A process as claimed in any one of the preceding claims wherein the process is carried out at atmospheric pressure at a temperature of from 0°C to 90°C.

Dated this October 3, 2006

We claim:
3. A process for extracting from aqueous solution the alkali metal 3r ammonium salt of a phenol, naphthol, anthrol or phenanthrol or the corresponding thiol, which comprises contacting an aqueous alkaline or neutral solution of the alkali metal or ammonium salt, in which is dissolved an alkali metal or ammonium fluoride, chloride, bromide, hydroxide, nitrate, nitrite, sulphate, sulphite, sulphide, thiosulphate, phosphate, hydrogen phosphate, carbonate, bicarbonate, cyanate, cyanide, thiocyanate, borate, chlorate, chorite, hypochlorite, perchlorate, chromate, dichromate or permanganate, with a partially water miscible organic solvent so as to transfer aqueous solution of the alkali metal or ammonium salt of the phenol, naphthol, janthrol or phenanthrol or corresponding thiol into the solvent whilst still retaining separate aqueous and solvent phases and thereafter separating the solvent phase containing the alkali metal or ammonium salt and water from the aqueous phase, the ratio of solvent to water in the separated solvent phase being from 0.5:1 to 10:1 wlw.
4. 2.A process as claimed in claim 1 wherein the ratio of solvent to water in the separated solvent phase is from 0.5:1 to 5:1 w/w.
3. A process as claimed in claim 1 wherein the ratio of solvent to water in the separated solvent phase is from 0.5:1 to 3:1 w/w.
4. A process as claimed in any one of claims 1 to 3 wherein the solvent is a cycloalkanone.
5. A process as claimed in any one of claims 1 to 3 wherein the solvent is cyclohexanone.

6. A process as claimed in any one of the preceding claims wherein the phenol, naphthol, anthrol or phenanthrol or the corresponding thiol is a compound of the general formula (I):


(I)

wherein X is S or O and any one of Rl to R5 is H, halo, alkyl, haloalkyl, alkoxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, alkylthio, haloalkylthio, cyano, nitro, amino alkylamino, dialkyamino, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, phenyl, phenoxy or phenylalkyl or Rl and R2 or R2 and R3 join to form a fused ring system or stable group.
A 7. process as claimed in claim 5 wherein Rl and R2 or R2 and R3 join to form a fused benzene ring or naphthalene ring system wherein the benzene ring or naphthalene ring system optionally carries one or more of the single substituents defined for Rl to R5 above.

8. A process as claimed in claim 5 wherein the compound of general formula (I) is 2-cyanopheno or 3-hydroxybenzotrifluoride.
9. A process as claimed in any one of the preceding claims wherein the amount of alkali metal or ammonium fluoride, chloride, bromide, hydroxide, nitrate, nitrite, sulphate, sulphite, sulphide, thiosulphate, phosphate, hydrogen phosphate, carbonate, bicarbonate, cyanate, cyanide, thiocyanate, borate, chlorate, chlorite, hypochlorite, perchlorate, chromate, dichromate or permanganate used is at least 0.5 mole for each

mole of the alkali metal or ammonium salt of the phenol, naphthol, anthrol or phenanthrol or the corresponding thiol present.
12. A process for extracting from aqueous solution an alkali metal salt of 2- cyanophenol or 3-benzotrifluoride which comprises contacting an aqueous alkaline solution of the alkali metal salt, wherein is dissolved an alkali metal halide, sulphate or phosphate, with a cycloalkanone, so as to transfer the metal salt into the cycloalkanone, and thereafter separating the cycloalkanone containing the metal salt from the aqueous solution.
13. A process as claimed in any one of the preceding claims wherein the process is carried out at atmospheric pressure at a temperature of from 0°C to 90°C.

Dated this October 3, 2006