A number of pesticidal compounds are known comprising a heteroaryl ring system linked via a chain which includes an amide or sulphonamide group, to a second aromatic ring system which may be aryl or heteroaryl and in which the nitrogen atom of the amide or sulphonamide bears an alkoxymethyl substituent. Examples of such compounds are given for example in WO 00/06566, copending British Patent Application Nos 00/02029. 7, 00/02032.1,00/02035.4,00/02037.0,00/02041.2,00/02031.3 and 00/02036.2 as well as WO95/31448 and in the J. Agric. Food Chem 1997,45,1920-1930.

The preparation of such compounds is generally effected by reacting a secondary amide with a suitable ether reagent under various conditions. These may include the presence of N, O-bis (trimethylsilyl) acetamide (see Example 10 of WO 00/06566).

Ether reagents which are suitable for use in such reactions are however, themselves quite hard to prepare in pure form. For example, there are two principal routes to chloromethylethers known from the literature.

In the first, formaldehyde is reacted with hydrogen chloride and the appropriate alcohol such as ethyl alcohol. However, a by-product of this process is bis-chloromethyl ether which is highly carcinogenic. In the second process, an acid chloride such as acetyl chloride is reacted with a dialkoxymethane. The acetyl chloride is, in general, reacted under acid catalysed conditions with the desired dialkoxy methane to give a mixture of the desired chloromethyl ether and an acetate ester. The boiling points of these two components are close together making it difficult to perform a high yielding fractional distillation to give the desired product in a high purity on a large scale.

The applicants have found a process which can readily be employed on a large scale.

According to the present invention there is provided a process for preparing a compound of general formula (1) where R1 and R2 are independently selected from hydrogen, C (O) OCl4alkyl or aryl; R3 is an optionally substituted Cl 6alkyl group, optionally substituted C2-6alkenyl, optionally substituted C26alkynyl or optionally substituted C3-locycloalkyl ; and Z is a leaving group, which process comprises reacting a compound of formula (111) where Ru, R2 and R3 are as defined in relation to formula (1) ; and R3 is selected from the groups listed above for R3, with a compound of formula (III) where n is 0 or an integer of from 1-5; R4 is a group C (O) Z; and each Z is, independently, as defined in relation to formula (I).

The reaction is suitably effected under acid catalysed conditions, for example in the presence of a mineral acid [such as sulphuric acid, hydrochloric acid or phosphoric acid], acid resins [such as Amberlyst 15TM or Nation resin] and p-toluenesulphonic acid; preferably sulphuric acid.

Elevated temperatures, for example, at from 50 to 200°C, are suitably employed.

Conveniently the reaction is conducted at the reflux temperature of the reaction mixture.

Suitable leaving groups Z include halo and in particular are halo, such as chloro or bromo and in particular chloro.

Suitable optional substitutents for alkyl, alkenyl, alkynyl, and cycloalkyl groups within R3 include halogen, nitro, cyano, NCS-, 3-7 cycloalkyl (which itself is optionally substituted with Cl-6 alkyl or halogen), 5-7 cycloalkenyl (which itself is optionally substituted with C1-6 alkyl or halogen), CI-10 alkoxy, CI-10 alkoxy (CI-io) alkoxy, tri (CI-4) alkylsilyl (Cl-6) alkoxy, CI-6 alkoxycarbonyl (Cl-lo) alkoxy, Cl-lo haloalkoxy, aryl (Cl-4) alkoxy (where the aryl group is itself optionally substituted), C3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with Cl 6 alkyl or halogen), Cl lu alkenyloxy, Cl-lo alkynyloxy, Cl-lo alkylthio, Cl lu haloalkylthio, aryl (C1-4 alkylthio (where the aryl group is itself optionally substituted), 3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with C1-6 alkyl or halogen), tri (CI 4) alkylsilyl (Cl 6) alkylthio, arylthio (where the aryl group is itself further optionally substituted), C1-6 alkylsulfonyl, Cl haloalkylsulfonyl, Cl-6 alkylsulfinyl, Cl-6 haloalkylsulfinyl, arylsulfonyl (where the aryl group is itself further optionally substituted), tri (C1-4) alkylsilyl, aryldi (CI-4) alkylsilyl, (Cl) alkyldiarylsilyl, triarylsilyl, Cl lu alkylcarbonyl, H02C, Cl-10 alkoxycarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di (C1-6 alkyl) aminocarbonyl, N- (1-3 alkyl)-N- (cul_3 alkoxy) aminocarbonyl, C1-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is itself optionally substituted), di (Cl-6) alkylaminocarbonyloxy, aryl (which itself is optionally substituted), heteroaryl (which itself is optionally substituted), heterocyclyl (which itself is optionally substituted with C1-6 alkyl or halogen), aryloxy (which itself is optionally substituted), heteroaryloxy (which itself is optionally substituted), heterocyclyloxy (which itself is optionally substituted with C1-6 alkyl or halogen), C1-6 alkylcarbonylamino and N- 6) alkylcarbonyl-N-(Cl 6) alkylamino.

Suitable optional substitutents for aryl, heteroaryl, aryloxy and heteroaryl groups listed above include halogen, nitro, cyano, NCS-, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy (Cl_6) alkyl, Ca6 alkenyl, 2-6 haloalkenyl, 2-6 alkynyl, 3-7 cycloalkyl (which itself

is optionally substituted with Cl 6 alkyl or halogen), C5-7 cycloalkenyl (which itself is optionally substituted with Cl 6 alkyl or halogen), C1-10 alkoxy, C1-10 alkoxy (Cl-lo) alkoxy, tri (Cl-4) alkylsilyl (Cl 6) alkoxy, C1-6 alkoxycarbonyl (C1-10) alkoxy, Cl-lo haloalkoxy, aryl (C1-4) alkoxy (where the aryl group is itself optionally substituted), C3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with C1-6 alkyl or halogen), Cl lu alkenyloxy, Cl-lo alkynyloxy, Cl-lo alkylthio, Cl-l4 haloalkylthio, aryl (CI-4) alkylthio (where the aryl group is itself optionally substituted with for example halo, cyano, Cl 6alkyl or C1-6alkoxycarbonyl), C3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with Cl 6 alkyl or halogen), tri (C1-4)alkylsilyl(C1-6) alkylthio, arylthio (where the aryl group is itself optionally substituted with for example halo, cyano, Cl 6alkyl or Cl-6alkoxycarbonyl), Cl-6 alkylsulfonyl, C1-6 haloalkylsulfonyl, C1-6 alkylsulfinyl, C1-6 haloalkylsulfinyl, arylsulfonyl (where the aryl group is itself optionally substituted with for example halo, cyano, Cl 6alkyl or C1-6 alkoxycarbonyl), tri (Cl4) alkylsilyl, aryldi (C1-6) alkylsilyl, (Cl-4) alkyldiarylsilyl, triarylsilyl, Cl-lo alkylcarbonyl, Ci-io alkoxycarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di (C1-6 alkyl) aminocarbonyl, N- (C1-3 alkyl)-N-(Cl 3 alkoxy) aminocarbonyl, C1-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is itself optionally substituted with for example halo, cyano, Cl 6alkyl or Cl 6alkoxycarbonyl), di (CI-6) alkylaminocarbonyloxy, aryl (which itself is optionally substituted with for example halo, cyano, Cl 6alkyl or Cl 6alkoxycarbonyl), heteroaryl (which itself is optionally substituted with for example halo, cyano, C1-6alkyl or C1-6alkoxycarbonyl), heterocyclyl (which itself is optionally substituted with C1-6 alkyl or halogen), aryloxy (which itself is itself optionally substituted with for example halo, cyano, Cl 6alkyl or Cl 6alkoxycarbonyl), heteroaryloxy (which itself is optionally substituted), heterocyclyloxy (which itself is optionally substituted with C1-6 alkyl or halogen), C1-6 alkylcarbonylamino and N- (C1-6) alkylcarbonyl-N- (C1-6) alkylamino but are preferably halo, Cl-6alkyl, cyano or C1-10alkoxycarbonyl.

Suitably at least one of Rl and R2 is hydrogen and the other is hydrogen, carboethoxy or phenyl. Most preferably both R1 and R2 are hydrogen.

Suitably R3 is Cl 6alkyl (where the alkyl group may be optionally substituted by halo, such as fluoro, or aryl), C2-6 alkenyl or 2-6 alkynyl.

Preferably R3 is Cl 6 alkyl, C26 alkenyl or 2-6 alkynyl.

Most preferably R3 is Cl-6 alkyl. In particular R3 is an alkyl group, such as methyl, ethyl, propyl, 2-butyl, 2-methylpropyl and n-pentyl, in particular ethyl.

Preferably R3 is the same as R3.

A preferred example of a compound of formula (I) is chloromethylethylether (CMEE).

Suitably n is 0 or I and most preferably n is 0.

In a preferred embodiment, the compound of formula (III) is benzoyl chloride.

In another preferred embodiment, the compound of formula (E) is a phthaloyl halide such as phthaloyl chloride.

When the reaction is complete, the product is suitably recovered from the reaction mixture by fractional distillation. Suitably the compounds are selected such that the volatility of the bi-product of the reaction (which will generally be of formula (IV)) is low. where R3' independently and n are as defined above. This will ensure that the fractional distillation can be effected readily and efficiently.

Compounds of formula (II) and (m) are either known compounds or they can be prepared from known compounds by conventional methods, described in the literature. For example, compounds of formula (II) where R3 and Rare the same, can be prepared by reacting an alcohol of formula (V) R30H (V) where R3 is as defined in relation to formula (I), with a compound of formula (VI) RIC (O) Ra (VI) where Rl and R2 are as defined in relation to formula (I), under conditions which would be

well known to a chemist, such as those described in Synthetic Communications 1995,25 (24), 3939-3944.

The present invention provides a process which utilises readily available reagents may be used and achieves good volume efficiency, whilst avoiding the generation of carcinogenic by products.

The invention will now be particularly described by way of example.

Example 1 Preparation of Chloromethyl ethyl ether Benzoylchloride (5. 12mole, 720g) and diethoxymethane (4.61mole, 480g) were mixed in a round bottomed flask with Billingham head and reflux condenser.

Sulphuric acid (7.2g) was added and the mixture heated to 105°C under reflux over an oil bath. The mixture was held at this temperature for 5 hours during which time the progress of the reaction was monitored by GLC.

The reaction mixture was then allowed to cool and stand overnight. The next morning, the reaction mixture was heated under reflux for a further 30 minutes after which a fractional distillation was carried out. The crude distillate collected at 82-105°C (bulk at 85-90°C) was re-distilled up a short column; under nitrogen to give the desired product (78% yield). The structure was confirmed by n. m. r.

'H NMR (CDCl3) 8 : 5.5 (2H) (S), 3.8 (2H) (Q) 1.3 (3H) (T) Example 2 Preparation of Chloromethyl ethyl ether This example illustrates an alternative preparation of chloromethyl ethyl ether from diethoxymethane and phthaloyl chloride, in the presence of sulphuric acid catalyst.

Phthaloyl chloride (42.8g, 0.206mol) and diethoxymethane (39.4g, 0.375mol) were charged to a reflux vessel, and sulphuric acid (0.6g, 0.06mol) added. The resulting pale yellow clear solution was heated to reflux with stirring for a total of 8 hours. Following GC analysis of the mixture at this point, further phthaloyl chloride (4.18g, nom. 0.02mol) was added and the heating under reflux continued for a further 13.5 hours. The mixture was then allowed to cool to ambient and left to stand overnight.

The mixture was then heated to the reflux temperature, subjected to fractional distillation and the desired product obtained in the boiling range 83° to 84 (62% yield).

Example 3 Preparation of Deuterated Chloromethvl Ethyl Ether

Benzoyl chloride (3.25 ml) was added to a stirred mixture of deuterated formal A (1.17g) and deuterated ethanol (0.77g), followed by concentrated sulphuric acid (O. llg). The mixture was warmed to 100°C for around 2 hours. The reaction mixture was allowed to cool a little, and then distilled under reduced pressure (-0.36). The desired product was obtained as a colourless distillate, collected at 62-68°C (approximately 0.3 ml in total). lH NMR (CDC13) 6 : 5.51 (s) (2H), 1.25 (s) (3H).

Example 4 Preparation of Alternative Deuterated Chloromethyl Ethyl Ether Benzoyl chloride (51.4 ml) was added to a stirred mixture of deuterated formal B (6.25g) and ethanol (14.93g), followed by concentrated sulphuric acid (0.62g). The mixture was warmed to 100°C for around for 61/2 hours, then allowed to cool to room temperature and stood overnight. The mixture was then distilled at atmosphere pressure, and the desired compound was obtained as a colourless liquid in a fraction which distilled at 80-93°C.

'H NMR (CDCl3) 8 : 82.41 (82.87) 65.91 (64.38), 14.34 (13.21).

Example 5 Preparation of Chloromethyl N-Propyl Ether Benzoyl chloride (10.74 ml) was added to a stirred mixture of formal C (6.1 lg) and propanol (2.78g), and concentrated H2S04 (0.2ml) was then added, the solution then being warmed to 115°C for a few hours. The reaction mixture was then distilled at atmospheric pressure and the desired product obtained from the fraction obtained at 93-103°C.

'H NMR (CDCl3) 8 : 5.52 (s) (2H), 3.66 (t) (2H), 1.65 (m) (2H), 0.97 (t) (3H).

Example 6 Preparation of Chloromethvl Iso-Propyl Ether Benzoyl chloride (15.48 ml) was added to a stirred mixture of formal D (5.70g) and iso-propanol (5.41g), followed by a few drops of concentrated H2S04. The mixture was then heated to 110°C for 4 hours. The reaction mixture was then distilled and the desired product obtained as a colourless liquid from the fraction boiling at 86-98°C. (46%).

'H NMR (CDCl3) 8 : 5.55 (s) (2H), 4.06 (m) (1H), 1.23 (d) (6H).

Example 7 Preparation of Chloromethyl sec-Butylether Benzoyl chloride (9.26 ml) was added to formal E (0.061M) and 1-methyl-propanol (0.0188M), followed by a few drops of concentrated H2S04, the mixture then being heated to 110°C for 21/2 hours. The reaction mixture was heated at reflux for a further 40 minutes, was allowed to cool a little and then distilled under reduced pressure. The desired product was obtained from the fraction boiling at 58-66°C.

H NMR (CDC13) 6 : 5.57 (s) (3H) 3.82 (m) (1H), 1.39-1.69 (m) (2H), 1.21 (d) (3H), 0.94 (t) (3H).

Example 8 Preparation of Chloromethvl 2-methylpropvlether

Benzoyl chloride (9.51 ml) was added dropwise from a syringe to a stirred mixture of formal F (10.4g) containing isobutanol (1.4g), and the mixture was heated to 120°C. After 30 minutes, GC analysis showed some product. A few drops of concentrated H2SO4 were added to the reaction mixture and heating/stirring continued. After 2 hours, the reaction mixture was allowed to cool slightly, and then distilled under reduced pressure. The desired product was obtained as a colourless liquid from the fraction boiling at 63-68°C. (4.63g, 60.2%).

H NMR (CDCl3) o : 5.51 (s) (2H), 3.47 (d) (2H), 1. 91 (sept. (1H), 0.93 (d) (6H).

Example 9 Preparation of Chloromethvl neo-Pentylether A mixture of dineopentyl formal G (13.23g) and 2,2-dimethylpropanol (0. 55g), was stirred at room temperature, and benzoyl chloride (8.89 ml) added, followed by a few drops of concentrated H2SO4. The mixture was warmed to 120°C for 2l/2 hours whereupon more benzoyl chloride (0. 5ml) was added and heating continued for a further 1 hour. Further concentrated H2S04 (0. 5ml) was added to the reaction mixture and heating continued for 30 minutes. The mixture was then distilled at reduced pressure, and the desired product obtained from the fraction boiling at 59-63°C, 6.93g (73%).

'H NMR (CDCl3) 8 : 5.52 (s) (2H), 3.35 (s) (2H), 0.93 (s) 9H), Example 10 Preparation of Chloromethvl (2-trifluoromethvlethvl) ether Formal (H) (1.2g) and benzoyl chloride (0.8g) were mixed together and concentrated

sulphuric acid (0. 05ml) added. The mixture was heated at 90°C for 3 hours, and then left to stand at room temperature for 20 hours. The mixture was then distilled, and the desired product obtained from the fraction boiling at 64°C, (0.36g).

'H NMR (CDCl3) 8 : 5.48 (s) (2H), 3.91 (t) (2H), 2.49 (m) (2H).

Example 11 Preparation of Chloromethvl (1-methvlprop-2-ynvl) ether The benzoyl chloride (1.75 ml) was added to the formal (J) (2.27g), followed by concentrated sulphuric acid (5ope). An exothermic reaction occurred, and the warm mixture was stirred for 10 minutes. Thereafter, it was heated at 70°C for 8 hours. The reaction mixture was then distilled and the desired product obtain as a yellow oil at 102°C (0.39g).

H NMR (CDCl3) o : 5.57,5,70 (dd) (2H), 4.68 (m) (lH), 2.51 (d) (1H), 1. 50 (d) (3H).

Example 12 Preparation of Chloromethvl (prop-2-ynvl) ether The formal L (15.58g) and benzoyl chloride (12.75 ml) were mixed at room temperature.

On adding concentrated sulphuric acid (O. lml), the mixture went black and grew warm. It was then heated at reflux for 3½ hours, after which it was distilled and the desired material obtained from the fraction boiling at 112°C.

'H NMR (CDCl3) 8 : 5.63 (s) (2H), 4. 40 (m) (2H), 2.52 (m) (1H).

Example 13 Preparation of Chloromethvl (2, 2, 2-trifluoroethvl) ether Benzoyl chloride (15.67 ml) and formal (M) (23.63g) were mixed and then concentrated sulphuric acid (100µl) added. The mixture was heated to reflux for 4 hours, and then distilled at 82°C to give the desired product.

'H NMR (CDCl3) 8 : 5.5 (s) (2H), 4.04 (q) (2H).

Example 14 Preparation of Ethvl (1-chloro-1-ethoxv) acetate Ethyl diethoxyacetate (8.81g), benzoyl chloride (5.8ml) and Amberlyst 15 (2.5 g) were mixed at room temperature and then heated with stirring at 120°C for 6 hours. After standing overnight, the presence of the desired product was confirmed by n. m. r.

'HNMR (CDCl3) S : 5.81 (s) (H), 4.35 (q) (2H), 1.35 (t) (3H).