PROCESS FOR THE PREPARATION OF 5-CHLORO-PYRIDIN-2-CARBOXYLIC ACIDS AND CARBOXYLATES WITH SUBSTITUENTS CONTAINING 3-SULFUR

Abstract

A process is provided for the preparation of the compound of formula I: (I) where R1 and R2 are as defined in the description. (see Formula).

Description

PROCESS FOR THE PREPARATION OF 5-CHLORO-PYRIDIN-2-CARBOXYLIC ACIDS AND CARBOXYLATES WITH SUBSTITUENTS CONTAINING 3-SULFUR Description of the Invention The present invention relates to the preparation of 5-chloro-pyridin-2-carboxylic acids and carboxylates with 3-sulfur-containing substituents, which are useful intermediate products for the preparation of agrochemical compounds. More specifically, the present invention relates to 5-chloro-pyridin-2-carboxylic acids of formula I and a process for the preparation thereof r2-s.^ci R<°Y^N^ O (l) wherein Ri is H or C1-C4 alkyl; R2 is C1-C4 alkyl; or an agrochemically acceptable salt of a compound of formula (I). 5-Halo-pyridin-2-carboxylic acids and carboxylates with 3-alkylsulfanyl substituents are useful intermediate products for the preparation of biologically active compounds in the agrochemical industries as described above, for example, in: documents WO 2016 / 005263, WO 2016 / 023954, WO 2016 / 030229, WO 2016 / 046071, WO 2016 / 059145, WO 2016 / 096584, WO 2016 / 104746 and WO 2019 / 065568. The known synthesis of 5-halo-pyridin-2qj acids cann / zznz / E / YiAi Ref. 334415 Carboxyls and carboxylates with 3-alkylsulfanyl (Y) substituents involve many reaction steps. For example, two routes to access 5-bromo (Y) compounds have been reported (route A: CN105218437; route B: US2012 / 0165338 or J. Org. Chem. 2009, 74, 45474553) as shown in Reaction Scheme 1 (Ri is H, C1-C4 alkyl, or an alkali metal ion) qj cann / zznz / E / YiAi - di1 Reaction scheme 1. Pathways for obtaining 5-Br (Y) compounds In document W02016 / 104746, the obtaining of the corresponding 5-iodine (Y) compounds from commercially available 5,6-dichloronicotinic acid has been reported in seven steps, as shown in Reaction Scheme 2. Reaction scheme 2. 5-iodine compounds Clearly, such lengthy and laborious syntheses are unsuitable for preparing large quantities of material due to low overall yields and the significant amount of waste generated. Therefore, a more efficient and economical method for producing these intermediate products would be advantageous. Furthermore, within the class of 5-halo-3-alkylsulfanyl-pyridin-2-carboxylic carboxylates, 5-chloro-3-alkylsulfanyl-pyridin-2-carboxylic acid and the corresponding esters have not been described, thus avoiding the explanation of a route for their preparation. Due to the lack of availability of chlorinated intermediate products of formula (I), until now, the synthetic community has been driven to employ bromine and iodine analogues for the preparation of biologically active agrochemical compounds (documents WO 2016 / 005263, WO 2016 / 096584, WO 2016 / 104746 WO 2016 / 023954, WO 2016 / 046071, WO 2016 / 087265, WO 2016 / 087257, WO 2016 / 030229, WO 2016 / 121997, WO 2016 / 104746).However, the use of building blocks of formula (I) in these syntheses would be highly advantageous for reducing the formation of bromine- and iodine-containing residues in subsequent functionalization reactions at position 5 (metal-catalyzed cross-coupling reactions, nucleophilic aromatic substitutions, etc.) in favor of a more benign chlorine-containing residue. Furthermore, compounds of formula (I) can be considered convenient alternative intermediates for significantly shortening the synthesis of other agrochemicals for which long and laborious routes were originally devised (documents WO 2019 / 065568, WO 2019 / 124529, WO 2020 / 050212). The commercially available 3,5-Dichloropyridine-2-carboxylate(VIII) acid and its corresponding esters (IX), where Ri is a C1-C4 alkyl, could be a convenient starting material for an intermediate product of formula (VI) and (VII). In principle, all that would be required is a selective displacement of the ortho chlorine to a carboxylate group with ethyl thiolate (Reaction Scheme 3). O (VIII) or (IX) o (VI) o (Vil) qj cann / zznz / E / YiAi Reaction scheme 3. Planned pathway for obtaining (VI) or (VII) from (VIII) or (IX) However, it is not clear that selectivity can be achieved, since the 2-carboxylate moiety makes the ortho position less spherically accessible and discourages the formation of the desired 3-alkylsulfanyl product. In fact, reacting the compound of formula (iXa) under conventional conditions for nucleophilic aromatic substitution reactions preferentially yields the undesired (Xa) isomer in all solvents tested (Reaction Scheme 4). qj cann / zznz / E / YiAi solvent-based EtSR R “ H, Na solvents is decn. NMP. toluene Reaction scheme 4. Observed selectivity for the reaction of (IXa) Ortho-selective thiolation reactions of polychlorinated aromatic compounds with a free acid moiety are quite challenging, rarely described, and are generally copper-mediated via a carboxylate-directed Ullmann-type coupling (as described, for example, in Sambiagio C., Marsden SP, Blacker AJ, McGowan PC Chem. Soc. Rev., 2014, 43, 3525-3550) as shown in Reaction Scheme 5. R-SH. K,CO, [Cu] solvent Reaction scheme 5. Cu-mediated Ullmann-type coupling in chlorinated benzoic acid No example of this reaction has ever been reported for polychlorinated picolinic acids. Thus, according to the present invention, a process is provided for the preparation of the compound of formula I (reaction scheme 6): R2-S^^.,CI Rf°Y^N^ O (l) wherein Ri is H or C1-C4 alkyl; preferably Ri is methyl, ethyl or t-butyl, more preferably Ri is ethyl; and R2 is C1-C4 alkyl; preferably R2 is ethyl; process comprising: (A) reacting a compound of formula IIhoyV0(II) wherein Xa is fluorine or chlorine; preferably Xa is chlorine; with a thiol compound R3-S-R2, wherein R2 is as defined in formula I and R3 is H or an alkali metal ion; preferably R3 is H, sodium, potassium or lithium, in the presence of a suitable base, in an appropriate solvent (or diluent) having a dielectric constant less than 15; to produce a compound of formula (la) or a salt of the same R2—S^^CI HO XJ θ (la); and, optionally, qj cann / zznz / E / YiAi esterify the compound of formula (la) or a salt thereof in the presence of a compound of formula ROH, wherein R is C1-4 alkyl; to produce the compound of formula (I) , wherein Ri is C1-C4 alkyl. This process proves to be very useful, as it allows the synthesis of key basic components for the preparation of agrochemical compounds with higher yields and under more favorable conditions compared to the routes described above. Compounds of formula I prepared by the inventive process having at least one basic center can form, for example, acid addition salts, for example, with strong inorganic acids, such as mineral acids, for example, perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorous acid or a hydrohalic acid, with strong organic carboxylic acids, such as C1-C4 alkanecarboxylic acids that are unsubstituted or substituted, for example, with halogen, for example, acetic acid, such as saturated or unsaturated dicarboxylic acids, for example, oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or italic acid, such as hydroxycarboxylic acids, for example, ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids,such as C1-C4 alkanes or arylsulfonic acids that are unsubstituted or substituted, for example, with a halogen, e.g., methanesulfonic acid or p-toluenesulfonic acid. Compounds of formula I that have at least one acid group can form, for example, salts with bases, e.g., mineral salts such as salts with an alkali metal or an alkaline earth metal, e.g., salts of sodium, potassium, lithium, or magnesium, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a lower mono-, di-, or trialalkylamine, e.g., ethyl-, diethyl-, triethyl-, or dimethylpropylamine, or a lower mono-, di-, or trihydroxyalkylamine, e.g., mono-, di-, or triethanolamine. In each case, the compounds of formula (I) prepared by the process according to the invention are in free form or in salt form, e.g., an agronomically useful salt form. The term C1-C4 alkyl, as used herein, refers to a linear or branched saturated hydrocarbon radical attached through any of the carbon atoms, having from 1 to 4 carbon atoms, e.g., any one of the methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl radicals. Surprisingly, it was found that, in the absence of any copper catalyst, high orthoselectivity was observed for the thiolation of 3,5-dichloropicolinic acid (a compound of formula (II) represented by formula (VIII)) in nonpolar, non-protic solvents. In particular, the selectivity was found to be markedly influenced by the nature of the solvent: in solvents with a relatively high permittivity (i.e., DMSO [dielectric constant of 46.7]), high selectivity for the para (XV) isomer was observed, whereas in solvents with a relatively low permittivity (i.e., dioxane, toluene, 2-MeTHF, etc. [dielectric constants of 2.25, 2.38, 6.97]), selective formation of the ortho isomer (a compound of formula (la) represented by formula (XIV)) was observed. This concept is shown in Reaction Scheme 6. base ^s^vent (VIII) (XW) M = Li Na K EtSH base or EtSNu EITHER M' N The solvent (XIV) Solvents Ce aHa p <?rm;SMd-id < XVi >(XIVi Solvents of ti.ija pe'tmsivdad iXIV; >> ¡XV; Reaction scheme 6. Observed selectivity for the thiolation of (VIII) In another embodiment of the present invention, a compound of formula I is provided, represented by a compound of formula la, or an agrochemically acceptable salt of a compound of la: S HO EITHER Cl > u NCNNCC σ Ca > G (la) · In another form of a compound with formula Ia-1: present invention, formula I s is provided MO Cl represented by a compound of (Ia-1) where M lithium. In another it is sodium, potassium or lithium; preferably sodium. In the embodiment of the present invention, a compound of formula 1-2 of formula I is provided, represented by a compound of an agrochemically acceptable salt of a compound of 1-2: (1-2) where Riaes alkyl Ci-¿; preferably Riaes methyl, ethyl or t-butyl, more preferably Riaes ethyl. In a further embodiment of the present invention, a compound of formula I-2a or an agrochemically acceptable salt of a compound is provided. I-2a: (l-2a) wherein Rib is Ci-alkyl; preferably Rib is methyl, ethyl or t-butyl, more preferably Rib is ethyl; yn is 1 or 2; preferably n is 2. Compounds of formula I-2a can be prepared by oxidation of compounds of formula 1-2 using known methods such as those described in WO 2016 / 005263. In the process according to the invention for preparing compounds of formula (I) (reaction scheme 6), some examples of suitable bases are alkali metal hydroxides or alkali metal carbonates. Some examples that can be mentioned are sodium hydroxide, sodium carbonate, lithium hydroxide, potassium hydroxide, and potassium carbonate; preferably an alkali metal carbonate, more preferably sodium or potassium carbonate, most preferably potassium carbonate. In the process according to the invention for preparing compounds of formula (I) (reaction scheme 6), some examples of suitable solvents (or diluents) are those having a dielectric constant less than 15; more preferably, solvents (or diluents) having a dielectric constant less than 12; even more preferably, solvents (or diluents) having a dielectric constant less than 10. In another embodiment, the suitable solvents (or diluents) have a dielectric constant less than 6. Some examples of suitable solvents (or diluents) are dioxane, methyltetrahydrofuran, toluene, anisole, pyridine; more preferably, nonpolar organic compounds selected from dioxane, methyltetrahydrofuran, or toluene; the most preferably suitable solvents are those with a dielectric constant in the range of 1.5 to 15. In one embodiment, in the process according to the invention for preparing compounds of formula (I) (reaction scheme 6), the reaction is advantageously carried out in a temperature range of approximately 0 °C to approximately +140 °C, preferably from approximately 0 °C to approximately +100 °C, in many cases in the range between ambient temperature and approximately +80 °C. In a preferred embodiment, the reaction of step a. is carried out at temperatures between 0 °C and the boiling point of the reaction mixture, more preferably at temperatures between 20 °C and 100 °C, most preferably in the temperature range of 60–100 °C. qj cann / zznz / E / YiAi In a preferred embodiment, the present invention provides highly selective thiolation reactions of 3,5-dichloropicolinic acid compounds and the corresponding carboxylate salts of formula (II), wherein Ri is as defined in formula I, under scalable conditions using sodium ethanethiolate or ethanethiol and a base in a selected nonpolar nonprotic solvent having a dielectric constant less than 15, producing intermediate products of alkyl 5-chloro-3-ethylsulfanylpyridin-2-carboxylate of formulas (1a) and (1b). qj cann / zznz / E / YiAi where R4 = C1-4 alkyl Having thus described the invention in general terms, reference will now be made to the accompanying figure, in which: FIG. 1 is a diagram showing the observed selectivity as a function of the solvent's dielectric constant. More specifically, Fig. 1 shows the correlation between the observed ortho-para-selectivity of the thiolation and the solvent's dielectric constant according to one embodiment of the invention. This solvent-dependent phenomenon was further explored, and a correlation was established between the observed selectivity and the dielectric constant of the solvent (Lide, DR, ed. (2005) CRC Handbook of Chemistry and Physics (86th ed.). Boca Raton (FL): CRC Press. ISBN 08493-0486-5) as shown in Figure 1. Preparation examples: Throughout this description, LC / MS stands for Liquid Chromatography-Mass Spectrometry, and the following methods were used for the analysis of the compounds: Method A: Spectra were recorded on a Waters (SQD [Single Quadrupole]) mass spectrometer equipped with an electronebulization source (polarity: positive and negative ions, capillarity: 3.00 kV, cone range: 30 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 350 °C, cone gas flow: 50 L / h, desolvation gas flow: 650 L / h, mass range: 100 to 900 Da) and a Waters Acquity UPLC (Ultra Performance Liquid Chromatography): binary pump, column thermal compartment, diode array detector, and ELSD (Evaporative Light Scattering Detector). evaporative light scattering). Column: Waters UPLC HSS T3, 1.8 pm, 30 x 2.1 mm, temp.: 60 °C, DAD (Diode Array Detector) wavelength range (nm): 210 to 500, solvent gradient: A = water + 5% MeOH + 0.05% HCOOH, B = Acetonitrile + 0.05% HCOOH, gradient: 10qj cann / zznz / E / YiAi. 100% of B for 1.2 min; flow (ml / min) 0.85. Method B: Spectra were recorded on a Waters mass spectrometer (SQD single quadrupole mass spectrometer) equipped with an electron fogging source (polarity: positive or negative ions, full sweep, capillarity: 3.00 kV, cone range: 41 V, source temperature: 150 °C, desolvation temperature: 500 °C, cone gas flow: 50 1 / h, desolvation gas flow: 1000 1 / h; mass range: 110 to 800 Da) and a Waters Class H UPLC: binary pump, heated column compartment, and diode array detector. Column: Waters UPLC HSS T3 C18, 1.8 pm, 30 x 2.1 mm, temp.: 40 °C, DAD wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: gradient: 10% B for 0 min; 10-50% B for 0-0.2 min; 50-100% B for 0.2-0.7 min; 100% B for 0.7-1.3 min; 100-10% B for 1.3-1.4 min; 10% B for 1.4-1.6 min; flow rate (ml / min) 0.6. Example 1: preparation of sodium 3,5-dichloropyridine-2carboxylate (XlIIa) qj cann / zznz / E / YiAi A mixture of 3,5-dichloropyridin-2-carboxylic acid (20.0 g, 104 mmol) and sodium hydroxide (1 M in water, 100 mL, 100 mmol, 0.96 equiv.) was stirred at room temperature for 2 hours. The solution was filtered and the water was concentrated under reduced pressure, yielding the desired product (94%, 22.0 g, 96.6 mmol, 93% yield) which was used without further purification. iH-NMR (400 MHz, DMSO-d6) δ ppm 8.04 (d, J = 2.20 Hz, 1 H) 8.38 (d, J = 2.20 Hz, 1 H). Example 2: Preparation of 5-chloro-3-ethylsulfanylpyridin-2-carboxylic acid (VI) qj cann / zznz / E / YiAi A round-bottom flask was filled with sodium 3,5-dichloropyridine-2-carboxylate (94%, 4.00 g, 17.2 mmol). The flask was purged with argon, and previously deoxygenated 2-methyltetrahydrofuran (86 mL) was added under an argon atmosphere. The reaction mixture was heated to 70 °C, and sodium ethanethiolate (1.82 g, 20.6 mmol, 1.19 equivalents) was added. The mixture was then stirred at 70 °C for 7 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in water (29 mL) and acetonitrile (12 mL). Insoluble particles were filtered out. The filtrate was heated to 80 °C, and more water (10 mL) and acetonitrile (5 mL) were added. At 80 °C, hot 1 N hydrochloric acid was added dropwise (45 °C, 16 ml) and stirred for a few minutes. The resulting precipitate was filtered while hot and dried under reduced pressure, yielding the desired product (94%, 2.30 g, 9.95 mmol, 58% yield). LC / MS (method A) : retention time 0.77 min, m / z 218 [M+H+] . NMR-!H (400 Hz, DMSO-d6) δ ppm 1.25 (t, J= 7.34 Hz, 3 H) 3.02 (c, J= 7.34 Hz, 2 H) 7.93 (d, J= 1.83 Hz, 1 H) 8.41 (d, J= 1.83 Hz, 1 H). Example 3: preparation of 5-chloro-3-ethylsulfanylpyridin-2-carboxylic (VI) acid O o qj cann / zznz / E / YiAi To a stirred solution of 3,5-dichloropyridin-2-carboxylic acid (1.00 g, 5.21 mmol) and sodium carbonate (0.662 g, 6.25 mmol, 1.20 equiv.) in previously deoxygenated 2-methyltetrahydrofuran (13 mL), sodium ethanethiolate (0.920 g, 10.9 mmol, 2.10 equiv.) was added at room temperature. The reaction mixture was heated to 50 °C and stirred for 3 hours. Additional 2-methyltetrahydrofuran (13 mL) was added, and the reaction mixture was stirred at 50 °C for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water, and the 2-methyltetrahydrofuran was removed under vacuum. Acetonitrile (6 ml) was added, followed by the dropwise addition of 1 N hydrochloric acid (21 ml). The resulting precipitate was filtered and dried under reduced pressure, yielding the desired product (71%, 1.00 g, 3.27 mmol, 63% yield). Example 4: Preparation of 3-chloro-5-ethylsulfanylpyridin-2-carboxylic acid (XVI) qj cann / zznz / E / YiAi A solution of 3,5-dichloropyridin-2-carboxylic acid (0.500 g, 2.47 mmol) in dimethyl sulfoxide (5.5 mL) was prepared and heated to 100 °C. Potassium carbonate (0.378 g, 2.60 mmol, 1.05 eV) was added, and the reaction mixture was stirred at 100 °C for 1 hour. Sodium ethanethiolate (0.250 g, 2.97 mmol, 1.20 eV) was then added, and the reaction mixture was stirred at 100 °C overnight. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and water. The aqueous layer was then acidified and extracted with more ethyl acetate. The combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the raw material by reversed-phase chromatography yielded the desired product as a white solid (0.536 mmol, % yield). LC / MS (method A) : retention time 0.74 min, m / z 218 [M+H+] . NMR-1H (400 MHz, DMSO-d6) δ ppm 1.26 (t, J = 7.15 Hz, 3 H) 3.10-3.18 (c, J= 7.15 Hz, 2 H) 7.95 (d, J = 2.20 Hz, 1 H) (8.4 Hz) (s). Example 5: preparation of 5-chloro-3-ethylsulfanyl-pyridin2-ethyl carboxylate qj cann / zznz / E / YiAi To a suspension of 5-chloro-3-ethylsulfanylpyridin-2-carboxylic acid (2.35 g, 10.6 mmol) in ethanol (26 mL), sulfuric acid (0.575 mL, 10.6 mmol, 1.00 equivalent) was slowly added at room temperature. The reaction mixture was heated to 70 °C and stirred for 15 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting residue was diluted in ethyl acetate, washed twice with saturated sodium bicarbonate solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure, yielding the desired product (90%, 2.55 g, 9.34 mmol, 88% yield), which was used without further purification. LC / MS (method A): retention time 0.99 min, m / z 246 [M+H+] . 1H-NMR (400 MHz, chloroform-d) δ ppm 1.39-1.47 (m, 6 H) 2.93 (c, J= 7.34 Hz, 2 H) 4.48 (c, J= 7.21 Hz, 2 H) 7.62 (d, J= 2.20 Hz, 1 H) 8.37 (d, J= 1.83Hz, 1H). Example 6: Preparation of ethyl 3-chloro-5-ethylsulfanylpyridin-2-carboxylate (Vlla) O solvent qq (Vlla) (Xa) qj cann / zznz / E / YiAi To a stirred solution of ethyl 3,5-dichloropyridin-2-carboxylate (96%, 0.200 g, 0.873 mmol) in toluene (2 mL), sodium ethanethiolate at 0 °C (0.122 g, 1.31 mmol, 1.50 equiv.) was added. The reaction mixture was allowed to reach room temperature and was stirred first at this temperature for 24 hours and then for 15 hours at 80 °C. After cooling to room temperature, an LC / MS sample was measured to determine the ratio of the products VIIa and Xa formed. The results showed a 60% conversion of the starting material and the formation of VIIa:Xa in a ratio of 1:1.9. LC / MS (method B): retention time 1.08 min, m / z 246 [M+H+] . 1H-NMR (400 MHz, chloroform-d) δ ppm 1.36-1.47 (m, 6 H) 3.04 (c, J= 7.42 Hz, 2 H) 4.47 (c, J= 7.09 Hz, 2 H) 7.62 (d, J= 2.08 Hz, 1 H) 8.42 (d, J= 1.96Hz, 1H). Example 7: Preparation of ethyl 3-chloro-5-ethylsulfanylpyridin-2-carboxylate (Vlla) Cl ... Cl S Cl C' .... s -· - ΠΞΝθ '· ' ' · - ' - ..0- --------------- -.0.-,- ·. ··' N N- N O tooth0o IVim(Xai To a stirred solution of ethyl 3,5-dichloropyridine-2-carboxylate (95%, 0.200 g, 0.863 mmol) in l-methyl-2-pyrrolidinone (2 mL), sodium ethanethiolate at 0 °C (0.099 g, 1.04 mmol, 1.20 equiv.) was added. The reaction mixture was allowed to reach room temperature and stirred for 6 hours. An LC / MS sample was measured to determine the ratio of the products VIIa and Xa formed. The results showed a 70% conversion of the starting material and the formation of VIIa:Xa in a ratio of 1:10.2. LC / MS (method B) : retention time 1.08 min, m / z 246 [M+H+] . RME-^ (400 MHz, chloroform-d) δ ppm 1.36-1.47 (m, 6 H) 3.04 (c, J = 7.42 Hz, 2 H) 4.47 (c, J= 7.09 Hz, 2 H) 7.62 (d, J= 2.08 Hz, 8 Hz, 2 Hz). J= 1.96 Hz, 1 H) . Example 8: solvent effect on the thiolation reaction of 3,5-dichloropyridine-2-sodium carboxylate (XlIIa) qj cann / zznz / E / YiAi A 5 mL microwaveable vial was loaded with sodium 3,5-dichloropyridin-2-carboxylate (94%, 100 mg, 0.422 mmol). The vial was purged with argon, and previously deoxygenated solvent (2.2 mL) was added under an argon atmosphere. The reaction mixture was heated to 80 °C, and sodium ethanethiolate (42.6 mg, 0.507 mmol, 1.20 equiv.) was added. The reaction mixture was stirred for 3.5 hours at 80 °C. After cooling to room temperature, the reaction mixture was stopped, and an NMR sample was measured to determine the ratio of products (XIV) to (XV) formed. The results are summarized in the table shown in Figure 2. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A process for the preparation of a chloropyridine compound of formula (I): R2-S,^\OI Rf°Y^N^ O (i) wherein Ri is H or C1-C4 alkyl; preferably Ri is methyl, ethyl or t-butyl, more preferably Ri is ethyl; and R2 is C1-C4 alkyl; preferably R2 is ethyl; characterized in that it comprises: (A) reacting a compound of formula II wherein Xa is fluorine or chlorine; preferably Xa is chlorine; with a thiol compound R3-S-R2, wherein R2 is as defined in formula I and R3 is H or an alkali metal ion; preferably R3 is H or sodium, in the presence of a suitable base, in a suitable solvent (or diluent) having a dielectric constant less than 15; to produce a compound of formula (la) or a salt thereof qj cann / zznz / E / YiAi (la); and, optionally, esterify the compound of formula (la) or a salt thereof in the presence of a compound of formula ROH, wherein R is C1-4 alkyl;to produce the compound of formula (I), where Ri is C1-C4 alkyl.; 2. A process according to claim 1, characterized in that Xa is chlorine; Ri is ethyl; R2 is ethyl; and R3 is sodium.

3. A process according to claim 1, characterized in that the suitable base is selected from an alkali metal carbonate or an alkali metal hydroxide, more preferably sodium or potassium carbonate, most preferably potassium carbonate.

4. A process according to claim 1, characterized in that the appropriate solvent (or diluent) is selected from those with a dielectric constant in the range of 1.5 to 15.

5. A process according to claim 4, characterized in that the appropriate solvent (or diluent) is selected from dioxane, methyltetrahydrofuran, toluene, anisole, pyridine; preferably dioxane, methyltetrahydrofuran or toluene. qj cann / zznz / E / YiAi 6. A process according to claim 1, characterized in that the reaction of step a. is carried out at temperatures between 0 °C and the boiling point of the reaction mixture, more preferably at temperatures between 20 °C and 100 °C, most preferably in the temperature range of 60-100 °C.

7. A compound of formula la, or an agrochemically acceptable salt of a compound of la: (la) .

8. A compound of formula Ia-1: characterized in that M is sodium, potassium or lithium; preferably sodium or lithium.

9. A compound of formula 1-2, or an agrochemically acceptable salt of a compound of 1-2: (1-2) characterized in that Ria is C1-4 alkyl; preferably Ria is methyl, ethyl or t-butyl, more preferably Ria is ethyl.

10. A compound of formula I-2a, or an agrochemically acceptable salt of a compound of I-2a: qj cann / zznz / E / YiAi characterized in that Rib is C1-4 alkyl; preferably Rib is methyl, ethyl or t-butyl, more preferably Rib is ethyl; yn is 1 or 2; preferably n is 2.