TW202419442A - New processes for synthesis of (3-chloro-2-pyridyl)hydrazine - Google Patents

Abstract

Described herein are novel methods of synthesizing (3-chloro-2-pyridyl)hydrazine. Compounds prepared by the methods disclosed herein are useful for preparation of certain anthranilamide compounds that are of interest as insecticides, such as, for example, the insecticides chlorantraniliprole and cyantraniliprole.

Description

A new method for the synthesis of (3-chloro-2-pyridyl)hydrazine

The present disclosure relates to novel methods for synthesizing (3-chloro-2-pyridyl)hydrazine. The compounds prepared by the methods disclosed herein can be used to prepare certain amine-aminobenzamide compounds of interest as insecticides, such as the insecticides chloranilamide and cyanamide.

Conventional methods for producing (3-chloro-2-pyridyl)hydrazine have some industrial problems, such as hazardous materials, high cost, relatively long process steps and complicated operations. The use of expensive and difficult to recover reagents and organic solvents is undesirable.

Furthermore, some processes use phase catalysts which are hazardous and non-biodegradable. Additional process steps are required to treat the effluent stream containing such phase catalysts. It is desirable to avoid the use of such phase catalysts.

The present disclosure provides novel methods for preparing 5-bromo-2-(3-chloropyridin-2-yl) -2H -pyrazole-3-carboxylic acid and its derivatives. The methods of the present disclosure have many advantages over previous methods and include reduced costs, elimination of the need for mixed solvent separation, reduced waste, relatively short process steps, simplified operational complexity, reduced process hazards, and reduced environmental issues.

In one aspect, provided herein is a method of preparing a compound having formula II, wherein (Formula II) R ₆ -R ₁₀ are each independently selected from hydrogen, halogen and hydrazine; wherein at least one of R ₆ -R ₁₀ is hydrazine, the method comprising: I) forming a mixture comprising: A) a compound having Formula I, wherein (Formula I) R ₁ -R ₅ are each independently selected from hydrogen and halogen, wherein at least one of R ₁ -R ₅ is halogen; B) an inorganic hydrazine derivative; C) a phase transfer catalyst, wherein the phase transfer catalyst does not contain a quaternary ammonium phase transfer catalyst and a crown ether phase transfer catalyst; D) an inorganic base or salt; and E) a solvent optionally comprising an organic solvent and optionally water; and II) reacting the mixture.

As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," "characterized by," or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation expressly stated. For example, a composition, mixture, process, or method that comprises a list of elements is not necessarily limited to those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, or method.

The transitional phrase "consisting of" excludes any unspecified element, step, or ingredient. If in a claim, this phrase renders the claim closed, excluding materials other than those stated, except for impurities normally associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim rather than in the immediate preceding clause, the phrase limits only the elements stated in that clause; the claim as a whole does not exclude other elements.

The conjunction "consisting essentially of" is used to define a composition or method that includes materials, steps, features, components, or elements in addition to those literally disclosed, provided that such additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of" is intermediate between "comprising" and "consisting of."

When an invention or a portion thereof is defined by an open term such as "comprising", it should be readily understood that (unless otherwise indicated) the description should be interpreted as also using the term "consisting essentially of" or "consisting of" to describe such an invention.

In addition, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, condition A or B is satisfied by any of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

In addition, the indefinite articles "a and an" before an element or component of the present invention are intended to be non-restrictive regarding the number of instances (i.e., occurrences) of the element or component. Therefore, "a or an" should be understood to include one or at least one, and the singular form of an element or component also includes the plural unless the number obviously means the singular.

As used herein, the term "about" means plus or minus 10% of the value.

As used herein, the unit "m/m" refers to equivalent weight and is the same as "eq.".

The term "halogen", alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Furthermore, when used in compound words such as "haloalkyl", the alkyl group may be partially or fully substituted by halogen atoms which may be the same or different.

When a group contains a substituent which may be hydrogen, such as R ⁴ , then when the substituent is regarded as hydrogen, this is considered equivalent to the group being unsubstituted.

The term "hydrazino" includes but is not limited to functional groups containing a hydrazino bond (-HN-NH2).

Certain compounds of the present invention may exist as one or more stereoisomers. Various stereoisomers include mirror image isomers, non-mirror image isomers, atropisomers and geometric isomers. Those skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to one or more other stereoisomers, or when separated from one or more other stereoisomers. In addition, those skilled in the art know how to separate, enrich and/or selectively prepare the stereoisomers.

The implementation methods of this disclosure include:

Embodiment 1. A method for preparing a compound of formula II, wherein: (Formula II) R ₆ -R ₁₀ are each independently selected from hydrogen, halogen and hydrazine; wherein at least one of R ₆ -R ₁₀ is hydrazine, the method comprising: I) forming a mixture comprising: A) a compound having Formula I, wherein (Formula I) R ₁ -R ₅ are each independently selected from hydrogen and halogen, wherein at least one of R ₁ -R ₅ is halogen; B) an inorganic hydrazine derivative; C) a phase transfer catalyst, wherein the phase transfer catalyst does not contain a quaternary ammonium phase transfer catalyst and a crown ether phase transfer catalyst; D) an inorganic base or salt; and E) a solvent optionally comprising an organic solvent and optionally water; and II) reacting the mixture.

Embodiment 2. The method as described in Embodiment 1, wherein the mixture further comprises an aqueous solvent comprising water.

Embodiment 3. The method as described in Embodiment 2, wherein the aqueous solvent is water.

Embodiment 4. The method as described in Embodiment 1, wherein the inorganic hydrazine derivative is selected from aqueous hydrazine, hydrazine hydrate, hydrazine salts and combinations thereof.

Embodiment 5. The method as described in Embodiment 4, wherein the inorganic hydrazine derivative is aqueous hydrazine comprising hydrazine monohydrate.

Embodiment 6. The method of embodiment 1, wherein the inorganic hydrazine derivative is present in an amount greater than about 1 m/m.

Embodiment 7. The method as described in embodiment 1, wherein the phase transfer catalyst is selected from ethers, cyclic ethers, linear ethers, branched ethers, lauryl ethers, polyoxyethylene lauryl ethers, phenyl ethers, glycols, polyethylene glycols containing ethylene glycol units in an amount ranging from 400 to 1000, esters, sorbitan esters, polyoxyethylene sorbitan esters, carboxylic acids, saturated or unsaturated fatty acids, saturated or unsaturated _C12 to _C20 fatty acids, organic sulfur compounds, organic sulfates, and combinations thereof.

Embodiment 8. The method as described in embodiment 1, wherein the phase transfer catalyst is selected from polyethylene glycol dodecyl ether (Brij® 30), polyoxyethylene octylphenyl ether (Triton® X-100), polyethylene glycol (PEG) 600, sorbitan monolaurate (SPAN® 20), sorbitan tristearate (SPAN® 65), polyoxyethylene glycol sorbitan monolaurate (Tween® 20), polyoxyethylene sorbitan trioleate (Tween® 85), acetic acid, stearic acid, lauric acid, palmitic acid, sodium lauryl sulfate, and combinations thereof.

Embodiment 9. The method as described in Embodiment 1, wherein the phase transfer catalyst is biodegradable.

Embodiment 10. The method as described in Embodiment 1, wherein the phase transfer catalyst is a non-ionic phase transfer catalyst.

Embodiment 11. The method of embodiment 1, wherein the phase transfer catalyst is present in the mixture in an amount from about 0.1 wt.% to about 5 wt.%.

Embodiment 12. The method as described in Embodiment 1, wherein the inorganic base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, powdered potassium carbonate (400 mesh), potassium bicarbonate, sodium bicarbonate, dipotassium hydrogen phosphate, tripotassium phosphate, disodium hydrogen phosphate, trisodium phosphate, sodium methoxide, potassium tertiary butoxide and combinations thereof.

Embodiment 13. The method as described in Embodiment 9, wherein the inorganic base is potassium carbonate.

Embodiment 14. The method as described in Embodiment 1, wherein the salt is selected from sodium sulfate, potassium sulfate, sodium chloride, potassium chloride, and combinations thereof.

Embodiment 15. The method as described in Embodiment 1, wherein the organic solvent is selected from methanol, ethanol, propanol, isopropanol, n-butanol, tertiary butanol, heptane, toluene, n-octane and combinations thereof.

Embodiment 16. The method according to embodiment 1, wherein the mixture is substantially free of organic solvent.

Embodiment 17. The method according to embodiment 1, wherein the compound having formula I is selected from 2-chloropyridine, 2,3-dichloropyridine, 2,6-dichloropyridine and combinations thereof.

Embodiment 18. The method according to embodiment 1, wherein the compound of formula II is selected from 2-hydrazinopyridine, (3-chloro-2-pyridyl)hydrazine, (6-chloro-2-pyridyl)hydrazine and combinations thereof.

Embodiment 19. The method of embodiment 1, wherein the method step of reacting the mixture occurs at a temperature in the range of about 90°C to about 130°C.

Embodiment 20. The method of embodiment 1, wherein the method step of reacting the mixture occurs during a reaction time of less than about 50 hours.

Embodiment 21. The method of embodiment 1, wherein the method step of reacting the mixture occurs under a pressure in the range of about 1.0332 kg/cm ² to about 5 kg/cm ² .

In one aspect, a compound having Formula II is prepared according to the method represented by Scheme 1. The R group is as defined anywhere in this disclosure. Scheme 1.

This aspect comprises mixing a compound having formula I, an inorganic hydrazine derivative, a phase transfer catalyst free of quaternary ammonium phase transfer catalyst and crown ether phase transfer catalyst, an inorganic base or salt, and a solvent comprising an organic solvent and water as needed, and reacting the mixture.

In one embodiment, the mixture further comprises an aqueous solvent comprising water. In another embodiment, the mixture further comprises water.

In one embodiment, the inorganic hydrazine derivative is selected from aqueous hydrazine, hydrazine hydrate, hydrazine salts and combinations thereof. In one embodiment, the aqueous hydrazine comprises hydrazine monohydrate. In one embodiment, the inorganic hydrazine derivative is an aqueous solution of hydrazine having a concentration in the range of about 30% to about 64%. In one embodiment, the inorganic hydrazine derivative is an aqueous solution of hydrazine having a concentration in the range of about 30% to about 51%. In one embodiment, the inorganic hydrazine derivative is present in the mixture in an amount greater than 1 m/m, greater than 2 m/m, greater than 3 m/m, greater than 5 m/m or greater than 10 m/m; or from about 1 m/m to about 10 m/m, or from about 1 m/m to about 3 m/m, from about 2 m/m to about 5 m/m, or from about 3 m/m to about 10 m/m.

The phase transfer catalyst does not contain quaternary ammonium phase transfer catalyst and crown ether phase transfer catalyst. In one embodiment, the phase transfer catalyst does not contain non-biodegradable phase transfer catalyst. In one embodiment, the phase transfer catalyst is biodegradable.

In one embodiment, the phase transfer catalyst is selected from ethers, cyclic ethers, linear ethers, branched ethers, lauryl ethers, polyoxyethylene lauryl ethers, phenyl ethers, glycols, polyethylene glycols (PEG) containing ethylene glycol units in an amount ranging from 400 to 1000, esters, sorbitan esters, polyoxyethylene sorbitan esters, carboxylic acids, saturated or unsaturated fatty acids, saturated or unsaturated _C12 to _C20 fatty acids, organic sulfur compounds, organic sulfates, and combinations thereof. In one embodiment, the phase transfer catalyst is selected from polyethylene glycol lauryl ether (Brij® 30), polyoxyethylene octylphenyl ether (Triton® X-100), polyethylene glycol (PEG) 600, sorbitan monolaurate (SPAN® 20), sorbitan tristearate (SPAN® 65), polyoxyethylene glycol sorbitan monolaurate (Tween® 20), polyoxyethylene sorbitan trioleate (Tween® 85), acetic acid, stearic acid, lauric acid, palmitic acid, sodium dodecyl sulfate, and combinations thereof. In one embodiment, the phase transfer catalyst is a nonionic phase transfer catalyst. In one embodiment, the phase transfer catalyst is present in the mixture in an amount from about 0.1 wt.% to about 5 wt.%. In one embodiment, the phase transfer catalyst is present in the mixture in an amount from about 0.1 wt.% to about 3 wt.%.

In one embodiment, the inorganic base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, powdered potassium carbonate (400 mesh), potassium bicarbonate, sodium bicarbonate, dipotassium hydrogen phosphate, tripotassium phosphate, disodium hydrogen phosphate, trisodium phosphate, sodium methoxide, potassium tertiary butoxide, and combinations thereof. In one embodiment, the inorganic base is potassium carbonate. In one embodiment, the inorganic base is present in the mixture in an amount from about 0.1 m/m to about 2 m/m. In another embodiment, the inorganic base is present in the mixture in an amount from about 0.25 m/m to about 1.5 m/m.

In one embodiment, the salt is an inorganic salt. In another embodiment, the salt is selected from sodium sulfate, potassium sulfate, sodium chloride, potassium chloride, and combinations thereof.

The solvent comprises an organic solvent and optionally water. In one embodiment, the solvent comprises an organic solvent and water. In another embodiment, the solvent is substantially free of water. In another embodiment, water is not present in the solvent. In one embodiment, the organic solvent is selected from methanol, ethanol, propanol, isopropanol, n-butanol, tertiary butanol, heptane, toluene, n-octane, and combinations thereof. In another embodiment, the mixture is substantially free of organic solvent. In another embodiment, organic solvent is not present in the mixture.

In one embodiment, the compound having Formula I is selected from 2-chloropyridine, 2,3-dichloropyridine, 2,6-dichloropyridine, and combinations thereof.

In one embodiment, the compound having Formula II is selected from 2-hydrazinopyridine, (3-chloro-2-pyridinyl)hydrazine, (6-chloro-2-pyridinyl)hydrazine, and combinations thereof.

In one embodiment, the method step of reacting the mixture occurs at an elevated temperature. In another embodiment, the method step of reacting the mixture occurs at a temperature in the range of about 90°C to about 130°C.

In one embodiment, the method step of reacting the mixture occurs during a reaction time of less than about 50 hours. In another embodiment, the method step of reacting the mixture is mostly completed within about 10 hours.

In one embodiment, the process step of reacting the mixture occurs at a pressure in the range of about 1.0332 kg/cm ² to about 10 kg/cm ^2. In another embodiment, the process step of reacting the mixture occurs at a pressure in the range of about 1.0332 kg/cm ² to about 5 kg/cm ² .

In one aspect, (3-chloro-2-pyridyl)hydrazine is prepared according to the method represented by Scheme 2. Scheme 2.

In one aspect, 2-hydrazinopyridine is prepared according to the method represented by Scheme 3. Scheme 3. Examples

Without further elaboration, it is believed that those familiar with the art can utilize the present invention to the greatest extent using the previous description. Therefore, the following examples should be interpreted as being illustrative only and not limiting the present disclosure in any way. The starting materials of the following examples may not necessarily be prepared by a specific preparation run, the procedures of which are described in other examples. It should also be understood that any numerical ranges listed herein include all values from the lower limit to the upper limit. For example, if a range is specified as 10-50, it is expected that values such as 12-30, 20-40 or 30-50 are explicitly listed in this specification. These are only examples of specific intent, and all possible combinations of numerical values between (and including the lowest and highest values) listed will be considered to be clearly stated in this application.

Example 1. Nonionic surfactants as phase transfer catalysts.

137 g (0.5 m/m) K ₂ CO ₃ was added to a mixture of 300 g (1.986 mol) 2,3-dichloropyridine, 248 g (2 m/m) hydrazine hydrate (80%), and 3 g Tween® 85 (% w/w wrt 2,3-dichloropyridine) at ambient temperature. For reference, 80% hydrazine hydrate is equivalent to 51% aqueous hydrazine. The reaction mixture was heated to 110°C-120°C in 1 hour and maintained at reflux temperature for 27 hours. The reaction monitored by LC A% showed 97.7% (3-chloro-2-pyridyl)hydrazine and 0.23% 2,3-dichloropyridine. The reaction mass was cooled to 80°C and diluted with 300 g water and further cooled to 25°C-30°C. The precipitate (3-chloro-2-pyridyl)hydrazine was separated from the reaction mass by filtration, the wet filter cake was washed with 600 g of water and dried at 60-65° C. under 100-150 torr vacuum for 10-12 hours until a constant weight was obtained.

[Table 1.] Output summary. Total weight of (3-chloro-2-pyridyl)hydrazine 274.3 g Nature of the product Light brown crystalline powder Purity 98.7% Yield 95% Melting point 163.5°C-164.9°C

Example 2. Phase catalyst screening using 80% hydrazine hydrate.

Various phase catalysts were screened to determine their relative effectiveness in reactions according to the present disclosure. Each phase catalyst was screened using the method of Example 1 with the catalyst and reactant amounts shown in Table 2. The results are shown in Table 3. In both tables, CE represents comparative examples, and IE represents inventive examples.

[Table 2.] Phase catalyst screening using 80% hydrazine hydrate. Examples Catalyst Amount of catalyst (wrt 2,3-dichloropyridine) 2,3-Dichloropyridine 80% Hydrazine Hydrate K ₂ CO ₃ Acetic acid (wrt 2,3-dichloropyridine) CE1 Methyltrioctylammonium chloride (Aliquat-336) 1% w/w 300 g 2 m/m 0.5 m/m 0.5% w/w CE2 Methyltrioctylammonium chloride 1% w/w 300 g 2 m/m 0.5 m/m CE3 TBAB 1% w/w 300 g 2 m/m 0.5 m/m 0.5% w/w CE4 TBAB 1.5% w/w 300 g 2 m/m 0.5 m/m CE5 Crown ether 1% w/w 300 g 2 m/m 0.5 m/m 0.5% w/w IE1 PEG 600 1% w/w 300 g 2 m/m 0.5 m/m 0.5% w/w IE2 PEG 600 1% w/w 300 g 2 m/m 0.5 m/m IE3 Brij® 30 1% w/w 300 g 2 m/m 0.5 m/m IE4 Tween® 85 1% w/w 300 g 2 m/m 0.5 m/m 0.5% w/w IE5 Tween® 85 1% w/w 300 g 2 m/m 0.5 m/m IE6 Acetic acid 3% w/w 300 g 2 m/m 0.5 m/m 3% w/w IE7 Acetic acid 5% w/w 300 g 2 m/m 0.5 m/m 5% w/w IE8 Stearic acid 1% w/w 300 g 2 m/m 0.5 m/m IE9 Stearic acid 2% w/w 300 g 2 m/m 0.5 m/m

[Table 3.] Phase catalyst screening using 80% hydrazine hydrate. Examples Response time (hours) Weight of dry (3-chloro-2-pyridyl)hydrazine (g) Purity of dry (3-chloro-2-pyridyl)hydrazine % Yield of dry (3-chloro-2-pyridyl)hydrazine % CE1 28 280.1 98.77 97.03 CE2 31 266.4 99.02 92.52 CE3 25 273 98.48 94.29 CE4 32 273.7 98.20 94.26 CE5 28 273.9 98.92 95.02 IE1 29 276.9 99.05 96.19 IE2 31 272 99.05 94.49 IE3 33 267.7 99.63 93.54 IE4 30 271.4 99.14 94.37 IE5 27 274.3 98.74 94.99 IE6 40 273.3 98.31 94.23 IE7 37 269.5 99.02 93.59 IE8 28 274 97.54 93.73 IE9 27 276 96.46 93.37

This example demonstrates comparable purity and yield between quaternary ammonium phase transfer catalysts and crown ether phase transfer catalysts and the phase transfer catalysts of the present invention.

Example 3. Phase catalyst screening using 100% hydrazine hydrate.

Various phase catalysts were screened to determine their relative effectiveness in the reaction according to the present disclosure. Each phase catalyst was screened using the method of Example 1 with the catalyst and reactant amounts shown in Table 4. The results after 5 hours of reaction are shown in Table 5, and the results after 10 hours of reaction are shown in Table 6. In all tables, CE represents comparative examples, and IE represents inventive examples.

[Table 4.] Phase catalyst screening using 100% hydrazine hydrate. Examples Catalyst Amount of catalyst (wrt 2,3-dichloropyridine) 2,3-Dichloropyridine 100% Hydrazine Hydrate K ₂ CO ₃ n-Butanol (wrt 2,3-dichloropyridine) CE6 without 0% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol CE7 Methyltrioctylammonium chloride 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol CE8 Cetylpyridinium chloride 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol CE9 Dodecyltrimethylammonium chloride 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE10 Sodium Lauryl Sulfate 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE11 Brij® 30 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE12 Tween® 20 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE13 Stearic acid 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE14 Triton® X-100 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE15 Tween® 85 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE16 SPAN® 20 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol IE17 SPAN® 65 1.4% w/w 30 g 3.03 m/m 1.01 m/m 3.5 vol

[Table 5.] Phase catalyst screening using 100% hydrazine hydrate after 5 hours. Examples (3-Chloro-2-pyridyl)hydrazine (%LCA) 2,3-Dichloropyridine (%LCA) Others (%LCA) CE6 67.01 13.13 19.86 CE7 68.99 13.19 17.82 CE8 75.74 13.82 10.44 CE9 70.73 14.27 15 IE10 66.83 14.09 19.08 IE11 84.32 12.95 2.73 IE12 63.37 12.74 23.89 IE13 69.37 13.85 16.78 IE14 63.73 11.76 24.51 IE15 83.58 13.05 3.37 IE16 74.24 13.85 11.91 IE17 71.4 12.72 15.88

[Table 6.] Phase catalyst screening using 100% hydrazine hydrate after 10 hours. Examples (3-Chloro-2-pyridyl)hydrazine (%LCA) 2,3-Dichloropyridine (%LCA) Others (%LCA) CE6 92.12 5.72 2.16 CE7 91.65 6.27 2.08 CE8 90.69 6.07 3.24 CE9 91.42 6.11 2.47 IE10 90.73 6.11 2.66 IE11 91.95 5.28 2.77 IE12 91.7 5.3 3 IE13 90.45 5.67 3.88 IE14 92.14 5.16 2.7 IE15 91.8 5.35 2.85 IE16 91.25 5.45 3.3 IE17 92.43 5.14 2.43

This example demonstrates comparable purity and yield over time between quaternary ammonium phase transfer catalysts and crown ether phase transfer catalysts and the phase transfer catalysts of the present invention.

This written description uses examples to illustrate the disclosure, including the best mode, and also to enable any person skilled in the art to practice the disclosure, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the disclosure is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements that do not differ substantially from the literal language of the claims.

without

without

without

Claims (21)

A method for preparing a compound of formula II, wherein (Formula II) R ₆ -R ₁₀ are each independently selected from hydrogen, halogen and hydrazine; wherein at least one of R ₆ -R ₁₀ is hydrazine, the method comprising: I) forming a mixture comprising: A) a compound having Formula I, wherein (Formula I) R ₁ -R ₅ are each independently selected from hydrogen and halogen, wherein at least one of R ₁ -R ₅ is halogen; B) an inorganic hydrazine derivative; C) a phase transfer catalyst, wherein the phase transfer catalyst does not contain a quaternary ammonium phase transfer catalyst and a crown ether phase transfer catalyst; D) an inorganic base or salt; and E) a solvent optionally comprising an organic solvent and optionally water; and II) reacting the mixture. The method of claim 1, wherein the mixture further comprises an aqueous solvent comprising water. The method of claim 2, wherein the aqueous solvent is water. The method as described in claim 1, wherein the inorganic hydrazine derivative is selected from aqueous hydrazine, hydrazine hydrate, hydrazine salts and combinations thereof. The method as described in claim 4, wherein the inorganic hydrazine derivative is aqueous hydrazine comprising hydrazine monohydrate. The method of claim 1, wherein the inorganic hydrazine derivative is present in an amount greater than about 1 m/m.s. The method as described in claim 1, wherein the phase transfer catalyst is selected from ethers, cyclic ethers, linear ethers, branched ethers, lauryl ethers, polyoxyethylene lauryl ethers, phenyl ethers, glycols, polyethylene glycols containing ethylene glycol units in an amount ranging from 400 to 1000, esters, sorbitan esters, polyoxyethylene sorbitan esters, carboxylic acids, saturated or unsaturated fatty acids, saturated or unsaturated _C12 to _C20 fatty acids, organic sulfur compounds, organic sulfates, and combinations thereof. The method as described in claim 1, wherein the phase transfer catalyst is selected from polyethylene glycol dodecyl ether (Brij® 30), polyoxyethylene octylphenyl ether (Triton® X-100), polyethylene glycol (PEG) 600, sorbitan monolaurate (SPAN® 20), sorbitan tristearate (SPAN® 65), polyoxyethylene glycol sorbitan monolaurate (Tween® 20), polyoxyethylene sorbitan trioleate (Tween® 85), acetic acid, stearic acid, lauric acid, palmitic acid, sodium dodecyl sulfate, and combinations thereof. The method of claim 1, wherein the phase transfer catalyst is biodegradable. The method of claim 1, wherein the phase transfer catalyst is a non-ionic phase transfer catalyst. The method of claim 1, wherein the phase transfer catalyst is present in the mixture in an amount from about 0.1 wt.% to about 5 wt.%. The method as described in claim 1, wherein the inorganic base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, powdered potassium carbonate (400 mesh), potassium bicarbonate, sodium bicarbonate, dipotassium hydrogen phosphate, tripotassium phosphate, disodium hydrogen phosphate, trisodium phosphate, sodium methoxide, potassium tertiary butoxide and combinations thereof. The method of claim 9, wherein the inorganic base is potassium carbonate. The method of claim 1, wherein the salt is selected from sodium sulfate, potassium sulfate, sodium chloride, potassium chloride, and combinations thereof. The method as described in claim 1, wherein the organic solvent is selected from methanol, ethanol, propanol, isopropanol, n-butanol, tert-butanol, heptane, toluene, n-octane and combinations thereof. The method of claim 1, wherein the mixture is substantially free of organic solvent. The method of claim 1, wherein the compound having formula I is selected from 2-chloropyridine, 2,3-dichloropyridine, 2,6-dichloropyridine and combinations thereof. The method as described in claim 1, wherein the compound having formula II is selected from 2-hydrazinopyridine, (3-chloro-2-pyridyl)hydrazine, (6-chloro-2-pyridyl)hydrazine and combinations thereof. The method of claim 1, wherein the method step of reacting the mixture occurs at a temperature in the range of about 90°C to about 130°C. The method of claim 1, wherein the method step of reacting the mixture occurs during a reaction time of less than about 50 hours. The method of claim 1, wherein the method step of reacting the mixture occurs at a pressure in the range of about 1.0332 kg/cm ² to about 5 kg/cm ² .