WO2024049748A1

WO2024049748A1 - A new and efficient process for preparing 3 -halo-4, 5-dihydro-1h-pyrazoles

Info

Publication number: WO2024049748A1
Application number: PCT/US2023/031258
Authority: WO
Inventors: Vikrant Arun ADSOOL; Ivan Sergeyevich BALDYCHEV
Original assignee: Fmc Corporation; Fmc Agro Singapore Pte. Ltd.
Priority date: 2022-08-29
Filing date: 2023-08-28
Publication date: 2024-03-07

Abstract

An improved method is disclosed for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I comprising reacting a compound of Formula II with a halide salt and a mineral acid to form the compound of Formula I. wherein X¹, R¹, R², R^x, k, Z and X² are as defined in the disclosure. Also disclosed are methods for preparing compounds of Formula III and Formula IV wherein R¹, X¹, R², R^x, k, R^6A, R^6B, R^6C, R^6D and R⁷ are as defined in the disclosure, using a compound of Formula I characterized by preparing the compound of Formula I by the method disclosed above or using a compound of Formula I prepared by the method disclosed above.

Description

TITLE A NEW AND EFFICIENT PROCESS FOR PREPARING 3-HALO-4,5-DIHYDRO-1H-PYRAZOLES CROSS-REFERENCE TO RELATED APPLICATION This application claims the benefit of U.S. Provisional Application No. 63/401868, filed August 29, 2022, all of which is incorporated by reference herein in its entirety. FIELD This disclosure relates to an improved method for preparing 3-halo-4,5-dihydro-1H- pyrazoles. Such compounds prepared by the method disclosed herein are useful for the preparation of diamide crop protection agents that are of interest as insecticides. BACKGROUND Ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate is an intermediate in the preparation of diamide crop protection agents, such as for example the insecticides cyantraniliprole, chlorantraniliprole and derivatives thereof. Conventional processes for the production of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro- 1H-pyrazole-5-carboxylate using hydrogen bromide as a gas or as a solution, are subject to several industrial concerns associated with the storage, handling, and use of cylinders and solutions containing corrosive gases (e.g. hydrogen bromide). Compared to conventional processes, halide salts reduce environmental hazards, high cost, reagent reactivity, the need for necessary specialized equipment, and limitations to operate the method on a commercial scale. The present disclosure provides novel methods useful for preparing 3-halo-4,5- dihydro-1H-pyrazoles. Benefits of the methods of the present disclosure compared to previous methods include a significant improvement in operating the process on a commercial scale which use relatively low-cost, milder reaction conditions and less hazardous reagents commercially available in industrial quantities. SUMMARY This disclosure is directed to a method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I _R ¹ N N R² Z x (R ⁾ _k I wherein R¹ is C(O)R³, halogen, cyano, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl or C₁-C₄ hydroxyalkyl; X¹ is a halogen; R² is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; each R^x is independently halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; Z is N or CR^z; R³ is H, OH, C₁-C₄ alkyl or C₁-C₄ alkoxy; R^z is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; and k is 0, 1, 2 or 3; the method comprising: reacting (1) a 4,5-dihydro-1H-pyrazole compound of Formula II

wherein X² is OS(O)_mR⁴, OP(O)_n(OR⁵)₂ or a halogen other than X¹; m is 1 or 2; n is 0 or 1; R⁴ is C₁-C₄ alkyl or C₁-C₄ haloalkyl; or phenyl optionally substituted with from 1 to 3 substituents selected from C₁-C₄ alkyl and halogen; and each R⁵ is independently C₁-C₄ alkyl or C₁-C₄ haloalkyl; or phenyl optionally substituted with from 1 to 3 substituents selected from C₁-C₄ alkyl and halogen; with (2) a halide salt wherein the halogen of the halide salt is X¹, and (3) a mineral acid to form the compound of Formula I, in the presence of a suitable solvent, and optionally in the presence of an organic acid. This disclosure is also directed to a method of preparing a compound of Formula III

wherein R¹ is C(O)R³, halogen, cyano, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl or C₁-C₄ hydroxyalkyl; X¹ is a halogen; R² is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; each R^x is independently halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; Z is N or CR^z; R³ is H, OH, C₁-C₄ alkyl or C₁-C₄ alkoxy; R^z is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; and k is 0, 1, 2 or 3; the method characterized by using a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I as prepared by the method disclosed above. This disclosure is also directed to a method of preparing a diamide compound of Formula IV

wherein X¹ is a halogen; R² is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; each R^x is independently halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; Z is N or CR^z; R^z is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; k is 0, 1, 2 or 3; R^6A is halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; R^6B is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; R^6C is halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; R^6D is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; and R⁷ is C₁-C₄ alkyl, C₃-C₆ cycloalkyl, C₄-C₈ cycloalkylalkyl, C₄-C₈ alkylcycloalkyl, or C₅-C₈ alkylcycloalkylalkyl; using a compound of Formula Ia

wherein R³ is OH or C₁-C₄ alkoxy; the method characterized by preparing the compound of Formula Ia by the method disclosed above. DETAILED DESCRIPTION The method of this disclosure is generally applicable to a wide range of starting compounds of Formula II and product compounds of Formula I. In the recitations herein, although the R¹ substituent is connected to the backbone of the 4,5-dihydro-1H-pyrazole ring, the R¹ substituent is separated from the reaction center. The R¹ substituent can encompass a great variety of carbon-based groups preparable by modern methods of synthetic organic chemistry. One skilled in the art will recognize that certain groups are sensitive to the reagents of this method and may be transformed under the reaction conditions. One skilled in the art will also recognize that certain groups are basic and can form salts when contacted with the reagents of this method, and thus the method of this disclosure can require additional halide salt and mineral acid. 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 explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only 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 element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those expressly recited except for impurities ordinarily associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. The transitional phrase "consisting essentially of" is used to define a composition, process or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the disclosure. The term "consisting essentially of" occupies a middle ground between "comprising" and "consisting of". Where applicants have defined an embodiment or a portion thereof with an open-ended term such as "comprising," it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an embodiment using the terms "consisting essentially of" or "consisting of." Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). Also, the indefinite articles "a" and "an" preceding an element or component of the disclosure are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular. As used herein, the term "about" means plus or minus 10% of the value. It also is understood that any numerical range recited herein includes all values from the lower value to the upper value. For example, if a numerical range is stated as 1 to 10, it is intended that values such as 2 to 9, 2.5 to 8.1, or 1 to 1.6, etc., are expressly enumerated in this specification. These are only examples of what is specifically intended, and all possible combinations of numerical values between and including the lowest value and the highest value enumerated are to be considered to be expressly stated in this application. It is further understood that if a range is recited in the "from/to" or "from about/to about" format, such as from 10:1 to 1:10, the range includes the endpoints (i.e., 10:1 and 1:10). In any of the various aspects of the disclosure, the mole ratio of the halide salt to a compound of Formula II is 20:1, 15:1, 10:1, 9:1, 8:1, 7.9:1, 7.8:1, 7.7:1, 7.6:1, 7.5:1, 7.4:1, 7.3:1, 7.2:1, 7.1:1, 7:1, 6.9:1, 6.8:1, 6.7:1, 6.6:1, 6.5:1, 6.4:1, 6.3:1, 6.2:1, 6.1:1, 6:1, 5.9:1, 5.8:1, 5.7:1, 5.6:1, 5.5:1, 5.4:1, 5.3:1, 5.2:1, 5.1:1, 5.1, 4.9:1, 4.8:1, 4.7:1, 4.6:1, 4.5:1, 4.4:1, 4.3:1, 4.2:1, 4.1:1, 4:1, 3.9:1, 3.8:1, 3.7:1, 3.6:1, 3.5:1, 3.4:1, 3.3:1, 3.2:1, 3.1:1, 3:1, 2.9:1, 2.8:1, 2.7:1, 2.6:1, 2.5:1, 2.4:1, 2.3:1, 2.2:1, 2.1:1, 2:1, 1.9:1, 1.8:1, 1.7:1, 1.6:1, 1.4:1, 1.3:1, 1.2:1, 1.1:1, 1:1, 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, 0.2:1 or 0.1:1, and any range constructed therefrom, such as from about 1:1 to about 6:1, from about 1:1 to about 5:1, from about 2:1 to about 5:1, from about 3.5:1 to about 4.5:1, or from about 3.9:1 to about 4.1:1. In any of the various aspects of the disclosure, the mole ratio of the mineral acid to a

range constructed therefrom, such as from about 0.5:1 to about 12:1, from about 0.5:1 to about 6:1, from about 2:1 to about 4:1, from about 2.5:1 to about 3.5:1, or from about 2.9:1 to about 3.1:1. In any of the various aspects of the disclosure, the weight to volume ratio of a compound of Formula II to the solvent is 1:500, 1:50, 1:40, 1:35, 1:30, 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:12, 1:11, 1:10, 1:9.9, 1:9.8, 1:9.7, 1:9.6, 1:9.5, 1:9.4, 1:9.3, 1:9.2, 1:9.1, 1:9, 1:8.9, 1:8.8, 1:8.7, 1:8.6, 1:8.5, 1:8.4, 1:8.3, 1:8.2, 1:8.1, 1:8, 1:7.9, 1:7.8, 1:7.7, 1:7.6, 1:7.5, 1:7.4, 1:7.3, 1:7.2, 1:7.1, 1:7, 1:6.9, 1:6.8, 1:6.7, 1:6.6, 1:6.5, 1:6.4, 1:6.3, 1:6.2, 1:6.1, 1:6, 1:5.9, 1:5.8, 1:5.7, 1:5.6, 1:5.5, 1:5.4, 1:5.3, 1:5.2, 1:5.1, 1:5, 1:4.9, 1:4.8, 1:4.7, 1:4.6, 1:4.5, 1:4.4, 1:4.3, 1:4.2, 1:4.1, 1:4, 1:3.9, 1:3.8, 1:3.7, 1:3.6, 1:3.5, 1:3.4, 1:3.3, 1:3.2, 1:3.1, 1:3, 1:2.9, 1:2.8, 1:2.7, 1:2.6, 1:2.5, 1:2.4, 1:2.3, 1:2.2, 1:2.1, 1:2, 1:1.9, 1:1.8, 1:1.7, 1:1.6, 1:1.5, 1:1.4, 1:1.3, 1:1.2, 1:1.1, 1:1, 1:0.9, 1:0.8, 1:0.75, 1:0.7, 1:0.6, 1:0.5 or 1:0.05, and any range constructed therefrom, such as from about 0.5:1 to about 12:1, from about 0.5:1 to about 6:1, from about 2:1 to about 4:1, from about 2.5:1 to about 3.5:1, or from about 2.9:1 to about 3.1:1. As used herein, the term "alkyl", used either alone or in compound words such as "haloalkyl," "alkylcycloalkyl," "cycloalkylalkyl" or "alkylcycloalkylalkyl," includes straight-chain or branched alkyl groups having one to four carbon atoms, e.g., methyl, ethyl, n-propyl, i-propyl, or the different butyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl and 1,3-butadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 1,3-butadiynyl. As used herein, the term "halogen" includes fluorine, chlorine, bromine and iodine. The term “halogen”, either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F₃C, ClCH₂, CF₃CH₂ and CF₃CCl₂. The term "Alkoxy" denotes alkyl attached to and linked through an oxygen atom such as, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy isomers. "Hydroxyalkyl" denotes an alkyl group substituted with one terminal hydroxy group. Examples of "hydroxyalkyl" include HOCH₂CH₂, CH₃CH₂(OH)CH and HOCH₂CH₂CH₂CH₂. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, i-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term “cycloalkylalkyl” denotes cycloalkyl substitution on an alkyl moiety. Examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, cyclohexylmethyl and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. “Alkylcycloalkylalkyl” denotes alkylcycloalkyl substitution on alkyl. Examples of “alkylcycloalkylalkyl” include methylcyclohexylmethyl and ethylcycloproylmethyl. The chemical abbreviations S(O) and S(=O) as used herein represent a sulfinyl moiety. The chemical abbreviations SO₂, S(O)₂ and S(=O)₂ as used herein represent a sulfonyl moiety. The chemical abbreviations C(O) and C(=O) as used herein represent a carbonyl moiety. The chemical abbreviations C(S) and C(=S) as used herein represent a thiocarbonyl moiety. The chemical abbreviations CO₂, C(O)O and C(=O)O as used herein represent an oxycarbonyl moiety. "CHO" means formyl. A "-" at the beginning of a fragment definition denotes the attachment point of said fragment to the remainder of the molecule; for example, "-CH₂CH₂OMe" denotes the fragment 2-methoxyethyl. Cyclic fragments are represented by the use of two "-" within parentheses; for example, the fragment 1-methylcyclopropyl is represented by "-C(CH₃)(-CH₂CH₂-)", wherein a carbon atom is bonded to both terminal carbon atoms of the two-carbon chain, as illustrated below.

The total number of carbon atoms in a substituent group is indicated by the "C_h–C_i" prefix where h and i are numbers from 1 to 8. For example, C₃–C₆ cycloalkyl designates cyclopropane through cyclohexane; C₅ alkylcycloalkylalkyl designates, for example, -CH₂C(CH₃)(-CH₂CH₂-) or -CH₂C(-CH(CH₃)CH₂-); C₆ alkylcycloalkylalkyl designates, for example, -CH₂CH₂C(CH₃)(-CH₂CH₂-), -CH₂CH₂C(-CH(CH₃)CH₂-), -CH₂C(CH₂CH₃)(-CH₂CH₂-), -CH₂C(-CH(CH₂CH₃)CH₂-), -CH₂C(CH₃)(-CH₂CH₂CH₂-), -CH₂C(-CH(CH₃)CH₂CH₂-) or -CH₂C(-CH₂CH(CH₃)CH₂-); and C₈ alkylcycloalkylalkyl designates the various isomers of an alkyl group substituted with an alkylcycloalkyl group containing a combined total of eight carbon atoms. When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents, for example (R^x)_k wherein k is 0, 1, 2 or 3. When a group contains a substituent which can be hydrogen, for example R² or R^6B, then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a variable group is shown to be optionally attached to a position, for example (R^x)_k wherein k may be 0, then hydrogen may be at the position even if not recited in the variable group definition. When one or more positions on a group are said to be "not substituted" or "unsubstituted", then hydrogen atoms are attached to take up any free valency. As used herein, the term "suitable" indicates that the entity so described is appropriate for use in the situation or circumstance indicated. The term "reacting" and the like refer to adding, contacting, or mixing two or more reagents under appropriate conditions to produce the indicated and/or the desired product. It should be appreciated that the reaction which produces the indicated and/or the desired product may not necessarily result directly from the combination of two reagents which were initially added, i.e. there may be one or more intermediates which are produced in the mixture which ultimately leads to the formation of the indicated and/or the desired product. Reacting can take place in the presence or absence of solvent, at a temperature above room temperature or below room temperature, under an inert atmosphere, etc. The term "optionally" when used herein means that the optional condition may or may not be present. For example, when a reaction is conducted optionally in the presence of an organic acid, the organic acid may or may not be present. The term "optionally substituted" refers to groups which are unsubstituted or have at least one non-hydrogen substituent that does not extinguish the chemical or biological activity possessed by the unsubstituted analog. As used herein, the following definitions shall apply unless otherwise indicated. The term "optionally substituted with" is used interchangeably with the phrase "unsubstituted or substituted with" or with the term "(un)substituted with." Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other. The term "salt" or "salts", as used herein, refers to any anionic and cationic complex. The term "halide" refers to an anion of a halogen. The term "halide salt" refers to a salt having one or more anions of a halogen and at least one other atom that is not a halogen. Halide salts can include but are not limited to inorganic halide salts. The term "inorganic halide salt" means a salt of an inorganic cation and one or more halogen anions. Inorganic cations can be selected from alkali and/or alkaline earth metals. The term "alkali", as used herein, refers to the alkali metals of the Periodic Table (i.e. lithium, sodium, potassium, rubidium, cesium and francium.) The term "alkaline earth", as used herein, refers to the alkaline earth metals of the Periodic Table (i.e. beryllium, magnesium, calcium, strontium, barium and radium). The term "organic halide salt" means a salt of an organic cation and one or more halogen anions. Non-limiting examples of organic cations include, for example, ammonium, quaternary ammonium, and amine cations such as ammonium, tetramethylammonium, tetraethylammonium, methylammonium, dimethylammonium, trimethylammonium, triethylammonium and ethylammonium, and the like. The term "mineral acid", as used herein, refers to an acid derived from one or more inorganic compounds that dissociates to produce hydrogen ions (H⁺) in water. Non-limiting examples of mineral acids include, for example, hydriodic acid, hydrobromic acid, hydrochloric acid, perchloric acid, sulfuric acid, nitric acid, sulfurous acid, phosphoric acid, boric acid, and combinations thereof. The term "organic acid", as used herein, refers to an organic compound that is characterized by weak acidic properties and does not dissociate completely in the presence of water. Examples of organic acids include, but are not limited, carboxylic acids such as formic acid, acetic acid, trifluoroacetic acid, oxalic acid, propanoic acid, lactic acid, butyric acid, fumaric acid, malic acid, maleic acid, succinic acid, tartaric acid, sorbic acid, citric acid, benzoic acid, and combinations thereof. As used herein, the term "weight to volume ratio" refers to the weight of a reactant to a quantity of solvent used in a reaction. Unless otherwise specified, the units of weight to volume ratios are in grams (g) to milliliters (mL). For example, a 1:5 weight to volume ratio of a compound of Formula II to the solvent means 1 gram of a compound of Formula II to 5 mL of solvent. Embodiments of the present disclosure as described in the Summary include those described below. In the following Embodiments, reference to "a compound of Formula I" includes the definitions of substituents specified in the Summary unless further defined in the Embodiments. Embodiment 1. A method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I wherein R¹ is C(O)R³, halogen, cyano, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl or C₁-C₄ hydroxyalkyl. Embodiment 2. The method of Embodiment 1 wherein R¹ is C(O)R³, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ hydroxyalkyl. Embodiment 3. The method of Embodiment 1 wherein R¹ is C(O)R³, cyano, C₁-C₄ alkyl or C₁-C₄ hydroxyalkyl. Embodiment 3a. The method of Embodiment 3 wherein R¹ is C(O)R³, cyano, methyl or hydroxymethyl. Embodiment 3b. The method of Embodiment 1 wherein R¹ is C(O)R³. Embodiment 4. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein X¹ is Cl, Br, or I. Embodiment 5. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of Embodiments 1 through 3 wherein X¹ is Cl, Br or F. Embodiment 6. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein X¹ is Cl or Br. Embodiment 7. The method Embodiment 6 wherein X¹ is Cl. Embodiment 8. The method Embodiment 6 wherein X¹ is Br. Embodiment 9. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein R² is halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl. Embodiment 10. The method of Embodiment 9 wherein R² is halogen, cyano, methyl, ethyl or C₁-C₄ haloalkyl. Embodiment 11. The method of Embodiment 9 wherein R² is halogen, cyano, methyl, ethyl or CF₃. Embodiment 12. The method of Embodiment 9 wherein R² is F, Cl, Br, cyano, methyl, ethyl or CF₃. Embodiment 13. The method of Embodiment 9 wherein R² is F, Cl, Br, cyano or CF₃. Embodiment 14. The method of Embodiment 9 wherein R² is F, Cl or Br. Embodiment 15. The method of Embodiment 9 wherein R² is F. Embodiment 16. The method of Embodiment 9 wherein R² is Cl. Embodiment 17. The method of Embodiment 9 wherein R² is Br. Embodiment 18. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein each R^x is independently F, Cl, Br, cyano or CF₃. Embodiment 19. The method of Embodiment 18 wherein each R^x is independently F, Cl or Br. Embodiment 20. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein R³ is OH or C₁-C₄ alkoxy. Embodiment 20a. The method of Embodiment 20 wherein R³ is OH, OCH₃ or OCH₂CH₃. Embodiment 20b. The method of Embodiment 20 wherein R³ is OH or OCH₃. Embodiment 20c. The method of Embodiment 20 wherein R³ is OH. Embodiment 20d. The method of Embodiment 20 wherein R³ is OCH₃. Embodiment 21. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein R^z is hydrogen, F, Cl, Br, cyano, methyl or CF₃. Embodiment 22. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of Embodiments 1 through 20 wherein Z is N. Embodiment 23. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein k is 0, 1 or 2. Embodiment 24. The method of Embodiment 23 wherein k is 0 or 1. Embodiment 25. The method of Embodiment 23 wherein k is 0. Embodiment 26. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein X² is OS(O)_mR⁴, or a halogen other than X¹. Embodiment 26a. The method of Embodiment 26 wherein X² is Cl or OS(O)_mR⁴. Embodiment 27. The method of Embodiment 26 wherein X² is OS(O)_mR⁴. Embodiment 28. The method of Embodiment 26 wherein X² is a halogen other than X¹. Embodiment 29. The method of Embodiment 28 wherein X² is Cl. Embodiment 30. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of Embodiments 1 through 25 wherein X² is OP(O)_n(OR⁵)₂. Embodiment 31. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of Embodiments 1 through 27 wherein m is 2. Embodiment 32. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of Embodiments 1 through 27 wherein R⁴ is C₁-C₄ alkyl; or phenyl optionally substituted with from 1 to 3 substituents selected from C₁-C₄ alkyl and halogen. Embodiment 33. The method of Embodiment 32 wherein R⁴ is methyl or ethyl; or phenyl optionally substituted with from 1 to 3 substituents selected from methyl, ethyl and halogen. Embodiment 34. The method of Embodiment 32 wherein R⁴ is methyl or ethyl; or phenyl optionally substituted with 1 substituent selected from methyl, ethyl and halogen. Embodiment 35. The method of Embodiment 32 wherein R⁴ is methyl, ethyl, phenyl or 4-methylphenyl. Embodiment 35a. The method of Embodiment 32 wherein R⁴ is methyl, phenyl or 4-methylphenyl. Embodiment 35b. The method of Embodiment 35 wherein R⁴ is methyl. Embodiment 35c. The method of Embodiment 35 wherein R⁴ is phenyl or 4-methylphenyl. Embodiment 35d. The method of Embodiment 35 wherein R⁴ is phenyl. Embodiment 35e. The method of Embodiment 35 wherein R⁴ is 4-methylphenyl. Embodiment 36. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of Embodiments 1 through 25 wherein n is 1. Embodiment 37. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of Embodiments 1 through 25 wherein each R⁵ is independently C₁-C₄ alkyl; or phenyl optionally substituted with from 1 to 3 substituents selected from C₁-C₄ alkyl and halogen. Embodiment 38. The method of Embodiment 37 wherein R⁵ is methyl or ethyl; or phenyl optionally substituted with from 1 to 3 substituents selected from methyl, ethyl and halogen. Embodiment 39. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the halide salt is selected from an alkali halide, an alkaline-earth halide, an ammonium halide, a quaternary ammonium halide, and combinations thereof. Embodiment 40. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the halide salt is selected from an alkali halide, an alkaline-earth halide, and combinations thereof. Embodiment 41. The method of Embodiment 40 wherein the halide salt is selected from an alkali halide, and combinations thereof. Embodiment 42. The method of Embodiment 40 wherein the halide salt is selected from an alkaline-earth halide, and combinations thereof. Embodiment 43. The method of Embodiment 39 wherein the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. Embodiment 44. The method of Embodiment 39 wherein the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, and combinations thereof. Embodiment 45. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments 1 through 40 wherein the halide salt is selected from an alkali bromide, an alkaline-earth bromide, and combinations thereof. Embodiment 46. The method of Embodiment 45 wherein the halide salt is selected from lithium bromide, sodium bromide, potassium bromide, cesium bromide, magnesium bromide, calcium bromide, and combinations thereof. Embodiment 47. The method of Embodiment 45 wherein the halide salt is selected from an alkali bromide, and combinations thereof. Embodiment 47a. The method of Embodiment 45 wherein the halide salt is selected from lithium bromide, sodium bromide, potassium bromide, cesium bromide, and combinations thereof. Embodiment 47b. The method of Embodiment 45 wherein the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. Embodiment 47c. The method of Embodiment 45 wherein the halide salt is sodium bromide or potassium bromide. Embodiment 48. The method of Embodiment 45 wherein the halide salt is sodium bromide. Embodiment 49. The method of Embodiment 45 wherein the halide salt is potassium bromide. Embodiment 50. The method of Embodiment 45 wherein the halide salt is selected from an alkaline-earth bromide, and combinations thereof. Embodiment 50a. The method of Embodiment 45 wherein the halide salt is selected from magnesium bromide, calcium bromide, and combinations thereof. Embodiment 51. The method of Embodiment 39 wherein the halide salt is selected from an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. Embodiment 51a. The method of Embodiment 51 wherein the halide salt is selected from an alkali chloride, an alkaline-earth chloride, and combinations thereof. Embodiment 51b. The method of Embodiment 51 wherein the halide salt is selected from an alkali chloride, and combinations thereof. Embodiment 52. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the mineral acid is selected from hydriodic acid, hydrobromic acid, hydrochloric acid, perchloric acid, sulfuric acid, nitric acid, sulfurous acid, phosphoric acid, boric acid, and combinations thereof. Embodiment 53. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments 1 through 51 wherein the mineral acid is other than hydriodic acid, hydrobromic acid, hydrochloric acid, or hydrofluoric acid. Embodiment 53a. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments one through 51 wherein the mineral acid is other than hydrobromic acid or hydrochloric acid. Embodiment 53b. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments 1 through 51 wherein the mineral acid is other than hydrochloric acid. Embodiment 53c. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments 1 through 51 wherein the mineral acid is other than hydrobromic acid. Embodiment 54. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the mineral acid is selected from perchloric acid, sulfuric acid, nitric acid, sulfurous acid, phosphoric acid, boric acid, and combinations thereof. Embodiment 54a. The method of Embodiment 54 wherein the mineral acid is selected from perchloric acid, sulfuric acid, nitric acid, oxalic acid, sulfurous acid, and combinations thereof. Embodiment 54b. The method of Embodiment 54 wherein the mineral acid is perchloric acid, sulfuric acid, nitric acid, oxalic acid or sulfurous acid. Embodiment 54c. The method of Embodiment 54 wherein the mineral acid is sulfuric acid or nitric acid. Embodiment 54d. The method of Embodiment 54 wherein the mineral acid is sulfuric acid. Embodiment 55. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the solvent is selected from nitriles, esters, alcohols, amides, ketones, haloalkanes, ethers, aromatic hydrocarbons, water; and combinations thereof. Embodiment 55a. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the solvent is selected from dichloromethane, dichloroethane, dibromomethane, dibromoethane, ethyl acetate, acetonitrile, ethanol, methanol, N,N- dimethylformamide, ethyl lactate, water, propionitrile, methyl acetate, butyl acetate, acetone, methyl ethyl ketone (MEK), methyl butyl ketone, trichloromethane; ethyl ether, methyl tert-butyl ether, benzene, p-dioxane, toluene, chlorobenzene, dichlorobenzene and combinations thereof. Embodiment 55b. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the solvent is selected from dichloromethane, dichloroethane, dibromomethane, dibromoethane, ethyl acetate, acetonitrile, ethanol, methanol, N,N- dimethylformamide, ethyl lactate, water and combinations thereof. Embodiment 55c. The method of Embodiment 55 wherein the solvent is selected from dichloromethane, dichloroethane, dibromomethane, dibromoethane, ethyl acetate, acetonitrile, ethyl lactate, water and combinations thereof. Embodiment 55d. The method of Embodiment 55 wherein the solvent is dichloromethane, dichloroethane, ethyl acetate or ethyl lactate. Embodiment 55e. The method of Embodiment 55 wherein the solvent is dichloromethane, dichloroethane or ethyl acetate. Embodiment 55f. The method of Embodiment 55 wherein the solvent is ethyl acetate or ethyl lactate. Embodiment 55g. The method of Embodiment 55 wherein the solvent is ethyl acetate. Embodiment 55h. The method of Embodiment 55 wherein the solvent is dichloromethane. Embodiment 55i. The method of Embodiment 55 wherein the solvent is dichloroethane. Embodiment 56. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the organic acid is selected from a carboxylic acid and combinations thereof. Embodiment 56a. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the organic acid is selected from formic acid, acetic acid, trifluoroacetic acid, oxalic acid, propanoic acid, lactic acid, butyric acid, fumaric acid, malic acid, maleic acid, succinic acid, tartaric acid, sorbic acid, citric acid, benzoic acid, and combinations thereof. Embodiment 56b. The method of Embodiment 56a wherein the organic acid is formic acid, acetic acid or trifluoroacetic acid. Embodiment 56c. The method of Embodiment 56a wherein the organic acid is formic acid or acetic acid. Embodiment 56d. The method of Embodiment 56a wherein the organic acid is acetic acid. Embodiment M1. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the reacting is performed at a temperature above -10 ℃. Embodiment M1a. The method of Embodiment M1 wherein the reacting is performed at a temperature above 0 ℃. Embodiment M2. The method of Embodiment M1 wherein the reacting is performed at a temperature from about 0 ℃ to about 100 ℃. Embodiment M2a. The method of Embodiment M1 wherein the reacting is performed at a temperature from about 0 ℃ to about 60 ℃. Embodiment M3. The method of Embodiment M1 wherein the reacting is performed at a temperature from about 10 ℃ to about 50 ℃. Embodiment M3a. The method of Embodiment M1 wherein the reacting is performed at a temperature from about 10 ℃ to about 40 ℃. Embodiment M4. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the mole ratio of the halide salt to the compound of Formula II is at least 0.1:1.0. Embodiment M4a. The method of Embodiment M4 wherein the mole ratio of the halide salt to the compound of Formula II is from about 0.2:1 to about 20:1. Embodiment M4b. The method of Embodiment M4 wherein the mole ratio of the halide salt to the compound of Formula II is from about 0.5:1 to about 10:1. Embodiment M4c. The method of Embodiment M4 wherein the mole ratio of the halide salt to the compound of Formula II is from about 1:1 to about 6:1. Embodiment M4d. The method of Embodiment M4 wherein the mole ratio of the halide salt to the compound of Formula II is from about 1:1 to about 5:1. Embodiment M4e. The method of Embodiment M4 wherein the mole ratio of the halide salt to the compound of Formula II is from about 1:1 to about 4:1. Embodiment M4f. The method of Embodiment M4 wherein the mole ratio of the halide salt to the compound of Formula II is about 4:1. Embodiment M5. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the mole ratio of the mineral acid to the compound of Formula II is at least 0.1:1.0. Embodiment M5a. The method of Embodiment M5 wherein the mole ratio of the mineral acid to the compound of Formula II is from about 0.1:1.0 to about 20.0:1.0. Embodiment M5b. The method of Embodiment M5 wherein the mole ratio of the mineral acid to the compound of Formula II is from about 0.5:1 to about 12:1. Embodiment M5c. The method of Embodiment M5 wherein the mole ratio of the mineral acid to the compound of Formula II is from about 0.5:1 to about 6:1. Embodiment M5d. The method of Embodiment M5 wherein the mole ratio of the mineral acid to the compound of Formula II is from about 1:1 to about 6:1. Embodiment M5e. The method of Embodiment M5 wherein the mole ratio of the mineral acid to the compound of Formula II is from about 2:1 to about 4:1. Embodiment M5f. The method of Embodiment M5 wherein the mole ratio of the mineral acid to the compound of Formula II is about 3:1. Embodiment M6. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the mole ratio of the mineral acid to the halide salt to compound of Formula II is about 3:4:1. Embodiment M7. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the weight to volume ratio of the compound of Formula II to the solvent is from about 1:0.05 to about 1:500. Embodiment M7a. The method of Embodiment M7 wherein the weight to volume ratio of the compound of Formula II to the solvent is from about 1:0.5 to about 1:50. Embodiment M7b. The method of Embodiment M7 wherein the mole ratio of the weight to volume ratio of the compound of Formula II to the solvent is from about 1:0.75 to about 1:25. Embodiment M7c. The method of Embodiment M7 wherein the weight to volume ratio of the compound of Formula II to the solvent is from about 1:1 to about 1:15. Embodiment M7d. The method of Embodiment M7 wherein the weight to volume ratio of the compound of Formula II to the solvent is from about 1:1 to about 1:10. Embodiment M7e. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the weight to volume ratio of the compound of Formula II to the solvent is about 1:5. Embodiment P1. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the average particle size of the halide salt is less than 1000 µm. Embodiment P2. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 1000 µm. Embodiment P3. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 1000 µm. Embodiment P4. The method of Embodiment P1 wherein the average particle size of the halide salt is less than 500 µm. Embodiment P5. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 500 µm. Embodiment P6. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 500 µm. Embodiment P7. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 500 µm. Embodiment P8. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 500 µm. Embodiment P9. The method of Embodiment P1 wherein the average particle size of the halide salt is less than 389 µm. Embodiment P10. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 389 µm. Embodiment P11. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 389 µm. Embodiment P12. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 389 µm. Embodiment P13. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 389 µm. Embodiment P14. The method of Embodiment P1 wherein the average particle size of the halide salt is less than 300 µm. Embodiment P15. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 300 µm. Embodiment P16. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 300 µm. Embodiment P17. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 300 µm. Embodiment P18. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 300 µm. Embodiment P19. The method of Embodiment P1 wherein the average particle size of the halide salt is less than 250 µm. Embodiment P20. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 250 µm. Embodiment P21. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 250 µm. Embodiment P22. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 250 µm. Embodiment P23. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 250 µm. Embodiment P24. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 20.0 µm to about 250 µm. Embodiment P25. The method of Embodiment P1 wherein the average particle size of the halide salt is less than 200 µm. Embodiment P26. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 200 µm. Embodiment P27. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 200 µm. Embodiment P28. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 200 µm. Embodiment P29. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 200 µm. Embodiment P30. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 20.0 µm to about 200 µm. Embodiment P31. The method of Embodiment P1 wherein the average particle size of the halide salt is less than 150 µm. Embodiment P32. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 150 µm. Embodiment P33. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 150 µm. Embodiment P34. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 150 µm. Embodiment P35. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 150 µm. Embodiment P36. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 20.0 µm to about 150 µm. Embodiment P37. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the average particle size of the halide salt is less than 100 µm. Embodiment P38. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 0.1 µm to about 100 µm. Embodiment P39. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 1.0 µm to about 100 µm. Embodiment P40. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 5.0 µm to about 100 µm. Embodiment P41. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 10.0 µm to about 100 µm. Embodiment P42. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 20.0 µm to about 100 µm. Embodiment P43. The method of Embodiment P1 wherein the average particle size of the halide salt is from about 30.0 µm to about 100 µm. Embodiment P44. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the average particle size of the halide salt is less than 80 µm. Embodiment P45. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the average particle size of the halide salt is from about 30.0 µm to about 80 µm. Embodiment P46. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the average particle size of the halide salt is less than 75 µm. Embodiment P47. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the average particle size of the halide salt is from about 35.0 µm to about 75 µm. Embodiment S1. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any of the preceding Embodiments wherein the mineral acid is added last. Embodiment S2. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments 1 through P47 wherein the mineral acid is first reacted with the halide salt. Embodiment S3. The method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I or any one of the Embodiments 1 through P47 wherein the mineral acid is first reacted with a mixture consisting of the halide salt and the organic acid. Embodiment X1. The method as described in the Summary for preparing a compound of Formula IV wherein R^6A is F, Cl, Br, I, cyano, CH₃ or CF₃. Embodiment X2. The method of Embodiment X1 wherein R^6A is F, Cl, Br or CH₃. Embodiment X3. The method of Embodiment X1 wherein R^6A is Cl or CH₃. Embodiment X4. The method of Embodiment X1 wherein R^6A is CH₃. Embodiment X5. The method of any one of Embodiments X1 through X4 wherein R^6B is hydrogen, F, Cl or Br. Embodiment X6. The method of Embodiment X5 wherein R^6B is hydrogen, Cl or Br. Embodiment X7. The method of Embodiment X5 wherein R^6B is hydrogen or Cl. Embodiment X8. The method of Embodiment X5 wherein R^6B is hydrogen. Embodiment X9. The method of any one of Embodiments X1 through X8 wherein R^6C is F, Cl, Br, I, cyano, CH₃ or CF₃. Embodiment X10. The method of Embodiment X9 wherein R^6C is F, Cl, Br, I or cyano. Embodiment X11. The method of Embodiment X9 wherein R^6C is Cl, Br, I or cyano. Embodiment X12. The method of Embodiment X9 wherein R^6C Cl or cyano. Embodiment X13. The method of Embodiment X9 wherein R^6C Cl. Embodiment X14. The method of Embodiment X9 wherein R^6C cyano. Embodiment X15. The method of any one of Embodiments X1 through X14 wherein R^6D is hydrogen, F, Cl or Br. Embodiment X16. The method of Embodiment X15 wherein R^6D is hydrogen, Cl or Br. Embodiment X17. The method of Embodiment X15 wherein R^6D is hydrogen or Cl. Embodiment X18. The method of Embodiment X15 wherein R^6D is hydrogen. Embodiment X19. The method of any one of Embodiments X1 through X18 wherein R⁷ is C₁-C₄ alkyl, C₃-C₆ cycloalkyl, C₄-C₈ cycloalkylalkyl or C₅-C₈ alkylcycloalkyl. Embodiment X20. The method of Embodiment X19 wherein R⁷ is methyl, ethyl, isopropyl, cyclopropyl, cyclopropylmethyl or (1-methyl)cyclopropyl. Embodiment X21. The method of Embodiment X19 wherein R⁷ is methyl or ethyl. Embodiment X22. The method of Embodiment X19 wherein R⁷ is methyl. Embodiments of this disclosure, including Embodiments 1-X22 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formulae I, III and IV but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formulae I, III and IV. In addition, embodiments of this disclosure, including Embodiments 1-X22 above as well as any other embodiments described herein, and any combination thereof, pertain to the methods of the present disclosure. Combinations Embodiments 1-X22 are illustrated by: Embodiment A. A method as described in the Summary for preparing a 3-halo-4,5-dihydro- 1H-pyrazole compound of Formula I wherein m is 2; and n is 1. Embodiment A1. The method of Embodiment A wherein X¹ is Cl or Br; and X² is OS(O)_mR⁴, or a halogen other than X¹. Embodiment A1A. The method of Embodiment A or Embodiment A1 wherein R¹ is C(O)R³, cyano, methyl or hydroxymethyl; X¹ is Cl or Br; X² is OS(O)_mR⁴, or a halogen other than X¹; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. Embodiment A1B. The method of Embodiment A or Embodiment A1 wherein R¹ is C(O)R³, cyano, methyl or hydroxymethyl; X¹ is Cl or Br; X² is OS(O)_mR⁴, or a halogen other than X¹; k is 0 or 1; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. Embodiment A1C. The method of Embodiment A or Embodiment A1 wherein R¹ is C(O)R³, cyano, methyl or hydroxymethyl; X¹ is Cl or Br; X² is OS(O)_mR⁴, or a halogen other than X¹; k is 0 or 1; R⁴ is methyl or ethyl; or phenyl optionally substituted with 1 substituent selected from methyl, ethyl and halogen; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. Embodiment A2. The method of anyone of Embodiments A through A1C wherein R¹ is C(O)R³; R² is halogen; alkoxy;

R⁴ is methyl, ethyl, phenyl or 4-methylphenyl. Embodiment A3. The method of anyone of Embodiments A through A2 wherein R² is Cl or Br; and R³ is OH, OCH₃ or OCH₂CH₃. Embodiment A3A. The method of anyone of Embodiments A through A3 wherein R² is Cl; and R³ is OH, OCH₃ or OCH₂CH₃. Embodiment A4. The method of anyone of Embodiments A through A3 wherein R² is Cl; X¹ is Br; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, and combinations thereof. Embodiment A4A. The method of anyone of Embodiments A through A4 wherein R² is Cl; X¹ is Br; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, and combinations thereof. Embodiment A5. The method of anyone of Embodiments A through A4 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OH, OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴, or Cl; m is 1; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. Embodiment A5A. The method of Embodiment A5 wherein R³ is OCH₃ or OCH₂CH₃; and X² is OS(O)_mR⁴. Embodiment A5B. The method of Embodiment A5 or Embodiment A5A wherein R⁴ is 4-methylphenyl. Embodiment A5C. The method of anyone of Embodiments A5 through A5B wherein the mineral acid is perchloric acid, sulfuric acid, nitric acid, oxalic acid or sulfurous acid; and the optional organic acid is formic acid or acetic acid. Embodiment A5D. The method of anyone of Embodiments A5 through A5C wherein the halide salt is sodium bromide or potassium bromide. Embodiment A6. The method of anyone of Embodiments A through A5 wherein R¹ is C(O)R³; X¹ is Br; R² is Cl; Z is N; R³ is OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴; m is 1; R⁴ is 4-methylphenyl; the halide salt is sodium bromide or potassium bromide; the mineral acid is sulfuric acid; and the optional organic acid is formic acid or acetic acid. Embodiment A6A. The method of Embodiment A6 wherein the organic acid is acetic acid. Embodiment A7. The method of anyone of Embodiments A through A6A wherein the solvent is dichloromethane, dichloroethane or ethyl acetate. Embodiment A8. The method of anyone of Embodiments A through A6A wherein the solvent is ethyl acetate. Embodiment A9. The method of anyone of Embodiments A through A6A wherein the solvent is dichloromethane. Embodiment A10. The method of anyone of Embodiments A through A6A wherein the solvent is dichloroethane. Embodiment B. A method as described in the Summary for preparing a compound of Formula III wherein R¹ is C(O)R³; X¹ is Cl or Br; R² is halogen; Z is N; R³ is OH or C₁-C₄ alkoxy; k is 0; X² is OS(O)_mR⁴, or a halogen other than X¹; m is 2; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. Embodiment B1. A method of Embodiment B wherein X¹ is Br; R² is Cl; R³ is OH OCH₃ or OCH₂CH₃; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, and combinations thereof. Embodiment B2. A method of Embodiment B or Embodiment B1 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OH, OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴, or Cl; m is 1; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. Embodiment B2A. The method of Embodiment B2 wherein R³ is OCH₃ or OCH₂CH₃; and X² is OS(O)_mR⁴. Embodiment B2B. The method of Embodiment B2 or Embodiment B2A wherein R⁴ is 4-methylphenyl. Embodiment B2C. The method of anyone of Embodiments B2 through B2B wherein the mineral acid is perchloric acid, sulfuric acid, nitric acid, oxalic acid or sulfurous acid; and the optional organic acid is formic acid or acetic acid. Embodiment B2D. The method of anyone of Embodiments B2 through B2C wherein the halide salt is sodium bromide or potassium bromide. Embodiment B3. The method of anyone of Embodiments B through B2 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴; m is 1; R⁴ is 4-methylphenyl; the halide salt is sodium bromide or potassium bromide; the mineral acid is sulfuric acid; and the optional organic acid is formic acid or acetic acid. Embodiment B3A. The method of Embodiment B3 wherein the organic acid is acetic acid. Embodiment C. A method as described in the Summary for preparing a compound of Formula IV wherein R^6A is F, Cl, Br or CH₃; R^6B is hydrogen, F, Cl or Br; R^6C is F, Cl, Br, I or cyano; and R^6D is hydrogen, F, Cl or Br. Embodiment C1. A method of Embodiment C wherein R¹ is C(O)R³; X¹ is Cl or Br; R² is halogen; Z is N; R³ is OH or C₁-C₄ alkoxy; k is 0; X² is OS(O)_mR⁴, or a halogen other than X¹; m is 2; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof.; and R⁷ is methyl, ethyl, isopropyl, cyclopropyl, cyclopropylmethyl or (1-methyl)cyclopropyl. Embodiment C2. A method of anyone of Embodiments C through CA1 wherein X¹ is Br; R² is Cl; R³ is OH, OCH₃ or OCH₂CH₃; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, and combinations thereof. Embodiment C2A. The method of Embodiment C1 or C2 wherein R^6B is hydrogen or Cl; and R^6D is hydrogen or Cl. Embodiment C3. A method of anyone of Embodiments C through C2 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OH, OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴, or Cl; m is 1; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. Embodiment C3A. The method of Embodiment C3 wherein R³ is OCH₃ or OCH₂CH₃; and X² is OS(O)_mR⁴. Embodiment C3B. The method of Embodiment C3 or Embodiment C3A wherein R⁴ is 4-methylphenyl. Embodiment C3C. The method of anyone of Embodiments C3 through C3B wherein the mineral acid is perchloric acid, sulfuric acid, nitric acid, oxalic acid or sulfurous acid; and the optional organic acid is formic acid or acetic acid. Embodiment C3D. The method of anyone of Embodiments C3 through C3C wherein the halide salt is sodium bromide or potassium bromide. Embodiment C3E. The method of anyone of Embodiments C3 through C3D wherein R^6A is Cl, or CH₃; R^6B is hydrogen or Cl; R^6C is Cl, Br, I or cyano; and R^6D is hydrogen or Cl. Embodiment C4. The method of anyone of Embodiments C through C3 wherein R¹ is C(O)R³; X¹ is Br; R² is Cl; Z is N; R³ is OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴; m is 1; R⁴ is 4-methylphenyl; the halide salt is sodium bromide or potassium bromide; the mineral acid is sulfuric acid; and the optional organic acid is formic acid or acetic acid. Embodiment C4A. The method of Embodiment C4 wherein R^6A is CH₃; R^6B is hydrogen; R^6C is Cl or cyano; and R^6D is hydrogen. Embodiment C4B. The method of Embodiment C4 or Embodiment C4A wherein the organic acid is acetic acid. Compounds of Formula I can be prepared by one or more of the following methods and variations as described in Scheme 1. The definitions of substituents in the compounds of Formulae I–IV are as defined above in the Summary unless otherwise noted. Compounds of Formula Ia is a subset of the compounds of Formula I. Compounds of Formula IIa is a subset of the compounds of Formula II. Substituents for each subset formula are as defined for its parent formula unless otherwise noted. Ambient or room temperature is defined as about 20-25 °C. As shown in Scheme 1, according to a method of this disclosure a 4,5-dihydro-1H- pyrazole of Formula II is contacted with a halide salt and a mineral acid to form a different 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I, wherein the halogen of the halide salt is X¹. The definitions of X¹, X², R¹, R², Z, R^x and k are as defined in the Summary and description of Embodiments unless otherwise indicated. Scheme 1

The reaction is typically conducted in a suitable solvent, however, in some cases the reaction can be carried out without solvent other than the compound of Formula II, the halide salt, the mineral acid, and the optional organic acid. For best results the solvent should be non-nucleophilic, relatively inert to the reagents, and capable of dissolving the compound of Formula II. A variety of solvents can be used to form the suitable solvent for this method. In suitable solvents, the compound of Formula II is preferably completely or at least substantially (e.g., at least about 10%) soluble in the volume of solvent used. Examples of suitable solvents for this method include nitriles such as acetonitrile and propionitrile; esters such as methyl acetate, ethyl acetate, ethyl lactate and butyl acetate; alcohols such as ethanol and methanol; amides such as N,N-dimethylformamide; haloalkanes such as dichloromethane, dichloroethane, dibromomethane, dibromoethane and trichloromethane; ethers such as tetrahydrofuran (THF); water; and mixtures of the foregoing. Solvents of note include dichloromethane, dichloroethane, dibromomethane, dibromoethane and ethyl acetate. The total volume of the solvent used in the method of Scheme 1 is preferably between about 1 mL/g and about 10 mL/g relative to the weight of the compound of Formula II. The solvent can be added in various ways and times during the course of the reaction, such as, in one batch at the start of the reaction sequence, portion-wise during the reaction sequence or intermittently during the course of adding one or more reagents. For example, one or more reagents can be dispersed, dissolved or partially dissolved in the suitable solvent and then added to the reaction mixture, which comprises one or more reagents and the suitable solvent. Regardless of the order of addition, the total amount of reagents added during the course of the reaction is as described herein and in the Embodiments. In one embodiment the order of addition includes first forming a slurry of the halide salt with the optional organic acid, then adding the mineral acid to the slurry, and then adding the compound of Formula II in the suitable solvent to the mixture comprising the halide salt, the mineral acid, and the optional organic acid. This order of addition is illustrated in Examples 1-5. In another embodiment the order of addition includes first forming a mixture of the compound of Formula II in the suitable solvent, optionally adding the organic acid, then adding the halide salt followed by the mineral acid. This order of addition is illustrated in Examples 6-18. The reaction is typically conducted between about 10 and 50 °C, most conveniently between about 10 and 40 °C, and most preferably near ambient temperature (e.g., about 20- 25 °C). The reaction times are typically less than 72 h. In the method of Scheme 1, the halide salt is typically an alkali halide or alkaline-earth halide, preferably an alkali halide, more preferably a potassium halide or sodium halide, and most preferably potassium bromide or sodium bromide. As the halide anion provided by the halide salt becomes X¹ of Formula I, the stoichiometry of the reaction requires at least one molar equivalent of the halide anion relative to the sum of the number of moles of the compound of Formula II. Typically the molar ratio of the halide salt relative to the compound of Formula II is from about 1:1 to about 6:1. Although higher levels of halide salt can be used there is no particular advantage in doing so and higher levels increase raw material and waste processing costs. The highest product yields were usually achieved with molar ratios of sodium bromide of about 4:1 relative to the compound of Formula II. One skilled in the art will appreciate that an increased solid reagent surface area can exhibit beneficial effects (e.g. increased reactivity, improved yields, decreased reaction times and decreased reagent molar ratios). In one embodiment the halide salt particle size may be reduced to improve the yield of the compound of Formula I. Typically higher product yields were achieved with an average halide salt particle size (i.e. Dv(50) value) of less than 100 µm. Typically the molar ratio of the mineral acid relative to the compound of Formula II is from about 0.5:1 to about 12:1. Although other levels of mineral acid can be used there is no particular advantage in doing so. The highest product yields were usually achieved with molar ratios of sulfuric acid of about 3:1 relative to the compound of Formula II. The addition of an optional organic acid in the process can also influence the optimal ratios of the present process. For Example, with the addition of acetic acid the most favorable reaction rates providing the highest yields of compounds of Formula I, were typically obtained with lower ratios of the halide salt and the mineral acid relative to the compound of Formula II than without the addition of acetic acid (i.e. with acetic acid present the halide salt and mineral acid ratios relative to the compound of Formula II were both preferred to be about 2:1). The product of Formula I can be isolated by standard techniques known in the art, including pH adjustment, extraction, evaporation, crystallization, and chromatography. For example, the reaction medium can be diluted with about 10 to 75 parts by weight of water relative to the starting compound of Formula II, the pH can be optionally adjusted with either acid or base to optimize the removal of either acidic or basic impurities, the water phase can be optionally separated, and most of the solvent can be removed by distillation or evaporation at reduced pressure. Typically acidic impurities in the reactions of this disclosure are removed by using a saturated aqueous solution of sodium bicarbonate or a 10% aqueous solution of sodium hydroxide. Although solvents can be removed from the compounds of Formula I by such methods as evaporation or distillation of the solvent at reduced pressure, typically concentration and purification of the Formula I compound is not necessary. The solvents used to prepare the compounds of Formula I are generally compatible with the method of the present invention to prepare the compounds of Formula III, and therefore the method of the present invention works well starting with compositions of compounds of Formula I wherein the concentration of the Formula I compound is less than 100%. Therefore a composition of Formula I compound useful for the method of the present invention to prepare the compounds of Formula III typically also comprises a solvent, particularly a solvent used to prepare the Formula I compound. Typical solvents include dichloromethane, dichloroethane or ethyl acetate. Typically the composition comprises about 20 to 99% of Formula I compound on a weight basis. 4,5-dihydro-1H-pyrazoles of Formula II can be prepared by a wide variety of methods known in the art, see for example, WO 2004/011453 A2, as well as references cited within. Depending on the reaction conditions and the means of isolation, an ester function on the compound of Formula Ia, wherein R³ is C₁-C₄ alkoxy, may be hydrolyzed to carboxylic acid, wherein R³ is OH. For example, the presence of water in the reaction mixture can promote such a hydrolysis. If the carboxylic acid is formed, it can be converted back to an ester (i.e., -C(=O)R³, wherein R³ is C₁–C₄ alkoxy) using esterification methods well-known in the art. The desired product, a compound of Formula 1a, can be isolated by methods known to those skilled in the art, such as crystallization, extraction or distillation. It is recognized that some reagents and reaction conditions described above for preparing compounds of Formulae I, III and IV may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after introduction of the reagents depicted in the individual schemes, additional routine synthetic steps not described in detail may be needed to complete the synthesis of compounds of Formulae I, III and IV. One skilled in the art will also recognize that compounds of Formulae I, II, III, and IV described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents. For example, compounds of Formula I may contain cyano groups, which can be converted to carboxylic acids via hydrolysis conditions. Likewise, alcohol, aldehyde and alkyl groups can be oxidized to provide carboxylic acid compounds of Formula Ia, wherein R³ is OH. These types of reactions are well documented in the literature; see, for example, March and Smith, March’s Advanced Organic Chemistry, 5^th ed., John Wiley & Sons, Inc., New York, 2001, and references cited within. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present disclosure to its fullest extent. The following examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other examples or steps. Ambient or room temperature is defined as about 20–25 °C. Percentages are by weight except where otherwise indicated. All patents and publications cited herein are fully incorporated by reference in their entirety. ¹H NMR spectra are reported in ppm downfield from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "q" means quartet, "m" means multiplet, and "dd" means doublet of doublets. As can be observed in Examples 9 through 18, as the halide salt particle size is decreased in comparable examples, the yield of the compound of Formula I improves. Particle size distribution data were determined for Dv50, Dv10 and Dv90, using a Malvern Mastersizer MS3000. Dv50 Particle size distribution data of the halide salt samples used in Examples 9 through 18 is shown in Table A. Samples were ground using a Retsch MM400 Mixer Mill. The abbreviation “rpm.” stands for revolutions per minute. Dv50 values indicate the particle size, wherein 50% of the sample contains particles that size or smaller. Dv10 values indicate the particle size, wherein 10% of the sample contains particles that size or smaller. Dv90 values indicate the particle size, wherein 90% of the sample contains particles that size or smaller. Table A Halide Salt Sample Description Dv(50) NaBr (Unground) 389 µm 20 g NaBr (10 g in each holder) ground for 1.5 h at 1200 rpm followed by 2 h at 1800 rpm. 73 µm 20 g NaBr (10 g in each holder) ground for 1.5 h at 1200 rpm followed by 4 h at 1800 rpm. 40 µm EXAMPLE 1 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:2:2:73 ratio of the compound of Formula II to halide salt to mineral acid to organic acid To a slurry of sodium bromide (1.51 g, 14.64 mmol) in acetic acid (30.5 mL) was added sulfuric acid (1.43 g, 14.64 mmol) over a period of 15 min. The reaction mixture was stirred at ambient temperature for 30 min. Ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3- [(phenylsulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloromethane (25 mL) was added to the reaction mixture and stirred at ambient for 24 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 222.53 g, 556.32 mmol) at 15 °C. The organic layer was separated and concentrated in vacuo to afford the title compound as a brown oil (2.21 g, 91% Yield). ¹H NMR (CDCl₃, 400 MHz,) δ 8.07 (dd, J=4.8, 1.5 Hz, 1H), 7.65 (dd, J=7.9, 1.5 Hz, 1H), 6.86 (dd, J=7.9, 4.8 Hz, 1H), 5.25 (dd, J=11.9, 9.1 Hz, 1H), 4.19 (q, J=7.1 Hz, 2H), 3.43 (dd, J=17.4, 11.9 Hz, 1H), 3.23 (dd, J=17.4, 9.1 Hz, 1H), 1.19 (t, J=7.1 Hz, 3H). EXAMPLE 2 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate in ClCH₂CH₂Cl To a slurry of sodium bromide (1.51 g, 14.64 mmol) in acetic acid (30.5 mL) was added sulfuric acid (1.43 g, 14.64 mmol) over a period of 15 min. The reaction mixture was stirred at ambient temperature for 30 min. Ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3- [(phenylsulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloroethane (25 mL) was added to the reaction mixture and stirred at ambient for 24 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 222.53 g, 556.32 mmol) at 15 °C. The organic layer was separated and concentrated in vacuo to afford the title compound as a brown oil (2.20 g, 90% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 3 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:2:2:6 ratio of the compound of Formula II to halide salt to mineral acid to organic acid To a slurry of sodium bromide (0.15 g, 1.46 mmol) in acetic acid (0.25 mL) was added sulfuric acid (0.14 g, 1.46 mmol) dropwise and stirred at ambient temperature for 30 min. Ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)oxy]-1H-pyrazole-5- carboxylate (PCT Patent Publication WO 2004/011453) (0.3 g, 0.73 mmol) in dichloromethane (3 mL) was added to the reaction mixture and stirred at ambient for 3 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 2.93 g, 7.32 mmol) at 15 °C. The organic layer was separated and concentrated in vacuo to afford the title compound as a brown oil (0.08 g, 33% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 4 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:2:2:17 ratio of the compound of Formula II to halide salt to mineral acid to organic acid To a slurry of sodium bromide (0.15 g, 1.46 mmol) in acetic acid (0.71 mL) was added sulfuric acid (0.14 g, 1.46 mmol) dropwise and stirred at ambient temperature for 30 min. Ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)oxy]-1H-pyrazole-5- carboxylate (PCT Patent Publication WO 2004/011453) (0.3 g, 0.73 mmol) in dichloromethane (3 mL) was added to the reaction mixture and stirred at ambient for 3 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 5.85 g, 14.64 mmol) at 15 °C. The organic layer was separated and concentrated in vacuo to afford the title compound as a brown oil (0.19 g, 78% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 5 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:2:2:36 ratio of the compound of Formula II to halide salt to mineral acid to organic acid To a slurry of sodium bromide (0.15 g, 1.46 mmol) in acetic acid (1.5 mL) was added sulfuric acid (0.14 g, 1.46 mmol) dropwise and stirred at ambient temperature for 30 min. Ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)oxy]-1H-pyrazole-5- carboxylate (PCT Patent Publication WO 2004/011453) (0.3 g, 0.73 mmol) in dichloromethane (3 mL) was added to the reaction mixture and stirred at ambient for 3 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 10.83 g, 27.08 mmol) at 15 °C. The organic layer was separated and concentrated in vacuo to afford the title compound as a brown oil (0.19 g, 78% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 6 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:4:3.1 ratio of the compound of Formula II to halide salt to mineral acid To a solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)- oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) was added sodium bromide (3.01 g, 29.28 mmol) followed by the addition of sulfuric acid (2.20 g, 22.40 mmol) over a period of 5 min. The mixture was stirred at 20 °C for 30 min. To the resultant mixture was added a saturated aqueous solution of sodium bicarbonate (170 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford the title compound as a brown oil (2.27 g, 90% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 7 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:3:3.1 ratio of the compound of Formula II to halide salt to mineral acid To a solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)- oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) was added sodium bromide (2.26 g, 21.96 mmol) followed by the addition of sulfuric acid (2.20 g, 22.40 mmol) in one portion. The mixture was stirred at 20 °C for 15 h. To the resultant mixture was added a saturated aqueous solution of sodium bicarbonate (170 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford the title compound as a brown oil (2.11 g, 87% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 8 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:2:12 ratio of the compound of Formula II to halide salt to mineral acid To a solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)- oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) was added sodium bromide (1.51 g, 14.64 mmol) followed by the addition of sulfuric acid (8.61 g, 87.84 mmol) in one portion. The mixture was stirred at 20 °C for 24 h. To the resultant mixture was added a saturated aqueous solution of sodium bicarbonate (170 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford the title compound as a brown oil (2.05 g, 84% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 9 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:1.6:2:3.9 ratio of the compound of Formula II to halide salt (Dv50 = 389 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloromethane (7 mL) at 20 °C was added acetic acid (1.62 mL, 28.3 mmol) followed by sodium bromide (Dv50 = 389 µm) (1.21 g, 11.71 mmol). The mixture was cooled to 0 °C. Concentrated sulfuric acid (1.43 g, 14.64 mmol) was added to the mixture over a period of 5 min. The mixture was stirred at 0 °C for 1 h, heated to 20 °C, stirred at 20 °C for 5 h and then cooled to 0 °C. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 10 g, 25 mmol). The layers were separated, and the aqueous layer was extracted with methylene chloride (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a brown oil (0.47 g, 19% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 10 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:4:3.1:0 ratio of the compound of Formula II to halide salt (Dv50 = 389 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) at 20 °C was added sodium bromide (Dv50 = 389 µm) (3.01 g, 29.28 mmol) followed by the addition of concentrated sulfuric acid (2.20 g, 22.40 mmol) over a period of 5 min. The mixture was stirred at 20 °C for 6 h. To the resultant mixture was slowly added a saturated aqueous solution of sodium bicarbonate (50 mL) over a period of 15 min. The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (0.63 g, 26% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 11 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:1.6:2:3.9 ratio of the compound of Formula II to halide salt (Dv50 = 73 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloromethane (7 mL) at 20 °C was added acetic acid (1.62 mL, 28.3 mmol) followed by sodium bromide (Dv50 = 73 µm) (1.21 g, 11.71 mmol). Concentrated sulfuric acid (1.43 g, 14.64 mmol) was added to the mixture over a period of 5 min. The mixture was stirred at 20 °C for 6 h and then cooled to 0 °C. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 10 g, 25 mmol). The layers were separated, and the aqueous layer was extracted with methylene chloride (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (0.77 g, 32% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 12 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:4:3.1:0 ratio of the compound of Formula II to halide salt (Dv50 = 73 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) at 20 °C was added sodium bromide (Dv50 = 73 µm) (3.01 g, 29.28 mmol) followed by the addition of concentrated sulfuric acid (2.20 g, 22.40 mmol) over a period of 5 min. The mixture was stirred at 20 °C for 6 h. To the resultant mixture was slowly added a saturated aqueous solution of sodium bicarbonate (50 mL) over a period of 15 min. The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (1.74 g, 71% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 13 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:1.6:2:3.9 ratio of the compound of Formula II to halide salt (Dv50 = 73 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloromethane (7 mL) at 20 °C was added acetic acid (1.62 mL, 28.3 mmol) followed by sodium bromide (Dv50 = 73 µm) (1.21 g, 11.71 mmol). The mixture was cooled to 0 °C. Concentrated sulfuric acid (1.43 g, 14.64 mmol) was added to the mixture over a period of 5 min. The mixture was stirred at 0 °C for 1 h, heated to 20 °C and stirred at 20 °C for 5 h. The mixture was cooled to 0 °C and stirred 17 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 10 g, 25 mmol). The layers were separated, and the aqueous layer was extracted with methylene chloride (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (0.81 g, 33% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 14 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:4:3.1:0 ratio of the compound of Formula II to halide salt (Dv50 = 73 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) at 20 °C was added sodium bromide (Dv50 = 73 µm) (3.01 g, 29.28 mmol) followed by the addition of concentrated sulfuric acid (2.20 g, 22.40 mmol) over a period of 5 min. The mixture was stirred at 20 °C for 23 h. To the resultant mixture was slowly added a saturated aqueous solution of sodium bicarbonate (50 mL) over a period of 15 min. The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (2.0 g, 82% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 15 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:1.6:2:3.9 ratio of the compound of Formula II to halide salt (Dv50 = 40 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloromethane (7 mL) at 20 °C was added acetic acid (1.62 mL, 28.3 mmol) followed by sodium bromide (Dv50 = 40 µm) (1.21 g, 11.71 mmol). The mixture was cooled to 0 °C. Concentrated sulfuric acid (1.43 g, 14.64 mmol) was added to the mixture over a period of 5 min. The mixture was stirred at 0 °C for 1 h, heated to 20 °C and stirred at 20 °C for 5 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 10 g, 25 mmol). The layers were separated, and the aqueous layer was extracted with methylene chloride (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (0.85 g, 35% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 16 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:4:3.1:0 ratio of the compound of Formula II to halide salt (Dv50 = 40 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) at 20 °C was added sodium bromide (Dv50 = 40 µm) (3.01 g, 29.28 mmol) followed by the addition of concentrated sulfuric acid (2.20 g, 22.40 mmol) over a period of 5 min. The mixture was stirred at 20 °C for 6 h. To the resultant mixture was slowly added a saturated aqueous solution of sodium bicarbonate (50 mL) over a period of 15 min. The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (1.76 g, 72% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 17 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:1.6:2:3.9 ratio of the compound of Formula II to halide salt (Dv50 = 40 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in dichloromethane (7 mL) at 20 °C was added acetic acid (1.62 mL, 28.3 mmol) followed by sodium bromide (Dv50 = 40 µm) (1.21 g, 11.71 mmol). The mixture was cooled to 0 °C. Concentrated sulfuric acid (1.43 g, 14.64 mmol) was added to the mixture over a period of 5 min. The mixture was stirred at 0 °C for 1 h, heated to 20 °C and stirred at 20 °C for 5 h. The mixture was cooled to 0 °C and stirred 17 h. To the resultant mixture was added sodium hydroxide (10% aqueous solution, 10 g, 25 mmol). The layers were separated, and the aqueous layer was extracted with methylene chloride (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (0.99 g, 41% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. EXAMPLE 18 Preparation of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole- 5-carboxylate using a 1:4:3.1:0 ratio of the compound of Formula II to halide salt (Dv50 = 40 µm) to mineral acid to organic acid To a stirred solution of ethyl-1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenyl- sulfonyl)oxy]-1H-pyrazole-5-carboxylate (PCT Patent Publication WO 2004/011453) (3.0 g, 7.32 mmol) in ethyl acetate (15 mL) at 20 °C was added sodium bromide (Dv50 = 40 µm) (3.01 g, 29.28 mmol) followed by the addition of concentrated sulfuric acid (2.20 g, 22.40 mmol) over a period of 5 min. The mixture was stirred at 20 °C for 23 h. To the resultant mixture was slowly added a saturated aqueous solution of sodium bicarbonate (50 mL) over a period of 15 min. The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 x 30 mL). The organic extracts were combined, dried over magnesium sulfate, filtered, and purified by silica gel chromatography (eluting with 20% ethyl acetate in hexanes) to provide the title compound as a pale yellow oil (2.03 g, 84% Yield). The ¹H NMR spectrum of the product was the same as reported for the product of Example 1. By the procedures described herein together with methods known in the art, the compounds of Formula II can be converted to compounds of Formula I as illustrated for Formulae Ia and IIa in Table 1. The following abbreviations are used in the Table: Me is methyl, Et is ethyl, n-Pr is n-propyl, i-Pr is isopropyl, t-Bu is tertiary butyl and Ph is phenyl. TABLE 1

X¹ _{is Br; X} ² _{is OS(O)2Ph; k is 0} Z is N Z is CH Z is CCl Z is CBr R² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ Cl H Br H Cl H Br H Cl H Br H Cl H Br H Cl Me Br Me Cl Me Br Me Cl Me Br Me Cl Me Br Me Cl Et Br Et Cl Et Br Et Cl Et Br Et Cl Et Br Et Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu X¹ _{is Br; X} ² _{is OS(O)2Ph-4-Me; k is 0} Z is N Z is CH Z is CCl Z is CBr R² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ Cl H Br H Cl H Br H Cl H Br H Cl H Br H Cl Me Br Me Cl Me Br Me Cl Me Br Me Cl Me Br Me Cl Et Br Et Cl Et Br Et Cl Et Br Et Cl Et Br Et Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu _X ¹ _{is Br; X} ² _{is OS(O)2Me; k is 0} Z is N Z is CH Z is CCl Z is CBr _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ Cl H Br H Cl H Br H Cl H Br H Cl H Br H Cl Me Br Me Cl Me Br Me Cl Me Br Me Cl Me Br Me Cl Et Br Et Cl Et Br Et Cl Et Br Et Cl Et Br Et Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl n-Pr Br n-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl i-Pr Br i-Pr Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl n-Bu Br n-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl i-Bu Br i-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl s-Bu Br s-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu

X¹ _{is Cl; X} ² _{is OS(O)2Ph-4-Me; k is 0} Z Z is Z is Z is _R ² _R ³ _R ³ _R ³ _R ² _R ³ _R ³ _R ³ Cl H H H Cl H H H Cl Me Me Me Cl Me Me Me Cl Et Et Et Cl Et Et Et Cl n-Pr n-Pr n-Pr Cl n-Pr n-Pr n-Pr Cl i-Pr i-Pr i-Pr Cl i-Pr i-Pr i-Pr Cl n-Bu n-Bu n-Bu Cl n-Bu n-Bu n-Bu Cl i-Bu i-Bu i-Bu Cl i-Bu i-Bu i-Bu Cl s-Bu

s-Bu

s-Bu Cl s-Bu

s-Bu

s-Bu _X ¹ _{is Cl; X} ² _{is OS(O)2Ph-4-Me; k is 0} Z is N Z is CH Z is CCl Z is CBr R² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ _R ² _R ³ Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu Cl t-Bu Br t-Bu X¹ _{is Br; k is 0} _R ² _R ³ _{Z X} ² _R ² _R ³ _{Z X} ² ^{Cl H N OS(O)} ₂ ^{Et Cl H N OS(O)} ₂ ^CF ₃ B^{r Me CH OS(O)Me Br Me CH OS(O)} ₂ ^-n-Bu ^{Cl Et N OP(O)(OMe)} ₂ ^{Cl Et N OP(O)(O-i-Pr)} ₂ B^{r n-Pr CH OP(OMe)} ₂ ^{Br n-Pr CH OS(O)} ₂ ^{Ph-2,4,6-tri-Me} ^{Cl i-Pr N OP(O)(OEt)} ₂ ^{Cl i-Pr N OP(O)(OPh-4-Me)} ₂ B^{r n-Bu CH OP(O)(OPh)} ₂ ^{Br n-Bu CH OS(O)} ₂ ^Ph-4-Cl The 3-halo-4,5-dihydro-1H-pyrazole preparation method of the present invention can be used to prepare a wide variety of compounds of Formula I that are useful as intermediates for the preparation of crop protection agents. In another aspect of the present invention compounds of the Formula I prepared by the method of Scheme 1 are useful as intermediates for preparing compounds of Formula III and Formula IV. Compounds of Formula IV are useful as insecticides, as previously disclosed in WO 2003/015518 and WO 2006/055922. Compounds of Formula IV can be prepared from compounds of Formula III and in turn from compounds of Formula II and I by a variety of processes previously disclosed in WO 2003/016283, WO 2004/067528, WO 2004/087689 and WO 2006/062978.

Claims

CLAIMS What is claimed is: 1. A method for preparing a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I

wherein R¹ is C(O)R³, halogen, cyano, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl or C₁-C₄ hydroxyalkyl; X¹ is a halogen; R² is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; each R^x is independently halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; Z is N or CR^z; R³ is H, OH, C₁-C₄ alkyl or C₁-C₄ alkoxy; R^z is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; and k is 0, 1, 2 or 3; the method comprising: reacting (1) a 4,5-dihydro-1H-pyrazole compound of Formula II

wherein X² is OS(O)_mR⁴, OP(O)_n(OR⁵)₂ or a halogen other than X¹; m is 1 or 2; n is 0 or 1; R⁴ is C₁-C₄ alkyl or C₁-C₄ haloalkyl; or phenyl optionally substituted with from 1 to 3 substituents selected from C₁-C₄ alkyl and halogen; and each R⁵ is independently C₁-C₄ alkyl or C₁-C₄ haloalkyl; or phenyl optionally substituted with from 1 to 3 substituents selected from C₁-C₄ alkyl and halogen; with (2) a halide salt wherein the halogen of the halide salt is X¹, and (3) a mineral acid to form the compound of Formula I, in the presence of a suitable solvent, and optionally in the presence of an organic acid. 2. The method of Claim 1 wherein m is 2 and n is 1. 3. The method of Claim 2 wherein X¹ is Cl or Br; and X² is OS(O)_mR⁴, or a halogen other than X¹. 4. The method of Claim 3 wherein R¹ is C(O)R³; R² is halogen; Z is N; R³ is OH or C₁-C₄ alkoxy; k is 0; and R⁴ is methyl, ethyl, phenyl or 4-methylphenyl. 5. The method of Claim 4 wherein R² is Cl or Br; and R³ is OH, OCH₃ or OCH₂CH₃. 6. The method of Claim 5 wherein R² is Cl; X¹ is Br; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, and combinations thereof. 7. The method of Claim 1 wherein R¹ is C(O)R³; X¹ is Br; R² is Cl; Z is N; R³ is OH, OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴, or Cl; m is 1; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. 8. The method of Claim 1 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴; m is 1; R⁴ is 4-methylphenyl; the halide salt is sodium bromide or potassium bromide; the mineral acid is sulfuric acid; and the optional organic acid is formic acid or acetic acid. 9. The method of Claim 1 wherein the solvent is dichloromethane, dichloroethane or ethyl acetate. 10. A method of preparing a compound of Formula III

wherein R¹ is C(O)R³, halogen, cyano, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl or C₁-C₄ hydroxyalkyl; X¹ is a halogen; R² is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; each R^x is independently halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; Z is N or CR^z; R³ is H, OH, C₁-C₄ alkyl or C₁-C₄ alkoxy; R^z is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; and k is 0, 1, 2 or 3; the method characterized by using a 3-halo-4,5-dihydro-1H-pyrazole compound of Formula I as prepared by the method of anyone of Claims 1-9. 11. The method of Claim 10 wherein R¹ is C(O)R³; X¹ is Cl or Br; R² is halogen; Z is N; R³ is OH or C₁-C₄ alkoxy; k is 0; X² is OS(O)_mR⁴, or a halogen other than X¹; m is 2; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof. 12. The method of Claim 11 wherein X¹ is Br; R² is Cl; R³ is OH OCH₃ or OCH₂CH₃; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, and combinations thereof. 13. The method of Claim 12 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OH, OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴, or Cl; m is 1; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. 14. The method of Claim 13 wherein R¹ is C(O)R³; X¹ is a Br; R² is Cl; Z is N; R³ is OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴; m is 1; R⁴ is 4-methylphenyl; the halide salt is sodium bromide or potassium bromide; the mineral acid is sulfuric acid; and the optional organic acid is formic acid or acetic acid. 15. A method of preparing a diamide compound of Formula IV

wherein X¹ is a halogen; R² is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; each R^x is independently halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; Z is N or CR^z; R^z is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; k is 0, 1, 2 or 3; R^6A is halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; R^6B is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; R^6C is halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; R^6D is hydrogen, halogen, cyano, C₁-C₄ alkyl or C₁-C₄ haloalkyl; and R⁷ is C₁-C₄ alkyl, C₃-C₆ cycloalkyl, C₄-C₈ cycloalkylalkyl, C₄-C₈ alkylcycloalkyl, or C₅-C₈ alkylcycloalkylalkyl; using a compound of Formula Ia _X ¹ O N N R³ R² Z x (R ⁾ _k Ia wherein R³ is OH or C₁-C₄ alkoxy; the method characterized by: preparing the compound of Formula Ia by the method by the method of anyone of Claims 1-9. 16. The method of Claim 15 wherein R^6A is F, Cl, Br or CH₃; R^6B is hydrogen, F, Cl or Br; R^6C is F, Cl, Br, I or cyano; and R^6D is hydrogen, F, Cl or Br. 17. The method of Claim 16 wherein R¹ is C(O)R³; X¹ is Cl or Br; R² is halogen; Z is N; R³ is OH or C₁-C₄ alkoxy; k is 0; X² is OS(O)_mR⁴, or a halogen other than X¹; m is 2; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; the halide salt is selected from an alkali bromide, an alkaline-earth bromide, ammonium bromide, a quaternary ammonium bromide, an alkali chloride, an alkaline-earth chloride, ammonium chloride, a quaternary ammonium chloride, and combinations thereof; and R⁷ is methyl, ethyl, isopropyl, cyclopropyl, cyclopropylmethyl or (1-methyl)cyclopropyl. 18. The method of Claim 17 wherein X¹ is Br; R² is Cl; R³ is OH, OCH₃ or OCH₂CH₃; X² is Cl or OS(O)_mR⁴; and the halide salt is selected from an alkali bromide, and combinations thereof. 19. The method of Claim 18 wherein R¹ is C(O)R³; X¹ is Br; R² is Cl; Z is N; R³ is OH, OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴, or Cl; m is 1; R⁴ is methyl, ethyl, phenyl or 4-methylphenyl; and the halide salt is selected from sodium bromide, potassium bromide, and combinations thereof. 20. The method of Claim 19 wherein R¹ is C(O)R³; X¹ is Br; R² is Cl; Z is N; R³ is OCH₃ or OCH₂CH₃; k is 0; X² is OS(O)_mR⁴; m is 1; R⁴ is 4-methylphenyl; the halide salt is sodium bromide or potassium bromide; the mineral acid is sulfuric acid; and the optional organic acid is formic acid or acetic acid. 21. The method of any one of Claims 1-20 wherein the average particle size of the halide salt is less than 389 µm.