WO1997019935A1

WO1997019935A1 - Processes and compounds for preparing cyclic urea fungicides

Info

Publication number: WO1997019935A1
Application number: PCT/US1996/019207
Authority: WO
Inventors: Richard James Brown; Dilon J. Daniel; Deborah Ann Frasier; Stephen Lee Hartzell; Gerard Michael Koether; Paul Walter Wojtkowski
Original assignee: E.I. Du Pont De Nemours And Company
Priority date: 1995-12-01
Filing date: 1996-12-02
Publication date: 1997-06-05
Also published as: EP0874831A1; AU1408297A

Abstract

Processes are disclosed for preparing compounds of Formula (I), for preparing a compound of Formula (II), for preparing a compound of Formula (III) and for preparing a compound of Formula (IV), wherein R?3 and R4¿ are each independently H, halogen, cyano, nitro, C¿1?-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C4 alkoxycarbonyl; or C2-C6 alkynyloxy; R?5¿ is H or C¿1?-C3 alkyl, Lg is halogen, acetoxy, OSO2Q or (a); Q is C1-C6 alkyl, C1-C6 alkenyl, or phenyl optionally substituted with C1-C3 alkyl; R?16 is C¿1-C6 alkyl, C1-C6 alkenyl or phenyl; and Z, R?1 and R2¿ are as defined in the disclosure. Also disclosed are advantageous process sequences and process conditions; as well as novel compounds of Formula (III) and novel compounds of Formula (IV).

Description

TITLE

PROCESSES AND COMPOUNDS FOR PREPARING

CYCLIC UREA FUNGICIDES

FIELD OF THE INVENTION

This invention pertains to compounds and processes which are useful for preparing cyclic urea fungicides.

BACKGROUND OF THE INVENTION WO 95/14009-A1 discloses cyclic urea fungicides for crop protection. There is a continuing need to develop compounds and processes useful for efficiently preparing these cyclic urea fungicides.

SUMMARY OF THE INVENTION This invention provides advantageous processes for preparing compounds of Formula III and compounds of Formula IV which are useful compounds for preparing cyclic urea fungicides.

wherein:

R³ and R⁴ are each independently H; halogen; cyano; nitro; C_rC₆ alkyl; C_rC_(: haloalkyl; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; C₂-C₆ haloalkynyl; C_rC₆ alkoxy; C_rC₆ haloalkoxy; C₂-C₆ alkenyloxy; C -C4 alkoxycarbonyl; or C₂-C₆ alkynyloxy;

R⁵ is H; or C_rC₃ alkyl;

O

.16,

Lg is halogen; acetoxy; OSO2Q; or OP(OR )2;

Q is C _ΓC₆ alkyl; C]-C₆ haloalkyl; or phenyl optionally substituted with -C3 alkyl; and

R¹⁶ is C_]-C_£ alkyl; C C^ alkenyl; or phenyl.

A process for the preparation of a compound of Formula III is provided which comprises reacting a compound of Formula IV with a phosgenatmg agent in a suitable solvent. Advantageous processes include those wherein the compounds of Formula IV are reacted with phosgene at a temperature from about 20 to 100°C in a solvent selected from the group consisting of ethyl acetate, toluene, xylenes, tetrahydrofuran, and 1 ,4-dioxane.

This invention further provides a process for the preparation of a compound of Formula V. This process uses a compound of Formula V.

wherein Y is N=C=O , - NHC(O)Cl or

and R- R⁴, R⁵ and Lg are as indicated above. This process comprises reacting a compound of Formula V with 1 , 1 -dimethylhydrazine in a suitable solvent. Advantageous processes include those wherein the compounds of Formula V are reacted with 1,1 -dimethylhydrazine at a temperature from about 0 to 60°C in a solvent selected from the group consisting of tetrahydrofuran, ethyl acetate, toluene, xylenes, and 1 ,4-dioxane.

This invention also provides processes for preparing cyclic urea fungicides of Formula I and cyclic urea fungicides of Formula II.

wherein:

R¹ is C_rC₆ alkyl; C_rC₆ haloalkyl; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; 2-C_(i haloalkynyl; or C3-C₅ cycloalkyl; R² is H; C_rC₆ alkyl; C,-C₆ haloalkyl; C_rC₆ alkoxy; C_rC₆ haloalkoxy; C_rC alkylthio; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; C -C₆ haloalkynyl, C₃-C₆ cycloalkyl; C -C₄ alkylcarbonyl, C₂-C₄ alkoxycarbonyl, cyano; or morphohnyl; Z is C_]-C₁₀ alkyl, C -C₁₀ alkenyl, or C₂-C₁₀ alkynyl each optionally substituted with R⁶; or Z is C3~Cg cycloalkyl or phenyl each optionally substituted with one of R⁷, R⁸, or both R⁷ and R⁸; or Z is a 3 to 14-membered nonaromatic heterocyclic ring system selected from the group monocyc c ring, fused bicychc ring and fused tπcyclic ring, or Z is a 5 to 14-membered aromatic heterocyclic ring system selected from the group monocychc ring, fused bicychc ring and fused tπcyclic ring, each nonaromatic or aromatic ring system containing 1 to 6 heteroatoms independently selected from the group

1-4 nitrogen, 1-2 oxygen, and 1-2 sulfur, each nonaromatic or aromatic ring system optionally substituted with one of R⁷, R⁸, or both R⁷ and R⁸; or R² and Z are taken together to form CH₂CH₂CH₂, CH₂CH₂CH₂CH₂,

CH₂(CH₂)₃CH₂, CH₂CH₂OCH₂CH₂, each CH₂ group optionally substituted with 1-2 halogen;

R⁶ is 1-6 halogen; C C₆ alkoxy; C C^ haloalkoxy, C_j-C₆ alkylthio; Cι-C₆ haloalkylthio; C_rC₆ alkylsulfinyl; C_rC₆ alkyisulfonyl; C3-C6 cycloalkyl;

C_VC₆ alkenyloxy; CO₂(C_rC₆ alkyl); NH(C_rC₆ alkyl), N(C_rC₆ alkyl)₂; cyano; or nitro; or R⁶ is phenyl, phenoxy, pyridinyl, pyπdinyloxy, thienyl, furanyl, pyπmidmyl, or pyrimidinyloxy each optionally substituted with one of R⁹, R¹⁰, or both R⁹ and R¹⁰; R⁷ is 1-2 halogen; C_j-C^ alkyl; C_j-C₆ haloalkyl; C_j-C^ alkoxy; C_j-C₆ haloalkoxy;

C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; C_rC₆ alkylthio; C_]-C₆ haloalkylthio; alkylsulfinyl; Cι-C₍, alkyisulfonyl, C₃-C5 cycloalkyl, C₃-C₆ alkenyloxy; CO₂(C_rC₆ alkyl); NH(C_rC₆ alkyl); N(C_rC₆ alkyl)₂;

-C(R' ')=NOR¹²; cyano; nitro; SiR¹³R¹⁴R¹⁵, GeR¹³R¹⁴R¹⁵; or R⁷ is phenyl, benzyl, benzoyl, phenoxy, pyridinyl, pyridmyloxy, thienyl, thienyloxy, furanyl, pyπmidinyl, or pyrimidinyloxy each optionally substituted with one of R⁹, R¹⁰, or both R⁹ and R^l0_; R⁸ is halogen, C_j-C₄ alkyl; C C₄ haloalkyl, ^-C_> alkoxy, nitro; or cyano; or

R⁷ and R⁸, when attached to adjacent atoms, can be taken together as -OCH₂O- or

-OCH₂CH₂O-, each CH₂ group optionally substituted with 1-2 halogen; R⁹ and R^lϋ are each independently halogen; C_rC alkyl, C_rC₄ haloalkyl; C_] -C₄ alkoxy; C_]-C₄ haloalkoxy; nitro; or cyano; R^{1 J} and R¹² are each independently H; C_]-C3 alkyl; or phenyl optionally substituted with halogen, C_}-C₄ alkyl, C₁-C₄ haloalkyl, C_rC₄ alkoxy, C C₄ haloalkoxy, nitro or cyano, R¹³, R¹⁴, and R¹⁵ are each independently C_rC₆ alkyl; C_rC₆ alkenyl; C_rC₄ alkoxy; or phenyl; and R³, R⁴ and R⁵ are as indicated above. A process for the preparation of a compound of Formula II is provided which comprises reacting a compound of Formula III in a suitable solvent with an oxime of the formula HONR²Z (wherein R² and Z are as indicated above) in the presence of a base or with a preformed salt of an oxime of said formula. Advantageous processes include those wherein the compounds of Formula III are reacted with the oxime at a temperature from about 0°C to 100°C in the presence of a base selected from the group consisting of alkali metal alkoxides or inorganic bases in a solvent selected from the group consisting of ethers (e.g., in the presence of NaOH, NaH or potassium t-butoxide in tetrahydrofuran or, preferably, 1 ,4-dioxane).

In accordance with this invention, the compounds of Formula II may be further reacted with a compound of the formula MOR¹, wherein M is lithium, sodium or potassium and R^s as defined above, to form compounds of Formula I . The processes of this invention as described above may be combined such that fungicidal cyclic urea compounds of Formula II may be prepared from compounds of Formula III, Formula IV, or Formula V; and fungicidal cyclic urea compounds of Formula 1 may be prepared from compounds of Formula II, Formula III, Formula IV or Formula V. This invention also provides novel compounds of Formula III and novel compounds of Formula IV.

DETAILED DESCRIPTION OF THE INVENTION In the above recitations, the term "alkyl", used either alone or in compound words such as "haloalkyl" denotes straight-chain or branched alkyl; e.g., methyl, ethyl, /<-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers. "Alkenyl" denotes straight-chain or branched alkenes; e.g., 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also denotes polyenes such as 1,3-hexadiene. "Alkynyl" denotes straight-chain or branched alkynes; e.g., ethynyl, 1-propynyl, 3-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also denote moieties comprised of multiple triple bonds; e.g., 2,4-hexadiync. "Alkoxy" denotes, for example, methoxy, ethoxy, «-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkenyloxy" denotes straight-chain or branched alkenyloxy moieties. Examples of alkenyloxy include H₂C=CHCH₂O, (CH₃)₂C=CHCH₂O, (CH₃)CH=CHCH₂O, (CH₃)CH=C(CH₃)CH₂O and CH₂=CHCH₂CH₂O. "Alkynyloxy" denotes straight-chain or branched alkynyloxy moieties. Examples include HC≡CCH₂O, CH₃C=CCH₂O and CT^C≡CCHoCHoO. The term "halogen", either alone or in compound words such as "haloalkyl", denotes 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, C1CH₂, CF₃CH₂ and CF₃CC1₂. The term "cycloalkyl" denotes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl moieties. The term "nonaromatic heterocyclic ring system" includes fully saturated heterocycles and partially aromatic heterocycles. The total number of carbon atoms in a substituent group is indicated by the "C_j-Cj" prefix where i and j are numbers from 1 to 10. For example, C_]-C₃ alkyl designates methyl through propyl; C₂ alkoxy designates CH₃CH₂O; C₃ alkoxy designates, for example, CH₃CH₂CH₂O or (CH₃)₂CHO; and C₂ alkoxycarbonyl designates CH₃O(O)C. In the above recitations, when a compound of Formula I is comprised of one or more aromatic nitrogen-containing rings (e.g., pyridinyl and pyrimidinyl), all bonds to these heterocycles are made through the carbon atom(s) of the moieties.

Examples of compounds of Formula III include compounds of Table A below. The compounds of Formula III include compounds where Lg (leaving group) is Cl or Br. However, Formula III compounds (e.g., compounds where R³, R⁴ and R⁵ are all H) also include embodiments where Lg is neither Cl nor Br.

Preferred R³ groups for Formula III compounds include H, CH₃, OCH3, Cl and Br. Preferred R⁴ groups for Formula III compounds include H, CH3, OCH3, Cl and Br. Preferred R⁵ groups for Formula III include H and CH₃. Preferred Lg groups for Formula III compounds include Cl, Br, acetoxy and OSO₂CH₃. Preferred compounds for Formula III include 5-chloro-4-[2-(chloromethyl)phenyl]-2,4-dihydro-2-methyl-3H- l,2,4-triazol-3-one, 4-[2-[(ace.yloxy)methyl]phenyl]-5-chloro-2,4-dihydro-2-methyl-3H- 1,2,4- triazol-3-one, 5-chloro-2,4-dihydro-2-methyl-4-[2- [[(methylsulfonyl)oxy]methyl]phenyl]-3H-l,2,4-triazol-3-one, 4-[2-[(acetyloxy)methyl]- 4-methylphenyl]-5-chloro-2,4-dihydro-2-methyl-3H- 1 ,2,4-triazol-3-one, 5-chloro-2,4- dihydro-2-methyl-4-[4-methyl-2-[[(methylsulfonyl)oxy]methyl]phenyl]-3H-l,2,4-triazol- 3-one, 4-[2[(acetyloxy)methyl]-4-chlorophenyl]-5-chloro-2,4-dihydro-2-methyl-3H- l,2,4-triazol-3-one, 4-[2-[(acetyloxy)methyl]-4-bromophenyl]-5-chloro-2,4-dihydro-2- methyl-3H- 1 ,2,4-triazol-3-one, 5-chloro-4-[2-(chloromethyl)-4-methylphenyl]-2,4- dihydro-2-methyl-3H- 1 ,2,4-triazol-3-one, 5-chloro-4-[4-chloro-2-(chloromethyl)phenyl]- 2,4-dihydro-2-methyl-3H- 1 ,2,4-triazol-3-one, 4-[4-bromo-2-(chloromethyl)pheny l]-5- chloro-2,4-dihydro-2-methyl-3H-l,2,4-triazol-3-one, 5-chloro-4-[2-chloromethyl)-6- methoxyphenyl]-2,4-dihydro-2-methyl-3H-l,2,4-triazol-3-one, 5-chloro-4-[4-chloro-2- [[(methylsulfonyl)oxy]methyl]phenyl]-2,4-dihydro-2-methyl-3H-l,2,4-triazol-3-one, and 4-[4-bromo-2-[[(methylsulfonyl)oxy]methyl]phenyl]-5-chloro-2,4-dihydro-2-methyl-3H- l ,2,4-triazol-3-one

Examples of compounds of Formula IV include compounds of Table B below. Preferred R³ groups for Formula IV compounds include H, CH3, OCH₃, Cl and Br. R⁴ groups for Formula IV compounds include H, CH₃, OCH₃, Cl and Br. Preferred R⁵ groups for Formula IV compounds include H and CH₃. Preferred Lg groups for Formula IV compounds include Cl, Br, acetoxy and OSO₂CH₃. Preferred compounds for Formula IV include N-[2-(chloromethyl)phenyl]-2,2-dimethylhydrazinecarboxamide, N-[2-[(acetyloxy)methyl]phenyl]-2,2-dimethylhydrazinecarboxamide, 2,2-dimethyl-N-[2- [[(methylsulfonyl)oxy]methyl]phenyl]hydrazinecarboxamide, N-[2-[(acetyloxy)methyl]- 4-methylphenyl]-2,2-dimethylhydrazinecarboxamide, N-[2-[(acetyloxy)methyl]-4- chlorophenyl]-2,2-dimethylhydrazinecarboxamide, N-[4-chloro-2- [[(methylsulfonyl)oxy]methyl]phenyl]-2,2-dimethylhydrazinecarboxamide, N-[2- [(acetyioxy)methyl]-4-bromophenyl]-2,2-dimethylhydrazinecarboxamide, N-[4-bromo-2- [[(methylsulfonyl)oxy]methyl]phenyl]-2,2-dimethylhydrazinecarboxamide, N-[2- (chloromethyl)-4-methyJphenyl]-2,2-dimethylhydrazinecarboxamide, N-[4-chloro-2- (chloromethyl)phenyl]-2,2-dimethylhydrazinecarboxamide, N-[4-bromo-2- (chloromethyl)phenyl]-2,2-dimethylhydrazinecarboxamide, N-[2-(chloromethyl)-6- methoxyphenyl]-2,2-dimethylhydrazine carboxamide, and 2,2-dimethyI-N-[4-methyl-2- [[(methylsulfonyl)oxy]methyl]phenyl]hydrazinecarboxamide.

Of note, is one embodiment of this invention where R³ and R⁴ are each independently H; halogen; cyano; nitro; C Cg alkyl; C_j -C₆ haloalkyl; Co-C₆ alkenyl; Cη- C₆ haloalkenyl; 0₂-C^ alkynyl; C₂-Cg haloalkynyl; C_j-C₆ alkoxy; C_]-C₆ haloalkoxy; C₂-C₆ alkenyloxy; or C₂-C₆ alkynyloxy.

The processes of this invention use one or more reaction steps as described herein. The reaction steps may be advantageously combined in a series for preparation of the cyclic urea fungicides. Indeed, one aspect of this invention pertains to a process for preparing compounds of Formula I comprising all four of the following reaction steps: Step 1

Step 1 forms compounds of Formula IV by reacting compounds of Formula V with 1 , 1 -dimethylhydrazine in a suitable solvent.

Isocyanate compounds of Formula V may be prepared for example, from the reaction of chlorine with otolylisocyanate as described in Synthesis, 376 ( 1978). Other compounds of Formula V can be prepared by the methods of March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, ( 1985). Other methods are also known to the skilled artisan. For the process of Step 1, the reaction temperature is typically from about -20 to 100°C. The temperature is preferably from about 0 to 60°C, and is more preferably from about 0 to 35°C (e.g., 0 to 30°C). The reaction times are typically from about 0.5 to 24 h. Typically, the pressure is from about 1 to about 5 atmospheres. By suitable solvent for Step 1 is meant, a liquid wherein the reactant(s) can be dissolved and the process of Step 1 proceeds. Suitable solvents for Step 1 include polar aprotic solvents such as acetonitrile, dimethylformamide or dimethylsulfoxide; ethers such as tetrahydrofuran, dimethoxyethane, diethyl ether, or 1,4-dioxane; ketones such as acetone or 2-butanone; or acetates such as ethyl acetate; hydrocarbons such as toluene or xylene; or halocarbons such as dichloromethane or chloroform. The mole ratio of the Formula V compound to dimethylhydrazine is typically from about 1 : 1 to 1 : 10. Preferred Step 1 processes include those using Formula V isocyanate, where the reaction time is from 0.5 to 6 h; the temperature is from 0 to 60°C; the pressure is about 1 atmosphere; the mole ratio of the Formula V isocyanate to 1,1 -dimethylhydrazine is from about 1 : 1 to 1 :5; and the solvent is ethyl acetate, toluene, xylenes, or 1,4-dioxane. Particularly preferred for achieving high yields of Formula IV compounds are the processes of Step 1 wherein the reaction time is from about 0.5 to 3 h; the temperature is from about 0 to 35°C (e.g., 0 to 30°C); the pressure is about 1 atmosphere; the mole ratio of isocyanate to 1 , 1 -dimethylhydrazine is about 1 : 1 ; and the solvent is 1 ,4-dioxane or ethyl acetate. The 1,1 -dimethylhydrazine can be added neat, as an aqueous solution or as a salt (e.g., its HC1 salt). Excess 1,1 -dimethylhydrazine can also be used, with the excess discarded or recovered for recycle. The product of Formula IV can be isolated, by for example filtration, or used directly in the next process step without isolation. Examples of the process of Step 1 include the reaction of 2-(chloromethyl)phenyl isocyanate with 1 ,1 -dimethylhydrazine to form N-[2-(chloromethyl)phenyl]-2,2- dimethylhydrazinecarboxamide; the reaction of 2-

[[(methylsulfonyl)oxy]methyl]phenylisocyanate with 1,1 -dimethylhydrazine to form 2,2- dimethyl-N-[2-[[(methylsulfonyl)oxy]methyl]phenyl]hydrazinecarboxa ide. Preferred Step 1 processes for reasons of cost and ease of synthesis, include processes for preparing compounds of Formula IV wherein R³ and R⁴ are H, CH₃, OCH₃, Br or Cl; R⁵ is H or CH₃; and Lg is halogen. Particularly preferred are processes for preparing compounds of Formula IV wherein R³ and R⁴ are H; R5 is H; and Lg is chlorine. Preferably, the reaction conditions (e.g., temperature, mole ratio, reaction time and solvent) are balanced to achieve a Step 1 yield (based on a Formula V compound reacted to give a Formula IV compound) of at least about 75%, more preferably at least about 85%. Step 2

Step 2 forms compounds of Formula III by reacting compounds of Formula IV with a phosgenatmg agent (e.g., phosgene) in a suitable solvent

By phosgenatmg agent is meant a compound having a carbonyl group and chlorine which reacts with the Formula IV compound to undergo cychzation, chlorine addition and demethylation to give Formula III compounds Examples of phosgenatmg agents are phosgene, diphosgene, tπphosgene. Phosgene is a preferred phosgenatmg agent For the process of Step 2, the reaction temperature is typically from about 0 to 200°C The temperature is preferably from about 0 to 100°C, and is more preferably from about 20 to 100°C Typically, the pressure is from about 1 to 5 atmospheres By suitable solvent for Step 2 is meant a liquid wherein the reactant(s) can be dissolved and the process of Step 2 proceeds Suitable solvents for Step 2 include polar aprotic solvents such as acetonitπle, dimethylformamide or dimethylsulfoxide; ethers such as 1 ,4-dioxane, tetrahydrofuran, dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone, or acetates such as ethyl acetate, hydrocarbons such as toluene or xylene, or halocarbons such as dichloromethane or chloroform The reaction times are typically from about 0.5 to 24 h. The mole ratio of the semicarbazide of Formula IV to the phosgenatmg agent is typically from about 1 :2 to 1 :20. Steps 1 and 2 may be accomplished as separate processes such that the product of Step 1 (I e , the compound of Formula IV) is isolated However, the processes of Step 1 and Step 2 may be combined such that the product of Step 1 is not isolated but reacted with the phosgenatmg agent in a suitable solvent in a second reaction zone (e g , added to a second vessel containing phosgene) to give a product of Formula III Preferred Step 2 processes include those using phosgene as the phosgenatmg agent where the reaction time is from about 1 to 6 h (e g , 2 to 6 h), the temperature is from about 0 to 100°C, the pressure is about 1 atmosphere, the mole ratio of semicarbazide to phosgene is from about 1 1 5 to 1 '5 (e g , 1.2 to 1 5), and the solvent is ethyl acetate, toluene, xylenes, tetrahydrofuran or 1 ,4-dioxane Particularly preferred for achieving high yields of Formula III compounds are the processes of Step 2 wherein the reaction time is from about 2 to 6 h; the temperature is from about 20 to 100°C; the pressure is about 1 atmosphere; the mole ratio of semicarbazide to phosgene is about 1.2 to 1:4 (e.g., 1.2 or, preferably, 1 :3.5) and the solvent is tetrahydrofuran or, more preferably, ethyl acetate or 1 ,4-dioxane At least two molar equivalents o phosgene and preferably more should be used It is preferred to slowly add III to at least two molar equivalents of phosgene The reaction can be run batch or continuous. The reaction can be run by simultaneously feeding and maintaining at least two molar equivalents of phosgene and compounds of Formula III into a vessel thereby avoiding the presence of large amounts of hazardous phosgene in the reaction vessel at one time. Compounds of Formula III can be isolated by removing volatiles or used directly in the next process step, preferably after removal of excess unreacted phosgene

Preferred Step 2 processes include processes for preparing compounds of Formula III wherein R³ and R⁴ are H, CH₃, OCH₃, Br or Cl, R⁵ is H or CH₃, and Lg is Cl, Br, acetoxy or OSO₂CH₃. Particularly preferred are processes for preparing compounds of Formula III wherein R³ and R⁴ are H; R⁵ is H, and Lg is chlorine Examples of the process of Step 2 includes the reaction of N-[2- (chloromethyl)phenyl]-2,2-dιmethylhydrazιnecarboxamιde with phosgene to form 5- chloro-4-[2-(chloromethyl)phenyl]-2,4-dιhydro-2-methyl-3H-l ,2,4-tπazol-3-one; the reaction of N-[2-[(acetyloxy)methyl]-4-bromophenyl]-2,2- dimethyl hydrazinecarboxamide with phosgene to form 5-chloro-4-[[[2-

(methylsulfonyl)oxy]methyl]phenyl]-2,4-dιhydro-2-methyl-3H-l,2,4-tπazol-3-one

Preferably, the reaction conditions (e.g , temperature, mole ratio, reaction time and solvent) are balanced to achieve a Step 2 yield (based on a Formula IV compound reacted to give a Formula III compound) of at least about 75%, more preferably at least about 85%

Preferred combined processes include embodiments where the solvent from Step 1 is the same as the solvent from Step 2 (e.g., 1 ,4-dioxane or ethyl acetate) Examples of the combined processes of Step 1 and 2 include the reaction of 2-(chloromethyl)phenyl isocyanate with 1 , 1 -dimethylhydrazine and then the subsequent reaction of the product of that reaction with phosgene to form 5-chloro-4-[2-(chloromethyl)phenyl]-2,4- dιhydro-2-methyl-3H- l,2,4-tπazol-3-one; the reaction of

2-[f(methyisulfonyl)oxy]methyl]phenyl isocyanate with 1 ,1 -dimethylhydrazine to form 2,2-dιmethyl-/V-[2-[[(methylsulfonyl)oxy]methyl]-phenyl]hydrazιnecarboxamide; and then the subsequent reaction of 2,2-dιmethyl-/V-[2 [[(methylsulfonyl)oxy]methyl]phenyl]hydrazιnecarboxamιde with phosgene to form 5- chloro-2,4-dιhydro-2-me.hyl-4-[2-[[(methyIsulfonyl)oxy]methyl]phenyl]-3H- 1,2,4- tπazol-3-one Preferably, the reaction conditions (e.g., temperature, mole ratio, reaction time and solvent) are balanced to achieve a combined Step 1 and 2 yield (based on a Formula V compound reacted to give a Formula III compound) of at least about 60%, more preferably at least about 70%.

For example Steps 1 and 2 can be combined by reacting 2-(chloromethyl)phenyl isocyanate and 1,1 -dimethylhydrazine in a mole ratio and about 1: 1 to form N-[2- (chloromethyl)phenyl]-2,2-dimethylhydrazinecarboxamide, which is subsequently reacted with at least two molar equivalents of phosgene in the same vessel to form 5-chloro-4- [2-(chloromethyl)phenyl]-2,4-dihydro-2-methyl-3H-l,2,4-triazol-3-one (using a reaction time for combined Steps 1 and 2 within the range from about 0.5 to 5 h; a reaction temperature within the range from about 0 to 100°C; a pressure of about 1 atmosphere; and ethyl acetate or 1,4-dioxane) to achieve a combined Steps 1 and 2 yield of at least about 60% 5-chloro-4-[2-(chloromethyl)phenyl]-2,4-dihydro-2-methyl-3H- 1 ,2,4-triazol- 3-one. Step 3

Step 3 forms compounds of Formula II by reacting compounds of Formula III in a suitable solvent with an oxime of the formula HONR²Z in the presence of a base, or with a preformed salt of said oxime.

Where the Step 3 starting material is prepared using the Step 2 process described above, it is typically separated from other Step 2 material which might adversely influence the Step 3 reaction (e.g., solvents which substantially inhibit the effect of the base).

For the process of Step 3, the reaction temperature is typically from about 0 to 200°C. The temperature is preferably from about 0 to 100°C and is more preferably from about 20 to 100°C. Typically, the pressure is from about 1 to 5 atmospheres. By suitable solvent for Step 3 is meant a liquid wherein the reactant(s) can be dissolved and the process of Step 3 proceeds. Suitable solvents for Step 3 include polar aprotic solvents such as acetonitrile, dimethylformamide or dimethylsulfoxide; ethers such as tetrahydrofuran, 1 ,2-dimethoxyethane, diethoxymethane, or dioxane (e.g. 1,4-dioxane), or diethyl ether; ketones such as acetone or 2-butanone; or acetates such as ethyl acetate; hydrocarbons such as toluene or xylene; or halocarbons such as dichloromethane or chloroform or protic solvents such as methanol, ethanol and water. Suitable bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate, or tertiary amines such as triethylamine, pyridine, 1 ,8-diazabicyclo- [5.4.0]undec-7-ene (DBU), or triethylenedia ine. The reaction times are typically from about 0.5 to 48 h. The mole ratio of the cyclic urea of Formula III to the oxime is typically from about 1: 1 to 1 :3 and the mole ratio of the oxime to the base is typically from about 1 :0.75 to 1 : 10 (e.g., 1 : 1 to 1: 10). Oximes of the formula HONR Z may be prepared from ketones, (e.g., acetophenone and hydroxylamine) using conventional chemistry known to one skilled in the art.

Preferred Step 3 processes include those wherein the reaction time is from about 1 to 6 h (e.g., 2 to 6 h); the temperature is from about 0 to 100°C; the pressure is about 1 atmosphere; the mole ratio of cyclic urea to oxime is from about 1 : 1 to 1 :2; the mole ratio of the oxime to base is from about 1 :0.75 to 1:5 (e.g., 1 : 1 to 1:5); the solvent is tetrahydrofuran, dimethylformamide, diethoxymethane, 1 ,2-dimethoxy ethane, acetonitrile, dimethylsulfoxide, dioxane (e.g., 1,4-dioxane), methanol, toluene, water, or a mixture thereof (optionally in the presence of a phase transfer catalyst), and the base is sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or potassium t-butoxide. Particularly preferred for achieving high yields of Formula II compounds are processes of Step 3 wherein the reaction time is from about 2 to 6 h; the temperature is from about 20 to 100°C; the pressure is about 1 atmosphere; the mole ratio of cyclic urea to oxime is about 1 : 1 ; the mole ratio of the oxime to base is about 1 :0.75 to 1 :5 (e.g., 1: 1 or, more preferably, 1 :0.75); the solvent is tetrahydrofuran or 1,4-dioxane; and the base is sodium hydroxide, potassium hydroxide or sodium hydride. Alternatively for product isolation, compounds of Formula II can be reacted with a preformed salt of the oxime. When hydroxides are used as base, water is formed as a by-product. This water by-product can be left in the reaction mixture or partially or totally removed by distillation or other means during the course of the reaction. Compounds of Formula II can be isolated by standard methods such as removal of most solvent under reduced pressure, addition of water and filtration. Alternatively for product isolation, the reaction mixture can be poured into a methylene chloride/hexane mixture, filtered through silica gel and volatiles removed.

Preferred oximes of Formula VI for use in this process include l-[3- (trifluoromethyl)phenyl]ethanone oxime, l-[3,5-(bistrifluoromethyl)phenyl]ethanone oxime, and l -[3,5-dichlorophenyl]ethanone oxime. Examples of the process of Step 3 include the reaction of 5-chloro-4-[2-(chloromethyl)phenyl]-2,4- dihydro-2-methyl-3H-l,2,4-triazol-3-one with -l-[3,5-

(bistrifluoromethyl)phenyl]ethanone oxime to form 5-chloro-2, 4-dihydro-2-methyl-4-[2- [[[[l-[3(trifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]- 3H-l,2,4-triazol- 3-one; the reaction of 5-chloro-4-[2-(chloromethyl)phenyl]-2,4- dihydro-2-methyl-3H- l,2,4-triazol-3-one with l-[3,5-

(bistrifluoromethyl)phenyl]ethanone oxime to form 5-chloro-2,4-dihydro-2-methyl-4-[2- [[[[ 1 -[3(bistrifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]-3H- 1 ,2,4- triazol-3-one. Compounds where Lg is Cl or Br are preferred for this process, with Cl being most preferred. Preferred Step 3 processes for reasons of cost, ease of synthesis, and fungicidal activity, are processes for preparing compounds of Formula II wherein R² is C_]-C₆ alkyl; Z is an aromatic ring system optionally substituted with one of R⁷, R⁸, or both R⁷ and R⁸; R⁵ is H or C_rC₃ alkyl; R⁷ is 1-2 halogen, C,-C₆ alkyl, C_rC₆ haloalkyl, Cι-C₆ alkoxy or C_j-Cg haloalkoxy; R⁸ is halogen, C_]-C₄ alkyl or C_rC₄ haloalkyl; C_]-C₄ alkoxy; R¹³, R¹⁴, and R¹⁵ are each independently C_rC₆ alkyl, C_rC₆ alkenyl, C_j-C₄ alkoxy or phenyl; and R³, and R⁴ are as indicated above. Particularly preferred are processes for preparing compounds of Formula II wherein R² is CH₃; Z is aromatic ring system substituted with R⁷, R⁸ or both R⁷ and R⁸; R⁵ is H; and R⁷ is 1-2 halogen or CF₃; and R⁸ is CF₃.

Preferably, the reaction conditions (e.g., temperature, mole ratio, reaction time, base and solvent) are balanced to achieve a Step 3 yield (based on a Formula III compound reacted to give a Formula II compound) of at least about 75%, more preferably at least about 85%. The product of process Step 3 may be further reacted with a compound of MOR¹ in a suitable solvent. This is illustrated in the process of Step 4. Step 4

Step 4 forms compounds of Formula I by reacting compounds of Formula II with an alkoxy lating agent of the formula MOR¹ in a suitable solvent.

Alkoxylating compounds of the formula MOR¹ are defined above. For the process of Step 4, the reaction temperature is typically from about 0 to 200°C. The temperature is preferably from about 0 to 100°C. Typically the pressure is from about 1 to about 5 atmospheres. By suitable solvent for Step 4 is meant, a liquid wherein the reactant(s) can be dissolved and the process of Step 4 proceeds. Suitable solvents for Step 4 include ethers such as tetrahydrofuran, dimethoxyethane, diethoxymethane, diethyl ether, or 1,4-dioxane, and alcohols such as methanol, and ethanol. Typically when an alcohol is used as a solvent, methanol would be used with MOCH3, ethanol would be used for MOCH CH₃. The reaction times are typically from about 0.5 to 48 h. The mole ratio of the coupled product of Formula II to alkoxylating agent is typically from about 1 : 1 to 1 :20. Preferred Step 4 processes include those wherein the reaction time is from about 1 to 6 h (e.g., 2 to 6 h); the temperature is from about 0 to 100°C; the pressure is about 1 atmosphere; the mole ratio of coupled product to alkoxylating agent is from about 1 : 1 to 1:5; the solvent is tetrahydrofuran, methanol, diethoxymethane or 1,4-dioxane; and the alkoxylating agent is sodium methoxide or potassium methoxide. Particularly preferred for achieving high yields of Formula I compounds are processes of Step 4 wherein the reaction time of Step 4 is from about 1 to 6 h (e.g., 2 to 6 h); the temperature is from about 0 to 100°C; the pressure is about 1 atmosphere; the mole ratio of coupled product to alkoxylating agent is about 1 :2, the solvent is tetrahydrofuran or 1 ,4-dioxane; and the alkoxylating agent is sodium methoxide. The methoxide can be preformed or formed in situ, by for example reaction of sodium hydride or sodium hydroxide with methanol. Preferred alkoxylating agents of Formula MOR¹ for use in this process include sodium methoxide and potassium methoxide. Examples of the process of Step 4 include the reaction of sodium methoxide with 5-chloro-2, 4-dihydro-2-methyl-4-[2-[[[[ l- [3(trifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]- 3H- 1 ,2,4-triazol-3-one to form 2,4-dihydro-5-methoxy-2-methyl-4-[2-[[[[l-[3-trifluoromethyl)phenyl]- ethylidene]amino]oxy]methyl]phenyl]- 3H-l,2,4-trιazol-3-one; the reaction of potassium methoxide with 5-chloro-2, 4-dihydro-2-methyl-4-[2-[[[[l-[3(trifluoromethyl)phenyl]- ethylidene]amino]oxy]methyl]phenyl]- 3H-l,2,4-triazol-3-one to form 2,4-dihydro-5- methoxy-2-methyl-4-[2-[[[[l-[3-trifluoromethyl)phenylJ- ethylidenelamino]oxy]methyllphenyl]- 3H-l,2,4-triazol-3-one.

Preferred Step 4 processes for reasons of cost, ease of synthesis, and fungicidal activity are processes for preparing compounds of Formula I wherein R¹ is C_j-C₆ alkyl, C_rC₆ haloalkyl, C₂-C₆ alkenyl, C -C₆ haloalkenyl, C -C₆ alkynyl, C₂-C₆ haloalkynyl or C3-C6 cycloalkyl; R² is C1-C alkyl; Z is an aromatic ring system containing 1 to 6 heteroatoms independently selected from the group 1-4 nitrogen, 1-2 oxygen, and 1 -2 sulfur, each nonaromatic or aromatic ring system optionally substituted with one of R⁷, R⁸, or both R⁷ and R⁸; R⁵ is H or C_rC₃ alkyl; R⁷ is 1-2 halogen, C,-C₆ alkyl, C,-C₆ haloalkyl, C C₆ alkoxy or C_]-C₆ haloalkoxy, R⁸ is halogen, C_rC₄ alkyl, Cι -C haloalkyl or C_rC₄ alkoxy, R¹³, R¹⁴, and R¹⁵ are each independently C_rC₆ alkyl, C,-C₆ alkenyl, C_]-C₄ alkoxy or phenyl, and R³, and R⁴ are as indicated above Particularly preferred are processes for preparing compounds of Formula I wherein R² is CH₃, Z is aromatic ring system substituted with R⁷, R⁸ or both R⁷ and R⁸, R⁵ is H; R⁷ is 1-2 halogen or CF₃; R⁸ is CF₃ and R¹ is CH₃

Preferably, the reaction conditions (e g , temperature, mole ratio, reaction time, base and solvent) are balanced to achieve a Step 4 yield (based on a Formula II compound reacted to give a Formula I compound) of at least about 75%, more preferably at least about 85%

Step 3 and Step 4 may be accomplished as separate processes such that the product of Step 3 (I e , the compound of Formula II) is isolated However, the processes of Step 3 and Step 4 may be combined such that the product of Step 3 is not isolated but is reacted with an alkoxylating agent without isolation (e g , in the same vessel) to give a product of Formula I It is noteworthy that Steps 3 and 4 can typically be carried out sequentially in the same vessel without isolation of compounds of Formula II by adding alkoxylating agent (e.g , methoxide) to the product of Step 3 in situ, as described in Example 5

Preferably, the reaction conditions (e g , temperature, mole ratio, reaction time, base and solvent) are balanced to achieve a combined Step 3 and 4 yield (based on a Formula III compound reacted to give a Formula I compound) of at least about 60%. more preferably at least about 70%

Examples of the combined processes of Steps 3 and 4 include the reaction of 5- chloro-2, 4-dιhydro-2-methyl-4-[2-[[[[l-[3(tπfluoromethyl)phenyl]- ethyhdene]amιno]oxy]methyl]phenyl]- 3H-l,2,4-tπazol-3-one with l -[3-

(tπfluoromethyl)phenyl]ethanone oxime in the presence of a base (e g , KOH, NaH or K t-butoxide) in a suitable solvent (e g , THF) and the subsequent reaction of the product of that reaction with methanol in the THF solution to form 2,4-dιhydro-5-methoxy-2- methyl-4-[2-[[[[l-[3- (tπfluoromethyl)phenyl]-ethylιdene]amιno]oxy]methyl]phenyl] 3H- 1 ,2,4-tπazol-3-one , the reaction of 5-chloro-2, 4-dιhydro-2-methyl-4-[2-[[[[ ] -

[3(tπfluoromethyl)phenyl]-ethyhdene]amιno]oxy]methyl]phenyl]- 3H- 1 ,2,4-tridzol-3-one with l-[3,5-(bιstπfluoromethyl)phenyl]ethanone oxime in the presence of a base and the subsequent reaction of the product of that reaction with methanol to form 5-chloro-2, 4- dιhydro-2-methyl-4-[2-[[[[ 1 -[3(tπfluoromethyl)phenyl]- ethyhdene]amιno]oxy]methyl]phenyl]- 3H-l ,2,4-tπazol-3-one

The compounds of Formula II can be provided from the compounds of Formula III in accordance with Step 3, the compounds of Formula III can be provided from the compounds of Formula IV in accordance with Step 2, and the compounds of Formula IV can be provided from the compounds of Formula V in accordance with Step 1. Accordingly, Step 3 can be combined (a) with Step 2 or (b) with both Step 1 and Step 2, as necessary to provide cyclic urea fungicides of Formula II from compounds of Formula III, Formula IV or Formula V; and Step 4 can be combined (a) with Step 3, (b) with both Step 2 and Step 5, or (c) with Step 1 , Step 2, and Step 3, as necessary to provide cyclic urea fungicides of Formula I from compounds of Formula II, Formula III, Formula IV or Formula V. For example, this invention provides a process for the preparation of cyclic urea fungicides of Formula I comprising reacting an isocyanate of Formula V with 1 , 1 -dimethylhydrazine in the presence of a suitable solvent at a temperature of from about -20 to 100°C and a pressure of from about 1 to 5 atmospheres to give a semicarbazide of Formula IV, which is then reacted with an excess of phosgene in a suitable solvent at from about 0 to 200°C and a pressure of from about 1 to 5 atmospheres to give a cyclic urea of Formula III, which is then coupled with an oxime of the formula HONR²Z in the presence of a suitable base which has sufficient basicity to form an oxime salt, or with the preformed salt of the oxime of the formula HONR²Z and in a suitable solvent at a temperature of from about 0 to 200°C and a pressure of from about 1 to 5 atmospheres to give a compound of Formula II, and then treating a compound of Formula II with an excess of alkoxylating agent in a suitable solvent at a temperature of about 0 to 200°C and a pressure of from about 1 to 5 atmospheres to give cyclic urea fungicides of Formula I. Thus, preferably, the reaction conditions (e.g. temperature, mole ratio, reaction time and solvent) are balanced to achieve a combined Step 1, 2 , 3 and 4 yield (based on a Formula V compound reacted to give a Formula I compound) of at least about 50%, more preferably at least about 60%. Thus, for example 2,4-dihydro-5-methoxy-2-methyl-4-[2-[[[[l-[3- trifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]- 3H- 1 ,2,4-triazol-3-one can be advantageously prepared by reacting 2-(chloromethyl)phenyl isocyanate with 1,1- dimethylhydrazine in a mole ratio of from about 1 : 1 to 1 :5 in a solvent selected from the group consisting of ethyl acetate, toluene, xylenes, and 1 ,4-dioxane at a temperature of from about 0 to 60°C, and the desired product (i.e., N-[2-(chloromethyl)phenyl]-2,2- dimethylhydrazinecarboxamide) can be reacted (with or without isolation) with from about 2 to 5 molar equivalents of phosgene in a solvent selected from the group consisting of ethyl acetate, toluene, xylenes, tetrahydrofuran and 1,4-dioxane at a temperature of from about 0 to 100°C for from about 2 to 6 h to obtain 5-chloro-4-[2- (chloromethyl)phenyll-2,4-dihydro-2-methyl-3H-l ,2,4-triazol-3-one. The 5-chloro-4-[2- (chloromethyl)phenyl]-2,4-dihydro-2-methyI-3H-l,2,4-triazol-3-one can be recovered and reacted with l-[3-(trifluoromethyl)phenyl] ethanone oxime in the presence of a base selected from the group consisting of sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and potassium t-butoxide (where the mole ratio of the oxime to base is from about 1.0.75 to 1:5 (e g , 1 1 to 1 5) and the mole ratio of the cyclic urea to oxime is from about 1 : 1 to 1 2) in a solvent selected from the group consisting of tetrahydrofuran, dimethylformamide, diethyoxymethane, 1,2- dimethoxyethane, acetonitrile, dimethylsulfoxide, dioxane (e.g., 1,4-dioxane), methanol, toluene, water and mixtures thereof (optionally in the presence of a phase transfer catalyst) at a temperature of from about 0 to 100°C for from about 1 to 6 h (e.g., 2 to 6 h); and the desired product 5-chloro-2, 4-dιhydro-2-methyl-4-[2-[[[[l- [3(trifluoromethyl)phenyl]-ethylιdene]amιno]oxy]methyl]phenyl]- 3H- 1 ,2,4-tπazol-3-one can be reacted (with or without isolation) with sodium methoxide or potassium methoxide in a mole ratio of from about 1 1 to 1 :5 at a temperature of from about 0 to 100°C in a solvent selected from the group consisting of tetrahydrofuran, methanol, diethoxymethane, and 1,4-dioxane for from about 1 to 6 h (e g, 2 to 6 h) to obtain said 2,4-dιhydro-5-methoxy-2-methyl-4-[2-[[[[l-[3-trιfluoromethyl)phenyl]- ethyhdene]amιnoloxy]methyl]phenyll- 3H- 1 ,2,4-tπazol-3-one The following examples are representative of the production of cyclic urea fungicides H'NMR Spectra are reported in ppm downfield from tetramethylsilane, s=sιnglet, d=doublet, t=tπplet, dt=doublet of triplets, td= triplet of doublets, m=multιplet

EXAMPLE 1 Preparation of N-f2-(chloromethyl)phenyll-2.2-dιmethylhydrazιnecarboxamιde

(Step 1) A 250 mL 3-necked round bottom flask is fitted with thermometer, nitrogen by-pass, dropping funnel and magnetic stirrer. The flask is charged with 40 mL of ethyl acetate and 17 83 g of 94% pure 2-(chloromethyl)phenyl isocyanate (0 10 mol) The resultant solution is cooled to approximately 0°C and to this is added dropwise with stirring over approximately 45 min, 6 61 g of 1,1 -dimethylhydrazine (0 1 1 mol) keeping the mixture at approximately 0°C After addition is complete, the resultant slurry is allowed to stir for one hour at approximately 0°C The mixture is suction-filtered through sintered glass and the collected solid is washed one time with cold ethyl acetate (approximately 10 mL) and allowed to dry at room temperature yielding 22 4 g of white solid, m.p 132 5- 134°C (dec), H^!NMR (CDCl₃) 52 65 (s,6H), 4.62 (s.2H), 5 43 (s, lH), 7 06 (m,lH), 7 27 (m,lH), 7 36 (m, lH), 8 00 (m, lH), 8 65 (s, lH)

EXAMPLE 2 Preparation of 5-chloro-4-f2-(chloromethyl)phenyl]-2,4-dιhydro-2-methyl- 3H-1.2.4-tπazol-3-one (Step 2)

A 3-liter 4-necked round-bottomed flask is fitted with overhead stirrer, thermometer, inlet tube and air-cooled reflux condenser capped with a dry ice condenser The dry ice condenser is fitted with a nitrogen bypass The flask is charged with 450 mL of ethyl acetate followed by 74.16 g phosgene (0.75 mol). The mixture is heated to reflux and stirred. To the stirred mixture, 34.17 g of N-[2-(chloromethyl)phenyl]-2,2- dimethylhydrazinecarboxamide (0.15 mol) in 1350 mL ethyl acetate is added over three hours via the inlet tube. The reflux temperature increased from 56 to 72°C during the addition. When addition is complete, the mixture is allowed to reflux for one hour, then cooled to room temperature and allowed to stand overnight.

The condensers are replaced with a dry ice-cooled distillation head. The mixture is heated to reflux and 1300 mL of a mixture of excess phosgene and ethyl acetate is removed by distillation. The resultant mixture is allowed to cool to room temperature and one liter of hexane is added with stirring. This is filtered through a 2 inch bed of silica gel twice and the silica gel is rinsed with one liter of 30% ethyl acetate in hexanes. These organic filtrates are combined and solvents are removed on the rotary flash evaporator. The residue is triturated with 500 mL of hexanes. The resultant solids are filtered through sintered glass, collected, and allowed to dry at room temperature yielding 32.4 g of white solid, m.p . 1 19.5-120.5°C. The filtrate is concentrated to 100 mL under reduced pressure and then cooled to approximately 0°C. Filtration through sintered glass gives 2.39 g of white solid, m.p. 1 19-120.5°C, upon drying. H^]NMR (CDC1₃): δ 3.55 (s,3H), 4.46 (d,lH), 4.69 (d,lH), 7.25 (m, lH), 7.51 (m,3H).

EXAMPLE 3 Preparation of 5-chloro-2. 4-dihvdro-2-methyl-4-r2-rrrri-

[3(trifluoromethyl)phenyH-ethylidenelaminoloxy]methyllphenyl^"|- 3H-1.2,4-triazol-3-one (Step 3) A 100-mL 2-necked round bottom flask is fitted with thermometer, reflux condenser capped with nitrogen bypass and magnetic stirrer. The flask is charged with 30 mL tetrahydrofuran and 0.22 g 60% sodium hydride in mineral oil (5.5 mmol). To this is added with stirring, 1.02 g l-[3-(trifluoromethyl)phenyl]ethanone oxime (5 mmol) resulting in a vigorous reaction with off-gassing. When the off-gassing ceases (approximately two minutes), 1.29 g of 5-chloro-4-[2-(chloromethyl)phenyl]-2,4- dihydro-2-methyl-3H-l,2,4-triazol-3-one (5 mmol) is added. The resultant mixture is heated at reflux (approximately 62°C) for 3 h. The mixture is allowed to cool to room temperature and poured into approximately 100 mL of 30% methylene chloride in hexane. This mixture is filtered through a 1 inch thick bed of silica gel which is then rinsed with approximately 500 mL 40% ethyl acetate in methylene chloride. The organic filtrates are combined and volatiles are removed on the rotary flash evaporator to yield 2.13 g of yellow oil. Addition of hexane to the oil results in the formation of crystals which are then triturated with hexane. Filtration and drying gives 1.83 g of solid product, m.p. 95-97°C. H*NMR (CDC1₃): δ 2.20 (s,3H), 3.47 (s,3H), 5.19 (d,lH), 5.31 (d,l H), 7.26 (m. lH), 7.54 (m,5H), 7.83 (m,2H). EXAMPLE 4 Preparation of 2,4-dihydro-5-methoxy-2-methyl-4-12-[r[[ l-[3- trifluoromethyDphenyll-ethylidenelaminoloxylmethyllphenyn- 3H- 1 ,2.4-triazol- 3-one (Step 4) A 100 mL 1 -necked round bottom flask is fitted with a magnetic stirrer and reflux condenser capped with a nitrogen bypass. The flask is charged with 50 mL of tetrahydrofuran, 2.12 g of 5-chloro-2,4-dihydro-2-methyl-4-[2-[[[[l-[3- (trifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]-3H-l,2,4-triazol-3-one (5 mmol) and 1.19 g of 25% sodium methoxide in methanol (5.5 mmol). The mixture is heated to reflux with stirring. After 4 h, 0.10 g of 25% sodium methoxide in methanol is added. After an additional 2 h, 0.30 g of 25% sodium methoxide in methanol is added. The mixture is then stirred at reflux for one additional hour at which time analysis of an aliquot by high pressure liquid chromatography indicates the presence of essentially no starting material. The mixture is allowed to cool to room temperature and left stirring overnight. The mixture is then worked up as in Example 3 to yield 2.06 g of pale yellow oil which crystallized upon seeding with an authentic sample of 2,4-dihydro-5-methoxy- 2-methyl-4-[2[[[[ l-f3-(trifluoromethyl)phenyl-ethylidene]amino]oxy]methyl]phenyl]-3H- l,2,4-triazol-3-one. Trituration with hexanes followed by filtration and drying gave 1.97 g of white solid, m.p. 97-98.5°C. A portion ( 1.00 g) of this was recrystallized from 10 mL of 10% ethyl acetate-hexane to yield 0.94 g of white solid, m.p. 101 -102°C.

H 'NMR (CDC1₃) δ 2.21 (s,3H), 3.40 (s,3H), 3.89 (s,3H), 5.24 (d,2H), 5.28 (d,2H), 7.26 (m, lH), 7.47 (m,3H), 7.58 (m,2H), 7.85 (m,2H).

EXAMPLE 5 Preparation of 2,4-dihydro-5-methoxy-2-methyl-4-f2-ffrπ-f3- (trifluoromethyl)phenyll-ethylidenelaminoloxylmethyllphenyn- 3H- 1 ,2,4-triazol-

3-one (Steps 3 and 4) A 200 mL 2-necked round bottom flask is fitted with thermometer, reflux condenser capped with nitrogen bypass and magnetic stirrer. The flask is charged with 100 mL of tetrahydrofuran, 1.28 g of 60% sodium hydride in mineral oil (32 mmol). To this is added with stirring 2.03 g of l-[3-(trifluoromethyl)phenyl]ethanone oxime

( 10 mmol). When offgassing ceases (approximately 15 min) 2.58 g of 5-chloro-4-[2- (chloromethyl)phenyl]-2,4-dihydro-2-methyl-3H-l,2,4-triazol-3-one heterocycle (10 mmol) is added. The resultant mixtures is heated to reflux approximately 65°C for 5 h. It is then allowed to cool to approximately 60°C and 2.56 g of methanol (80 mmol) is added slowly. The resultant mixture is heated to reflux (approximately 65°C) for an additional 3 h at which time analysis of an aliquot by high pressure liquid chromatography shows the reaction to be essentially complete. The mixture is allowed to cool to room temperature and worked up as described in Examples 3 and 4 giving 4 15g of red oil Addition of hexane results in crystallization of the oil Tnturation of these crystals with hexane followed by filtration and drying gives 3 32 g of yellow solid m p 96-99°C

EXAMPLE 6 Preparation of 5-chloro-2, 4-dιhydro-2-methyl-4- 2-frrπ- 3(trιfluoromethyl)phenyll-ethylιdene1amιnoloxy1methyllphenyl]- 3H- 1.2.4-tπazol-3-one (Step 3) A 100 mL 2-necked round bottom flask is fitted with thermometer, distillation head with nitrogen-bypass, and magnetic stirrer The flask is charged with 25 mL of tetrahydrofuran, 0 18 g of potassium hydroxide (85% assay, 2 75 mmol), 0 51 g of l-[3- (tπfluoromethyl)phenyl]ethanone oxime (2 5 mmol) and 0 65 g of 5-chloro-4-[2 (chloromethyl)phenyl]-2,4-dιhydro-2-methyl-3H-l,2,4-tπazol-3-one (2 5 mmol) The resultant mixture is heated and reaction followed by high pressure liquid chromatography (HPLC) After 0 5 h at 50°C, 10 mL of tetrahydrofuran is added After 1 h at 65°C, 10 mL of distillate is removed from the reaction The mixture is heated at 66°C for an additional 2h, at which analysis of a reaction aliquot by HPLC indicated the absence of starting material oxime The mixture is allowed to cool to room temperature It is worked up using the method in Example 3 by addition to methylene chloride in hexanes followed by silica gel filtration and solvent removed to yield 1 02 g of yellow crude product Quantitative analysis by HPLC indicated this to be 89% desired product 5- chloro-2, 4-dιhydro-2 methyl-4-[2-[[[[ 1 -[3(tπfluoromethyl)phenyl]- ethylιdene]amιno]oxy]methyl]-phenyl]- 3H- 1 ,2,4-tπazol-3-one

EXAMPLE 7 Preparation of 2,4-dιhydro-5-methoxy-2-methyl-4 [2-f[[ l-[3- (tπfluoromethyl)phenyll-ethylιdenelamιnoloxylmethyllphenyn- 3H- 1 ,2,4-tπazol-

3-one (Steps 3 and 4)

A 200 mL 2-necked round bottom flask is fitted with thermometer, distillation head with nitrogen-bypass, and magnetic stirrer The flask is charged with 100 mL of tetrahydrofuran, 0 52 g of potassium hydroxide (85% assay, 7 9 mmol), 1 09 g of l-[3- (tπfluoromethyl)phenyl]ethanone oxime (7 2 mmol) and 1 93 g of 5-chloro-4-[2- (chloromethyl)phenyl]-2,4-dιhydro-2-methyl-3H-l,2,4-tπazol-3-one (96% pure, 7 2 mmol) The resultant mixture is stirred at room temperature (approximately 23°C) and reaction is followed by high pressure liquid chromatography (HPLC) After 20 h, the mixture is heated and approximately 40 mL of distillate is removed The mixture is then heated for one additional hour at approximately 65°C, at which analysis of an aliquot by HPLC shows very little oxime remaining To the mixture is then added 3 11 g of 25% sodium methoxide in methanol (14 4 mmol) and the resultant mixture is heated at approximately 65°C for 4 5 h To the mixture is then added 1 04 g of 25% sodium methoxide in methanol. The mixture is heated for 1.5 h at approximately 65°C and then allowed to stir overnight at room temperature. The mixture is then heated to approximately 65°C for 2 h at which analysis of an aliquot by HPLC indicated very little starting materials remaining. The reaction mixture is allowed to cool to room temperature. It is worked up as described in Examples 5 and 6 giving 3.06 g of yellow oil. Quantitative analysis by HPLC indicated this to be 83% desired product 2,4- dihydro-5-methoxy-2-methyl-4-[2-[[[[l-[3- (trifluoromethyl)phenyl]- ethylidene]amino]oxy]methyl]phenyl]- 3H- l,2,4-triazol-3-one.

EXAMPLE 8 Preparation of 5-chloro-4-[2-(chloromethyl)phenyll-2,4-Dihydro-2-

Methyl-3H-1.2.4-Triazol-3-one (Steps 1 and 2) 1 ,1 -Dimethylhydrazine (0.263 mol) was added to a solution of 0.276 moles of 2-(chloromethyl)phenyl isocyanate in 350 mL of 1 ,4-dioxane. The addition required about 10 min and the temperature was kept belwo 35°C by external cooling. The hydrazine addition funnel was rinsed with another 50 mL of 1 ,4-dioxane after the charge. The resulting slurry was then transferred to a second flask which contained 0.934 mol of phosgene dissolved in 600 mL of 1,4-dioxane. The transfer required about 20 min; the transfer line and flask were chased with another 140 mL of 1 ,4 dioxane. The temperature in the phosgene solution rose from 9 to 24°C during the transfer. The resulting slurry was heated from 24 to 61 °C during 5.42 h. The heating rate was then increased until the solution was distilling. A total of 606 g of condensate was recovered, and the residue weighed 601 g. HPLC analysis showed that the residue contained 10.7% of the desired triazol, or a 94.7% yield based on 1 , 1 -dimethylhydrazine.

EXAMPLE 9 Preparation of 2.4-dihydro-5-methoxy-2-methyl-4-.2-rrrri-r3- trifluoromethvDphenyπ-ethylidenclaminoloxylmethyllphenyll- 3H- 1 ,2,4-triazol- 3-one (Steps 3 and 4) 525 g of 9.90% triazol solution (0.201 mol) was distilled until 328 g of 1 ,4-dioxane was collected. The residue was cooled to about 40°C and 40.6 g (0.200 mol) of oxime was added. The solution was then reheated to 75°C and 12.0 g (0.15 mol) of NaOH was added during 30 min. The resulting reaction mass was then stirred for 2 h at 75°C.

After 2 h, the mixture was cooled to 65°C and 65 g (0.300 mol) of 25% NaOMe was added. Heating at 65°C was continued for 5 h. The mixture was then cooled to room temperature and 300 mL of water and 250 L of n-hexane were added along with 1 g of seed crystals. The resulting mixture was stirred in an ice bath for 1.5 h before filtration. The solids were washed with water and hexane and then dried to give 56.3 g. HPLC analysis showed that the product was 89.1 % pure, or a yield of 59.7% based on oxime. Recrystallization can be used if higher purity material is desired.

Table A

Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl

Cl

Br

Cl

Br

Index Table A

Compound mp (°C)

Claims

1. A process for preparing a compound of Formula I

wherein

R¹ is C₁-C₆ alkyl; _C1-C₆ haloalkyl; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆

alkynyl; C₂-C₆ haloalkynyl; or C₃-C₆ cycloalkyl;

R² is H; C₁-C₆ alkyl; C₁-C₆ haloalkyl; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; C₁-C₆ alkylthio; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; C₂-C₆ haloalkynyl; C₃-C₆ cycloalkyl; C₂-C₄ alkylcarbonyl; C₂-C₄ alkoxycarbonyl; cyano; or morpholinyl;

Z is C₁-C₁₀ alkyl; C₂-C₁₀ alkenyl; or C₂-C₁₀ alkynyl each optionally substituted with R⁶; or Z is C₃-C₈ cycloalkyl or phenyl each optionally substituted with one of R⁷; R⁸; or both R⁷ and R⁸; or Z is a 3 to 14-membered nonaromatic heterocyclic ring system selected from the group monocyclic ring; fused bicyclic ring and fused tricyclic ring; or Z is a 5 to 14-membered aromatic heterocyclic ring system selected from the group monocyclic ring; fused bicyclic ring and fused tricyclic ring; each nonaromatic or aromatic ring system containing 1 to 6 heteroatoms independently selected from the group 1-4 nitrogen; 1-2 oxygen; and 1-2 sulfur; each nonaromatic or aromatic ring system optionally substituted with one of R⁷; R⁸; or both R⁷ and R⁸ ; or

R² and Z are taken together to form CH₂CH₂CH₂; CH₂CH₂CH₂CH₂;

CH₂(CH₂)₃CH₂; CH₂CH₂OCH₂CH₂; each CH₂ group optionally substituted with 1-2 halogen;

R³ and R⁴ are each independently H; halogen; cyano; nitro; C₁-C₆ alkyl; C₁-C₆ haloalkyl; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; C₂-C₆ haloalkynyl; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; C₂-C₆ alkenyloxy; C₂-C₄ alkoxycarbonyl; or C₂-C₆ alkynyloxy;

R⁵ is H; or C₁-C₃ alkyl;

R⁶ is 1 -6 halogen; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; C₁-C₆ alkylthio; C₁-C₆

haloalkylthio; C₁-C₆ alkylsulfinyl; C₁-C₆ alkyisulfonyl; C₃-C₆ cycloalkyl; C₃-C₆ alkenyloxy, CO₂(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₆ alkyl)₂, cyano, or nitro, or R⁶ is phenyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, furanyl, pyrirmdinyl, or pyrimidinyloxy each optionally substituted with one of R⁹, R¹⁰, or both R⁹ and R¹⁰;

R⁷ is 1-2 halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,

C₂-C₆ alkenyl; C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkyisulfonyl, C₃-C₆ cycloalkyl, C₃-C₆ alkenyloxy, CO₂(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₆ alkyl)₂, -C(R^{1 1} )=NOR¹², cyano, nitro, SiR¹³R¹⁴R¹⁵; GeR¹³R¹⁴R¹⁵, or R⁷ is phenyl, benzyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl, or pyrimidinyloxy each optionally substituted with one of R⁹, R¹⁰, or both R⁹ and R¹⁰,

R⁸ is halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, nitro; or cyano, or

R⁷ and R⁸, when attached to adjacent atoms, can be taken together as -OCH₂O- or -OCH₂CH₂O-, each CH₂ group optionally substituted with 1-2 halogen,

R⁹ and R¹⁰ are each independently halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, nitro, or cyano;

R^{1 1} and R¹² are each independently H; C₁-C₃ alkyl, or phenyl optionally

substituted with halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, nitro or cyano; and

R¹³, R¹⁴, and R¹⁵ are each independently C₁-C₆ alkyl, C₁-C₆ alkenyl; C₁-C₄

alkoxy, or phenyl; comprising

reacting a compound of Formula III

wherein Lg is halogsn, acetoxy, OSO₂Q, or

;

R¹⁶ is C₁-C₆ alkyl, C₁-C₆ alkenyl, or phenyl, and

Q is C₁-C₆ alkyl; C₁-C₆ haloalkyl, or phenyl optionally substituted with C₁-C₃ alkyl, in a suitable solvent with an oxime of the formula HONR²Z in the presence of a base or with a preformed salt of an oxime of said formula to produce a compound of Formula II.

; and

reacting said compound of Formula II with a compound of the formula MOR¹ wherein M is lithium, sodium or potassium.

2. The process of Claim 1 wherein for the reaction of the compound of Formula III, the base is sodium hydroxide and the solvent is 1 ,4-dioxane.

3. The process of Claim 1 wherein an oxime is reacted with a compound of Formula III in the presence of a base, and wherein for the reaction of said Formula III compound the reaction time is from about 1 to 6 h, the temperature is from about 0 to 100°C; the pressure is about 1 atmosphere, the mole ratio of cyclic urea of

Formula III to oxime is from about 1:1 to 1.2, the mole ratio of the oxime to base is from about 1: 0.75 to 1 :5; the solvent is tetrahydrofuran, dimethyl formamide, diethoxymethane, 1,2-dimethoxyethane, acetonitrile, dimethylsulfoxide, methanol, 1 ,4-dioxane, toluene, water, or a mixture thereof, and the base is sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or potassium t-butoxide.

4. The process of Claim 3 wherein for the reaction of the compound of Formula III, the temperature is from about 20 to 100°C, the mole ratio of cyclic urea of

Formula III to oxime is about 1: 1; the mole ratio of the oxime to base is about 1:0.75, and the solvent is 1 ,4-dioxane; and the base is sodium hydroxide or sodium hydride.

5 . The process of Claim 1 wherein for the reaction of the compound of Formula II, the reaction time is from about 0.5 to 48 h; the temperature is from about 0 to 200°C, the pressure is from about 1 to 5 atmospheres; and the mole ratio of the compound of Formula II to alkoxylating agent is from about 1:1 to 1 :20.

6. The process of Claim 5 wherein the compound of Formula II is not isolated prior to its reaction with the compound of Formula MOR¹.

7. The process of Claim 6 wherein the solvent for the reaction of the

Formula III compound is the same as the solvent for the reaction of the Formula II compound.

8. The process of Claim 7 wherein for the reaction of the compound of Formula II, the mole ratio of Formula II compound to alkoxylating agent is about 1 2, the solvent is 1,4-dioxane and the alkoxylating agent is sodium methoxide.

9. The process of Claim 1 wherein the compound of Formula III is prepared by reacting a compound of Formula IV

with a phosgenating agent in a suitable solvent.

10. The process of Claim 9 wherein for the reaction of the compound of Formula IV, phosgene is used as the phosgenating agent, the reaction time is from about 2 to 6 h; the temperature is from 20 to 100°C; the pressure is about 1 atmosphere; the mole ratio of semicarbazide of Formula IV to phosgene is about 1.3 5, and the solvent is 1 ,4-dioxane, ethyl acetate or tetrahydrofuran.

1 1. The process of Claim 9 wherein the compound of Formula IV is prepared by reacting a compound of Formula V

wherein Y is— N=C=O,— NHC(O)Cl or , with

1 , 1 -dimethylhydrazine in a suitable solvent

12 The process of Claim 1 1 wherein for the reaction of the compound of Formula V, the reaction time is from about 0 5 to 3 h; the temperature is from about 0 to 35°C; the pressure is about 1 atmosphere, the mole ratio of the Formula V isocyanate to 1 , 1 -dimethylhydrazine is about 1 1; and the solvent is 1,4-dioxane

13 The process of Claim 12 wherein the compound of Formula IV is not isolated prior to its reaction with the phosgenating agent.

14 The process of Claim 1 1 wherein 2,4-dihydro-5-methoxy-2-methyl-4-[2- [[[[1 -[3-trifluoromethyl)phenyl]-ethylidene]amino]oxylmethyl]phenyl]- 3H- 1 ,2,4-triazol- 3-one is prepared by (1) reacting 2-(chloromethyl)phenyl isocyanate with 1,1-dimethylhydrazine in a mole ratio of from about 1 : 1 to 1 :5 in a solvent selected from the group consisting of ethyl acetate, toluene, xylenes, and 1,4-dioxane at a temperature of from about 0 to 60°C to produce N-[2-(chloromethyl)phenyI]-2,2-dimethylhydrazinecarboxamide; (2) reacting said N-[2-(chloromethyl)phenyl]-2,2-dimethylhydrazinecarboxamide with from about 1.5 to 5 molar equivalents of phosgene in a solvent selected from the group consisting of ethyl acetate, toluene, xylenes, 1,4-dioxane and tetrahydrofuran at a temperature of from about 0 to 100°C for about 2 to 6 h to obtain 5-chloro-4-[2-(chloromethyl)phenyl]-2,4-dihydro-2-methyl-3H- 1 ,2,4-triazol-3-one; (3) recovering said 5-chloro-4-[2-(chloromethyl)phenyI]-2,4-dihydro-2- methyl-3H- 1,2,4-triazol-3-one and reacting it with 1-[3-(trifluoromethyl)phenyl] ethanone oxime in the presence of a base selected from the group consisting of sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and potassium t-butoxide in a solvent selected from the group consisting of tetrahydrofuran, dimethylformamide, diethyoxymethane, 1,2-dimethoxyethane, acetonitrile, dimethylsulfoxide, 1,4-dioxane, methanol, toluene, water and mixtures thereof, at a temperature of from about 0 to 100°C for from about 2 to 6 h, to produce 5-chloro-2, 4-dihydro-2-methyl-4-[2-[[[[1-[3(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,4-triazol-3-one, the mole ratio of said oxime to said base being from about 1:0.75 to 1:5 and the mole ratio of said cyclic urea to said oxime being from about 1 : 1 to 1 :2; and (4) reacting said 5-chloro-2, 4-dihydro-2- methyl-4-[2-[[[[1-[3(trifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]-3H- 1 ,2,4-triazol-3-one with sodium methoxide or potassium methoxide in a mole ratio of about 1 : 1 to 1 :5 at a temperature of from about 0 to 100°C in a solvent selected from the group consisting of 1 ,4-dioxane, tetrahydrofuran, methanol and diethoxymethane for from about 2 to 6 h to obtain said 2,4-dihydro-5-methoxy-2-methyl-4-[2-[[[[1-[3-trifluoromethyl)phenyl]-ethylidene]amino]oxy]methyl]phenyl]- 3H- 1,2,4-triazol-3-one.

15. A process for the preparation of a compound of the Formula II

wherein

R² is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ halodlkynyl, C₃-C₆ cycloalkyl, C₂-C₄ alkylcarbonyl, C₂-C₄ alkoxycarbonyl, cyano, or morphohnyl;

Z is C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl, or C₂-C_{1 0} alkynyl each optionally substituted with R⁶, or Z is C₃-C₈ cycloalkyl or phenyl each optionally substituted with one of R⁷, R⁸, or both R⁷ and R⁸, or Z is a 3 to 14-membered nonaromatic heterocyclic ring system selected from the group monocvclic ring, fused bicyclic ring and fused tricyclic ring, or Z is a 5 to 14-membered aromatic heterocyclic ring system selected from the group monocyclic ring, fused bicyclic ring and fused tricyclic ring, each nonaromatic or aromatic ring system containing 1 to 6 heteroatoms independently selected from the group 1-4 nitrogen, 1-2 oxygen, and 1-2 sulfur, each nonaromatic or aromatic ring system optionally substituted with one of R⁷, R⁸, or both R⁷ and R⁸, or

R² and Z are taken together to form CH₂CH₂CH₂, CH₂CH₂CH₂CH₂,

R³ and R⁴ are each independently H, halogen, cyano, nitro, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyloxy, C₂-C₄ alkoxycarbonyl, or C₂-C₆ alkynyloxy;

R⁵ is H, or C₁-C₃ alkyl,

R⁶ is 1 -6 halogen, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆

haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkyisulfonyl, C₃-C₆ cycloalkyl,

C₃-C₆ alkenyloxy, CO₂(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₆ alkyl)₂, cyano, or nitro, or R⁶ is phenyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, furanyl, pyrimidinyl, or pyrimidinyloxy each optionally substituted with one of R⁹, R¹⁰, or both R⁹ and R¹⁰,

C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsullonyl, C₃-C₆ cycloalkyl, C₃-C₆ alkenyloxy, CO₂(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁ -C₆ alkyl)₂; -C(R^{1 1})=NOR¹², cyano, nitro, SiR¹³R¹⁴R¹⁵, GeR¹³R¹⁴R¹⁵; or R⁷ is phenyl, benzyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl, or pyrimidinyloxy each optionally substituted with one of R⁹ R¹⁰, or both R⁹ and R¹⁰;

R⁸ is halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy nitro, or cyano; or R⁷ and R⁸, when attached to adjacent atoms, can be taken together as -OCH₂O- or

-OCH₂CH₂O-, each CH₂ group optionally substituted with 1-2 halogen; R⁹ and R¹⁰ are each independently halogen; C₁-C₄ alkyl; C₁-C₄ haloalkyl, C₁-C₄ alkoxy; C₁-C₄ haloalkoxy; nitro; or cyano;

R^{1 ]} and R¹² are each independently H; C₁-C₃ alkyl; or phenyl optionally

R¹³, R¹⁴, and R^{1 5} are each independently C₁-C₆ alkyl, C₁-C₆ alkenyl; C₁-C₄

alkoxy; or phenyl; comprising:

reacting a compound of Formula III

wherein Lg is halogen; acetoxy; OSO ₂Q; or

;

R¹⁶ is C₁-C₆ alkyl, C₁-C₆ alkenyl; or phenyl; and

Q is C₁-C₆ alkyl; C₁-C₆ haloalkyl; or phenyl optionally substituted with C₁-C₃ alkyl, in a suitable solvent with an oxime of the formula HONR²Z in the presence of a base or with a preformed salt of an oxime of said formula.

16. The process of Claim 15 wherein the compound of Formula III is prepared by reacting a compound of Formula IV

with a phosgenating agent in a suitable solvent.

17. The process of Claim 16 wherein the compound of Formula IV is prepared by reacting a compound of Formula V

wherein Y is— N=C=O,— NHC(O)Cl or ; with

1,1-dimethylhydrazine in a suitable solvent.

18. A compound of Formula III

wherein

R³ and R⁴ are each independently H; halogen; cyano; nitro, C₁-C₆ alkyl; C₁-C₆ haloalkyl; C₂-C₆ alkenyl; C₂-C₆ haloalkenyl; C₂-C₆ alkynyl; C₂-C₆ haloalkynyl; C₁-C₆ alkoxy; C₁-C₆ haloalkoxy; C₂-C₆ alkenyloxy; C₂-C₄ alkoxycarbonyl; or C₂-C₆ alkynyloxy;

R⁵ is H, or C₁-C₃ alkyl; Lg is halogen; acetoxy; OSO ₂Q; or

,

Q is C₁-C₆ alkyl; C₁-C₆ haloalkyl; or phenyl optionally substituted with C₁-C₃ alkyl; and

R¹⁶ is C₁ -C₆ alkyl; C₁-C₆ alkenyl; or phenyl.

19. A process for the preparation of a compound of Claim 18, comprising reacting a compound of Formula IV

with a phosgenating agent in a suitable solvent.

20. A compound of Formula IV

wherein

R⁵ is H; or C₁-C₃ alkyl; Lg is halogen; acetoxy; OSO₂Q; or

;

R¹⁶ is C₁ -C₆ alkyl; C₁-C₆ alkenyl; or phenyl; and

Q is C₁-C₆ alkyl; C₁-C₆ haloalkyl; or phenyl optionally substituted with C₁-C₃ alkyl.

21. A process for the preparation of a compound of Claim 20, comprising reacting a compound of Formula V

wherein Y is— N=C=O,— NHC(O)Cl or ; with U-dimethyl

hydrazine in a suitable solvent.