WO2002059119A1

WO2002059119A1 - Acylation of amino-isothiazoles using trialky-aluminium agents

Info

Publication number: WO2002059119A1
Application number: PCT/GB2002/000331
Authority: WO
Inventors: Steven Fitzjohn
Original assignee: Syngenta Ltd
Current assignee: Syngenta Ltd
Priority date: 2001-01-26
Filing date: 2002-01-25
Publication date: 2002-08-01
Anticipated expiration: 2003-07-26
Also published as: GB0102110D0

Abstract

Method for preparing a compound (I): from the corresponding isothiazole amine and for example an ester, using a trialkyl-aluminium compound R?50R51R52¿AI where R?50, R51 and R52¿ are each independently C¿1-10? alkyl. The method is particularly suitable for use when the ester is base- and/or nucleophile-sensitive, especially when R?7¿ is an electron withdrawing group. Also provided is a trialkyl-aluminium intermediate compound formed during the method.

Description

_AC_YLATION OF AMINO-ISOTHIAZOLES USING TRIA KY-AUMINIUM AGENTS

This invention relates to a method for preparing an isothiazole derivative. Certain compounds, comprising an isothiazole ring system linked to a second heteroaryl ring system via an amide or analogous linkage, are known from WO-95/31448, WO-97/18198, WO-98/02424, WO-98/05670, WO-98/17630 and WO-00/06566. Further examples of such compounds are given in co-pending UK patent applications nos. 0002031.3, 0002035.4, 0002036.2 and 0002041.2. Some of the compounds have pesticidal (which includes fungicidal, insecticidal, acaricidal, molluscicidal and/or nematicidal) activity. Particular examples of such compounds are those of the general formula (I):

wherein A is optionally substituted Q.₆ alkylene, optionally substituted C .₆ alkenylene, optionally substituted C₂.₆ alkynylene, optionally substituted cycloalkylene, optionally substituted Q-₆ alkylenoxy, optionally substituted oxy(Q-₆)alkylene, optionally substituted Cι-₆ alkylenethio, optionally substituted thio(C₁-₆)alkylene, optionally substituted Ci-₆ alkylenamino, optionally substituted amino(Cι-₆)alkylene, optionally substituted [Cι-₆ alkyleneoxy(Cι-₆)alkylene], optionally substituted [Cι-₆ alkylenethio(Cι-₆)alkylene], optionally substituted [Q-₆ alkylenesulfinyl(Cj_.-₆)alkylene], optionally substituted [Q-₆ alkylenesulfonyl(C₁-6)alkylene] or optionally substituted [Q-₆ alkyleneamino(Cι-₆)alkylene]; B is N, N-oxide or CR⁸;

Z is O, S orNR¹⁰;

R¹ is hydrogen, halogen, optionally substituted Q-₆ alkyl, optionally substituted C₂-₆ alkenyl, optionally substituted C₂-₆ alkynyl, optionally substituted -₆ alkoxy, optionally substituted Q-₆ alkylthio, optionally substituted C₃-₇ cycloalkyl, cyano, nitro or SF₅; R² is hydrogen, halogen, optionally substituted Q-6 alkyl, optionally substituted C₂-₆ alkenyl, optionally substituted C₂-₆ alkynyl, optionally substituted Ci-₆ alkoxy, optionally substituted d-β alkylthio, optionally substituted -₆ alkylsulfmyl, optionally substituted Q-₆ alkylsulfonyl, cyano, nitro, formyl, optionally substituted Ci-6 alkylcarbonyl, optionally substituted Q-₆ alkoxycarbonyl, SF₅ or RⁿON=C(R¹²); or R¹ and R² together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Q-₆ alkyl, Q-₆ haloalkyl or halogen; R³ is hydrogen, optionally substituted Q.io alkyl, optionally substituted [C -6 alkenyl(Q.₆)alkyl], optionally substituted [C₂-₆ alkynyl(Q-₆)alkyl], optionally substituted C₃-₇ cycloalkyl, optionally substituted Q-1₀ alkylcarbonyl, optionally substituted Q-io alkoxycarbonyl, formyl, optionally substituted Q-ioalkylan-rinocarbonyl, optionally substituted &(Q-ιo)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted Q-₆ alkylthio, optionally substituted Q-₆ alkylsulfinyl, optionally substituted Q-₆ alkylsulfonyl, optionally substituted Q-₆ arylthio, optionally substituted Ci-₆ arylsulfinyl, optionally substituted Q-₆ arylsulfonyl or R¹³R¹⁴NS(O)_p; p is 0, 1 or 2;

R⁴, R⁵ and R⁶ are, independently, hydrogen, halogen, optionally substituted Q-₆ alkyl, optionally substituted Q-₆ alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q-₆ alkylsulfinyl, optionally substituted Q-₆ alkylsulfonyl, cyano, nitro, optionally substituted Q-₆ alkylcarbonyl, optionally substituted Q-₆ alkoxycarbonyl or SF₅; R⁷ is hydrogen, halogen, cyano, optionally substituted Q- o alkyl, optionally substituted C₂-2₀ alkenyl, optionally substituted C₂-₂₀ alkynyl, optionally substituted C₃- cycloalkyl, optionally substituted C₅-₆ cycloalkenyl, formyl, optionally substituted Q-₂₀ alkoxycarbonyl, optionally substituted Q- o alkylcarbonyl, aminocarbonyl, optionally substituted Q-₂₀ alkylaminocarbonyl, optionally substituted di(Q-₂o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-(C₁-₆)alkyl-N-arylarninocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted N-(C₁-₆)alkyl-N-heteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, SH, optionally substituted Q.₂₀ alkylthio, optionally substituted Q_₂₀ alkylsulfinyl, optionally substituted Q-₂o alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, R¹⁵O, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹); R⁸ is hydrogen, halogen, nitro, cyano, optionally substituted Q-g alkyl, optionally substituted C₂-₆ alkenyl, optionally substituted C₂.₆ alkynyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Ci-₆ alkylcarbonyl, optionally substituted Q-₆ alkylaminocarbonyl, optionally substituted di(Q-₆)alkylaminocarbonyl, optionally substituted phenyl or optionally substituted heteroaryl;

R⁹ is hydrogen, cyano, nitro, optionally substituted Ci-₆ alkyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted (C₂-₆)alkenyl(Q-₆)alkyl, optionally substituted (C₂-₆)alkynyl(Q-₆)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Q-₆ alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q-₆ alkylamino, optionally substituted di(Q-₆)alkylamino, optionally substituted Q-₆ alkylcarbonylamino, optionally substituted Ci-₆ alkoxycarbonylamino, optionally substituted Q-₆ alkoxy, optionally substituted Ci-₆ alkylthio, optionally substituted Ci-₆ alkylsulfinyl, optionally substituted Q-₆ alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or Ci-₆ alkylcarbonyloxy;

R¹⁰ is hydrogen, cyano, optionally substituted Q-₈ alkyl, optionally substituted [C₂-₆ alkenyl(C₁-₆)alkyl], optionally substituted [C₂-₆ alkynyl(Q-₆)alkyl], optionally substituted C₃-₇ cycloalkyl, optionally substituted [C₃- cycloalkyl(Cι-₆)alkyl], Q-₆ alkoxy(Q-₆)alkyl, optionally substituted Q-₆ alkoxycarbonyl, optionally substituted Q-₆ alkylcarbonyl, optionally substituted Q-₆ alkylaminocarbonyl, optionally substituted di(Q-₆)alkyl-uminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted alkylsulfonyl or optionally substituted arylsulfonyl;

R¹¹ and R¹⁸ are, independently, hydrogen, optionally substituted phenyl (Q_₂)alkyl or optionally substituted.Q-20 alkyl;

R¹² and R¹⁹ are, independently, hydrogen, optionally substituted phenyl or optionally substituted Q-₆ alkyl;

R¹³ and R¹⁴ are, independently, optionally substituted Ci-₆ alkyl; or R¹³ and R¹⁴ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N and S and which is optionally substituted by one or two independently selected Q-6 alkyl groups;

R¹⁵ is hydrogen, optionally substituted Q-₂₀ alkyl, optionally substituted [C₂-₂o alkenyl(Q-₆)alkyl], optionally substituted [C₂-2₀ alkynyl(Q-₆) alkyl], optionally substituted C₃. cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, (Q-₆)alkylCH=N, optionally substituted arylCH=N, optionally substituted [aryl(Q-₆)alkyl]CH=N, optionally substituted heteroarylCH=N, optionally substituted [heterocyclyl(Q-₆)alkyl]CH=N, optionally substituted arylC(CH )=N, optionally substituted heteroarylC(CH₃)=N or optionally substituted di(Q-₆)alkylC==N; and

R¹⁶ and R¹⁷ are, independently, hydrogen, optionally substituted Q-₂₀ alkyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted [C₂-₂₀ alkenyl(Q-₆)alkyl], optionally substituted [C₂-₂o alkynyl(Q-₆)alkyl], optionally substituted Ci-₂₀ alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q-₂o alkylcarbonyl, optionally substituted Q-₂o alkylsulfonyl or optionally substituted phenylsulfonyl. Methods for preparing certain compounds of formula (I) are disclosed in WO-00/06566; they involve acylation of an amino-isothiazole (which provides the left-hand ring system) with an appropriate acid, acid chloride or acid anhydride to provide the right-hand ring system and an appropriate linking group. The reaction is carried out in the presence of an alkoxide base such as sodium methoxide or potassium tertiary-butoxide. A first aspect of the present invention provides an alternative method for the preparation of a compound of formula (I) which makes use of so-called "Weinreb" chemistry. [Jeremy I Levin, Edward Turos and Steven M Weinreb; Synthetic Communications, 12(13), 989-993 (1982) - 'An Alternative Procedure for the Aluminum-Mediated Conversion of Esters to Amides'; Anwer Basha, Michael Lipton and Steven M Weinreb; Tetrahedron Letters, 18(48), 4171-4174 (1977) - 'A Mild, General Method for the Conversion of Esters to A-rnides'; Michael F Lipton, Anwer Basha, Steven M Weinreb; Organic Syntheses, 59, 49-53 (1979) - 'Conversion of Esters to Amides with Dimethylaluminum Amides: N,N-Dimethylcyclohexanecarboxamide'.] The "Weinreb" reaction has not previously been used to prepare compounds of formula (I). It utilises a trialkyl-aluminium agent to complex with an amine nitrogen atom and hence activate the nitrogen to electrophilic attack, for instance by an ester so as to form an amide product. The reaction avoids the use of strongly acidic or basic conditions, under which certain reagents can be susceptible to nucleophilic attack, ring opening and other undesired reactions.

The method of the present invention comprises reacting together an amino-isothiazole of the general formula (II):

(π) in which R¹, R² and R³ are as defined above in relation to formula (I), and a compound

(conveniently an ester) of the general formula (HI):

(HI) in which A, B, Z and R⁴ - R⁷ are as defined above in relation to formula (I) and L is a leaving group such as halo (in particular chloro) or R³⁰-O-, where R³⁰ is hydrogen or a Q-₆ alkyl group, in the presence of a trialkyl-aluminium compound R⁵⁰R⁵¹R⁵²A1 where R⁵⁰, R⁵¹ and R⁵² are each independently selected from Q-io, preferably Q-₆, alkyl.

This method can provide a ready means of preparing compounds of formula (I), in particular where the requisite reactant (IU) is base- or nucleophile-sensitive. It may be of particular use where the reactant (III) is a benzoxazole derivative (ie, B is nitrogen and Z is oxygen) such as a benzoxazole ester (ie, L is R³⁰-O-), especially where the substituent R⁷ is electron withdrawing.

Examples of compounds of formula (I), which may be produced using the method of the present invention, are disclosed in WO-00/06566 and in co-pending UK patent applications nos. 0002031.3, 0002035.4, 0002036.2 and 0002041.2. Some compounds of formula (I) have been found to be pesticidally (in particular insecticidally and/or fungicidally) active.

Preferred compounds (I) will now be described. It is to be understood that certain compounds of formula (I) may exist in different geometrically or optically isomeric or tautomeric forms; this invention extends to all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. One group of preferred compounds of formula (I), which may be prepared using the method of the present invention, is a group wherein: A is optionally substituted Ci-₆ alkylene, optionally substituted C₂-₆ atkenylene, optionally substituted C₂-₆ alkynylene, optionally substituted Q-₆ alkylenoxy, optionally substituted oxy(Ci-₆)alkylene, optionally substituted Q-₆ alkylenethio, optionally substituted thio(Q-₆)alkylene, optionally substituted Q-₆ alkylenamino, optionally substituted arnino-(Q-₆)alkylene, optionally substituted [Q-₆ alkyleneoxy(Q-₆)alkylene], optionally substituted [Q-₆ alkylenethio(Q-₆)alkylene], optionally substituted [Ci-₆ alkylenesulfinyl(Q-₆)alkylene], optionally substituted [Ci-₆ alkylenesulfonyl(Q-₆)alkylene] or optionally substituted [Q-₆ a-kyleneamino(Q-₆)alkylene]; B is N, N-oxide or CR⁸; Z is O. S or NR¹⁰;

R³is hydrogen, optionally substituted Q-₁₀ alkyl, optionally substituted [C₂-₆ alkenyl(Ci-₆)alkyl], optionally substituted [C₂-₆ alkynyl(Ci-₆)alkyl], optionally substituted C₃-₇ cycloalkyl, optionally substituted Q-₁₀ alkylcarbonyl, optionally substituted C^o alkoxycarbonyl, formyl, optionally substituted Q-io alkylaminocarbonyl, optionally substituted di(Q-ιo)alkylanτinocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted Ci-₆ alkylthio, optionally substituted Q-₆ alkylsulfinyl, optionally substituted Q-e alkylsulfonyl, optionally substituted Q-₆ arylthio, optionally substituted Q-₆ arylsulfinyl, optionally substituted Q-₆ arylsulfonyl or R¹³R¹⁴NS;

R⁴, R⁵ and R⁶ are, independently, hydrogen, halogen, optionally substituted Q-₆ alkyl, optionally substituted Q-₆ alkoxy, optionally substituted Ci-₆ alkylthio, optionally substituted Q-₆ alkylsulfinyl, optionally substituted Q-₆ alkylsulfonyl, cyano, nitro, optionally substituted Q-₆ alkylcarbonyl, optionally substituted Q-₆ alkoxycarbonyl or SF₅;

R⁷ is hydrogen, halogen, cyano, optionally substituted Q.₂o alkyl, optionally substituted C -₂o alkenyl, optionally substituted C₂-₂₀ alkynyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted C₅-₆ cycloalkenyl, formyl, optionally substituted Q-₂o alkoxycarbonyl, optionally substituted Q-₂o alkylcarbonyl, aminocarbonyl, optionally substituted Q-₂o alkylaminocarbonyl, optionally substituted di(Q-₂o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-alkyl-N-arylaminocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted alkylheteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, R¹⁵O, HS, optionally substituted Q.₂o alkylthio, optionally substituted Q-₂₀ alkylsulfinyl, optionally substituted Ci-₂o alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹); R¹ is hydrogen, halogen, optionally substituted Ci-₆ alkyl, optionally substituted C₂-₆ alkenyl, optionally substituted C₂-₆ alkynyl, optionally substituted Ci-₆ alkoxy, optionally substituted Ci-6 alkylthio, optionally substituted C₃-₇ cycloalkyl, cyano, nitro or SF₅;

R² is hydrogen, halogen, optionally substituted Q-₆ alkyl, optionally substituted C₂-₆ alkenyl, optionally substituted C₂-₆ alkynyl, optionally substituted Q-₆ alkoxy, optionally substituted Ci-6 alkylthio, optionally substituted Ci-₆ alkylsulfinyl, optionally substituted Ci-₆ alkylsulfonyl, cyano, nitro, formyl, RⁿON=C(R¹²), optionally substituted Q-₆ alkylcarbonyl, optionally substituted Ci-₆ alkoxycarbonyl or SF₅;

1 9 or R and R together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated ring carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which may be optionally substituted by -₆ alkyl, Q-₆ haloalkyl or halogen;

R⁹ is hydrogen, cyano, nitro, optionally substituted Q-₆ alkyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted (C₂-₆)alkenyl(Q-₆)alkyl, optionally substituted (C₂-₆)alkynyl(Q-₆)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Ci-6 alkylcarbonyl, optionally substituted Ci-₆ alkoxycarbonyl, optionally substituted Ci-₆ alkylamino, optionally substituted di(Q-₆)alkylamino, optionally substituted Ci-6 alkylcarbonylamino, optionally substituted Q-₆ alkoxycarbonylamino, optionally substituted Ci-6 alkoxy, optionally substituted Q- alkylthio, optionally substituted Q-₆ alkylsulfinyl, optionally substituted Q-₆ alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or Q-₆ acyloxy;

R¹⁰ is hydrogen, cyano, optionally substituted Q-₈ alkyl, optionally substituted [C₂-₆ alkenyl(Ci-6)alkylJ. optionally substituted [C₂-₆ alkynyl(Q-₆)alkyl], optionally substituted C₃-₇ cycloalkyl, optionally substituted [C₃-₇ cycloalkyl(Q-₆)alkyl], Q-₆ alkoxy(Q-₆)alkyl, optionally substituted Q-₆ alkoxycarbonyl, optionally substituted Ci-₆ alkylcarbonyl, optionally substituted Q-₆ alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted alkylsulfonyl or optionally substituted arylsulfonyl; R⁸ is hydrogen, halogen, nitro, cyano, optionally substituted Q.₈ alkyl, optionally substituted C2-₆ alkenyl, optionally substituted -₆ alkynyl, optionally substituted C₃.₇ cycloalkyl, optionally substituted Ci-₆ alkoxycarbonyl, optionally substituted Ci-6 alkylcarbonyl, optionally substituted Ci-₆ alkylaminocarbonyl, optionally substituted di(Ci-₆)alkylaminocarbonyl, optionally substituted phenyl or optionally substituted heteroaryl;

R¹³ and R¹⁴ are, independently, optionally substituted Ci-₆ alkyl or R¹³ and R¹⁴ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-₆ alkyl groups;

R¹⁵ is hydrogen, optionally substituted Ci.₂₀ alkyl, optionally substituted [C₂-₂o alkenyl(Ci-₆)alkyl], optionally substituted [C₂-₂₀ alkynyl(Q-₆)alkyl], optionally substituted C₃-₇ cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted [heterocyclyl(Q-₆)alkylCH=N] or di(Q-₆)alkylC=N; R¹⁶ and R¹⁷ are, independently, hydrogen, optionally substituted Q-₂o alkyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted [C2-₂₀ alkenyl(Q-₆)alkyl]. optionally substituted [C₂-₂o alkynyl(Q-₆)alkyl], optionally substituted Ci-₂₀ alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q-₂o alkylcarbonyl, optionally substituted Ci-₂₀ alkylsulfonyl or optionally substituted phenylsulfonyl; or R¹⁶ and R¹⁷ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-₆ alkyl groups;

R¹⁸ and R¹¹ are, independently, hydrogen, optionally substituted phenyl (Q_₂)alkyl or optionally substituted Q-₂o alkyl; and R¹⁹ and R¹² are independently hydrogen, optionally substituted phenyl or optionally substituted Ci-6 alkyl.

When present, optional substituents on alkylene, alkenylene or alkynylene moieties include (subject to valency constraints) one or more of hydroxy, halogen, Q-₆ alkyl, Q-₆ haloalkyl, Q-6 cyanoalkyl, Q-₆ alkoxy(Q-₆) alkyl, Q-₆ alkoxy, cyano, =O, =NR²⁰ and =CR²¹R²²; and, especially, one or more of halogen, Ci-₆ alkyl, Ci-₆ haloalkyl, Q-₆ cyanoalkyl, Q-6 alkoxy(Q-6) alkyl, Q-₆ alkoxy, cyano, =O, =NR²⁰ and =CR²¹R²²; wherein R²⁰ is Q-₆ alkyl, Q-₆ haloalkyl, OR²³ or NR²⁴R²⁵; where R²¹ and R²² are, independently, hydrogen, Q-6 alkyl, Q-₆ alkoxy, Q-₆ haloalkyl, cyano, Q-₆ alkoxycarbonyl, Q-₆ alkylcarbonyl or NR²⁶R²⁷; R²³ is Q-₆ alkyl, Q-₆ haloalkyl or phenyl(Q-₂)alkyl; R²⁴ and R²⁵ are, independently, hydrogen, Q-₈ alkyl, C₃- cycloalkyl, C₂-6 alkenyl(C₁-₆)alkyl, C₂-β alkynyl(Q-₆)alkyl, C₂.₆ haloalkyl, Q-₆ alkoxy(Ci-₆)alkyl, Ci-₆ alkoxycarbonyl(Ci-6)alkyl, carboxy(Q-₆)alkyl or phenyl(Cι-₂)alkyl; or R²⁴ and R²⁵ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from O, N or S and which is optionally substituted by one or two Q-₆ alkyl groups; R²⁶ and R²⁷ are, independently, hydrogen, Q-₈ alkyl, C₃- cycloalkyl, C₂-₆ alkenyl(Q-₆)alkyl, C₂-₆ alkynyl(Q-₆)alkyl, C₂-₆ haloalkyl, Q-6 alkoxy(Q- ₆)alkyl, Ci-₆ alkoxycarbonyl(Q-₆)alkyl, carboxy(Q-₆)alkyl or phenyl(Cι-₂)alkyl; or R²⁶ and R²⁷ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two Ci-₆ alkyl groups.

Each alkyl moiety is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, ra-butyl, n-pentyl, n-hexyl, wo-propyl, n-butyl, -fee-butyl, wo-butyl, tert-butyl or neo-pentyl.

When present, the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, NCS-, C₃-₇ cycloalkyl (itself optionally substituted with Ci-₆ alkyl or halogen), C₅- cycloalkenyl (itself optionally substituted with Q-₆ alkyl or halogen), hydroxy, Q-io alkoxy, Q_io alkoxy(Q-ιo)alkoxy, tri(Q-₄)alkylsilyl(Q-6)alkoxy, Ci-₆ alkoxycarbonyl(Q-ιo)alkoxy, Q.i₀ haloalkoxy, aryl(Q. )alkoxy (where the aryl group is optionally substituted), C₃.₇ cycloalkyloxy (where the cycloalkyl group is optionally substituted with Q-e alkyl or halogen), Q-io alkenyloxy, Q-io alkynyloxy, SH, Q-io alkylthio, Q.io haloalkylthio, aryl(Q-₄)alkylthio (where the aryl group is optionally substituted), C₃- cycloalkylthio (where the cycloalkyl group is optionally substituted with Q-₆ alkyl or halogen), tti(Q-₄)alkylsilyl(Q-₆)alkylthio, arylthio (where the aryl group is optionally substituted), Q-₆ alkylsulfonyl, Q-₆ haloalkylsulfonyl, Q-₆ alkylsulfinyl, Ci-₆ haloalkylsulfinyl, arylsulfonyl (where the aryl group may be further optionally substituted), tri(Q-₄)alkylsilyl, aryldi(Q- )alkylsilyl, (Q-₄)alkyldiarylsilyl, triarylsilyl, Q-io alkylcarbonyl, HO2C, Q-₁₀ alkoxycarbonyl, aminocarbonyl, Q-₆ alkylaminocarbonyl, di(Q-₆ alkylaminocarbonyl, N-(Q-₃ alkyl)-N-(Ci-₃ alkoxy)aminocarbonyl, Ci-₆ alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(Q-₆)alkylaminocarbonyloxy, aryl (itself optionally substituted), heteroaryl (itself optionally substituted), heterocyclyl (itself optionally substituted with Q-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy, (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with Ci-₆ alkyl or halogen), amino, Q-₆ alkylamino, di(Q-6)alkylamino, Q-6 alkylcarbonylamino and N-(C₁-₆)alkylcarbonyl-N-(Q-₆)alkylamino. Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E or ©-configuration. Examples are vinyl, allyl and propargyl.

When present, the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety. In the context of this specification acyl is optionally substituted Q-6 alkylcarbonyl (for example acetyl), optionally substituted C₂-₆ alkenylcarbonyl, optionally substituted C₂-6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroarylcarbonyl.

Halogen is fluorine, chlorine, bromine or iodine. Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF₃, CF₂C1, CF₃CH₂ or CHF₂CH₂.

Haloalkenyl groups are alkenyl groups which are substituted with one or more of the same or different halogen atoms.

Aryl includes naphthyl, anthracyl, fluorenyl and indenyl but is preferably phenyl. The term heteroaryl refers to an aromatic ring containing up to 10 atoms including one or more heteroatoms (preferably one or two heteroatoms) selected from O, S and N. Examples of such rings include pyridine, pyrimidine, furan, quinoline, quinazoline, pyrazole, thiophene, thiazole, oxazole and isoxazole.

The terms heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1,3-dioxolane, tetrahydrofuran and morpholine.

When present, the optional substituents on heterocyclyl include Q-₆ alkyl as well a those optional substituents given above for an alkyl moiety.

Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl. Cycloalkenyl includes cyclopentenyl and cyclohexenyl.

When present, the optional substituents on cycloalkyl or cycloalkenyl include Q-₃ alkyl as well as those optional substituents given above for an alkyl moiety. Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups. When present, the optional substituents on aryl or heteroaryl are selected, independently, from halogen, nitro, cyano, NCS-, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy(Q-₆)alkyl, C₂-₆ alkenyl, C₂-₆ haloalkenyl, -₆ alkynyl, C₃.₇ cycloalkyl (itself optionally substituted with -₆ alkyl or halogen), Q- cycloalkenyl (itself optionally substituted with Q-₆ alkyl or halogen), hydroxy, Q-jo alkoxy, Q-io alkoxy(Q-ιo)alkoxy, tri(Q- )alkylsilyl(Q-₆)alkoxy, Q-₆ alkoxycarbonyl(Ci-io)alkoxy, CM_O haloalkoxy, aryl(Ci- )alkoxy (where the aryl group is optionally substituted), C₃-₇ cycloalkyloxy (where the cycloalkyl group is optionally substituted with Ci-₆ alkyl or halogen), Q-₁₀ alkenyloxy, Q_ιo alkynyloxy, SH, Q-io alkylthio, Cι-ιo haloalkylthio, aryl(Q-₄)alkylthio (where the aryl group may be further optionally substituted), C₃- cycloalkylthio (where the cycloalkyl group is optionally substituted with Q-e alkyl or halogen), tei(Q.₄)alkylsilyl(Q-6)alkylthio, arylthio (where the aryl group is optionally substituted), Q-₆ alkylsulfonyl, Q.₆ haloalkylsulfonyl, Ci-₆ alkylsulfinyl, Q-₆ haloalkylsulfinyl, arylsulfonyl (where the aryl group is optionally substituted), tri(Cι_4)a--kylsiryl, aryld Q-^alkylsilyl, (Q-₄)alkyldiarylsilyl, triarylsilyl, Cno alkylcarbonyl, HO₂C, Cι-ιo alkoxycarbonyl, aminocarbonyl, Q-₆ alkylaminocarbonyl, di(Q-₆ alkylaminocarbonyl, N-(Q,₃ alkyl)-N-(Ci-₃ alkoxy)aminocarbonyl, Ci-₆ alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(Q-₆)alkylaminocarbonyloxy, aryl (itself optionally substituted), heteroaryl (which itself may be further optionally substituted), heterocyclyl (itself optionally substituted with Ci-₆ alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with Q-₆ alkyl or halogen), amino, Q-₆ alkylamino, cϋ(Q-₆)a-kylamino, Q-₆ alkylcarbonylamino and N-(Q-₆)alkylcarbonyl-N-(Q.₆)alkyl-unino. For substituted phenyl moieties, heterocyclyl and heteroaryl groups it is preferred that one or more substituents are independently selected from halogen, Q,₆ alkyl, Ci-₆ haloalkyl, Ci-₆ alkoxy(Q-₆)alkyl, Q-₆ alkoxy, Ci-₆ haloalkoxy, Ci-₆ alkylthio, Q-₆ haloalkylthio, Q-₆ alkylsulfinyl, Q-6 haloalkylsulfinyl, Q-₆ alkylsulfonyl, Q-₆ haloalkylsulfonyl, -₆ alkenyl, C₂-₆ haloalkenyl, C₂-6 alkynyl, Q-₇ cycloalkyl, nitro, cyano, CO₂H, Q-₆ alkylcarbonyl, Q-₆ alkoxycarbonyl, R²⁸R²⁹N or R³⁰R³¹NC(O); wherein R²⁸, R²⁹, R³⁰ and R³¹ are, independently, hydrogen or Q-₆ alkyl.

It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (Q-₆)alkyl groups. When heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (Ci-₆) alkyl groups. Phenyl(Q--t.)alkyl is, for example, 1-phenyleth-l-yl, 2-phenyleth-l-yl, 2-phenylprop-2-yl, 3-phenylprop-l-yl, but is preferably benzyl. Analogous terms are to be interpreted in corresponding fashion.

Preferably the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, HO₂ Ci-₁₀ alkoxy (itself optionally substituted by Q-io alkoxy), aryl(Q-₄)alkoxy, Q-₁₀ alkylthio, Q-₁₀ alkylcarbonyl, Q-io alkoxycarbonyl, Ci-₆ alkylaminocarbonyl, di(Q-₆ alkylaminocarbonyl, (Q-₆)alkylcarbonyloxy, optionally substituted phenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, C₃-₇ cycloalkyl (itself optionally substituted with (Q-₆)alkyl or halogen), C₃-₇ cycloalkyloxy, Q-₇ cycloalkenyl, Q-e alkylsulfonyl, Q-₆ alkylsulfinyl, tri(Q-

₄)alkylsilyl, tri(Q- )alkylsilyl(Q-₆)alkoxy, aryldi(Q-₄)alkylsilyl, (Q-^alkyldiarylsilyl and triarylsilyl.

Preferably the optional substituents on alkenyl or alkynyl include one or more of halogen, aryl and C₃-₇ cycloalkyl. It is more preferred that heterocyclyl is optionally substituted by Q-₆ alkyl.

Preferably the optional substituents for cycloalkyl include halogen, cyano and Q-₃ alkyl.

Preferably the optional substituents for cycloalkenyl include Q.₃ alkyl, halogen and cyano. The method of the present invention preferably produces a compound of formula

CIA):

wherein A, B, Z, R¹, R² , R³, R⁴, R⁵, R⁶ and R⁷ are as defined above for a compound of formula (I). More preferred compounds of formula (LA) are those wherein: R¹ is hydrogen, halogen, Q-₆ alkyl, Q-₆ alkenyl, -₆ alkynyl, Q-₆ cyanoalkyl, Q-₆ haloalkyl, Q-6 alkoxy, Q-₆ haloalkoxy, Ci-₆ alkylthio, Ci-₆ haloalkylthio, C₃-6 cycloalkyl, C₃- ₇ cycloalkyl(Q-₄)alkyl, Q-₆ alkoxy(Q-₆)alkyl, cyano, nitro or SF₅; A is Ci-₆ alkylene, Q-6 alkenylene , Ci-₆ alkylenoxy, oxy(Q-₆)alkylene, Ci-₆ alkylenamino or Ci-₆ alkylenethio, each of which is optionally substituted by Q-₃ alkyl, Q-₃ haloalkyl, Q-₃ cyanoalkyl, halogen, Q-₃ alkoxy, Q-₆ alkoxycarbonyl, cyano, =O, =NR²⁰ or =CR²¹R²²; B is N or CR⁸; Z is O, S or NR¹⁰; R is hydrogen, Q.io alkyl, benzyloxymethyl, benzoyloxymethyl, Ci-₆alkoxy(Q-₆) alkyl, C₂.6 alkenyl(Cι-₆)alkyl (especially allyl), C₂-₆ alkynyl(Cι-₆)alkyl (especially propargyl), Q-io alkylcarbonyl or Ci-io alkoxycarbonyl (especially wobutoxycarbonyl); R⁴, R⁵ and R⁶ are independently selected from hydrogen, halogen, Q-₆ alkyl, Ci-₆ alkoxy, Q-6 haloalkoxy, Ci-6 alkylthio, Ci-₆ haloalkylthio, Q-₆ alkylsulfinyl, Q_6 haloalkylsulfinyl, Ci-6 alkylsulfonyl, Q-e haloalkylsulfonyl, Q-₆ haloalkyl, cyano, nitro, Q-₆ alkylcarbonyl, Q-6 alkoxycarbonyl or SF₅;

R⁷ is cyano, Q-₈ alkyl, Q-₈ haloalkyl, Cι-₈ cyanoalkyl, C₂-₆ alkenyl, C₂-₆ alkynyl, C₃-₇ cycloalkyl, C₃.₇ halocycloalkyl, C₃-₇ cyanocycloalkyl, Q-₃ alkyl(C₃-₇)cycloalkyl, Q-₃ alkyl(C₃.₇)halocycloalkyl, C₅-₆ cycloalkenyl, C₃-₇ cycloalkyl(Cι-₆)alkyl, C₅-₆ cycloalkenyl (Q-₆)alkyl, C2-6 haloalkenyl, Ci-₆ cyanoalkenyl, Ci-₆ alkoxy(Ci-₆)alkyl, C₃-e alkenyloxy

(Q-6)alkyl, C₃-6 alkynyloxy(Cι-₆)alkyl, aryloxy(Q-₆)alkyl, formyl, Q-₆ carboxyalkyl, Ci-6 alkylcarbonyl(Cι-6)alkyl, C₂-e alkenylcarbonyl(Q-₆)alkyl, C₂-₆ alkynylcarbonyl(Ci- ₆)alkyl, Ci-6 alkoxycarbonyl(Q-₆)alkyl, C₃-₆ alkenyloxycarbonyl(Q-₆)alkyl, C₃-₆ alkynyloxycarbonyl(Q-6)alkyl, aryloxycarbonyl(Q-₆)alkyl, Ci-₆ alkylthio(Cι-₆)alkyl, Ci-₆ alkylsulfinyl(Q-6)alkyl, Cι-₆ alkylsulfonyl(Ci-₆)alkyl, aminocarbonyl(Cι-₆)alkyl, aminocarbonyl(C₂-6)alkenyl, aminocarbonyl(C₂-6)alkynyl, Ci-₆ alkylaminocarbonyl(Cι-₆) alkyl, di(Cι-6)alkylaminocarbonyl(Ci-₆)alkyl, Q-₆ alkylaminocarbonyl(C₁-₆)alkenyl, di(Ci-₆)alkylaminocarbonyl(Q-₆)alkenyl, alkylaminocarbonyl(Cι-₆)alkynyl, di(Ci-₆)alkylaminocarbonyl(Ci-₆)alkynyl, Ci-₆ alkoxycarbonyl, Ci-₆ alkylcarbonyl, aminocarbonyl, Q-₆ alkylaminocarbonyl, di(Ci-₆)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), phenyl(Q-₄)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Ci-6 haloalkyl, Q-₆ alkoxy or Q-6 haloalkoxy), phenyl(C₂-₄)alkenyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-β haloalkyl, Ci-₆ alkoxy or Ci-₆ haloalkoxy), heteroaryl(Q- ) alkyl (where the heteroaryl may be substituted by halo, nitro, cyano, Q-₆ alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy), heterocyclyl(Q- )alkyl (where the heterocyclyl may be substituted by halo, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), R¹⁵O, Q-₈ alkylthio, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹);

R is hydrogen, halogen, Ci-₆ alkyl, -₆ alkenyl, Q-₆ alkynyl, Q-₆ haloalkyl, Q-₆ alkoxy, Q-₆ alkoxy (Q.₆)alkyl, Q-₆ haloalkoxy, Q-₆ alkylthio, Ci-₆ haloalkylthio, Q-₆ alkylsulfinyl, Q-6 haloalkylsulfinyl, Q-₆ alkylsulfonyl, Q-6 haloalkylsulfonyl, Ci-₆ haloalkyl, cyano, nitro, formyl, CH=NOR^π, Q-₆ alkylcarbonyl, Q-₆ alkoxycarbonyl or SF₅; or together R¹ and R² together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated ring carbocylic or heterocyclic ring which may contain one or two hetero atoms selected from O, N or S and which may be optionally substituted by Q-₆ alkyl, Q-₆ haloalkyl or halogen;

R⁹ is cyano, nitro, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₇ cycloalkyl, C₃-₇ cycloalkyl(Q- e)alkyl,

CH₂- (C2-6) alkenyl, CH2(C2-₆)alkynyl, phenyl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Ci-₆ alkoxy or Ci-₆ haloalkoxy) heteroaryl (optionally substituted by halo, nitro, cyano, Q-e alkyl, Ci-₆ haloalkyl, -₆ alkoxy or Q-6 haloalkoxy), Q-₆ alkylcarbonyl, Ci-₆ alkoxycarbonyl, Q-₆ alkylamino, di(Q-₆)alkylamino, Ci-₆ alkylcarbonylamino, Q-₆ alkoxycarbonylamino, Q-₆ alkoxy, Ci-₆ alkylthio, Ci-₆ alkylsulfinyl, Ci-₆ alkylsulfonyl, Q-₆ haloalkylthio, -₆ haloalkylsulfinyl, Q-₆ haloalkylsulfonyl, arylthio, arylsulfinyl, arylsulfonyl or OCO(Q-₆)alkyl;

R¹⁰ is hydrogen, Q-₈ alkyl, Q-₆ haloalkyl, Q.₆ cyanoalkyl, Q-₆ alkenyl, Q-₆ alkynyl, Q-₇ cycloalkyl, Q-₆ haloalkenyl, Q_₇ cycloalkyl(Q-₆)alkyl, Ci-₆ alkoxy(Q-₆)alkyl, Q-₆ alkoxycarbonyl, Ci-₆ alkylcarbonyl, Ci-₆ alkylaminocarbonyl, di(Q-6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy) or heteroaryl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Ci-₆ haloalkyl, Ci-6 alkoxy or Q-₆ haloalkoxy); R²⁰ is Q-6 alkyl, OR²³ or NR²⁴R²⁵; R²¹ is hydrogen, Q-₆ alkyl or Q-₆ haloalkyl; R²² is hydrogen, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy, cyano, Q-₆ alkoxycarbonyl, Q-₆ alkylcarbonyl orNR²⁶R²⁷;

R⁸ is hydrogen, halogen, nitro, cyano, Q-₈ alkyl, Ci-₆ haloalkyl, Ci-₆ cyanoalkyl, -₆ alkenyl, Q-₆ alkynyl, Q-₇ cycloalkyl, C₂-₆ haloalkenyl, Q-₇ cycloalkyl(Q-₆)alkyl, Ci-₆ alkoxy(Q.₆)alkyl, Ci-₆ alkoxycarbonyl, Q-₆ alkylcarbonyl, Ci-₆ alkylaminocarbonyl, di(Q-₆) alkylaminocarbonyl, Ci-₆ alkoxycarbonyl(Cι-₆)alkyl, Ci-₆ alkylcarbonyl(Q-₆)alkyl, Ci-₆ alkylaminocarbonyl(Ci-₆)alkyl, di(Ci-₆)alkylaminocarbonyl(Q-₆)alkyl, phenyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Ci-₆ haloalkoxy), phenyl(Q-₆)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy) or heteroaryl(Q-₆)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-e haloalkyl, Ci-6 alkoxy or Q-₆ haloalkoxy);

R²³ is Q-e alkyl or optionally substituted phenyl(Ci-₂)alkyl; R²⁴ and R²⁵ are, independently, hydrogen, Q-₈ alkyl or phenyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, -₆ alkoxy or Ci-₆ haloalkoxy);

R¹⁵ is hydrogen, Q-₈ alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, -₆ alkenyl, -6 alkynyl, Q-₆ alkoxy(Q-₆)alkyl, phenyl(Q--ι)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl(Q--t)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-6 alkoxy or Q-₆ haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy), heterocyclyl(Q-₄)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q_₆ alkyl, Q-₆ haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Q-₆ alkoxycarbonyl(Q-₆)alkyl or N=C(CH₃)₂;

R¹⁹ is Ci-₆ alkyl, Q-e haloalkyl or phenyl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Ci-6 alkoxy or Q-₆ haloalkoxy);

R¹⁶ and R¹⁷ are, independently, hydrogen, Q-₈ alkyl, -₇ cycloalkyl, -₆ alkenyl, -₆ alkynyl, Q-₇ cycloalkyl(Q-₄)alkyl, Q-β haloalkyl, Q-₆ alkoxy(Q-₆)alkyl, Q-₆ alkoxycarbonyl, or R¹⁶ and R¹⁷ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from O, N or S and which may be optionally substituted by one or two Ci-₆ alkyl groups; R¹⁸ and R¹¹ are, independently, Ci-₆ alkyl or phenyl(Q-₂)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-6 haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy); and

R²⁶ and R²⁷ are, independently, hydrogen, Q-₈ alkyl, Q-₇ cycloalkyl, -₆ alkenyl, -6 alkynyl, -6 haloalkyl, Q-₆ alkoxy(Q-₆)alkyl, Q-₆ alkoxycarbonyl(Q-6)alkyl, carboxy(Q-6)alkyl or phenyl(Q-₂)alkyl; or R²⁶ and R²⁷ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Ci-₆ alkyl groups. It is preferred that A is Q-6 alkylene, Q-6 alkenylene, Ci-6 alkylenoxy, oxy(Q-6)alkylene or Ci-6 alkylenamino, each of which is optionally substituted by Q-₃ alkyl, Q-₃ haloalkyl, Q-₃ cyanoalkyl, halogen, Q-₃ alkoxy, Ci-6 alkoxycarbonyl, cyano, =O, =NR²⁰ or =CR²¹R²²; where R²⁰ is Q-₆ alkyl, OR²³ or NR²⁴R²⁵; R²³ is Q-₆ alkyl or phenyl(Q-₂)alkyl (where the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy); R²⁴ and R²⁵ are, independently, hydrogen, Q-₈ alkyl or phenyl (which may be optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy); R²¹ is hydrogen, Q.6 alkyl or Q-₆ haloalkyl; R²² is hydrogen, Ci-6 alkyl, Ci-6 haloalkyl, Q_6 alkoxy, cyano, Ci-6 alkoxycarbonyl, Q-6 alkylcarbonyl or NR²⁶R²⁷; and R²⁶ and R²⁷ are, independently, hydrogen, Q-₈ alkyl, Q-₇ cycloalkyl, -₆ alkenyl, -6 alkynyl, Q-β haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl(Q-₆)alkyl, carboxy(Q-₆)alkyl or phenyl(Q-₂)alkyl; or R²⁶ and R²⁷ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-₆ alkyl groups. A is more preferably Q^ alkylene (optionally substituted by halogen, Q-₃ alkyl or

Q-₃ alkoxy, -C(O)- or Q-₄ alkyleneoxy (which may be optionally substituted by Q-₃ alkyl).

It is even more preferred that A is Q-₂ alkyl-substituted Q-₄ alkylene, fluoro- substituted Q-₄ alkylene, methoxy-substituted Q-₄ alkylene, -C(O)- or Q-₄ alkyleneoxy; still more preferably A is Q-₂ alkyl-substituted Q- alkylene, fluoro-substituted C_M alkylene or methoxy-substituted Q- alkylene.

It is further preferred that A is CH(CH₃)CH₂, CH₂CH(CH₃), CH(CH₃), CHF, CH(OCH₃) or CH(CH₃)O; yet further preferred is for A to be CH(CH₃)CH₂, CH₂CH(CH₃), CH(CH₃), CHF or CH(CH₃)O; it is especially preferred that A is CHF, CH(OCH₃) or CH(CH₃); and most preferably A is CHF or CH(CH₃).

B is preferably N.

Z is preferably O or S, more preferably O. It is preferred that R¹ is hydrogen, halogen, Ci-₆ alkyl, Q-₆ cyanoalkyl, Ci-₆ haloalkyl, -₇ cycloalkyl(Q- )alkyl, Q-₆ alkoxy(Q-₆)alkyl, Q-₆ alkenyl, Q-6 alkynyl, Q-6 alkoxy, Q-₆ haloalkoxy, Ci-₆ alkylthio, Ci-₆ haloalkylthio, Q-₆ cycloalkyl, cyano, nitro or SF₅.

R¹ is more preferably hydrogen, halogen, Q-₆ alkyl, C₂-6 alkenyl, Ci-6 haloalkyl, Q-₆ alkoxy, Ci-₆ haloalkoxy, Q-₆ alkylthio, Q-₆ haloalkylthio, C₃-₆ cycloalkyl, cyano, nitro or SF₅.

It is even more preferred that R¹ is hydrogen, halogen, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy(Q-₆)alkyl, -₆ alkenyl, Q-₆ alkoxy, Q-₆ haloalkoxy, Q-6 alkylthio, Ci-₆ haloalkylthio, -₆ cycloalkyl or cyano.

It is most preferred that R¹ is halogen, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Ci-₆ haloalkoxy.

It is preferred that R² is hydrogen, halogen, Ci-₆ alkyl, Ci-6 haloalkyl, Ci-₆ alkoxy(Q-₆)alkyl, -₆ alkenyl, Q-₆ alkynyl, Q-₆ alkoxy, Q-₆ haloalkoxy, Q-₆ alkylthio, Ci-₆ haloalkylthio, Ci-₆ alkylsulfinyl, Q-₆ haloalkylsulfinyl, Ci-6 alkylsulfonyl, Ci-₆ haloalkylsulfonyl, cyano, nitro, formyl, Ci-₆ alkylcarbonyl, Q-₆ alkoxycarbonyl or CH=NOR^π; or that R¹ and R² together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Q-₆ alkyl, Q-₆ haloalkyl or halogen; where R¹¹ is phenyl(Q-₂)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Ci-₆ haloalkoxy) or Q-₆ alkyl.

It is more preferred that R² is hydrogen, halogen, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy (Q-₆)alkyl, Q-₆ alkoxy, Q-₆ haloalkoxy, Ci-₆ alkylthio or SF₅; or R¹ and R² together with the atoms to which they are attached form a cyclopentane or benzene ring optionally substituted by Ci-6 alkyl, Q-6 haloalkyl or halogen. R² is even more preferably hydrogen, halogen, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy,

Q-6 haloalkoxy, Q-₆ alkoxy(Q-₆)alkyl, Q-₆ alkylthio or SF₅; or R¹ and R² together with the atoms to which they are attached form a benzene ring optionally substituted by Q-₆ alkyl, Q-₆ haloalkyl or halogen. It is further preferred that R² is hydrogen, halogen, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆

1 alkoxy(Q-₆)alkyl, Ci-₆ alkoxy, Ci-₆ haloalkoxy, or R and R together with the atoms to which they are attached form a cyclopentane ring optionally substituted by Q-₆ alkyl, Q-₆ haloalkyl or halogen. R² is most preferably halogen, Ci-₆ alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy, Q-₆ alkoxy (Q-₆)alkyl or Ci-₆ haloalkoxy.

It is preferred that R³ is hydrogen, Q-₁₀ alkyl, Ci-₆ alkylcarbonyloxy(Q-₆)alkyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or CM alkyl), Q-₆ alkoxy(Q-₆)alkyl (where the alkyl group is optionally substituted by aryl or C_M alkoxycarbonyl), Q-₆ alkenyloxy(Q-₄)alkyl, -₆ alkynyloxy(Q-₄)alkyl, benzyloxy(Q- )alkyl (where the phenyl ring is optionally substituted with halogen or Q-₄ alkyl), Q-₇ cycloalkyl(Q--_t)alkyl, heteroaryl(Q-₃)alkyl (where the heteroaryl group is optionally substituted with halogen), tri(C₁-₄)alkylsilyl(C₁-₆)alkyl, Q-₆ alkenyl(Q-₆)alkyl (especially allyl), Q-₆ haloalkenyl(Q-₆)alkyl, CM alkoxycarbonyl(C₂-₆)alkenyl(Q-₆)alkyl, Q-₆ alkynyl(Q-₆)alkyl, tri(Q- )aιkylsilyl(Q-₆)alkynyl(Q-₆)alkyl or Q-₁₀ alkylcarbonyl.

It is further preferred that R³ is hydrogen, Ci-₆ alkyl, Q-₆ alkylcarbonyloxymethyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or CM alkyl), Ci-₆ alkoxymethyl, -₆ alkenyloxymethyl, Q-₆ alkynyloxymethyl, benzyloxymethyl (where the phenyl ring is optionally substituted with halogen or Q- alkyl), -₆ alkynyl(Q-₆)alkyl (especially propargyl) or Q_ιo alkylcarbonyl.

R³ is more preferably hydrogen, Q-₆ alkyl, Ci-₆ alkoxy(Q-6)alkyl, benzyloxymethyl or benzoyloxymethyl; or alternatively R³ may be Q-e alkylcarbonyloxymethyl.

It is most preferred that R³ is hydrogen, Q-₆ alkyl, Q-₆ alkylcarbonyloxymethyl or Q-₆ alkoxymethyl. It is preferred that R⁴, R⁵ and R⁶ are, independently, hydrogen, halogen, Ci-₆ alkyl,

Q-₆ haloalkyl, Ci-₆ alkoxy, Q-e haloalkoxy, Q-₆ alkylthio, Ci-₆ haloalkylthio, Q-₆ alkylsulfinyl, Q_₆ haloalkylsulfinyl, Q-₆ alkylsulfonyl, Q-₆ haloalkylsulfonyl, cyano, nitro, Q-₆ alkylcarbonyl or Ci-6 alkoxycarbonyl.

It is more preferred that R⁴, R⁵ and R⁶ are, independently, hydrogen, halogen or Q-₃ alkyl.

It is even more preferred that R⁴, R⁵ and R⁶ are, independently, hydrogen or halogen (especially fluorine). It is preferred that R⁷ is cyano, Q-₈ alkyl, Q-₈ haloalkyl, Q-₈ cyanoalkyl, C₃-₇ cycloalkyl(Q-₆)alkyl, C₅-₆ cycloalkenyl(Q-₆)alkyl, Ci-₆ alkoxy(Ci-₆)alkyl, C₃-₆ alkenyloxy(Cι-₆)alkyl, Q-₆ alkynyloxy(Cι-₆)alkyl, aryloxy(Ci-₆)alkyl, Ci-₆ carboxyalkyl, Q-₆ alkylcarbonyl(Ci-₆)alkyl, C₂-₆ alkenylcarbonyl(Cι-₆)alkyl, C₂-₆ aιkynylcarbonyl(Q-₆)alkyl, Q-6 alkoxycarbonyl(Cι-₆)alkyl, C₃-₆ alkenyloxycarbonyl(Q-₆)alkyl, C₃-₆ alkynyloxycarbonyl(Cι-₆)alkyl, aryloxycarbonyl(Cι-₆)alkyl, Ci-₆ alkylthio(Q-₆)alkyl, Ci-₆ alkylsulfinyl(Q-₆)alkyl, Ci-₆ alkylsulfonyl(Cι-₆)alkyl, aminocarbonyl(C₁-₆)alkyl, Ci-₆ alkylarninocarbonyl(Ci-₆)alkyl, di(Cι-₆)alkylaminocarbonyl(Cι-₆)alkyl, phenyl(Cι- )alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q.₆ haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-₄)alkyl (where the heteroaryl group is optionally substituted by halo, nitro, cyano, Q_₆ alkyl, Ci-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), heterocyclyl(Q-₄)alkyl (where the heterocyclyl group is optionally substituted by halo, cyano, Q-6 alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy or Ci-e haloalkoxy), -6 alkenyl, Q-6 haloalkenyl, Q-₆ cyanoalkenyl, -₆ cycloalkenyl, aιmnocarbonyl(Q-₆)alkenyl, Q-₆ alkylarninocarbonyl(Q-₆)alkenyl, άi(Q-₆)alkylaminocarbonyl(Q-₆)alkenyl, phenyl(Q-₄)alkenyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), Q-β alkynyl, aminocarbonyl(C₂-₆)alkynyl, alkylaminocarbonyl(Q-₆)alkynyl, di(Cι-6)alkylaminocarbonyl(Cι-₆)alkynyl, Q-₇ cycloalkyl, -₇ halocycloalkyl, Q-₇ cyanocycloalkyl, Q-₃ alkyl(Q-₇)cycloalkyl, Q.₃ alkyl(Q-₇)halocycloalkyl, -₆ cycloalkenyl, formyl, Ci-₆ alkoxycarbonyl, Ci-₆ alkylcarbonyl, aminocarbonyl, Ci-₆ alkylaminocarbonyl, di(Q-₆)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Ci-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-e haloalkoxy), Q.₈ alkylthio, R¹⁵O, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹); where R¹⁵ is hydrogen, Q-₈ alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, Q-₆ alkoxy(Q-₆)alkyl, phenyl(Q--ι)alkyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl(Q-₄)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heterocyclyl(Q_4)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), Q-₆ alkoxycarbonyl(Q-₆)alkyl, Q-₆ alkenyl, Q-e alkynyl or N=C(CH₃)₂; R¹⁹ is phenyl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), Q-₆ alkyl or Ci-₆ haloalkyl; R¹⁶ and R¹⁷ are, independently, hydrogen, Q-₈ alkyl, Q-₇cycloalkyl(Q-₄)alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy(Q-₆)alkyl, C₃- cycloalkyl, Q-₆ alkenyl, -₆ alkynyl or Q-₆ alkoxycarbonyl; and R¹⁸ is phenyl(Q-₂)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Ci-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy) or Q-₆ alkyl.

R⁷ is more preferably Q-₈ alkyl, Q-₈ haloalkyl, Q-₈ cyanoalkyl, Q-₆ alkenyl, Q-₆ alkynyl, Q- cycloalkyl, Q_₇ halocycloalkyl, Q-₇ cyanocycloalkyl, Q-₃ alkyl(Q. )cycloalkyl, Q-₃ alkyl(C₃-₇)halocycloalkyl, C₅-₆ cycloalkenyl, C₃-₇ cyclθ-dkyl(Q-₆)alkyl, C₅-₆ cycloalkenyl(Q-₆)alkyl, C₂-₆ haloalkenyl, Ci-₆ cyanoalkenyl, Ci-6 alkoxy(Q-₆)alkyl, -6 alkenyloxy(Q-₆)alkyl, C₃-₆ alkynyloxy(Ci-₆)alkyl, aryloxy(Ci-₆)alkyl, Q-β carboxyalkyl, Q-₆ alkylcarbonyl(Ci-₆)alkyl, C₂-₆ alkenylcarbonyl(Q-₆)alkyl, C₂-₆ alkynylcarbonyl(Q-₆)alkyl, Ci-₆ alkoxycarbonyl(Ci-₆)alkyl, Q-e alkenyloxycarbonyl(Q-₆)alkyl, C₃-₆ alkynyloxycarbonyl(Ci.₆)alkyl, aryloxycarbonyl(Cι-₆)alkyl, Q-₆ alkylthio(Q-₆)alkyl, Ci-e alkylsulfinyl(Q-₆)alkyl, Ci-₆ alkylsulfonyl(Q-₆)alkyl, aminocarbonyl(Cι-6)alkyl, aminocarbonyl(C₂-₆)alkenyl, aminocarbonyl(C₂-₆)alkynyl, Q-₆ alkylaminocarbonyl(Q- e)alkyl, di(Ci-₆)alkylaminocarbonyl(Ci-₆)alkyl, Q-₆ alkylaminocarbonyl(Q-₆)alkenyl, di(Cι-₆)alkylarninocarbonyl(Ci-₆)alkenyl, alkylaminocarbonyl(Ci-₆)alkynyl, di(Ci-₆)alkylaminocarbonyl(Ci-₆)alkynyl, phenyl (optionally substituted by halo, nitro, cyano, Q.₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-e haloalkoxy), pheny^Q-^alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-₆ haloalkyl, Q. ₆ alkoxy or Q-₆ haloalkoxy), phenyl(Q-₄)alkenyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-e alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-₆ haloalkoxy), heterocyclyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), heteroaryl (Q.- alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), heterocyclyl(Cι-₄)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q. ₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), R¹⁵O, Q-₈ alkylthio, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹); where R¹⁵ is Q_₈ alkyl, Ci-6 haloalkyl; R¹⁹ is Q-₆ alkyl, Ci-₆ haloalkyl or phenyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy); R¹⁶ and R¹⁷ are, independently, hydrogen, Q-₈ alkyl, Q-₇ cycloalkyl, Q-₆ alkenyl, Q-₆ alkynyl, C₃.₇ cycloalkyl(Cι-₄)alkyl, C₂-₆ haloalkyl, Q-6 alkoxy(Q-₆)alkyl, Q-6 alkoxycarbonyl, or R¹⁶ and R¹⁷ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-₆ alkyl groups; and R¹⁸ is Ci-₆ alkyl or phenyl(Q-₂)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy); and R⁷ is more preferably Q-₈ alkyl, Q-₈ haloalkyl, Q-₈ cyanoalkyl, Q-7 cycloalkyl, Q.₃ alkyl(C₃_₇)cycloalkyl, Q-₆ alkoxy(Q-₆)alkyl, heterocyclyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy) or R¹⁶R¹⁷N; where R¹⁶ and R¹⁷ are, independently, Q-₈ alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-₆ alkyl groups.

It is further preferred that R⁷ is Q-₈ alkyl, Q-₈ haloalkyl, Q-₈ cyanoalkyl, Q-7 cycloalkyl(Q-₆)alkyl, -₆ cycloalkenyl(Q-₆)alkyl, Ci-₆ alkoxy(Q-₆)alkyl, Q-e alkenyloxy(Q-₆)alkyl, -₆ alkynyloxy(Q-₆)alkyl, _tryloxy(Q-₆)alkyl, Q-₆ carboxyalkyl, Q-6 alkylcarbonyl(Q-₆)alkyl, Q-β alkenylcarbonyl(Q-₆)alkyl, Q-₆ alkynylcarbonyl(Q-6)alkyl, Q-₆ alkoxycarbonyl(Q-₆)alkyl, -₆ alkenyloxycarbonyl(Q_₆)alkyl, Q-6 alkynyloxycarbonyl- (Q-₆)alkyl, aryloxycarbonyl(Ci-₆)alkyl, Q-₆ alkylthio(Cι-₆)alkyl, Q-₆ a]kylsulfinyl(Q-6) alkyl, Q-₆ alkylsulfonyl(Q-₆)alkyl, arninocarbonyl(Q-6)alkyl, Ci-₆ alkylarninocarbonyl(Q-6) alkyl, di(Q-₆)alkylaminocarbonyl(Q-₆)alkyl, phenyl(Q-₄)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-₆ haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-₄)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q_₆ alkyl, Ci-₆ haloalkyl, Q.₆ alkoxy or Q-₆ haloalkoxy), heterocyclyl- (CM) alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q_6 haloalkoxy), Q-₆ alkenyl, Q-6 haloalkenyl, Ci-₆ cyanoalkenyl, -₆ cycloalkenyl, aminocarbonyl(Q-6)alkenyl, Q-₆ alkylaminocarbonyl(Q-₆) alkenyl, di(Q₆)alkylarmnocarbonyl(Q-₆)alkenyl, phenyl(Q-₄)alkenyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Ci-e haloalkyl, Q-₆ alkoxy or Ci-₆ haloalkoxy), Q-6 alkynyl, aminocarbonyl(Q-6)alkynyl, alkylaminocarbonyl(Q-6) alkynyl, di(Q-₆)alkylan nocarbonyl(Q-₆)alkynyl, Q-₇ cycloalkyl, Q-₇ halocycloalkyl, Q-₇ cyanocycloalkyl, Q-₃ alkyl(C₃- )cycloalkyl, Q-₃ alkyl(C₃-₇)halocycloalkyl, phenyl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Ci-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-6 haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), Q-₈ alkylthio, R¹⁵O, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹); where R¹⁵ is Q-₈ alkyl or Ci-₆ haloalkyl; R¹⁹ is phenyl (optionally substituted by halo, nitro, cyano, Q.₆ alkyl, Q-₆ haloalkyl, Q-₆ alkoxy or Q-₆ haloalkoxy), Q_₆ alkyl or Ci-₆ haloalkyl; R¹⁶ and R¹⁷ are, independently, hydrogen, Q-₈ alkyl, -₇ cycloalkyl(Q-₄)alkyl, Q-₆ haloalkyl, Q.₆ alkoxy(Q-₆)alkyl, Q.₇ cycloalkyl, Q-₆ alkenyl, -₆ alkynyl or Q-e alkoxycarbonyl; and R¹⁸ is phenyl(Q_₂)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q.₆ haloalkyl, Ci-₆ alkoxy or Ci-e haloalkoxy) or Q-e alkyl.

It is even more preferred that R⁷ is Q-₈ alkyl, Q-₈ haloalkyl, Q_₈ cyanoalkyl, Q-₆ alkoxy (Q-₆) alkyl, Q-₇ cycloalkyl, Q-₃ alkyl (Q.₇) cycloalkyl, heterocyclyl (optionally substituted by halo, nitro, cyano, Q_₆ alkyl, Ci-₆ haloalkyl, Q.₆ alkoxy or Q-₆ haloalkoxy) or di(Q.₈)alkylamino. It is yet more preferred that R⁷ is Q-₈ alkyl, Q-₈ haloalkyl, Q.₈ cyanoalkyl, Q.₆ alkoxy (Q-₆) alkyl, Q.₇ cycloalkyl, Q.₃ alkyl (Q-₇) cycloalkyl, heterocyclyl (optionally substituted by Ci-₆ alkyl) or di(Q-₈)alkylamino.

R⁷ is most preferably Q-₈ alkyl, Q-₈ haloalkyl, Q-₈ cyanoalkyl, Q-₇ cycloalkyl, Q-₃ alkyl(C₃-₇)cycloalkyl, Q-₆ alkoxy(Q-₆)alkyl or R¹⁶R¹⁷N; where R¹⁶ andR¹⁷ are, independently, Cι_₈ alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one further heteroatom selected from O, N or S and which may be optionally substituted by one or two Ci-₆ alkyl groups. It is preferred that R is hydrogen, halogen, nitro, cyano, Q-₈ alkyl, -₆ haloalkyl, Ci-₆ cyanoalkyl, Q-₇ cycloalkyl(Q-₆)alkyl, Q-₆ alkoxy(Q-₆)alkyl, Q-₆ alkoxycarbonyl(Q.₆)alkyl, Q-6 aιkyιcarbonyl(Q.₆)alkyl, Q-₆ alkylaminocarbonyl(Q-₆)alkyl, di(Q-6)alkylamino-carbonyl(Ci-₆)alkyl, phenyl(Q-₆)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Ci-₆ haloalkyl, Q-e alkoxy or Q.₆ haloalkoxy), heteroaryl(Q-₆)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy), Q-₆ alkenyl, Q-6 haloalkenyl, -6 alkynyl, C₃-₇ cycloalkyl, Q.₆ alkoxycarbonyl, Q-₆ alkylcarbonyl, Ci-e alkylaminocarbonyl, di(Ci-₆)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q_₆ alkoxy or Ci-₆ haloalkoxy) or heteroaryl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-β haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy).

It is more preferred that R⁸ is hydrogen, halogen, Q-₈ alkyl or Ci-₆ haloalkyl.

It is preferred that R⁹ is cyano, nitro, Ci-₆ alkyl, Q.₆ haloalkyl, Q-₇ cycloalkyl(Q-₆)alkyl, Q-₇ cycloalkyl, CH₂(Q-₆)alkenyl, CH₂(Q-₆)alkynyl, phenyl

(optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-₆ haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q_₆ alkyl, Ci-₆ haloalkyl, Q.₆ alkoxy or Q-₆ haloalkoxy), Q-₆ alkylcarbonyl, Q.₆ alkoxycarbonyl, Q.₆ alkylamino, ck(Q-₆)alkylanτino, Ci-₆ alkylcarbonylamino, Q.₆ alkoxycarbonylamino, Q-₆ alkoxy, Q-₆ alkylthio, Ci-₆ haloalkylthio, Ci-₆ alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-e alkylsulfonyl, Q-₆ haloalkylsulfonyl, arylthio, arylsulfinyl, arylsulfonyl or (Q. ₆)alkylcarbonyloxy.

It is preferred that R¹⁰ is hydrogen, Q-₈ alkyl, Q-₆ haloalkyl, Q-6 cyanoalkyl, Q-₆ alkenyl, Q-6 haloalkenyl, Q-β alkynyl, Q-₇ cycloalkyl, Q-₇ cycloalkyl(Q-6)alkyl, Ci-6 alkoxy(Q-6)alkyl, Q.₆ alkoxycarbonyl, Ci-₆ alkylcarbonyl, Ci-6 alkylaminocarbonyl, di(Q-₆)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Ci-₆ alkyl, Ci-e haloalkyl, Q-₆ alkoxy or Ci-e haloalkoxy) or heteroaryl (optionally substituted by halo, nitro, cyano, Q-₆ alkyl, Q-₆ haloalkyl, Ci-₆ alkoxy or Q-₆ haloalkoxy).

It is more preferred that R¹⁰ is hydrogen, Q-₈ alkyl or Q-₆ haloalkyl. Certain compounds of formula (IA) are described in WO 00/06566, and recited in

Tables A1-A70, B1-B70, C1-C70, D1-D70, E1-E70, F1-F70, G1-G70, H1-H70, 11-170, J1-J70, K1-K70, L1-L70, M1-M70, N1-N70, O1-O70, P1-P70, Q1-Q70, R1-R70, S1-S70, T1-T70, U1-U70 and V1-V20 of that document.

The natures of B, Z and R⁴ - R⁷ are typically such that the right hand bicyclic ring system is vulnerable to nucleophilic attack and/or ring opening, particularly in the presence of a strong base. Thus, R⁷ may be an electron-withdrawing group, such as haloalkyl (in particular a poly-rhalogenated group such as QF₇).

Compounds of formula (II) are either known compounds or may be prepared from commercially available starting materials by methods described in the literature (see, for example, C. Oliver Kappe, Robert Flammang, and Curt Wentrup, Heterocycles, Vol. 37, No. 3, 1615, (1994); A. Adams and R. Slack, J. Chem. Soc, 3061, (1959); and Ronald E Hackler, Kenneth W. Burow, Jr., Sylvester V. Kaster and David I. Wickiser, J. Heterocyclic Chem, 26, 1575, (1989)). A compound of formula (HI) in which L is OH (Ilia) may be prepared by hydrolysis of the corresponding compound (lTlb) in which L is Ci-₆ alkyl, by a method known in the art. The hydrolysis may be carried out under neutral, basic or acidic conditions; the conditions should be chosen such that substituent R⁷ is unchanged during the hydrolysis reaction. Compounds of formula (nib) are capable of ready hydrolysis under different conditions, as known in the literature. Suitable compounds of formula (IDb) may be selected, for example, by reference to Theodora W. Greene, Protective Groups in Organic Synthesis, Chapter 5, John Wiley and Sons, New York, 1981.

A compound of formula (Hla) may be converted to for instance an acid chloride, anhydride or chloroformate suitable for use in the method of the present invention; such procedures are well known and are described, for example, in J. March, Advanced Organic Chemistry, Third Edition, John Wiley and Sons, New York, 1985, pages 370-376 and references therein.

Alternatively, compounds of formula (πi)/(ffla)/(IιTb) may be prepared by cyclisation of a compound of formula (V):

(N) where A, L and R⁴-R⁶ are as defined above in relation to formula (DI) and R⁷⁰ and R⁷¹ are cyclisable groups, such as in formula (Na):

(Na)

(see, for example, David W. Dunwell, Delme Evans, Terence A. Hicks, J. Med. Chem.,

1975, Vol. 18, No. 1, 53; Abdou O. Abdelhamid, Cyril Parkanyi, S.M. Khaledur Rashid and

Winston D. Lloyd, J. Heterocyclic Chem., 25, 403, (1988); Teruyuki Kondo, Sungbong Yang, Keun-Tae Huh, Masanobu Kobayashi, Shinju Kotachi and Yoshihisa Watanabe,

Chemistry Letters, 1275-1278, 1991; Dale L. Boger, J. Org. Chem., 43, No 11, 2296, 1978 ). The substituent R⁷ may be an atom or group which itself may be converted into other functional groups; procedures are known in the literature for such transformations involving benzoxazoles and benzothiazoles (for example, Lazer, Edward S., Adams, Julian; Miao, Clara K.; Farina, Peter, Eur. Pat. Appl. EP0535521). Alternatively R may contain atoms or groups which may be replaced by other moieties under known conditions.

A compound of formula (N) may be prepared by reduction of a compound of formula (NI):

(NI) where A, Z, L and R⁴ - R⁶ are as defined above in connection with formula (HI), and such procedures are known in the art (see, for example, J. March, Advanced Organic Chemistry, Third Edition, John Wiley and Sons, New York, 1985, and references therein).

A compound of formula (VI), wherein Z is oxygen, may be prepared by the nitration of a compound of formula (NH):

(VΓJ) under known conditions. A compound of formula (NI) in which Z is sulfur may be prepared from a compound of formula (NI) in which Z is oxygen, using conditions similar to those described by J. Scheigetz, R. Zamboni and B. Roy, Synth. Commun., 25 (1995) (18), pages 2791-2806. A compound of formula (NI) in which Z is nitrogen may be prepared from a compound of formula (NH) by a sequence of acylation, nitration and deacylation, using conditions known in the art.

In the trialkyl-aluminium agent, R , R and R are each independently selected from alkyl groups, preferably Q-Q alkyl groups, more preferably either methyl or ethyl, most preferably methyl such as in the preferred reagent Me₃ Al. Suitable solvents for the reaction include toluene, benzene, hexane and other inert hydrocarbons. Selection of an appropriate solvent for given reactants (H) and (HI) is well within the capabilities of the average person skilled in the art.

The method of the invention is suitably effected at a fairly high temperature, for instance between about 40°C and 120°C, more preferably between about 50°C and 100°Q most preferably between about 70°C and 100°C. Reaction times may vary, but in general the reaction will be completed in between 2 and 8 hours, more typically between 2 and 4 hours. After the reaction, the reaction mixture may suitably be left to stand at room temperature for between 12 and 48 hours, then worked up prior to product isolation. Suitably, between 1 and 1.2 molar equivalents of the trialkyl-aluminium agent may be used for between 1 and 1.2 molar equivalents of the amine reactant (H).

Suitable reaction conditions may in particular be derived from the published literature on the Weinreb reaction (supra).

The reactant (HI) is preferably added to a pre-prepared mixture of the amine isothiazole (JJ) and the trialkyl-aluminium agent.

A second aspect of the present invention provides a dialkylaluminium intermediate compound (X):

(X) formed during the method of the first aspect. This intermediate has the general formula (H) but with the group A1-R⁵⁰R⁵¹ attached to the amine nitrogen. R⁵⁰ and R⁵¹ are as defined above in connection with the trialkyl-aluminium agent.

A third aspect of the present invention provides a method for the preparation of a compound of formula (I) as defined above, which method involves reacting a compound of formula (HI) (also as defined above) with the intermediate compound (X) of the second aspect of the invention.

Certain compounds of formula I, NIH and IX are novel and as such form a further aspect of the invention.

The following examples demonstrate the preparation of two pesticidally active benzoxazoles (VIH) and (IX), using Weinreb chemistry to react together an amino-isothiazole of the formula (H) and a benzoxazole ester of the formula (HI), in the presence of a trialkyl-aluminium catalyst.

EXAMPLE 1

Toluene, hexane

C_I4H₁₀F₇NO₃ C₁₈H₁₃CIF₇N₃θ₂S MW 373 MW 503.5 Compound (VDIa) Compound (Vm)

Materials

Method The amino-isothiazole (4.77 g) was dissolved in toluene (30 ml) and washed in with further toluene (10 ml) and the mixture stirred at room temperature under nitrogen. Trimethylaluminium (2M, 15.06 ml) was charged to a pressure equalising dropping funnel via a cannula and added dropwise over 20 mms maintaining the reaction temperature between 20 and 25°C (water bath cooling). During this addition evolution of methane was observed and around three quarters of the way through the addition a solid began to fall out of solution resulting in a thin easily stirred orange slurry. The slurry was stirred at room temperature for 30 mins and then a solution of the benzoxazole ester (NJHa) (9.854 g) in toluene (25 ml) was added dropwise over 20 mins (little exotherm). The resultant orange suspension was heated at reflux (reflux temp ~ 96°C) under nitrogen, resulting in the suspension dissolving to afford a dark red solution. The progress of the reaction was followed by HPLC (HP1100, KROMASIL KR100-3.5C18-35AS, 35 x 3.2 mm column, water/acetonitrile 98:2 to 10:90 gradient, 1.5 ml/min, UN 254 nm) of samples (10% v/v H₂SO-t/EtOAc). After 70 mins - HPLC retention time (rt) 3.39 (2.8%) - amine isothiazole; 4.84 (20.8%) - toluene; 6.18 (6.3%) - ester (VHIa); 6.34 (4.3%) - bώ-alkylated benzoxazole ester (impurity in starting material); 6.68 (61.2%) - Compound (NHI). After 3 hours - HPCL rt 3.39 (1.0%); 4.85 (20.7%) - toluene; 6.18 (0.6%); 6.35 (4.3%); 6.68 (69.1%) - Compound (NHI). Note - it appears that the bw-alkylated ester present in the starting material does not react in the Weinreb reaction. The mixture was left undisturbed at room temperature for 40 hours. The reaction mixture was then worked up by diluting with EtOAc (70 ml) with stirring and cooling the resultant brown solution in an ice bath while aqueous 10% v/v sulphuric acid (16 ml) was added dropwise over 20 mins. During this addition the temperature of the mixture was maintained at <10°C (exothermic). Thereafter the mixture was allowed to warm to room temperature as effervescing subsided. It was stirred at room temperature for 30 mins and the layers then separated (some solid at the interface). The aqueous layer was re-extracted with further EtOAc (2 x 30 ml) and the combined extracts were washed with brine (100 ml), dried over magnesium sulphate, filtered and concentrated under reduced pressure to give an orange solid, yield 13.30 g. Gas chromatography results (CPSIL 5CB, 100- 270°C, 16°C/min) rt 10.62 (0.9%); 10.79 (93.7%) - Compound (NHI); 11.15 (5.4%).

ΝMR in CDC1₃ -consistent with crude product. HPLC rt 3.40 (2.2%) - amino isothiazole; 6.19 (2.1%) - ester (VHIa); 6.35 (6.5%) - impurity in starting material; 6.69 (82.5%) - Compound (NHI). The product (Compound (NIH)) was purified by recrystallisation from 1,2-dichloroethane (20 ml)/hexane (50 ml) to give a cream solid. Results

Yield: 9.80g (74%) HPLC: UN detection (254 nm): rt 6.35 (6.2%); 6.68 (92.1%) evaporative light-scattering detection: rt 6.36 (1.3%); 6.77 (91.6%) ΝMR in CDC1₃: consistent with pure product.

GC (CPSIL 5CB, 100-270°C, 16°C/min): rt 10.79 (100%) Mpt: 149.6 - 150.8°C (corrected). EXAMPLE 2 This experiment attempted a reaction between the benzoxazole ester (TXa) and the amino-aluminium species generated from trimethyl-aluminium and the aminoisothiazole (IXb), to form Compound (IX):

Compound (IXb) / Me₃Al toluene/hexane

Compound (IXa) Compound (TX) [489.5]

Materials

Method

A 3-necked round bottomed flask was pre-purged with nitrogen for 15 minutes and the nitrogen purging was continued during the subsequent reaction.

Compound (JXb) (5-amino-4-chloro-3-ethylisothiazole) was dissolved in toluene (200 ml) (slightly endothermic), charged to the flask and the residuals washed in with more solvent (25 ml). The mixture was stirred for 15 min, under nitrogen purging, at room temperature. The trimethylaluminium solution was added, via a pressure-equalising addition funnel, slowly over 30 mins. The exotherm was easily controlled (by water bath), holding the temperature in the range 21° to 25°C; there was continuous evolution of methane throughout and for about 10 mins after. After addition of about half of the trimethylaluminium solution, solid had begun to precipitate, finally forming a thin, easily stirred slurry. This slurry was stirred at room temperature for 30 mins, then the ester (IXa) (in dry toluene, 125 ml) was added dropwise over 30 mins (negligible exotherm). The resulting thin slurry was heated to reflux, under nitrogen (by about 80°C a solution had apparently reformed).

The mixture was refluxed for 2 hours at 94°C to 96°C (pressure of hexanes in solvent mixture). It was then cooled slightly and a sample taken for monitoring the reaction.

Results & subsequent analysis The reaction mixture was sampled for HPLC thus: the sample was removed, diluted approximately 1:1 with ethyl acetate and carefully shaken with aqueous 10% v/v sulphuric acid. The organic phase was dried over magnesium sulphate, then vacuum evaporated. The residue was dissolved in acetonitrile for injection into the column.

The progress of the reaction was followed by HPLC (HPl 100, KROMASIL KR100-3.5C18- 35AS, 35 x 3.2 mm column, water/acetonitrile 98:2 to 10:90 gradient, 1.5 ml/min, UN 254 nm). The results were: rt = 3.384 [2.6%] (isothiazole (IXb)); rt = 6.335 [84.3%] (the product Compound (TX)); no ester (IXa) (rt = 5.830) observed.

Thus heating was stopped and the mixture allowed to cool to room temperature and left to stand overnight. The following day, the reaction mixture was diluted with ethyl acetate (350 ml), stirred and the resulting solution cooled in an ice bath. The cooled solution was treated with ~ 10% v/v aqueous sulphuric acid (90 ml), dropwise, over 45 mins (the initial addition gave a rapid exothermic reaction and the temperature rose to ~20°C, but it subsequently became possible to keep the temperature <10°C, allowing for a controlled effervescent hydrolysis, the exotherm being controlled by the ice bath). The mixture was then allowed to warm to room temperature over 30 mins, as effervescence subsided.

The phases were then separated - a little white solid present in the (lower) aqueous phase caused slight interference with separation. The aqueous phase was re-extracted with more ethyl acetate (2 x 250 ml). The combined organic phase (containing some of the white solid) was washed with saturated aqueous ammonium chloride (500 ml) - this possibly removed some of the solid into solution, but was still a slow separation - then brine (1 x 500 ml).

Finally the deep red organic phase was dried over magnesium sulphate.

The dried solution was filtered and concentrated to give an orange-yellow solid.

Yield of crude product = 68.6 g [>100%; contains solvent] The crude reaction product was analysed by HPLC (HPl 100, KROMASIL KR100-3.5C18-

35AS, 35 x 3.2 mm column, water/acetonitrile 98:2 to 10:90 gradient, 1.5 ml/min, UN 254 nm). The results were: rt = 6.332 (compound (TX) = 89.76% pure) with -1.62% amino-isothiazole (IXb) + other impurities. Following recrystallization from 1,2 dichloroethane (100 ml) and hexane (200 ml) [a fine pale yellow solid was filtered off and dried]:

Yield: 50 g (73.14% yield)

NMR: consistent with required product.

HPLC (HPl 100, KROMASIL KR100-3.5C18-35AS, 35 x 3.2 mm column, water/acetonitrile 98:2 to 10:90 gradient, 1.5 ml/min, UN 254 nm): rt = 6.345 (compound

(IX) = 99.0% pure).

Melting point: 128 - 129°C

(The recrystallization filtrate liquors were concentrated to give an orange thick oily gum.)

Claims

1. A method for the preparation of a compound of formula (I):

wherein A is optionally substituted Q-₆ alkylene, optionally substituted Q-6 alkenylene, optionally substituted Q-₆ alkynylene, optionally substituted cycloalkylene, optionally substituted Q-₆ alkylenoxy, optionally substituted oxy(Q-₆)alkylene, optionally substituted Q_₆ alkylenethio, optionally substituted thio(Q-₆)alkylene, optionally substituted Q.₆ alkylenamino, optionally substituted amino(Q-₆)alkylene, optionally substituted [Ci-e alkyleneoxy(Q-₆)-ilkylene], optionally substituted [Ci-₆ alkylenethio(Cι-₆)alkylene], optionally substituted [Ci-e alkylenesulfinyl(Cι.₆)alkylene], optionally substituted [Ci-₆ alkylenesulfonyl(Q-₆)alkylene] or optionally substituted [Q-₆ alkyleneamino(Q-₆)alkylene] ; B is N, N-oxide or CR⁸; Z is O, S or NR¹⁰;

R¹ is hydrogen, halogen, optionally substituted Q-₆ alkyl, optionally substituted Q-β alkenyl, optionally substituted Q-₆ alkynyl, optionally substituted Q.₆ alkoxy, optionally substituted Q-₆ alkylthio, optionally substituted C₃-₇ cycloalkyl, cyano, nitro or SF₅; R² is hydrogen, halogen, optionally substituted Q-₆ alkyl, optionally substituted Q-₆ alkenyl, optionally substituted Q-₆ alkynyl, optionally substituted Ci-₆ alkoxy, optionally substituted Q-₆ alkylthio, optionally substituted Ci-₆ alkylsulfinyl, optionally substituted Ci-₆ alkylsulfonyl, cyano, nitro, formyl, optionally substituted Q_₆ alkylcarbonyl, optionally substituted Ci-₆ alkoxycarbonyl, SF₅ or RⁿON=C(R¹²); or R and R together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Ci-₆ alkyl, Q-₆ haloalkyl or halogen; R³ is hydrogen, optionally substituted Q-₁₀ alkyl, optionally substituted [Q-6 alkenyl(Q-₆)alkyl], optionally substituted [Q-₆ alkynyl(Q-₆)alkyl], optionally substituted Q-₇ cycloalkyl, optionally substituted Q-₁₀ alkylcarbonyl, optionally substituted C_MO alkoxycarbonyl, formyl, optionally substituted Q.io alkylaminocarbonyl, optionally substituted di(Q-ιo)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted Ci-e alkylthio, optionally substituted Ci-₆ alkylsulfinyl, optionally substituted Ci-₆ alkylsulfonyl, optionally substituted Q-₆ arylthio, optionally substituted Ci-₆ arylsulfinyl, optionally substituted Q-₆ arylsulfonyl or R¹³R¹⁴NS(O)_p; p is 0, 1 or 2;

R⁴, R⁵ and R⁶ are, independently, hydrogen, halogen, optionally substituted Ci-₆ alkyl, optionally substituted Q-₆ alkoxy, optionally substituted Q-₆ alkylthio, optionally substituted Q-e alkylsulfinyl, optionally substituted Q-e alkylsulfonyl, cyano, nitro, optionally substituted Q-₆ alkylcarbonyl, optionally substituted Ci-₆ alkoxycarbonyl or SF₅;

R⁷ is hydrogen, halogen, cyano, optionally substituted Ci.₂₀ alkyl, optionally substituted Q-20 alkenyl, optionally substituted Q-2₀ alkynyl, optionally substituted Q-₇ cycloalkyl, optionally substituted .₆ cycloalkenyl, formyl, optionally substituted Q-20 alkoxycarbonyl, optionally substituted Q-₂₀ alkylcarbonyl, aminocarbonyl, optionally substituted Q-₂o alkylaminocarbonyl, optionally substituted di(Ci-2o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-(Q-₆)alkyl-N-arylarninocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted N-(Q-₆)alkyl-N-heteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, SH, optionally substituted Q.₂o alkylthio, optionally substituted Q_₂o alkylsulfinyl, optionally substituted Q.₂o alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, R¹⁵O, R¹⁶R¹⁷N or R¹⁸ON=C(R¹⁹); R is hydrogen, halogen, nitro, cyano, optionally substituted Q-₈ alkyl, optionally substituted -₆ alkenyl, optionally substituted C₂-₆ alkynyl, optionally substituted C₃-₇ cycloalkyl, optionally substituted Ci-₆ alkoxycarbonyl, optionally substituted Q-₆ alkylcarbonyl, optionally substituted Ci-₆ alkylaminocarbonyl, optionally substituted di(Ci-₆)alkylaminocarbonyl, optionally substituted phenyl or optionally substituted heteroaryl; R⁹ is hydrogen, cyano, nitro, optionally substituted Q-₆ alkyl, optionally substituted

Q-₇ cycloalkyl, optionally substituted (Q-₆)alkenyl(Q_₆)alkyl, optionally substituted (Q-₆)alkynyl(Q-₆)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Ci-₆ alkylcarbonyl, optionally substituted Ci-₆ alkoxycarbonyl, optionally substituted Q-₆ alkylamino, optionally substituted di(Cι-₆)alkylamino, optionally substituted Ci-₆ alkylcarbonylamino, optionally substituted Ci-₆ alkoxycarbonylamino, optionally substituted Q-6 alkoxy, optionally substituted Q-₆ alkylthio, optionally substituted Q-₆ alkylsulfinyl, optionally substituted Q-e alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or Ci-₆ alkylcarbonyloxy; R¹⁰ is hydrogen, cyano, optionally substituted Q.₈ alkyl, optionally substituted [Q.₆ alkenyl(Q.₆)alkyl], optionally substituted [ -₆ alkynyl(Q-₆)alkyl], optionally substituted C₃.₇ cycloalkyl, optionally substituted [Q.₇ cycloalkyl(Q-₆)alkyl], Q-₆ alkoxy(Q.₆)alkyl, optionally substituted Q-e alkoxycarbonyl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q-₆ alkylaminocarbonyl, optionally substituted di(Q-6)alkylarr-inocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted alkylsulfonyl or optionally substituted arylsulfonyl;

R and R are, independently, hydrogen, optionally substituted phenyl (Q-₂)alkyl or optionally substituted Q-₂₀ alkyl; R¹² and R¹⁹ are, independently, hydrogen, optionally substituted phenyl or optionally substituted Q-₆ alkyl;

R¹³ and R¹⁴ are, independently, optionally substituted Q-₆ alkyl; or R¹³ and R¹⁴ together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N and S and which is optionally substituted by one or two independently selected Q-₆ alkyl groups;

R¹⁵ is hydrogen, optionally substituted Q-₂o alkyl, optionally substituted [Q-₂₀ alkenyl(Q-₆)alkyl], optionally substituted [Q-₂₀ aIkynyl(Q-₆) alkyl], optionally substituted -₇ cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, (Q-₆)alkylCH=N, optionally substituted arylCH=N, optionally substituted [aryl(Q-₆)alkyl]CH=N, optionally substituted heteroarylCH=N, optionally substituted [heterocyclyl(Q-₆)alkyl]CH=N, optionally substituted arylC(CH₃)=N, optionally substituted heteroarylC(CH₃)=N or optionally substituted di(Ci-₆)alkylC=N; and

R¹⁶ and R¹⁷ are, independently, hydrogen, optionally substituted Q-₂₀ alkyl, optionally substituted Q.₇ cycloalkyl, optionally substituted [Q-2₀ alkenyl(Q-₆)alkyl], optionally substituted [Q-₂₀ alkynyl(Q-₆)alkyl], optionally substituted Ci.₂₀ alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q.₂₀ alkylcarbonyl, optionally substituted Ci.₂₀ alkylsulfonyl or optionally substituted phenylsulfonyl, the method involving reacting together a compound of the formula (H):

R²

(π) wherein R¹, R² and R³ are as defined above in relation to formula (I), and a compound of formula (HI):

(HI) in which A, B, Z and R⁴ - R⁷ are as defined above in relation to formula (I) and L is a leaving group, in the presence of a trialkyl-aluminium compound R⁵⁰R⁵¹R⁵²A1 where R⁵⁰, R⁵¹ and R⁵² are each independently selected from Q-io alkyl.

2. A method according to claim 1, wherein in the compound (HI), L is halo or R³⁰-O-, where R³⁰ is hydrogen or a Q.₆ alkyl group.

3. A method according to claim 2, wherein in the compound (HI), L is R³⁰-O-.

4. A method according to any one of the preceding claims, wherein the compound (IH) is base- and/or nucleophile-sensitive.

5. A method according to any one of the preceding claims, wherein in the compound (HI), B is nitrogen and Z is oxygen.

6. A method according to any one of the preceding claims, wherein in the compound (IH), the substituent R⁷ is electron withdrawing.

7. A method according to claim 6, wherein R⁷ is a haloalkyl group.

8. A method according to claim 7, wherein R⁷ is QF₇.

9. A method according to any one of the preceding claims, wherein in the ttrriiaallkkyyll--aalluummiinniiuumm aaggeenntt,, AA11RR⁵⁵⁰⁰RR⁵¹R⁵², R⁵⁰, R⁵¹ and R⁵² are each independently selected from Q-Q alkyl groups.

10. A method according to claim 9, wherein R⁵⁰, R⁵¹ and R⁵² are each independently selected from either methyl or ethyl.

11. A method according to claim 10, wherein the trialkyl-aluminium agent is Me₃Al.

12. A method according to any one of the preceding claims, wherein the compound (HI) is added to a pre-prepared mixture of the compound (H) and the trialkyl-aluminium agent.

13. A method according to any one of the preceding claims, wherein the compound (I) produced by the method is a compound of formula (IA):

wherein A, B, Y, Z, R¹, R² , R³, R⁴, R⁵, R⁶ and R⁷ are as defined in the preceding claims.

14. A method for the preparation of a compound of formula (I) or (IA), as defined in claim 1 or claim 13, the method being substantially as herein described.

15. An intermediate compound of the formula (X):

(X) wherein R¹, R² , R³, R⁵⁰ and R⁵¹ are as defined in any one of the preceding claims.

16. A method for the preparation of a compound of formula (I) as defined in claim 1, the method involving reacting a compound of formula (IH) (also as defined in claim 1) with an intermediate compound (X) according to claim 15.