CZ2000870A3 - Novel derivatives of pyrimidin-4-one and pyrimidin-4-thione for application as fungicidal agents, process of their preparation and preparations in which they are comprised - Google Patents

Abstract

New pyrimidin-4-one and pyrimidine-4-thione derivatives of formula I, wherein the substituents have specific meanings. New compounds have plant protection properties and are suitable for plant protection against phytopathogenic attack microorganisms, in particular fungi.

Description

Novel pyrimidin-4-one and pyrimidin-4-thione derivatives for use as fungicides, processes for their preparation and compositions containing them

Technical field

The present invention relates to novel pyrimidin-4-one and pyrimidine-4-thione derivatives of the formula I having pesticidal activity, in particular fungicidal activity.

SUMMARY OF THE INVENTION

The invention relates to compounds of formula I

where:

A is thienyl (including all three isomers), thiazolyl, pyridyl or pyridazinyl;

X is an oxygen atom or a sulfur atom;

R 1 is hydrogen, halogen or trimethylsilyl;

R ₂ is hydrogen, halogen or trimethylsilyl; at least one of R ₁ and R ₂ is not hydrogen;

R ₃ is C 1 -C 8 alkyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl that are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen, alkoxy C 1 -C 6 or C 1 -C 6 haloalkoxy; O-alkyl of up to 6 carbon atoms, O-alkenyl of 2 to 6 carbon atoms, O-alkynyl of 2 to 6 carbon atoms which are unsubstituted or mono-tri-substituted cycloalkyl of 3 to 6 carbon atoms, a halogen atom or an alkoxy group having 1 to 6 carbon atoms; N-alkyl having 1 to 6 carbon atoms; or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety;

R ₄ is C 1 -C 8 alkyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl that are unsubstituted or mono- to trisubstituted C 3 -C 6 cycloalkyl, halogen, cyano , (C 1 -C 6) alkoxy or (C 1 -C 6) haloalkoxy; nitro; -CO-alkyl having 1 to 6 carbon atoms in the alkyl moiety; (C 3 -C 6) cycloalkyl; or a phenyl group which is unsubstituted or mono- to trisubstituted by a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, cyano, nitro, amino, C 1 -C 6 monoalkylamino, C 1 -C 6 dialkylamino, C 1 -C 6 alkylthio, phenyl or phenoxy, and wherein the phenyl moiety is unsubstituted or mono-trisubstituted a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a haloalkoxy group having 1 to 6 carbon atoms.

• · · · · · · · · · · · · · · · · · · · · · · · · · · ·

........ * · · · · ► ► ► ► ► ► ► ►

The present invention also relates to a process for the preparation of these compounds, agrochemical compositions containing at least one of the compounds as active ingredient, as well as the use of active ingredients or pest control agents, in particular as fungicides, in agriculture and forestry.

The compounds of formula I and, optionally, their tautomers, can be obtained in the form of salts. Since the compounds of formula I have at least one basic center, they can, for example, form acid addition salts. Said acid addition salt is formed, for example, with mineral acids, typically sulfuric acid, phosphoric acid or hydrogen halides, with organic carboxylic acids, typically with acetic acid, oxalic acid, malonic acid, maleic acid, fumaric acid or phthalic acid, with hydroxycarboxylic acids, typically with ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid or benzoic acid or with organic sulfonic acids, typically methanesulfonic acid or p-toluenesulfonic acid.

Compounds of formula I containing at least one acidic group may also form salts with bases. Suitable base salts are, for example, metal salts, typically alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts or salts with ammonia or organic amines, for example with morpholine, piperidine, pyrrolidine and mono-, di- or trialkylamine, typically ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di- or trihydroxyalkylamine, typically mono-, di- or triethanolamine. If appropriate, the formation of suitable internal salts is also possible. Agrochemically acceptable salts are preferred within the scope of the present invention.

9

9 9 9

9 99 · · 9 9 9 9 Λ 9 9 9 9 · · 9 9 9 · 9 ·

• ....... 9 9 9 ·

9 9 9 9 9 9 9

If asymmetric carbon atoms are present in the compounds of formula I, the compounds are in optically active form. Due to the presence of double bonds, the compounds can be obtained in form [E] and / or in form [Z]. Atropoisomerism may also occur. The present invention relates to pure forms such as enantiomers or diastereoisomers, as well as to all possible mixtures of isomers, for example mixtures of diastereomers, racemates or mixtures of racemates.

Unless otherwise indicated, the general terms used herein have the following meanings:

The alkyl group as such or as a structural element of other groups, such as an alkoxy group, is linear or branched depending on the number of carbon atoms and is typically methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl , isobutyl, tert-butyl, n-amyl, tert-butyl, 1-hexyl, 3-hexyl 1-heptyl or 1-octyl.

Alkenyl is a straight or branched alkenyl group such as allyl, methalllyl, 1-methylvinyl, but-2-en-1-yl, 1-pentenyl, 1-hexenyl, 1-heptenyl or 1-octenyl . Preferred alkenyl groups contain 3 to 4 carbon atoms in the chain.

The alkynyl group may be linear or branched depending on the number of carbons and is typically propargyl, but-1-yn-1-yl, but-1-m-3-yl, 1-pentinyl, 1-hexinyl, 1-heptinyl or 1-octyl. A propargyl group is preferred.

• a

A halogen atom and a halogen substituent are a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. Fluorine, chlorine or bromine are preferred.

A haloalkyl group may contain the same or different halogen atoms and is typically fluoromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2fluoroethyl, 2-chloroethyl , 2,2,2-trichloroethyl, 3,3,3-trifluoropropyl.

The cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl depending on the ring size.

Preferred are compounds of formula I wherein

A is a thienyl group, including all three isomers (subgroup A).

Within the scope of this subgroup A, compounds of formula I, wherein

R 1 is an atom iodine atom; hydrogen, atom fluorine, atom chlorine atom, bromine atom or R ₂ is hydrogen hydrogen, atom fluorine, atom chlorine, bromine atom or iodine atom; least one of R 1 and R ₂ is not atom

hydrogen;

R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono- to trisubstituted C 3 -C 6 cycloalkyl, halogen or (C 1 -C 4) alkoxy; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, O-C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl halogen or (C 1 -C 4) alkoxy; N-C 1 -C 6 -alkyl; or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety;

R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; or a phenyl group which is unsubstituted or mono-trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy And wherein the phenyl moiety is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, alkyl of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, Or (C 1 -C 4) haloalkoxy (subgroup B).

A particular group within the scope of subgroup B are compounds of formula I wherein

R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted;

bold or mono to tri - substituted cycloalkyl of 3 to 4 carbon atoms, fluorine, chlorine, bromine or C 1 -C 4 alkoxy; O-C 1 -C 6 -alkyl; A (C 2 -C 6) -alkenyl group; (C 2 -C 6) alkynyl; N-C 1 -C 6 -alkyl; or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety;

R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted C 3 -C 4 cycloalkyl, fluoro, atom chlorine, bromine or C1-C4alkoxy; or a phenyl group which is unsubstituted or mono- to trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy And wherein the phenyl moiety is unsubstituted or mono to trisubstituted with a fluorine atom, a chlorine atom or a bromine atom (subgroup C).

A preferred group within the subgroup C range are compounds of formula I wherein

A is thienyl [2,3-d],

X is an oxygen atom,

R; is hydrogen, chlorine or bromine;

R ₂ is hydrogen, chlorine or bromine; at least one of R, _T and R ₂ is not hydrogen;

• • •

R ₃ is C 3 -C 5 alkyl or C 1 -C 4 alkyl;

R ₄ is C 2 -C 5 alkyl or phenyl which is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl or phenoxy, and wherein the phenoxy group is unsubstituted or mono to trisubstituted by fluorine atom, chlorine atom or bromine atom (subgroup D1).

Another preferred group within the subgroup C range is the

of formula I wherein

A is thienyl [2,3-d],

X is a sulfur atom,

R 1 is hydrogen, chlorine or bromine;

R ₂ is hydrogen, chlorine or bromine; at least one of R ₂ and R ₂ is not hydrogen;

R ₃ is C 3 -C 5 alkyl or C 1 -C 4 alkyl;

R ₄ is C 2 -C 5 alkyl or phenyl which is unsubstituted or mono-trisubstituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl or phenoxy, and wherein the phenoxy group is unsubstituted or mono up to trisubstituted by fluorine atom, chlorine atom or bromine atom (subgroup D2).

Another preferred group within the subgroup C range are compounds of formula I wherein

A is a thienyl [3,2-d] group, and is a group of thienyl [3,2-d]. »· ·» ··· 9 · 9 ·

X is an oxygen atom,

R 1 is hydrogen, chlorine or bromine;

R ₂ is hydrogen, chlorine or bromine; at least one of R ₃ and R ₂ is not hydrogen;

R ₃ is C 3 -C 5 alkyl or C 1 -C 4 alkyl;

R ₄ is C 2 -C 5 alkyl or phenyl which is unsubstituted or mono-trisubstituted with atorfium fluorine, chlorine, bromine, C 1 -C 4 alkyl or phenoxy, wherein the phenoxy group is unsubstituted or mono-trisubstituted a fluorine atom, a chlorine atom or a bromine atom (subgroup E).

Another preferred class of compounds are those compounds of formula I wherein

A is a pyridyl group (subgroup F).

Within the group F, compounds of formula I are preferred wherein:

X is an oxygen atom;

R ₃ is an atom hydrogen, fluorine atom, atom chlorine, atom bromine or iodine atom; R ₂ is hydrogen hydrogen, fluorine atom, atom chlorine, atom bromine or iodine atom; not less one of R ₃ and R ₂ it is not atom hydrogen;

R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono-trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; 0-alkyl group ¹⁰ containing from 1 to 6 carbon atoms, O-alkenyl of 2 to 6 carbon atoms, O-alkynyl of 2 to 6 carbon atoms which are unsubstituted or mono to tri-substituted by cycloalkyl having 3 to 6 carbon atoms, a halogen atom or a (C 1 -C 4) alkoxy group;

R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; or a phenyl group which is unsubstituted or mono- to trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy And wherein the phenyl moiety is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, alkyl of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or haloalkoxy having 1 to 4 carbon atoms (subgroup G).

Other preferred compounds are those compounds of formula I wherein

A is phenyl (subgroup H).

Within the scope of subgroup H, compounds of formula I are preferred wherein

X is an oxygen atom;

R 1 is hydrogen, fluorine, chlorine, bromine or iodine;

• · · ·

R ₂ is hydrogen, fluorine, chlorine, bromine or iodine atom; at least one of R ₁ and R ₂ is not hydrogen;

R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which is unsubstituted or mono-tri-substituted by C 3 -C 6 cycloalkyl, with halogen or (C 1 -C 4) alkoxy; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, O-C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl halogen or (C 1 -C 4) alkoxy; N-C 1 -C 6 -alkyl; or N = CH-alkyl of 1 to 6 carbon atoms;

R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl that are unsubstituted or mono-trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; or a phenyl group which is unsubstituted or mono- to trisubstituted by a fluorine atom, a chlorine atom, a bromine atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkoxy group And wherein the phenyl moiety is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, C1 -C4 alkyl, C1 -C4 haloalkyl, C1 -C4 haloalkyl, C1 -C4 haloalkyl, C1 -C4 haloalkyl or C1 -C4 haloalkyl; C 1 -C 4 or C 1 -C 4 haloalkoxy (subgroup J 1).

Another preferred group within the range of subgroup H are compounds of formula I wherein

X is a sulfur atom;

R 1 is hydrogen, fluoro, chloro or bromo;

R ₂ is hydrogen, fluorine, chlorine or bromine; at least one of R 1 and R ₂ is not hydrogen, R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted cycloalkyl a C 3 -C 6 group, a halogen atom, or an C 1 -C 4 alkoxy group; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, O-C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl halogen or (C 1 -C 4) alkoxy;

R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; or a phenyl group which is unsubstituted or mono-trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy 4-carbon atoms, phenyl or phenoxy, and wherein the phenyl moiety is unsubstituted or mono to trisubstituted with fluorine, chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl C 4 -C 4 alkoxy, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy (J2 subgroup).

Another preferred group of compounds are those compounds of formula I wherein

A is a thiazolyl group (subgroup K).

Within the scope of said group, compounds of formula I are preferred wherein

X is an oxygen atom;

Rx is an atom hydrogen, fluorine atom, atom chlorine, atom bromine or iodine atom; R ₂ is hydrogen hydrogen, fluorine atom, atom chlorine, atom bromine or iodine atom; least one of the substance Rents Rx and R ₂ it is not atom

hydrogen;

R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, O-C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl a carbon atom, a halogen atom or an alkoxy group having 1 to 4 carbon atoms;

• ·

R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; or a phenyl group which is unsubstituted or mono-trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy C 4 -C 4 alkyl, phenyl or phenoxy, wherein the phenyl moiety is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy carbon atoms or haloalkoxy having 1 to 4 carbon atoms (subgroup L).

Another preferred group of compounds are those compounds of formula I wherein

A is a pyridazinyl group (subgroup M).

Within the scope of said group M are preferred compounds of formula I wherein

X is an oxygen atom;

Rx is an atom hydrogen, fluorine atom, chlorine atom, atom bromine or iodine atom; R? is an atom hydrogen, fluorine atom, chlorine atom, atom bromine or iodine atom; not less one of R ₂ and R ₂ it is not atom hydrogen;

• • • •

R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, O-C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl, a halogen atom or a (C 1 -C 4) alkoxy group;

R ₄ is an alkyl group containing 1-6 carbon atoms, ^alkenyl-R a group having 2-6 carbon atoms, alkynyl of 2-6 carbon atoms which are unsubstituted or mono- to trisubstituted cycloalkyl "group containing from 3 to 6 carbon atoms, halogen or (C 1 -C 4) alkoxy; or a phenyl group which is unsubstituted or mono- to trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy And wherein the phenyl moiety is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy Or (C 1 -C 4) haloalkoxy (subgroup N).

The compounds of formula I can be prepared as follows:

• • • •

Scheme 1

O .H

2)

bases (eg NaH) or H ⁺ (HCl, H ₂ SO ₄ )

THF, Dioxane, Ether or other solvents. TM-var

3) P2S5 or p

Lawesson's reagent 1 benzene, toluene THF, dioxane

0 ° - var

The compounds of formula I are preferably prepared from α-amino-β-carboalkoxyheterocycles or α-amino-β-carboxyclic acid heterocycles, some of which, where Het = thienyl, are commercially available (2 isomers). Methyl thiophene-2 amino-3-carboxylate can be prepared, for example, according to Acta Pharm. Suecica 1968, vol. 5, p. 563, by S. Gronowitz et al. Additional heterocycles may be prepared according to literature procedures. For example, the synthesis of ethyl 5-aminothiazole-4Rarooxylate ethyl 5-amino-2-methylthiazole-4-carboxylate is described in Golankiewicz et al., Tetrahedron 1985. 41, 5989. Reactions of α-amino-4-carboalkoxyheterocycles or α-amino-β- carbooylic acid heterocycles with amides (step 1 in Scheme 1) are usually carried out in the presence of POCl ₃ , SOCl ₂ or SO ₂ Cl ₂ , in solvents such as 1,2-dichloroethane, chloroform, dichloromethane, benzene, toluene, hexane, cyclohexane or others, at a temperature between room temperature and boiling point. The amides III obtained are either spontaneously cyclized to pyrimidin-4-ones or converted to cyclic products by treatment with bases such as 3e. T-butyl-OK, sodium hydride, potassium hydride, n-butyllithium, sodium hydroxide, sodium carbonate or others, in solvents such as tetrahydrofuran, dioxane, hexane, toluene, dimethylsulfoxide, dimethylformamide, dimethylacetamide or others at a temperature between 20 ° C and boiling point.

Replacement of the 4-one group with sulfur to give the 4-thion group (step 3 in Scheme 1) is accomplished by reaction with P ₂ O ₅ or Lawesson's reagent in tetrahydrofuran, dioxane or toluene as the solvent, at a temperature between room temperature and boiling point.

The above-described synthetic route is the first method to exhibit the 3H-thieno [2,3-d] pyrimidin-4-one derivatives of formula I according to the invention.

as preprastructure

Methods for preparing compounds of formula I wherein R ₂ = R ₂ = hydrogen are described in Chemical Scripta 1981, 18, 135,

Synthesis 1977, 180, Chem. Pharm. Bull. 1989, 37, 2122 and DE-OS-2411273.

The present invention also relates to intermediates of formulas III, IV and V, and in particular those wherein A is thienyl [2,3-d].

The introduction of additional substituents at the 5-position of the thienopyrimidin-4-one can also be accomplished using organometallic compounds. Thieno [3,2-d] pyrimidin-4-ones and thieno [2,3-d] pyrimidin-4-ones, for example, can be selectively deprotonated at the 6-position. Particularly suitable bases for this purpose are lithium diisopropylamide (LDA), lithiumcyclohexylisopropylamide (LICA) or secondary butyllithium / TMEDA. Many of the R ₂ or R ₂ groups described above can be introduced by reaction of the formed anions with electrophiles (step 1 in Scheme 2), typically with Br ₂ , N ₃ S, F ₂ , IC ₁ , Cl ₂ , F ⁺ reagents, trimethylsilyl chloride.

N3S, •

E't.2 = NBS (N-Bromosuccinimide), NCS (N-Chlorosuccinimide), I ₂ ,

Cl ₂ , 3r ₂ , FC1, F ⁺ reagents, TMS and similar silicon reagents.

The following compounds can also be prepared according to the procedure described in Scheme 2:

Scheme 3: Synthesis of special thienopyrimidin-4-ones (special method for introducing halogen to the thiophene ring)

(a) Thieno [2,3-d] pyrimidin-4-ones:

O

N-halosuccinimide (or Cl ₂ or Br ₂ )

->

pyridine / 0 ° C-var Hal = I, Cl, Br

O

For the halogenation, using 1 to 3 molar equivalents of N-bromsukcmimidu or N-chlorosuccinimide (or _Cl2 gas or 3r _2). As the solvent, for example, pyridine is used at a temperature between 0 ° C and boiling point. The reaction is carried out 1 to 24 • a2)

Pure chlorination:

O

1-3 eq. SO ₂ CI ₂

CHCl 3 or CH ₂ Cl ₂ -20 ° C to + 50 ° C

«3 * 4

The reactions described are carried out by known methods, for example in the presence or absence of suitable solvents or diluents or mixtures thereof, if appropriate, with cooling, at room temperature or with heating, for example at 20 ° C to the boiling point of the reaction mixture. at a temperature in the range of -20 ° C to +150 ° C and, if appropriate, in a closed vessel, under pressure, under an inert gas atmosphere and / or under anhydrous conditions.

Illustrative examples of solvents and diluents include: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, typically benzene, toluene, xylene, chlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, dichloromethane or trichloroethane; ethers, typically diethyl ether, tert-butyl methyl ether, tetrahydrofuran or dioxane; ketones, typically acetone or methyl ethyl ketone; alcohols, typically methanol, ethanol, propanol, butanol, ethylene glycol or glycerol; esters, typically ethyl acetate or butyl acetate; amides, typically N, N-dimethylformamide, N, N-dimethyl acetamide, Nmethylpyrrolidone or hexamethylphosphoric triamide; mtriles, typically acetonitrile; and sulfoxides, typically dimethylsulfoxide. Excess bases such as triethylamine, pyridine, N-methylmorpholine or N, N-diethylaniline can also be used as solvents or diluents.

Boring bases are, for example, alkali metal hydroxides or alkaline earth metal hydroxides, alkali metal hydrides or alkaline earth metal hydrides, alkali metal amides.

or alkali earth metal amides, alkali metal alkanolates or alkali earth metal alkanolates, alkali metal carbonates or alkaline earth metal carbonates, alkali metal dialkylamides or alkaline earth metal dialkylamides or alkali metal alkylsilylamides or alkaline earth metal alkali silylamides, alkylamines, alkylenediamines, optionally alkylated, optionally unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples of such bases include sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium carbonate, potassium tert-butoxide, potassium carbonate, lithium diisopropylamide, potassium bis (trimethylsilyl) amide, calcium hydride, triethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl- N, N-dimethylamine, N, N-diethylaniline, pyridine, 4- (N, N-dimethylamino) pyridine, N-methylmorpholine, benzyltrimethylammonium hydroxide, and 1,8-diazabicyclo [5-. 0] undec-5-ene (DBU).

Compounds of formula I as follows:

can also be prepared

20 ° -200 ° C with or without sol.

(sometimes suitable acid cat.)

R 8 = C 1 -C 8 -alkyl

The aminocarboxylic acid amide of formula VI is reacted with an orthoester of formula XII in the presence or absence of a suitable solvent or diluent, if appropriate, in the presence of an acid catalyst, at room temperature or with heating, for example at 20 to 200 ° C. Illustrative examples of solvents or diluents are ethers such as tert-butyl methyl ether, tetrahydrofuran, dimethyl ether; amides such as N, N-dimethylformamide or N-methylpyrrolidone; sulfoxides, typically dimethylsulfoxide; and alcohols such as methanol, ethanol, propanol, butanol, ethylene glycol or glycerol. As the catalyst, hydrogen halides, methanesulfonic acid, trifluoromethylacetic acid, p-toluenesulfonic acid and others can be used in the absence of water. Generally used bases are sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate, sodium hydride, potassium hydride, sodium carbonate and others.

In particular, for thienopyrimidinone, Scheme 5 describes the reaction of an aminothiophenecarboxylic acid amide of Formula VIa with an orthoester XIII in the presence or absence of a solvent, where appropriate, in the presence of an acid catalyst, at a temperature of 20 to 200 ° C. The obtained intermediate of formula (VIIa) is then halogenated in the presence of a solvent, at a temperature of 20 ° C to boiling point. The halogenated intermediate of Formula VIIIa is then cyclized in the presence of a base, in the presence or absence of a suitable solvent, at a temperature of 20 ° C to the boiling point. Halogenating agents are typically N-bromosuccinimide, N-chlorosuccinimide, N-iodosuccinimide, chlorine gas, bromine, thionyl chloride and others. Preferred solvents for the halogenation reaction are tert-butyl methyl ether, tetrahydrofuran, chloroform, methylene chloride, pyridine and quinoline.

• · • ·

Scheme 5:

(Thienopyrimidinones)

^R 5 ° ^R 5 ^R £

R,

XIII

20 ° -200 ° C with or without sol.

(sometimes suitable acid cat.)

1.1

bases 0 ° C- var

IN

= NCS, NBS, NIS, Cl ₂ , Br ₂ , SO ₂ Cl solvents for halogenation: THF, TBME, CHCl ₃ , CH ₂ Cl ₂ , pyridine, chmoline and others

Another possibility is described in Scheme 6, where the aminocarboxyzhiophene of formula IIIa is reacted with an orthoester of formula XIII to form intermediate IXa, then compound IXa is converted to amidine IIIa and cyclized to thienopyrimidinone X. Halogenation of compound X to give compound 1.1 is described in scheme · · · · · ·

Scheme 6:

RcO ORc

Xj X ",

R; p ^ 'R'

-►

20 ° -200 ° C with or without sol.

(sometimes suitable acid cat.)

r ₃ nh ₂ exp. (THF, DMF, etc.) 0 ° C - var

base (NaH, NaOH, etc.) sol. (THF, DMF, etc.)

0 ° C - var

lila

R = C 1 -C 8 -alkyl

The conditions for the reaction of IIa to give IXa are described in Schemes 4 or 5, as well as the conditions for the cyclization of IIIa to X, as described above. Reaction of compound IXa to form compound IIIa requires a solvent such as tetrahydrofuran, N, N-dimethylformamide or other solvents, and a temperature in the range of 0 ° C to boiling point.

After

Scheme 7 describes the reaction of a compound of Formula IIa with an orthoester XIII to obtain intermediate IXa, which is converted to intermediate IIIa and then halogenated to thiophene XIa. cyclizing compound XIa to give compound 1.1.

4 · · ··· · ··· 44

Scheme 7

RcO ORc

X. xm ^R i ^r 4

20 ° -200 ° C with or without sol.

(sometimes suitable acid cat.)

r ₃ nh ₂ exp. (THF, DMF, etc.)

0 ° C- var

^{R c c} r ^c 8 ' ^{a, k} y ¹

The reaction conditions described for Method 4 are analogous to those described for Schemes 4, 5 or 6.

Scheme 8 describes an alternative method involving reacting a compound of Formula IIa with an orthoester XIII to form intermediate IXa, which is halogenated to form intermediate XIIa and then converted to thiophene XIIa. After cyclization of compound XIa, the target compound 1.1 is obtained. Reaction · ** · * ** ** ** ** ** ** ** ** ** ** ** 9 9 9 9 9 9 9 9 9 9 9 ···· 9 9 9 9 9 9 9 9 The conditions are the same as described for Schemes 4, 5, 6 and.

Scheme 8

>

20 ° -200 ° C with or without sol.

(sometimes suitable acid cat.)

C 1 -C 6 -alkyl · C 1 -C 6 -alkyl

Quinazolinone derivatives having fungicidal properties are known from WO 94/26722 or from EP-A-276825 and thienopyrimidines are known from WO 97/02262.

Surprisingly, it has now been found that the novel compounds of the formula I have, in practice, a very advantageous spectrum of activity for protecting plants against diseases caused by fungi as well as bacteria and viruses.

The compounds of formula I can be used in the agricultural sector and related areas as active ingredients for controlling plant pests. The novel compounds exhibit excellent activity at low application rates, good plant compatibility and environmental safety. They have very beneficial curative, preventive and systemic properties and are used to protect many crop plants. The compounds of formula (I) may be used to inhibit or control pests that occur on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) or on various fruits of useful plants, while protecting those plant parts, that grow up later, for example before phytopathogenic microorganisms.

It is also possible to use the compounds of the formula I as treatment agents for plant propagation materials, in particular seeds (fruit, tubers, grains) and plant cuttings (for example rice), for protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.

For example, the compounds of formula I are active against phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septcna, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctoma, Hemileia, Puccinia). Furthermore, they are effective against the Ascomycetes class (e.g. Venturia and Erysiphe, Podosphaera, Moni).

linia, Uncinula) and the Oomycetes class (e.g., Phytophthora, Pythium, Plasmopara). Furthermore, the novel compounds of the formula I are active against phytopathogenic bacteria and viruses (for example against Xanthomnas species, Pseudomnas species, Erwinia amylovora and also against mosaic tobacco virus).

Within the scope of the present invention, the target crops to be protected typically include the following plant species: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); puffs, drupes and soft fruits (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); legumes (beans, lentils, peas, soybeans); oil plants (oilseed rape, mustard, poppy, olives, sunflowers, coconuts, castor oil plants, cocoa beans, oilseed); cucumber plants (pumpkins, cucumbers, melons); fibrous plants (cotton, flax, hemp, jute); citrus fruits (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, peppers); laurel plants (avocado, cinnamon, camphor) or crops such as tobacco, nuts, coffee, eggplant, sugarcane, tea, pepper, wine, hops, bananas and natural rubber plants, as well as ornamental plants.

The compounds of formula I are generally used in the form of compositions and can be applied to the field or plants to be treated simultaneously or sequentially with other compounds. These other compounds may be, for example, fertilizers or nutrient donors or other agents which have an effect on plant growth. They may also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of some of these compositions, if appropriate, with other carriers, surfactants or application aids commonly used in the art.

• ·

U · ·· ·· ·· ··

The compounds of the formula I can be mixed with other fungicides, in some cases an unexpected synergistic effect is obtained.

Admixtures that are particularly preferred include azoles such as azaconazole, bitertanol, propiconazole, diphenoconazole, diniconazole, cyproconazole, epoxiconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, tebuconazole, metbuconilazole, tetraconazole, tetraconazole, tetraconazole, tetraconazole, , perfurazoate, penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon, triadimenol, triflumizole or triticonazole; pyrimidinylcarbinols such as ancymidol, phenarimol or nuarimol; 2-amino-pyrimidines such as bupirimate, dimethirimol or ethirimol; morpholines such as dodemorph, fenpropidine, fenpropimorph, spiroxamine or tridemorph; anilinopyrimidines such as cyproquinil, pyrimethanil or mepanipyrim; pyrroles such as fenpiclonil or fludioxonil; phenylamides such as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace or oxadixyl; benzimidazoles such as benomyl, carbendazim, debacarb, fuberidazole or thiabendazole; dicarboximides such as chlozolinate, dichlozolin, iprodin, myclozolin, procymidone or vinclozolin; carboxamides such as carboxin, fenfuram, flutolanil, mepronil, oxycarboxin or thifluzamide; guanidines such as guazatin, dodine or iminoctadine; strobilurins such as azoxystrobin, cresoximethyl, metominostrobin, SSF-129 or 2- [a {[(α-methyl-3-trifluoromethyl-benzyl) imino] oxy} -o-tolyl] -glyoxylic acid methyl ester; dithiocarbamates such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zinb or ziram; N-halomethylthiodicarboximides such as captafol, captan, dichlorofluanide, fluoride, folpet or tolyfluanide; media compounds such as Bordeaux mixture, copper hydroxide, copper oxychloride, copper sulfate, copper oxide, mancopper. or oxine-copper; nitrophenol derivatives such as dmocap or nitrothalisopropyl; organic phosphorus compounds such as edifenphos, iprobenfos, isoprothiolane, fosdifen, pyrazophos or toclofosmethyl; and other compounds of various structures such as acibenzolar-S-methyl, anilazine, blasticidin-S, quinomethionate, chlorneb, chlorthalonil, cymoxanil, dichlorone, diclomezin, dicloran, diethofencarb, dimethomorph, dithianone, etridiazole, famoxadone, fentin, ferazin, ferentin, fentin, flusulfamide, fenhexamide, fosetylaluminum, hymexazole, casugamycin, methasulfocarb, pencycuron, fthalid, polyoxins, probenazole, propamocarb, pyroquilone, quinoxyfen, quintozene, sulfur, triazoxide, tricyclazole, triforin or validamycin.

A preferred compound for mixing with the ingredients listed above is compound No. 3.30.

Another preferred compound for dami is compound number 3.31.

Another preferred compound for dami is compound No. 3.58.

Another preferred compound for dami is compound number 3.59.

mixing with the aforementioned ingredient mixing with the aforementioned ingredient mixing with the aforementioned ingredient

Suitable carriers and adjuvants may be solids or liquids and are those used in the formulation, for example natural or regenerated minerals, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.

A preferred method of applying a compound of formula I or agrochemical compositions containing at least one of said compounds is by foliar application. The frequency of application and the amount of substance administered will depend on the risk of attack by the corresponding pathogen. However, the compounds of formula I may also penetrate the plants through roots from the soil (systemic action; by embedding the plant growing area with a liquid composition or by applying the compound in solid form to the soil, for example. In the form of granules (soil application) In rice plants, The compounds of formula I may also be applied to the seeds (coating) by impregnating the seeds or tubers with either a liquid fungicide composition or by coating with said solid composition.

The compounds of the formula I are used in unprocessed form or preferably together with additives which are conventionally used in the field of such compositions. In this case, they are usually formulated by known methods into emulsifiable concentrates, coating pastes, solutions which can be directly applied or solutions to be diluted, dilute emulsions, wettable powders, soluble powders, dusts, granules and also in encapsulated forms, for example in polymeric substances. . As with the types of compositions, methods of application such as spraying, spraying, dusting, scattering, coating and spilling are selected according to the desired purpose and general circumstances.

The preferred application rate is usually between 5 g to 2 kg of active ingredient (a. I.) Per hectare (ha), preferably 10 g to 1 kg a.i./ha, most preferably 20 g to 600 g a.i./ha. When used as seed irrigation, the usual dose is between 10 mg and 1 g of active substance per kg of seed.

Compositions comprising a compound of formula I and, if appropriate, a solid or liquid additive are prepared in a known manner, typically by thoroughly mixing and / or grinding the compound with fillers, for example, solvents, solid carriers and, optionally, surfactants.

Suitable carriers and adjuvants may be solid or liquid substances and correspond to those commonly used in formulating such compositions as natural or regenerated minerals, solvents, dispersants, wetting agents, tackifiers, thickeners, binders. 9

Or fertilizers. Such carriers are described, for example, in WO 97/33890.

Other surfactants commonly used in the art of formulating such compositions are known to those skilled in the art or can be found in the relevant literature.

The agrochemical compositions will usually contain 0.1 to 99% by weight, preferably 0.1 to 95% by weight of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid additive and 0 to 25% by weight, preferably 0.1 to 25% by weight, of a surfactant.

While it is preferable to formulate commercial compositions in the form of a concentrate, the end user will routinely use dilute compositions.

The compositions will also contain other ingredients such as stabilizers, anti-foam agents, viscosity adjusting agents, binders or tackifiers, as well as fertilizers, nutrient donors (micronutrients) or other means to achieve the desired effect.

The present invention will be further illustrated by examples, but not by way of limitation. Temperatures are given in degrees Celsius. The following abbreviations are used: Et = ethyl; i-propyl = isopropyl; Me = methyl; m.p. = melting point. NMR refers to a nuclear resonance spectrum. MS = mass spectrum. % are percent by weight unless the corresponding concentrations are given in other units.

• · • ·

Examples of the invention;

Example P-1

2- (1-n-Butyl-1-methoxymethyleneamino) thiophene-3-carboxylic acid propyl amide

A mixture of 1.84 g of 2-aminothiophene-3-carboxylic acid propylamide and 2.43 g of trimethylorthovalerate was heated to 130 DEG C. in the distillation apparatus for 2 hours. The methanol formed during the reaction is distilled directly from the reaction vessel. After cooling, the crude product was purified by column chromatography (eluent: hexane / ethyl acetate = 1: 2). Yield: 1.9 g of pure 2- (1-n-butyl-1-methoxymethyleneamino) thiophene-3-carboxylic acid propylamide; mp 68-70 ° C.

Example P-2

5-Chloro-2- (1-n-butyl-1-methoxymethylenamino) thiophene-3-carboxylic acid propylamide

In a sulfation flask, 0.85 g of 2- (1-n-butyl-1-methoxymethyleneamino) thiophene-3-carboxylic acid propylamide is stirred with stirring.

I · «·» · ·

To 10 ml of absolute pyridine. The internal temperature was raised to 60 ° C and 0.5 g of N-chlorosuccinimide (NCS) was added in two portions. After stirring at 60 ° C for 1 hour, pyridine was removed using a water pump vacuum. The residue is taken up in ethyl acetate and the organic phase is washed twice with water. After drying of the organic phase, the solvent is removed under a water pump vacuum and the crude material is purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3: 1). Yield: 0.6 g of 5-chloro-2- (1-n-butyl-1-methoxymethyleneamino) thiofer-3-carboxylic acid propylamide as brownish crystals of m.p. 110-112 ° C.

Example P-3

2-n-3-Butyl-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one

In a sulfonation flask, 0.85 g of 2- (1-n-butyl-1-methoxymethyleneamino) -thiophene-3-carboxylic acid propylamide is dissolved in 20 ml of absolute tetrahydrofuran and 0.15 g of about 55% sodium hydride dispersion is added in small portions. The mixture was stirred at room temperature for 15 minutes and at reflux temperature for 1 hour. The solvent was removed under a water pump vacuum and the residue was taken up in ethyl acetate. The organic phase is washed twice with water and after drying the organic phase with sodium sulfate, the solvent is removed by means of a water pump vacuum. The product obtained (yield: 0.8 g of 2-n-butyl-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one as a brown liquid) can be used in the halogenation step without further purification.

Example P-4

-6-chloro-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one •

In a sulfonation flask, 0.36 g of 5-chloro-2- (1-n-butyl-1-methoxymethyleneamino) thiophene-3-carboxylic acid propylamide is dissolved in 20 ml of absolute tetrahydrofuran and 0.085 g of about 55% sodium hydride dispersion are added in one portion. The mixture was stirred at room temperature for 15 minutes and refluxed for 1 hour. The solvent was then removed in a water pump vacuum and the residue was taken up in ethyl acetate. The organic phase was washed twice with water and after drying the organic phase over sodium sulfate, the solvent was removed in a water pump vacuum. The crude product obtained is purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5: 1). Yield: 0.2 g of 2-n-butyl-6-chloro-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one as a yellowish powder, m.p. 67-69 ^° C.

Example P-3a

-n-butyl-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one

In a sulfonation flask, 11.0 g (70 mmol) of 2-amino-3-carbomethoxythiophene and 10.9 g (76 mmol) of propylamide propylamide are added to 60 ml of 1,2-dichloroethane. While stirring at room temperature, 7 ml of phosphorus oxychloride is slowly added dropwise. After 3 hours at reflux, the mixture was poured into ice water and the pH adjusted to slightly alkaline with sodium bicarbonate. The resulting mixture is then extracted three times with dichloromethane and the separated organic phase is dried over sodium sulfate. The solvent is then removed under a water pump vacuum.

In the sulfonation flask, the crude product was added to 100 mL of absolute tetrahydrofuran and 4.36 (0.1 mol) of sodium hydride in absolute tetrahydrofuran was carefully added with stirring. After stirring at reflux for 2 hours, the solvent was removed under a water pump vacuum and the residue was taken up in a mixture of ethyl acetate and water. The aqueous phase was extracted with additional ethyl acetate. The organic phase is dried over sodium sulfate and the solvent is removed under a water pump vacuum. The crude product was purified by silica gel column chromatography (eluent: TBME / hexane = 1: 2). 12.0 g of 2-n-butyl-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one are obtained in the form of a yellow powder, m.p. 70-72 ° C.

Example P-4a

2-n-Butyl-6-chloro-3-n-propyl-3H-thieno [2,3-d] pyrimidin-4-one

[merge. No. 3.31]

In a sulfonation flask, 2.0 g (8 mmol) of 2-n-butyl-3-propyl-3H-thieno [2,3-d] pyrimidin-4-one was added to 15 ml of absolute pyridine with stirring. The internal temperature was then raised to 80 ° C and then 1.87 g (14 mmol) of N-chlorosuccinimide (NCS) was added in small portions. After stirring at 90 ° C for 3 hours, 1.0 g of NCS was added and the mixture was stirred at 90 ° C for 3 hours. The pyridine was removed under a water pump vacuum and the crude product thus obtained was purified by silica gel column chromatography (eluent: nhexar / tert-butyl methyl ether = 3: 1) to obtain 0.9 g of 2-n-butyl-6-chloro-3-propyl -3H-thieno [2,3-d] pyrimidin-4-one as a beige powder, m.p. 67-69 ° C.

• · • ·

1 6-Br H Me Me 2 6-Cl H Me Et 3 6 -Br H Me n-Propyl Λ 1 6-Cl H Me n-Propyl 5 H 7-C1 Me n-Propyl 6 6-Br H Me n-Butyl 7 6-Cl H Me n-Butyl 8 H 7-C1 Me n-Butyl 9 6-Br H Me i-Butyl 10 6-Cl H Me i-Butyl 11 6-Br H Me n-Pentyl 12 6-Br H Me 13 6-Cl H Me 7 4 6 -Br H Et Me I 5 6-Cl H Et Et 16 6-Br H Et n-Propyl 17 6-Cl H Et n-Propyl 18 H 7-C1 Et n-Propyl 19 Dec 6-Br H Et n-Butyl 20 May 6-Cl H Et n-Butyl 21 H 7-C1 Et n-Butyl 2 2 6-3r H Et i-Butyl 2 3 6-Cl H Et i-Butyl

• · · · · · · · · · ·

1. 24 6-Br H Et n-Pentyl 1. 25 - 6-Br H Et 1. 26 6-Cl H Et 1.27 6-Br H n-Propyl Me 1.28 6-Cl H n-Propyl Et 1.29 6-Br H n-Propyl n-Propyl 1.30 6-Cl H n-Propyl n-Propyl 1.31 H 7-Cl n-Propyl n-Propyl 1. 32 H 7-1 n-Propyl n-Propyl 1.33 6-Br H n-Propyl Δ 1. 34 6-Cl H n-Propyl Δ 1 .35 H 7-Cl n-Propyl Δ 1. 36 6-Br H n-Propyl n-Butyl 1.37 6-Cl H n-Propyl n-Butyl 1.38 H 7-Cl n-Propyl n-Butyl 1.39 H 7-1 n-Propyl n-Butyl 1.40 6-Br H n-Propyl i-Butyl ^{Ί Δ} 7 6-Cl H n-Propyl i-Butyl 1.42 6-Br H n-Propyl 1.43 6-Cl H n-Propyl 1.44 • H 7-Cl n-Propyl 1.45 6-Br H n-Propyl Me to 1.46 6-Cl H n-Propyl Me TO

• • •

47 6-Br H n-Propyl Cyclobutyl 48 6-Br H n-Propyl n-Pentyl 49 6-Cl H n-Propyl n-Pentyl 50 H 7-C1 n-Propyl n-Pentyl 51 6-Br H n-Propyl Cyclopentyl 52 6-Br H n-Propyl n-Hexyl 53 6-Br H n-Propyl Cyclohexyl 54 6-Br H n-Propyl Phenyl 55 6-Br H n-Propyl 4-Chlorophenyl 56 6-Cl H n-Propyl 4-Chlorophenyl 57 6-Br H n-Propyl 4-Phenoxyphenyl 5 8 · 6-Br H n-Butyl Me 59 6-Cl H n-Butyl Et 60 6-Br H n-Butyl n-Propyl 61 6-Cl H n-Butyl n-Propyl 62 H 7-Cl n-Butyl n-Propyl 63 H 7-1 n-Butyl n-Propyl 64 6-Br H n -Butyl Δ 65 6-CI H n-Butyl Δ 66 H 7-C1 n-Butyl Δ 67 6-Br H n-Butyl n-Butyl 68 6-Cl H n-Butyl n-Butyl 69 H 7-C1 n-Butyl n-Butyl 70 H 7-1 n-Butyl n-Butyl 71 6-Br H n-Butyl i-Butyl 72 6-Cl H n-Butyl i-Butyl 73 6-Br H n-Butyl Δ ^ 74 6-Cl H n-Butyl

• · • ·

1.75 H 7-Cl n-Butyl / V ' Me 1. 76 6-Br H n-Butyl Me 1.77 6-C1 H n-Butyl 1.78 6-Br H n-Butyl Cyclobutyl i 7 o 6-Br H n-Butyl n-Pentyl - j-. O 6-Cl H n-Butyl n-Pentyl 1.31 H 7-Cl n-Butyl n-Pentyl 1. 82 6-Br H n-Butyl Cyclopentyl 1 .63 6-Br H n-Butyl n-Hexyl 1. 84 6-Br H · n-Butyl Cyclohexyl 1 .85 6-Br H n-Butyl Phenyl 1.86 6-Br H n-Butyl 4-Chlorophenyl 1. 87 6-Cl H n-Butyl 4-Chlorophenyl 1.88 6-Br H n-Butyl 4-Phenoxyphenyl 1.89 6-Br H i-Butyl n-Propyl 1.90 6-Cl H i-Butyl n-Propyl 1.91 6-3r H i-Butyl n-Butyl 1. 92 6-Cl H i-Butyl n-Butyl 1. 93 6 -Br -H n-Propyl 1. 94 6-Cl H n-Propyl 1.95 6-Br H n-Propyl 1.96 6-Br H ^ CK, n-Butyl -. 57 6 - Br H n-Pentyl Me

• • •

58 6-Cl H n-Pentyl Et 99 6-Br H n-Pentyl n-Propyl 100 ALIGN! 6-Cl H n-Pentyl n-Propyl 101 H 7-C1 n-Pentyl n-Propyl 102 H 7-1 n-Pentyl n-Propyl 103 6-Br H n-Pentyl Δ 104 6-Cl H n-Pentyl Δ 105 H 7-Cl n-Pentyl Δ 10 6 6-Br H n-Pentyl n-Butyl 107 6-Cl H n-Pentyl n-Butyl 106 H 7-C1 n-Pentyl n-Butyl 109 H 7-1 n-Pentyl n-Butyl 110 6-3r H n-Pentyl i-Butyl 111 6-Cl H n-Pentyl i-Butyl 112 6-Br H n-Pentyl 113 6-Cl H n-Pentyl 114 J-j 7-C1 n-Pentyl 115 6-3r H n-Pentyl Me 116 6-Cl H n-Pentyl Me to 117 6-Br H n-Pentyl Cyclobutyl 113 6-Br H n-Pentyl n-Pentyl 119 6-Cl H n-Pentyl n-Pentyl 12 0 ' H 7-C1 n-Pentyl n-Pentyl 121 6-3r H n-Pentyl Cyclopentyl

• · · · · · · ·

1. 122 6-Br H 41 n-Pentyl n-Hexyl 1. 123 6-Br H n-Pentyl Cyclohexyl 1. 124 6-Br H n-Pentyl Phenyl 1.125 6-Br H n-Pentyl 4-Chlorophenyl 1.12 6 6-C1 H n-Pentyl 4-Chlorophenyl 1.127 6-Br H n-Pentyl 4-Phenoxyphenyl 1.128 6-Br H OEt Me 1.129 6-C1 H OEt Et 1. 130 6-Br H OEt n-Propyl 1.131 6-C1 H OEt n-Propyl 1.13 2 H 7-Cl OEt n-Propyl 1.133 H 7-1 OEt n-Propyl ί. 1 ύ * ί 6-Br H OEt Δ 1. 135 6-C1 H OEt Δ 1.136 H 7-Cl OEt Δ 1. 137 6-Br H OEt n-Butyl 1. 138 6-C1 H OEt n-Butyl 1.139 H 7-Cl OEt n-Butyl 1.14 0 H 7-1 OEt n-Butyl ^Ί 4 2. 6-Br H OEt i-Butyl 1 .142 6-C1 H OEt i-Butyl 1.143 6-3r H OEt 1.144 6-C1 H OEt 1.145 H 7-Cl OEt 1.14 6 6-Br H OEt Me

• ·

. 147 6-Cl H OEt OF Me to .14 8 6-Br H OEt Cyclobutyl .14 9 6-Br H OEt n -Pentyl . 150 6-Cl H OEt n -Pentyl . 151 H 7-C1 OEt n -Pentyl . 152 6-Br H OEt Cyclopentyl . 153 6-Br H OEt n -Hexyl . 154 6-Br H OEt Cyclohexyl . 155 6-Br H OEt Phenyl . 156 6-3r H OEt 4 -Phenyl .157 6-Cl H OEt 4 -Chlorophenyl .158 6-Br H OEt 4 -Fenoxyphenyl 6-Br H O-n-Propyl Me .160 6-Cl H O-n-Propyl Et . 161 6-Br H O-n-Propyl n-Propyl . 162 6-Cl at O-n-Propyl n-Propyl . 163 H 7-C1 O-n-Propyl n-Propyl . 164 H 7-1 O-n-Propyl n-Propyl . 165 6-Br H O-n-Propyl Δ . 166 6-Cl H O-n-Propyl Δ .167 H 7-Cl O-n-Propyl Δ . 168 6-Br H O-n-Propyl n-Butyl . 169 6-Cl H O-n-Propyl n-Butyl .170 H 7-C1 O-n-Propyl n-Butyl . 171 H 7-1 O-n-Propyl n-Butyl . 172 6-Br H O-n-Propyl i-Butyl . 173 6-Cl H O-n-Propyl i-Butyl . 174 6-Br H O-n-Propyl

43 • · ·· ·· • · · · · • · · · · • · · · · · • · · · · • · · · · · 1.175 6-Cl H O-n-Propyl of to 1. 176 H 7-C1 O-n-Propyl of to 1.17 7 6-Br H O-n-Propyl 4e of to 1. 178 6-Cl H O-n-Propyl h 1e of to 1.179 6-Br H O-n-Propyl Cyclobutyl 1.18 0 6-Br H O-n-Propyl n-Pentyl 1.181 6-Cl H O-n-Propyl n-Pentyl 1.182 H 7-C1 O-n-Propyl n-Pentyl 1.18 3 6-Br at O-n-Propyl Cyclopentyl 1.184 6-Br H O-n-Propyl n-Hexyl 1.18 5 6-Br H O-n-Propyl Cyclohexyl 1.186 6-Br H O-n-Propyl Phenyl 1. 187 6-Br H O-n-Propyl 4-Chlorophenyl 1. 188 6-Cl H O-n-Propyl 4-Chlorfenvl 1.189 6-Br H O-n-Propyl 4-Phenoxyphenyl 1.190 6-Br H Et CH ₂ OMe 1.191 6-Cl H Et CH ₂ OMe 1.192 6-Br H n-Propyl CH ₂ OMe 1.193 6-Cl H n-Propyl CH ₂ OMe 1. 194 H 7-C1 n-Propyl CH ₂ OMe 1.195 6-Br H n-Butyl CH ₂ OMe 1.196 6-Cl H n-Butyl CH ₂ OMe 1.197 6-Br H ^ CH, CH ₂ OMe 1.198 6-Br H n-Pentyl CH ₂ OMe 1.199 6-Br H Et CH ₂ OEt 1.20 0 6-Cl H Et CH ₂ OEt . of '1 6-Br H n-Propyl CH ₂ OEt

• · • ·

6-Cl H n-Propyl CH ₂ OEt H 7-Cl n-Propyl CH ₂ OEt 6-Br H n-Butyl CH ₂ OEt 6-Cl H n-Butyl CH ₂ OEt 6-Br H AND CH ₂ OEt

CH,

6-Br H n-Pentyl CH ₂ OEt 6-Br H n-Propyl CH ₂ CN 6-Br H n-Butyl ch ₂ cn 6 - Br H N-Propyl t-Butyl 6-Br H n-Propyl t-Butyl 6-Cl H n-Propyl cf ₃ 6-Br H n-Propyl cf ₃ 6-Br H n-Butyl cf ₃

• · · · · · · · · · · ·

Table 2; A = Pyridyl

S1. no. Ri r ₂ r ₃ R4 2. 1 6-Br H Me Me 2. 2 6-Cl H Me Et 2. 3 6-Br H Me n-Propyl 2. 4 6-Cl H Me n-Propyl 2. 5 6-Br H Me n-Butyl 2. 6 6-Cl H Me n-Butyl 2. 7 6-Br H Me i-Butyl 2. 8 6-Cl H Me i-Butyl 2. 9 6-Br H Me n-Pentyl 2.10 6-Br H Me

Phys

t. t ° e ° C

2.11 6-Cl H

Me ^ K,

2. 12 6-Br H Et Me 2. 13 6-Cl H Et Et 2.14 6-Br H Et n-Propyl 2.15 6-Cl H Et n-Propyl 2. 16 6-Br H Et n-Butyl 2. 17 6-Cl H Et n-Butyl 2. 18 6-Br H Et i-Butyl 2.19 6-Cl H Et i-Butyl 2.20 6-Br H Et n-Pentyl 2.21 6-Br H Et 2. 22nd 6-Cl H Et

** ** ··· ** ** · · · ·

23 6-Br H n-Propyl Me 24 6-C1 H n-Propyl Et 25 6-Br H n-Propyl n-Propyl 26 6-C1 H n-Propyl n-Propyl 27 Mar: 7-1 H n-Propyl n-Propyl 28 6-Br H n-Propyl Δ 29 6-C1 H n-Propyl Δ 30 6-Br H n-Propyl n-Butyl 31 6-C1 H n-Propyl n-Butyl 32 6-1 H n-Propyl n-Butyl 33 6-Br. H n-Propyl i-Butyl 34 6-C1 H n-Propyl i-Butyl- 35 6-Br H n-Propyl A ^ 3 6 6-C1 H n-Propyl 37 6-Br H n-Propyl Me

oil, ¹ H-NMR

2.38. 6-C1 H n-Propyl

Me

39 6-Br H n-Propyl Cyclobutyl 40 6-Br H n-Propyl n-Pentyl 4 1 6-C1 H n-Propyl n-Pentyl 42 6-Br H n-Propyl Cyclopentyl 43 6-Br H n-Propyl n-Hexyl 44 6-Br H n-Propyl Cyclohexyl 45 6-Br H n-Propyl Phenyl 46 6-Br H n-Propyl 4-Chlorophenyl 47 6-C1 H n-Propyl 4-Chlorophenyl 48 6-Br H n-Propyl 4-Phenoxyphenyl

• ·· ·

2.49 β-Br H 2.50 6-Cl H 2. 51 6-Br H 2. 52 6-Cl H 2. 53 H 7-C1 2. 54 H 7-1 2. 55 6-Br H 2. 56 6-Cl H 2. 57 H 7-C1 2.58 6-Br H 2. 59 6-Cl H 2. 60 6-1 H 2. 61 6-Br H 2. 62 6-Cl H 2.63 6-Br H 2.64 6-Cl H ' 2. 65 6-1 H

2.66 6-Br H 2. 67 6-Cl H

n-Butyl Me n-Butyl Et n-Butyl n-Propyl n-Butyl n-Propyl n-Butyl n-Propyl n-Butyl n-Propyl n-Butyl Δ n-Butyl Δ n-Butyl Δ n-Butyl n-Butyl n-Butyl n-Butyl n-Butyl n-Butyl n-Butyl i -Butyl n-Butyl i-Butyl n-Butyl n-Butyl n-Butyl Me n-Butyl Me n-Butyl TO

2.68 6-Br

2.69 6-Br

n-Butyl Cyclobutyl n-Butyl n-Pentyl

2. 70 6-Cl 48 ·> · ♦ • · · · · * · · ♦ · • · 9 9 9 9 9 99 99 9 n-Pentyl H n-Butyl 2. 71 6-Br ' H n-Butyl Cyclopentyl 2. 72 6-Br H n-Butyl n-Hexyl 2.73 6-Br H n-Butyl Cyclohexyl 2. 74 6-3r H n-Butyl Phenyl 2.75 6 - Br H n-Butyl 4 -Chlor phenyl 2. 76 6-Cl H n-Butyl 4-Chlorophenyl 2. 77 6-Br H n-Butyl 4-Phenoxyphenyl 2. 78 6-Br H i-Butyl n-Propyl 2.79 6-Cl H i-Butyl n-Propyl 2.80 6-Br H i-Butyl n-Butyl 2. S1 6-Cl H i-Butyl n-Butyl 2. 82 6 - Br H n-Propyl 2, 83 6-Cl H ^ H, n-Propyl 2. 84 6-Br at n-Propyl 2. 85 6-Br H to n-Butyl 2. 86 6-Br H n-Pentyl Me 2. 87 6-Cl H n-Pentyl Et 2.33 6-Br H n-Pentyl n-Propyl 2.89 6-Cl H n-Pentyl n-Propyl 2. 90 6-Br H n-Pentyl Δ 2. 91 6-Cl H n-Pentyl Δ 2. 92 6-Br H n-Pentyl n-Butyl 2. 93 6-Cl H n-Pentyl n-Butyl 2. 94 6-1 H n-Pentyl n-Butyl 2. 95 6-Br H n-Pentyl i-Butyl of . r o 6-Cl H n-Pentyl i-Butyl

·· ·· 44 44 444 · ·. · 4 · 4 · · · · · ·

.......... i 4 4 4 4 4 4 4 44 44 44 44. 97

6-Br. 98

6-Cl

2.99

6-Br n-Pentyl n-Pentyl n-Pentyl

Me

2.100

6-Cl n-Pentyl

2.101 6-Br H n-Pentyl Cyclobutyl 2.102 6-Br H n-Pentyl n-Pentyl 2.103 6-Cl H n-Pentyl n-Pentyl 2.104 6-Br H n-Pentyl Cyclopentyl 2.105 6-Br H n-Pentyl n-Hexyl 2.106 6-Br H n-Pentyl Cyclohexyl 2.107 6-Br H n-Pentyl Phenyl 2 ¹ 0 7 6-Br H n-Pentyl 4-Chlorophenyl 2. 109 6-Cl H n-Pentyl 4-Chlorophenyl 2.110 6-Br H n-Pentyl 4-Phenoxyphenyl 2.111 6-Br H OEt Me 2.112 6-Cl H OEt Et 2. _ 13 6-Br H OEt n-Propyl 2.114 6-Cl H OEt n-Propyl 2.115 6-Br H OEt Δ 2.116 6-Cl H OEt Δ 2.117 6-Br H OEt n-Butyl 2.118 6-Cl H OEt n-Butyl 2.119 6-1 H OEt n-Butyl 2.120 6-Br H OEt i-Butyl 2.121 6-Cl H OEt i-Butyl 2.122 6-3r H OEt AND

• 1 · 1 · 1 · 1 · 1 · 1 · 1 · 1 · 1 123

6-Cl

6-Br

OEt

OEt

Me

2.125

6-Cl

OEt

.

of .

126 6-Br H OEt Cyclobutyl 127 6-Br H OEt n-Pentyl 12 8 6-Cl H OEt n-Pentyl 129 6-3r H OEt Cyclopentyl 130 6-Br H OEt n-Hexyl 131 6 - Br H OEt Cyclohexyl 132 6-Br H OEt Phenyl t 3 3 6-Br H OEt 4-Chlorophenyl 134 6-Cl H OEt 4-Chlorophenyl 13 5 6-Br H OEt 4-Phenoxyphenes 136 6-Br H O-n-Propyl Me 137 6-Cl H O-n-Propyl Et 138 6-Br H O-n-Propyl n-Propyl 139 6-Cl H O-n-Propyl n-Propyl 14 0 6-Br H O-n-Propyl Z 4 1 6-Cl H O-n-Propyl 142 6-Br H O-n-Propyl n-Butyl 14 3 6-Cl H O-n-Propyl n-Butyl 144 6-Br H O-n-Propyl i-Butyl 145 6-Cl H O-n-Propyl i-Butyl 146 6-Br H O-n-Propyl 14 7 6-Cl H O-n-Propyl A

·

9 9 9

9

Μθ

2.148 6-Br

O-n-Propyl

• · · · · ·

2.149 6-Cl H O-n-Propyl 1 2.150 6-Br H O-n-Propyl Cyclobutyl 2. 151 6-Br H O-n-Propyl n-Pentyl 2.152 6-Cl H O-n-Propyl n-Pentyl 2.153 6-Br H O-n-Propyl Cyclopentyl 2.154 6-Br H O-n-Propyl n-Hexyl 2.155 6-Br H O-n-Propyl Cyclohexyl 2. 156 6-Br H O-n-Propyl Phenyl 2.157 6-Br H O-n-Propyl 4-Chlor- phenyl 2. 158 6-Cl H O-n-Propyl 4-Chlor- phenyl 2.159 6-Br H O-n-Propyl 4-Phenoxyphenyl 2.160 6-Br H Et CH ₂ OMe 2. 161 6-Cl H Et CH ₂ OMe 2.162 6-Br H n-Propyl CH ₂ OMe 2 .163 6-Cl H n-Propyl CH ₂ OMe 2.164 6-Br H n-Butyl CH ₂ OMe 2.165 6-Cl H n-Butyl CH ₂ OMe 2.166 6-Br H Δ ^ ^ CH, CH ₂ OMe 2.167 6-Br H n-Pentyl CH ₂ OMe 2.168 6-Br H Et CH ₂ OEt 2.165 6-Cl H Et CH ₂ OEt 2.170 6-Br H n-Propyl CH ₂ OEt 2.171 6-Cl H n-Propyl CH ₂ OEt 2. 172 6-Br H n-Butyl CH ₂ OEt 2.173 6-Cl H n-Butyl CH ₂ OEt of . 1 7 4 6-Br H CH, CHnOEt

2. 175 6-Br H 2.176 6-Br H 2. 177 6-Br H 2.178 6-Br H 2.179 6-Br H 2.180 6-Br H 2.181 6-Br H

n-Pentyl CH ₂ OEt n-Propyl CH ₂ CN n-Butyl ch ₂ cn n-Propyl t-Butyl n-Propyl t-Butyl n-Propyl cf ₃ n-Butyl cf ₃

• ·

Table 3: A = Thienyl [2,3-d] r ₂ O n ³ - ^R ' 5 h, 1 Ji JI R, ^{6 p} N «4 1 Sl. C. Ri r ₂ r ₃ r ₄ physical data e mp ° C 3. 1 Cl H Me Me 139-141 3. 2 Cl H Me Et 3. 3 Br H Me n-Propyl 3. 4 Cl H Me n-Propyl 3. 5 Br H Me n-Butyl 3. 6 Cl H Me n-Butyl 63-65 3.7 Br H Me i-Butyl 3. 8 Cl H Me i-Butyl 87-89 3. 9 Br H Me n-Pentyl 3. 10 Br H Me \ h, 3. 11 Cl H Me

3.12 Br H 3.13 Cl H 3. 14 Br H 3.15 Cl H 3. 16 Br H 3. 17 Cl H 3. 18 Br H 3. 19 Dec Cl H 3.20 Br H 3.21 Br H j. 2 2 Cl TT

Et Me Et Et Et n-Propyl Et n-Propyl 80-82 Et n-Butyl Et n-Butyl oil, Et i-Butyl Et i-Butyl Et n-Pentyl Et Et

• · • ·

3. 23 Br H 54 n-Propyl · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·· · β ·· ·· Me 3. 24 Cl H n-Propyl Et 3.25 Br H n-Propyl n-Propyl 3. 26 Cl H n-Propyl n-Propyl 74-76 3.27 AND H n-Propyl n-Propyl 3. 2 S Br H n-Propyl Δ 3.29 Cl H n-Propyl Δ 3.30 Br H n-Propyl n-Butyl 63-66 3.31 Cl H n-Propyl n-Butyl 67-69 3.32 AND H n-Propyl n-Butyl 3.33 Br H n-Propyl i-Butyl 7 7 Cl H n-Propyl i-Butyl oil, 1 H-NMR 3 .35 Br H n-Propyl 3.36 Cl H n-Propyl oil, ¹ H-NMR 3 .37 Br H n-Propyl Me TO 3.38 Cl H n-Propyl Me 3.39 Br H n-Propyl Cyclobutyl 3.40 Br H n-Propyl n-pentyl 7/7 _. * 1 X Cl H n-Propyl n-Pentyl 3.42 Br H n-Propyl Cyclopentyl 3.43 Br H n-Propyl n-Hexyl 3.44 Br. H n-Propyl Cyclohexyl 3.45 Br H n-Propyl Phenyl 3.46 Br H n-Propyl 4-Chlorophenyl 3.47 Cl H n-Propyl 4-Chlorophenyl 126-128 7, 4 C Br H n-Propyl 4-Phenoxyphenyl

·

55 • 9 • 9 • 9 • 9 · 9 3.49 Br H n-Butyl Me 3.50 Cl Ή n-Butyl Et 3.51 Br H n-Butyl n-Propyl 3. 52 Cl H n-Butyl n-P ropyl oil 3. 53 AND H n-Butyl n-Propyl 3. 54 AND H n-Butyl n-Propyl 3.55 Br H n-Butyl Δ 3. 56 Cl H n-Butyl Δ 54-56 3.57 AND H n-Butyl Δ 3.58 Br H n-Butyl n-Butyl oil 3.59 Cl H n-Butyl n-Butyl 57-58 3. β 0 AND H n-Butyl n-Butyl 3.61 Br H n-Butyl i-Butyl 3. 52 Cl H n-Butyl i-Butyl 3. 63 Br H * -> D1 1 4- τ ' ¹ . L IN 3. 64 Cl H n-Butyl L in 3. 65 T H n-Butyl L TO 3.55 3r H n-Butyl Me 3.67 Cl H n-Butyl L fv to 1e 2 3.68 Br H n-Butyl Cyclobutyl 3 5 9 Br H n-Butyl n-Pentyl 3.70 Cl H n-Butyl n-Pentyl 3.71 Br H n-Butyl Cyclopentyl 3.72 Br H n-Butyl n-r iexyl

• · c •

73. Br H n-Butyl Cyclohexyl 74 Cl H n-Butyl Phenyl 75 Br H n-Butyl 4-Chlorophenyl 76 Cl H n-Butyl 4-Chlorophenyl 77 Br H n-Butyl 4-Phenoxyphenyl 78 Br H i-Butyl n-Propyl 79 Cl H i-Butyl n-Propyl o 80 Br H i-Butyl n-Butyl 81 Cl H i-Butyl n-Butyl 82 Br H n-Propyl 83 Cl H n-Propyl 84 Cl H n-Propyl 85 Br H n-Butyl 8 6 Br H n-Pentyl Me 87 Cl H n-Pentyl Et 88 Br H n-Pentyl n-Propyl 89 Cl H n-Pentyl n-Propyl 90 Br H n-Pentyl Δ 91 Cl H n-Pentyl Δ 92 Br H n-Pentyl n-Butyl 93 Cl H n-Pentyl n-Butyl 94 AND H n-Pentyl n-Butyl 95 Br H n-Pentyl i-Butyl 96 Cl H n-Pentyl i-Butyl 97 Br H n-Pentyl 98 Cl H n-Pentyl

• • •

3. 99 3.100 Br Cl H H n-Pentyl n-Pentyl Me and 3.101 Cl H n-Pentyl Cyclobutyl 3.102 Br H n-Pentyl n-Pentyl 3. 103 Cl H n-Pentyl n-Pentyl 3.104 Cl H n-Pentyl Cyclopentyl 3.105 Br H n-Pentyl n-Hexyl 3.106 Cl H n-Pentyl Cyclohexyl 3.107 Br H n-Pentyl Phenyl 3.108 3r H n-Pentyl 4-Chlorophenyl 3. 109 Cl H n-Pentyl 4-Chlorophenyl 3.110 Br H n-Pentyl 4-Phenoxyphenyl 3.111 Br H OEt Me 3.112 Cl H OEt Et 3. 113 Br H - OEt n-Propyl 3.114 Cl H OEt n-Propyl 3.115 Br H OEt Δ 3.116 Cl H OEt Δ 3.117 Br H OEt n-Butyl 75-77 3.118 Cl H OEt n-Butyl 66-69 3.119 T _L H OEt n-Butyl 3.120 Br H OEt i-Butyl 3.121 Cl H OEt i-Butyl 3. 122 Br H OEt 3.123 Cl H OEt

• • •

Ie

3,124 Br H OEt

3.125 Cl H

OEt

Ie

126 Br H OEt Cyclobutyl 127 Br H OEt n-Pentyl 12 8 Cl H OEt n-Pentyl 12 9 Br H OEt Cyclopentyl 130 Br H OEt n-Hexyl 131 Br H OEt Cyclohexyl 132 3r H OEt Phenyl 13 3 Br H OEt 4-Chlorophenyl 134 Cl H OEt 4-Chlorophenyl 135 Cl H OEt 4-Phenoxyphenyl 136 Br H O-n-Propyl Me 13 7 Cl H O-n-Propyl Et 138 Br H O-n-Propyl n-Propyl 139 Cl H O-n-Propyl n-Propyl 140 Br H O-n-Propyl 14 1 Cl H O-n-Propyl 142 Br H O-n-Propyl n-Butyl 143 Cl H O-n-Propyl n-Butyl 144 Br H O-n-Propyl i-Butyl 14 5 Cl H O-n-Propyl i-Butyl 14 6 Br H O-n-Propyl 14 7 Cl H O-n-Propyl 14 8 Br H O-n-Propyl

• · • ·

149 Cl H O-n-Propyl 1 150 Br H O-n-Propyl Cyclobutyl 151 Br H O-n-Propyl n-Pentyl 152 Cl H O-n-Propyl n-Pentyl 153 Br H O-n-Propyl Cyclopentyl 154 Cl H O-n-Propyl n-Hexyl 155 Br H O-n-propyl Cyclohexyl 156 Cl H O-n-Propyl Phenyl 157 Br H O-n-Propyl 4-Chlorophenyl 158 Cl H O-n-Propyl 4-Chlorophenyl 159 Br H O-n-Propyl 4-Phenoxyphenyl 160 Br H Et CH ₂ OMe 161 Cl H · Et CH ₂ OMe 162 Br H n-Propyl CH ₂ OMe 16 3 Cl H n-Propyl CH ₂ OMe oil, 164 Br H n-Butyl CH ₂ OMe 165 Cl H n-Butyl CH ₂ OMe 166 Br H ^ CH, CH ₂ OMe 16 7 Br H n-Pentyl CH ₂ OMe 168 Br H Et CH ₂ OEt 169 Cl H Et CH ₂ OEt 170 Br H n-Propyl CH ₂ OEt 171 'Cl H n-Propyl CH ₂ OEt 40-41 172 Br H n-Butyl CH ₂ OEt 173 Cl H n-Butyl CH ₂ OEt 174 Br H ^ CH, CH ₂ OEt 175 Br H n-Pentyl CH ₂ OEt 176 Br H n-Propyl CH ₂ CN 177 Cl H n-Butyl CH ₂ CN ί 73 Br H n-Propyl t-Butyl

• · · ·

179 Cl H 180 Br H 181 Cl H 182 Cl H 183 Cl Cl 184 Cl Cl 185 Br Br 186 Br Br

n-Propyl t-Butyl n-Propyl cf ₃ n-Butyl cf ₃ n-Pentyl cf ₃ n-Propyl n-Propyl n-Propyl n-3-butyl n-Propyl n-Butyl n-Butyl n-Butyl

• · · ·

Table 4: A thienyl [3.2-d]

. no. Ri r ₂ r ₃ r ₄ 1 Br H Me Me 2 H Cl Me Et 3 Br H Me n-Propyl 4 H Cl Me n-Propyl 5 H Cl Me n-Propyl 6 Br H Me n-Butyl 7 H Cl Me n-Butyl G H Cl Me n-Butyl Q Br H Me i-Butyl 10 H Cl Me i-Butyl 11 Br H Me n-Pentyl 12 Br H Me 13 H Cl Me ^ H, - £ Br H Et Me 15 Dec H Cl Et Et 1 ζ Br H Et n-Propyl 17 H Cl Et n-Propyl 13 H Cl Et n-Propyl 19 Dec Br H Et n-Butyl 20 May H Cl Et n-Butyl 2 1 H Cl Et n-Butyl 22nd Br H Et i-Butyl 23 H Cl Et i-Butyl 24 Br H Et n-Pentyl

f yz. data e • · • ·

25 Br Η Et 26 Η NO. 1 Et 27 Mar: Br Η η-Propyl Me 28 Η NO. 1 n-Propyl Et 29 Br Η n-Propyl n-Propyl 30 Η NO. 1 n-Propyl n-Propyl 31 Η NO. 1 n-Propyl n-Propyl 32 Η AND n-Propyl n-Propyl 33 Br Η n-Propyl Δ 34 Η NO. 1 n-Propyl Δ 3 5 Η NO. 1 n-Propyl Δ 36 Br Η n-Propyl n-Butyl 37 Η NO. 1 n-Propyl n-Butyl 38 Η NO. 1  n-Propyl n-Butyl 39 Η AND n-Propyl n-Butyl 40 Br Η n-Propyl i-Butyl 41 Η NO. 1 n-Propyl i-Butyl 4 2 Br Η n-Propyl 4 3 Η NO. 1 n-Propyl 4 4 Η NO. 1 n-Propyl 45 Η NO. 1 n-Propyl Me Me 46 Η NO. 1 n-Propyl

120-121

• • •

47 Br H n-Propyl Cyclobutyl 48 ' Br H n-Propyl n-Pentyl 49 H Cl n-Propyl n-Pentyl 50 H Cl n-Propyl n-Pentyl C τ Br H n-Propyl Cyclopentyl 52 Br H n-Propyl n-Hexyl 5 3 Br H n-Propyl Cyclohexyl Δ 1 Br H n-Propyl Phenyl 55 Br H n-Propyl 4-Chlorophenyl 55 H Cl n-Propyl 4-Chlorophenyl 56 Br H n-Propyl 4-Phenoxyphenyl 57 Br H n-Butyl Me 58 H Cl n-Butyl Et 59 Br H n-Butyl n-Propyl 60 H Cl n-Butyl n-Propyl 61 H Cl n-Butyl n-Propyl 62 H AND n-Butyl n-Propyl 62 Br H n-Butyl Δ 63 H Cl n-Butyl Δ 64 H Cl n-Butyl Δ 6 5 Br H n-Butyl n-Butyl 6 6 H Cl n-Butyl n-Butyl 67 H Cl n-Butyl n-Butyl 6 8 H AND n-Butyl n-Butyl r Cj C i / Br H n-Butyl i-Butyl 7C H Cl n-Butyl i-Butyl 71 Br H n-Butyl 72 H Cl n-Butyl A ^ 73 H Cl n-Butyl A ^

• · · ·

4.74. Br-n-Butyl

Me · · · · · · · · · · · · · · · · · · · ·

Cl n-Butyl Me

Λ z

η

76 Br H n-Butyl cyclobutyl 77 Br H n-Butyl n-Pentyl 78 H Cl n-Butyl n-Pentyl 79 H Cl n-Butyl n-Pentyl 8 0 Br H n-Butyl Cyclopentyl 81 Br H n-Butyl n-Hexyl 82 Br H n-Butyl Cyclohexyl 8 3 Br H n-Butyl Phenyl 84 Br H n-Butyl 4-Chlorophenyl 85 H Cl n-Butyl 4-Chlorophenyl 8 6 Br H n-Butyl 4-Phenoxyphenyl 87 Br H i-Butyl n-Propyl 88 H Cl i-Butyl n-Propyl 89 Br H i-Butyl n-Butyl 90 H Cl i-Butyl n-Butyl 91 Br H n-Propyl 92 H Cl n-Propyl 9 3 Br H n-Propyl 94 Br H n-Butyl 95 Br H n-Pentyl Me 96 H Cl n-Pentyl Et 97 Br H n-Pentyl n-Propyl 98 Cl H n-Pentyl n-Propyl 99 n Cl n-Pentyl n-Propyl

· · · · · · · · · · · · · · · · · · · ·

4. 100 ALIGN! H AND n-Pentyl n-Propyl 4.101 Br H n-Pentyl Δ 4 .102 H Cl n-Pentyl Δ 4.103 H Cl n-Pentyl Δ

104 Br H n-Pentyl n-Butyl 105 Ή Cl n-Pentyl n-Butyl 106 H Cl n-Pentyl n-Butyl 107 H ' AND n-Pentyl n-Butyl 108 Br H n-Pentyl i-Butyl 109 H Cl n-Pentyl i-Butyl 110 Br H n-Pentyl OF 111 H Cl n-Pentyl of in 112 H Cl n-Pentyl of in 113 Br H n-Pentyl h OF 4e to 114 H Cl n-Pentyl 0e

115 Br H n-Pentyl Cyclobutyl 116 Br H n-Pentyl n-Pentyl 117 Cl Cl n-Pentyl n-Pentyl 118 H Cl n-Pentyl n-Pentyl 119 Br H n-Pentyl Cyclopentyl 120 Br H n-Pentyl n-Hexyl 121 Br H n-Pentyl Cyclohexyl 122 Br H n-Pentyl Phenyl 123 Br H n-Pentyl 4-Chlorophenyl

• ·

4. 124 H Cl n-Pentyl 4-Chlorophenyl 4. 125 Br H n-Pentyl 4-Phenoxyphenyl 4.126 Br H OEt Me 4. 127 Cl H OEt Et 4.128 Br H OEt n-Propyl 4.129 H Cl OEt n-Propyl 4.130 H Cl OEt n-Propyl 4.131 H AND OEt n-Propyl 4. 132 Br H OEt Δ 4. 133 H Cl OEt Δ 4. 134 H Cl OEt Δ 4. 1 and 5 Br H OEt n-Butyl 4.136 H Cl OEt n-Butyl 4.137 H Cl OEt n-Butyl and 3 g H AND OEt n-Butyl 4.139 Br H OEt i-Butyl 4.14 0 H Cl OEt i-Butyl 4.141 Br H OEt 4.142 TO Cl OEt Δ, 4.143 H Cl OEt Δ. a and a Br H OEt AND 4.145 H Cl OEt Me

4.146 Br

OEt Cyclobutyl · · · ·

67 4.147 Br H OEt n-Pentyl 4.148 Η Cl OEt n-Pentyl 4.149 Η Cl OEt n-Pentyl 4. 150 Br H OEt Cyclopentyl 4.151 Br H OEt n-Hexyl 4. 152 Br H OEt Cyclohexyl 4. 153 Br H OEt Phenyl 4.154 Br H OEt 4-Chlorophenyl 4. 155 Cl OEt 4-Chlorophenyl 4.156 Br H OEt 4-Phenoxyphenyl

4 .157 Br H O-n-Propyl Me 4.158 H Cl O-n-Propyl Et 4.159 Br H O-n-Propyl n-Propyl 4.160 H Cl O-n-Propyl n-Propyl 4.161 H Cl O-n-Propyl n-Propyl 4.162 H AND O-n-Propyl n-Propyl 4. 163 Br H O-n-Propyl Δ 4. 164 H Cl ' O-n-Propyl Δ 4.165 H Cl O-n-Propyl Δ 4. 166 Br H O-n-Propyl n-Butyl 4.167 H Cl O-n-Propyl n-Butyl 4.168 at Cl O-n-Propyl n-3-butyl 4.169 H II O-n-Propyl n-Butyl 4. 170 Br H O-n-Propyl i-Butyl 4.171 H Cl O-n-Propyl i-Butyl 4.172 Br H O-n-Propyl 4. 173 H Cl O-n-Propyl 4. 174 H Cl O-n-Propyl

• t ···· · · · · · · · · · · ·

· »« * * * * *. 175

Br

O-n-Propyl

Me

4.176

Cl

O-n-Propyl

Me

177 Br H O-n-Propyl Cyclobutyl 17 8 Br H O-n-Propyl n-Pentyl 179 H Cl O-n-Propyl n-Pentyl 180 H Cl O-n-Propyl n-Pentyl 181 Br H O-n-Propyl Cyclopentyl 182 Br H O-n-Propyl n-Hexyl 183 Br H O-n-Propyl Cyclohexyl 184 Br H O-n-Propyl Phenyl 185 Br H O-n-Propyl 4-Chlorophenyl 186 H Cl O-n-Propyl 4-Chlorophenyl 187 Br H O-n-Propyl 4-Phenoxy phenyl 188 Br in Et CH ₂ OMe 189 H Cl Et CH ₂ OMe 190 Br H n-Propyl CH ₂ OMe 191 H Cl n-Propyl CH ₂ OMe 192 H Cl n-Propyl CH ₂ OMe 193 Br H n-Butyl CH ₂ OMe 194 H Cl n-Butyl CH ₂ OMe 195 Br H ^ CH, CH ₂ OMe 195 Br H n-Pentyl CH ₂ OMe 196 Br H Et CH ₂ OEt 197 H Cl Et CH ₂ OEt 198 Br H n-Propyl CH ₂ OEt 199 H Cl n-Propyl CH ₂ OEt 200 H Cl n-Propyl CH ₂ OEt 201 Br H n-Butyl CH ₂ OEt 2 02 H Cl n-Butyl CH ₂ OEt

• · · ·

69 4.203 Br H AND, ^ CH, CH ₂ OEt 4. 204 Br H n-Pentyl CH ₂ OEt 4.205 Br H n-Propyl CH ₂ CN 4.206 Br H n-Butyl ch ₂ cn 4.207 Br H n-Propyl t-Butyl 4.208 Br H n-Propyl t-Butyl 4.209 H Cl n-Propyl cf ₃ 4.210 Br H n-Propyl cf ₃ 4.211 H Cl n-Butyl cf ₃ 4.212 Br H n-Butyl cf ₃ 4. 213 Cl Cl n-Propyl n-Propyl 4.214 Cl Cl n-Propyl n-Butyl 4.215 Br Br n-Propyl n-Butyl 4.216 Br Br n-Butyl n-Butyl

Table 5: A = Thiazolyl C if 1 N Λ . with N S1. no. Ri r ₃ R ₄ phys. detail 5. 1 H Et n-Propyl 5.2 H n-Propyl n-Propyl 5. 3 H n-Propyl n-Butyl 5.4 H n-Butyl n-Butyl 5.5 Me n-Propyl n-Propyl 5. 6 Me n-Propyl n-Butyl 5.7 Me n-Butyl n-Butyl 5. 8 H n-Propyl Phenyl

• ·

Table 6: A = phenyl

. no. Ri r ₂ r ₃ r ₄ 1 6-Br H Me Me 2 6-Cl H Me Et 3 6-Br H Me n-Propyl 4 6-Cl H Me n-Propyl 5 H 7-Cl Me n-Propyl 6 6-Br H Me n-Butyl 7 6-Cl H Me n-Butyl 8 H 7-Cl Me n-Butyl WITH 6-Br H Me i-Butyl 10 6-Cl H Me i-Butyl 11 6-Br H Me n-Pentyl 12 6-3r H Me 13 6-Cl H Me 14 6-Br H Et Me 1 5 6-Cl H Et Et 16 6-Br H Et n-Propyl 17 6-Cl H Et n-Propyl 18 H 7-Cl Et n-Propyl 19 Dec 6-Br H Et n-Butyl 20 May 6-Cl H Et n-Butyl 21. H 7-Cl Et n-Butyl 22nd 6-Br H Et i-Butyl 23 6-Cl H Et i-Butyl 24 6-Br H Et n-Pentyl

° C · · · · · · · ·

6.25 6-Br H Et 6. 26 6-Cl H Et 6.27 6-3r H n-Propyl Me 6.28 6-Cl H n-Propyl Et 6.29 6-Br H n-Propyl n-Propyl 6.30 6-Cl H n-Propyl n-Propyl 6.31 H 7-C1 n-Propyl n-Propyl 6.32 H 7-1 n-Propyl n-Propyl 6.33 6-Br H n-Propyl Δ 6. 34 6-Cl H n-Propyl Δ 6.35 H 7-C1 n-Propyl Δ 6. 36 6-Br H n-Propyl n-3-butyl 6 3 7 6-Cl H n-Propyl n-Butyl 6. 38 H 7-C1 n-Propyl n-Butyl 6.39 H 7-1 n-Propyl n-Butyl 6.40 6-Br H n-Propyl i-Butyl 6.41 6-Cl H n-Propyl i-Butyl 6.42 6-Br H n-Propyl AND. 6.43 6-Cl H n-Propyl 6.44 H 7-C1 n-Propyl 6.45 6-Br H n-Propyl Me TO 6.46 6-Cl H n-Propyl Me

^{@ 1} H-NMR

• ·

47 6-Br H n-Propyl Cyclobutyl 48 6-Br H n-Propyl n-Pentyl 49 6-Cl H n-Propyl n-Pentyl 5 0 H 7-Cl n-Propyl n-Pentyl 51 6-Br H n-Propyl Cyclopentyl 52 6-Br H n-Propyl n-Hexyl 53 6-Br H n-Propyl Cyclohexyl 54 6-Br H n-Propyl Phenyl 5 5 6-Br H n-Propyl 4-Chlorophenyl 5 6 6-Cl H n-Propyl 4-Chlorophenyl 57 6-Br H n-Propyl 4-Phenoxyphenyl 58 6-Br H n-Butyl Me 59 6-Cl H n-Butyl Et 6 0 6-3r H n-Butyl n-Propyl 61 6-Cl H n-Butyl n-Propyl 62 H 7-Cl n-Butyl n-Propyl 63 H 7-1 n-Butyl n-Propyl 64  6-Br H n-Butyl Δ 65 6-Cl H n-Butyl Δ 66 H 7-Cl n-Butyl Δ 67 6-Br H n-Butyl n-Butyl 6 8 6-Cl H n-Butyl n-Butyl 69 H 7-Cl n-Butyl n-Butyl 70 H 7-1 n-Butyl n-Butyl 7 ^Ί 6-Br H n-Butyl i-Butyl 72 6-Cl H n-Butyl i-Butyl 73 6-Br H n-Butyl 74 6-Cl H n-Butyl 75 H 7-Cl n-Butyl

• · · · · · · · · · · · · ·

6.76 6-Br H n-Butyl 6.77 6-Cl H n-Butyl

6.78 6-Br H n-Butyl 6.79 6-Br H n-Butyl 6.80 6-Cl H n-Butyl 6.81 H 7- Cl n-Butyl 6. 82 6-Br H n-Butyl 6. 83 6-Br H n-Butyl 6. 84 6-Br H n-Butyl 6.35 6-Br H n-Butyl 6.86 6-Br H n-Butyl 6. 87 6-Cl H n-Butyl 6.88 6-Br H n-Butyl 6.89 6-Br H i-Butyl 6. 90 6-Cl H i-Butyl 6. 91 6-Br H i-Butyl 6.92 6-Cl H i-Butyl 6. 93 6-Br H 6. 94 6-Cl H 6. 95 6-Br H 6.96 6-Br H ^^ CH, 6.97 6-Br H n-Pentyl 6. 38 6-Cl H n-Pentyl 5. 99 6-Br H n-Pentyl 6.100 6-Cl H n-Pentyl 6.101 H 7- Cl n-Pentyl

Cyclobutyl n-Pentyl n-Pentyl n-Pentyl

Cyclopentyl n-Hexyl

Cyclohexyl

Phenyl

-Chlorophenyl 4-Chlorophenyl 4-Phenoxyphenyl n-Propyl n-Propyl n-Butyl n-Butyl n-Propyl n-Propyl n-Propyl n-Butyl

Me

Et n-Propyl n-Propyl n-Propyl

6. 102 Η 7-1 n-Pentyl n-Propyl 6.103 - 6-Br H n-Pentyl Δ 6.104 6-Cl H n-Pentyl Δ 6.105 H 7-Cl n-Pentyl Δ 6.106 6-Br H n-Pentyl n-Butyl 6. 107 6-Cl H n-Pentyl n-Butyl 6.108 H 7-Cl n-Pentyl n-Butyl 6.109 H 7-1 n-Pentyl n-Butyl 6.110 6-Br H n-Pentyl i-Butyl 6.111 6-Cl H n-Pentyl i-Butyl 6.112 6-Br H n-Pentyl 6.113 6-Cl H n-Pentyl 6.114 H 7-Cl n-Pentyl 6.115 6-Br H n-Pentyl Me

6.116 6-Cl H n-Pentyl 1 ' 6.117 6-Br H n-Pentyl Cyclobutyl 6.118 6-Br H n-Pentyl n-Pentyl - '' 9 6-Cl H n-Pentyl n-Pentyl 6.120 H 7-Cl n-Pentyl n-Pentyl 6.121 6-Br H n-Pentyl Cyclopentyl 6. 122 6-Br H n-Pentyl n-Hexyl 6. 123 6-Br H n-Pentyl Cyclohexyl 6.124 6-Br H n-Pentyl Phenyl 6.125 6-Br H n-Pentyl 4-Chlorophenes

• • • •

6.126 6-Cl H 75 n-Pentyl 4-Chlorophenyl 6. 127 6-Br H n-Pentyl 4- Phenoxyphenyl 6. 128 6-Br H OEt Me 6.129 6-Cl H OEt Et 6.130 6-Br H OEt n- Propyl 6.131 6-Cl H OEt n- Propyl 6. 132 H 7-C1 OEt n- Propyl 6.133 H 7-1 OEt n- Propyl 6. 134 6-Br H OEt Δ 6.135 6-Cl H OEt Δ 6.136 H 7-C1 OEt Δ 6.137 6-Br H OEt n- Butyl 5.138 6-Cl H OEt n- Butyl 6.139 H 7-C1 OEt n- Butyl 6.140 H 7-1 OEt ΤΊ - Butyl 5.141 6-Br H OEt i - Butyl 6. 142 6-Cl H OEt and- Butyl 6. 143 6-Br H OEt of to 6.144 6-Cl H OEt of to 6.145 H 7-C1 OEt of to 6.146 6-Br H OEt F] 4e 6.147 6-Cl H OEt of h to 4e 6.148 6-Br H OEt of Cy to clobutyl 6.149 6-Br H OEt n- Pentyl

· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

76 6. 150 6-Cl H OEt n-Pentyl 6.151 H 7-Cl OEt n-Pentyl 6. 152 6-Br H OEt Cyclopentyl 6.153 6-Br H OEt n-Hexyl 6.154 6-Br H OEt Cyclohexyl 6.155 6-Br H OEt Phenyl 6.156 6-Br H OEt 4-Chlorophenyl 6.157 6-Cl H OEt 4-Chlorophenyl 6.158 6-Br H OEt 4 - Phenoxyphenyl 6.159 6-Br H O-n-Propyl Me 6. 160 6-Cl H O-n-Propyl Et 6.161 6-Br H O-n-Propyl n-Propyl 6. 162 6-Cl H O-n-Propyl n-Propyl 6. 163 H 7-Cl O-n-Propyl n-Propyl 6.164 H 7-1 O-n-Propyl n-Propyl 6.165 6-Br H O-n-Propyl 6.166 6-Cl H O-n-Propyl 6.167 H 7-Cl O-n-Propyl 6. 168 6-Br H O-n-Propyl n-Butyl 6.169 6-Cl H O-n-Propyl n-Butyl 6.170 H 7-Cl O-n-Propyl n-Butyl 6.171 H 7-1 O-n-Propyl n-Butyl 6.172 6-Br H O-n-Propyl i-Butyl 6.173 6-Cl H O-n-Propyl i-Butyl 5.174 6-Br H O-n-Propyl 6. 175 6-Cl H O-n-Propyl 5.176 H 7-Cl O-n-Propyl

• · · · · · · · · · · ·

6. 177 6-Br H 77 O-n-Propyl Ř 4e 6. 178 6-Cl H O-n-Propyl L h to 5. 179 6-Br H O-n-Propyl L Cyk to lobutyl β. 180 6-Br H O-n-Propyl n-Pentyl 6.181 6-Cl H O-n-Propyl n-Pentyl 6.182 H 7- Cl O-n-Propyl n-Pentyl 6.183 6-Br H O-n-Propyl Cyclopentyl 6.184 6-Br H O-n-Propyl n-Hexyl 6.185 6-Br H O-n-Propyl Cyclohexyl 6.186 6-Br H O-n-Propyl Phenyl 6.187 6-Br H O-n-Propyl 4-Chlorophenyl 6. 188 6-Cl H O-n-Propyl 4-Chlorophenyl 6.189 6-Br H O-n-Propyl 4-Phenoxyphenyl 6.190 6-Br H Et CK ₂ OMe 6.191 6-Cl H Et CH ₂ OMe 6.192 6-Br H n-Propyl CH ₂ OMe 6. 193 6-Cl H n-Propyl CH ₂ OMe 6.194 H 7- Cl n-Propyl CH ₂ OMe 6.195 6-Br H n-Butyl CH ₂ OMe 6.196 6-Cl H n-Butyl CH ₂ OMe 5.197 6-Br H ^ CH, CH ₂ OMe 6.198 6-Br H n-Pentyl CH ₂ OMe 6.199 6-Br H Et CH ₂ OEt 6.200 6-Cl H Et CH ₂ OEt 6.201 6-Br H n-Propyl CH ₂ OEt 6.202 6-Cl H n-Propyl CH ₂ OEt 6.203 H 7- Cl n-Propyl CH ₂ OEt 6. 204 6-Br H n-Butyl CH ₂ OEt 6.205 6-Cl H n-Butyl CH ₂ OEt

• · · ♦ · · * * * * *

6.206 6-Br H ^ CH, CH ₂ OEt 6.207 6-Br H n-Pentyl CH ₂ OEt 6.208 6-Br H n-Propyl CH ₂ CN 6.209 6-Br H n-Butyl ch ₂ cn 6.210 6-Br H n-Propyl t-Butyl 6.211 6-Br H n-Propyl t-Butyl * 6.212 6-C1 H n-Propyl cf ₃ 6.213 6-Br H n-Propyl cf ₃ AND 6.214 6-Br H n-Butyl cf ₃

• • • •

Table

SI. no.

. 1

7.2. 3. 4

7.5. 6

7.7

7.8

7.9

7.10. 11

7.12. 13

7.14

7.15. 16

7.17

7.18

7.19 .20

7.21

7.22

Ri R ₂ r ₃ R ₄ Br H Me Me Cl H Me Et Br H Me n-Propyl Cl H Me n-Propyl Br H Me n-Butyl Cl H Me n-Butyl Br H Me i-Butyl Cl H Me i-Butyl Br H Me n-Pentyl Br H Me AND, Cl H Me Άη,

physical data, mp ° C

113-114

Br H Et Me Cl H Et Et Br H Et n-Propyl Cl H Et n-Propyl Br 'H Et n-Butyl Cl H Et n-Butyl Br H Et i-Butyl Cl H Et i-Butyl Br H Et n-Pentyl Br H Et Cl H Et

· · · · · · · · · · · · · · · · · · · · · · · ·

7.23

7.24

7.25

7.26

7.27

7.28. 29

7.30

7.31. 32

7.33

7.34. 35. 36

7.37. 38

7.39

7.40

7.41

7.42

7.43

7.44

7.45

7.46

7.47

7.43

Br H n-Propyl Cl H n-Propyl Br H n-Propyl Cl H n-Propyl AND H n-Propyl Br H n-Propyl Cl H n-Propyl Br H n-Propyl Cl H n-Propyl AND H n-Propyl Br H n-Propyl Cl H n-Propyl Br H n-Propyl Cl H n-Propyl Br H n-Propyl Cl H n-Propyl

Br H n-Propyl Br H n-Propyl Cl H n-Propyl Br H n-Propyl Br H n-Propyl Br H n-Propyl Br H n-Propyl Br H n-Propyl Cl H n-Propyl Br H n-Propyl

Me

Et n-Propyl n-Propyl n-Propyl

Δ

Δ n-Butyl n-Butyl oil, ¹ HMR n-Butyl i-Butyl i-Butyl 57-60

Cyclobutyl n-Pentyl n-Pentyl

Cyclopentyl n-Hexyl

Cyclohexyl

Phenyl

4-Chlorophenyl 4-Chlorophenyl 4-Phenoxyphenyl 9

7.49 Br H 7.50 ' Cl H 7.51 Br H 7. 52 Cl H 7. 53 AND H 7. 54 AND H 7. 55 Br H 7.56 Cl H 7.57 AND H 7.58 Br H 7. 59 Cl H 7.60 AND H 7. 61 Br H 7. 62 Cl H 7.63 Br H 7.64 Cl H 7.65 AND H 7.66 Br H

n-Butyl Me n-Butyl Et n-Butyl n-Propyl n-Butyl n-Propyl n-Butyl n-Propyl n-Butyl n-Propyl n-Butyl Δ n-Butyl Δ n-Butyl Δ n-Butyl n-Butyl n-Butyl n-Butyl n-Butyl n-Butyl n-Butyl i-Butyl n-Butyl i-Butyl n-Butyl n-Butyl n-Butyl n-Butyl Me

7.67 Cl H n-Butyl Me 7.68 Br H n-Butyl TO Cyclobutyl 7.69 Br H n-Butyl n-Pentyl 7.70 Cl H n-Butyl n-Pentyl 7.71 Br H n-Butyl Cyclopentyl 7. 72 Br H n-Butyl n-Hexyl

• · · · · ·

73 Br H n-Butyl Cyclohexyl 74 Cl H n-Butyl Phenyl 75 Br H n-Butyl 4-Chlorophenyl 76 Cl H n-Butyl 4-Chlorophenyl 77 Br H n-Butyl 4-Phenoxyphenyl 78 Br H i-Butyl n-Propyl 79 Cl H i-Butyi n-Propyl 80 Br H i-Butyl n-Butyl 81 Cl H i-Butyl n-Butyl 82 Br H n-Propyl 83 Cl H n-Propyl 84 Cl H n-Propyl 85 Br H and XX, n-Butyl 8 6 Br H n-Pentyl Me 87 Cl H n-Pentyl Et 88 Br H n-Pentyl n-Propyl 89 Cl H n-Pentyl n-Propyl 90 Br H n-Pentyl Δ 91 Cl H n-Pentyl Δ 92 Br H n-Pentyl n-Butyl 93 Cl H n-Pentyl n-Butyl 94 AND H n-Pentyl n-Butyl 95 Br H n-Pentyl i-Butyl 96 Cl H n-Pentyl i-Butyl 97 Br H n-Pentyl A ^ 98 Cl H n-Pentyl

• ·

0000

7.99

Br n-Pentyl

Me

7.100

Cl • 0

0 0 0 0 0

0 0 0 0 0

n-Pentyl Me

7.101

7.102

7.103

7.104

7.105

7.106

7.107. 1 0 N

7.109

7.110

7.111

7.112. 113

7.114. 115

7.116

Cl

Br

Cl

Cl

Br

Cl

Br

Br

Cl

Br

Br

Cl

Br

Cl

Br

Cl

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

N-Pentyl n-Pentyl n-Pentyl n-Pentyl n-Pentyl n-Pentyl n-Pentyl n-Pentyl n-Pentyl n-Pentyl

OEt

OEt

OEt

OEt

OEt

OEt

Cyclobutyl n-Pentyl n-Pentyl

Cyclopentyl n-Hexyl

Cyclohexyl

Phenyl

- Chlorophenyl 4-Chlorophenyl 4-Phenoxyphenyl Me-Propyl n-Propyl

7.117. US

7.119

7.120

7.121. 122

7.123

Br

Cl

AND

Br

Cl

Br

Cl

H

H

H

H

H

H

H

OEt

OEt

OEt

OEt

OEt

OEt

OEt n-Butyl n-Butyl n-Butyl i-Butyl i-Butyl

»Φ« ««> * * * «« «« «« «« «« «« «« «*« «« «« · · · · · · · · · · · · · · · · · · · · ·

7. 124 Br H OEt ^ř 1e 7.125 Cl H 2 OEt i to rte 7.126 Br H and OEt Cy] to clobutyl 7.127 Br H OEt n-Pentyl 7. 12g Cl H OEt n- Pentyl 7.129 Br H OEt Cyclopentyl 7.130 Br H OEt n-Hexyl 7.131 Br H OEt Cyclohexyl 7.132 Br H OEt Phenyl 7.133 Br H OEt 4 - Chlorophenyl 7.134 Cl H OEt 4- Chlorophenyl 7. 135 Cl H OEt 4- Phenoxyphenyl 7.136 Br H O-n-Propyl Me 7.137 Cl at O-n-Propyl Et 7.138 Br H O-n-Propyl n -Propyl 7.139 Cl H O-n-Propyl n -Propyl 7.140 Br H O-n-Propyl Δ 7.141 Cl H O-n-Propyl Δ 7. 142 Br H O-n-Propyl n -Butyl 7.143 Cl H O-n-Propyl n -Butyl 7. 144 Br H O-n-Propyl i -Butyl 7.145 Cl H O-n-Propyl i -Butyl 7.146 Br H O-n-Propyl 7.147 Cl H O-n-Propyl

• <»• · · · · · · · · · · · ·

• ......

• · · · · · · · · · · ·

7.148

Br

O-n-Propyl

7.149 Cl H

O-n-Propyl

Me

7. 150 Br H 7.151 Br H 7.152 Cl H 7. 153 Br H 7.154 Cl H 7.155 Br H 7 .156 Cl H 7.157 Br H 7. 158 Cl H 7.159 Br H 7.160 Br H 7.161 Cl H 7. 162 Br H 7. 163 Cl H 7.164 Br H 7. 165 Cl H 7.166 Br H 7.167 Br H 7. 168 Br H 7.169 Cl H 7.170 Br H 7.171 Cl H 7. 172 Br H 7. 173 Cl H 7.174 Br H 7. 175 Br H

O-n-Propyl Cyclobutyl O-n-Propyl n-Pentyl O-n-Propyl n-Pentyl O-n-Propyl Cyclopentyl O-n-Propyl n-Hexyl O-n-Propyl Cyclohexyl O-n-Propyl Phenyl O-n-Propyl 4-Chlorophenyl O-n-Propyl 4-Chlorophenyl O-n-Propyl 4-Phenoxyphenyl Et CH ₂ OMe Et CH ₂ OMe n-Propyl CH ₂ OMe n-Propyl CH ₂ OMe n-Butyl CH ₂ OMe n-Butyl CH ₂ OMe ^ k CH ₂ OMe n-Pentyl CH ₂ OMe Et CH ₂ OEt Et CH ₂ OEt n-Propyl CH ₂ OEt n-Propyl CH ₂ OEt n-Butyl CH ₂ OEt n-Butyl CH ₂ OEt CH ₂ OEt n-Pentyl CH ₂ OEt

• · · · · · · · · · · · · · · · · · · · · ·

7.176 Br H n-Propyl CH ₂ CN 7.177 Cl H n-Butyl ch ₂ cn 7.178 Br H n-Propyl t-Butyl 7.179 Cl H n-Propyl t-Butyl 7.180 Br H n-Propyl cf ₃ 7.181 Cl H n-Butyl cf ₃ 7. 182 Cl H n-Pentyl cf ₃ 7.183 Cl Cl n-Propyl n-Propyl 7.184 Cl Cl n-Propyl n-Butyl 7.185 Br Br n-Propyl n-Butyl 7.186 Br Br n-Butyl n-Butyl Examples biological activities: Fungicidal action

Example cucumbers Cclletotrichum lagenarium on Plants cucumbers are grown for 2 weeks, and then Spray and spray mixture o concentration of 0.002% prepared

from a wettable powder composition of a test compound. Two days later the plants are infected with a spore suspension containing 1.5 x 10 ⁵ spores / ml and incubated with £ 3 for 6 hours at 23 DEG C. and high atmospheric humidity. The incubation is then resumed at normal atmospheric humidity and at a temperature of approximately 22 ^° C.

The compounds of Tables 1 to 7, in particular compounds 1 3.17, 3.26, 3.30, 3.31, 3.47, show good to excellent 36, 2.30, 3.1, 3.6, 3.8, 3.15,

3.52, 3.56, 3.59, 3.79,

3.117, 3.118, 3.163, 3.171, 4.36, 6.29, 7.6, 7.31 and 7.34.

• · · · · · · · · · ·

Example B-2: Residual protective action against Venturia inaequalis on apple trees

Apple seedlings with fresh shoots of 10 to 20 cm in length are sprayed until spray dripping with a spray mixture containing 0.02% active ingredient prepared from the wettable powder composition of the test compound. 24 hours later they are infected with a conidia suspension of the fungus. The plants are incubated for 5 days at a relative atmospheric humidity of 90-100% and are placed in a greenhouse at 20-24 ° C for a further 10 days. The fungal infestation is evaluated 12 days after infection.

The compounds of Tables 1 to 7 show good activity, particularly compounds 1.36, 2.30, 3.1, 3.6, 3.8, 3.15, 3.17, 3.26, 3.30, 3.31, 3.34, 3.36, 3.47, 3.52, 3.56, 3.58, 3.59, 3.79, 3.117,

3.118, 3.163, 3.171, 4.36, 6.29, 7.6, 7.31 and 7.34.

Example B-3: Action against Erysiphe graminis on barley

(a) Residual protective action

Barley plants of approximately 8 cm in height are sprayed to a dripping condition with an aqueous spray mixture containing 0.02% active ingredient prepared from a wettable powder composition of the test compound, and 3 to 4 days later dusted with conidia of the fungus. The infected plants are placed in a greenhouse at 22 ° C. The fungal infestation is evaluated 12 days after infection.

b) Systemic effect

An aqueous spray mixture containing 0.002% active ingredient prepared from the wettable powder composition of the test compound, based on the soil volume, is poured into barley plants of about 8 cm in height. Care should be taken to ensure that the spray mixture does not come into contact with the aerial parts of the plants. 0 48 hours • ··· «···· · · · ··································· · · ···· · · · · · · ·

....... * later the plants are dusted with conidia of the fungus. The infected plants are placed in a greenhouse at 22 ° C. The fungal infestation is evaluated 12 days after infection.

Compared to control plants, infestation of plants treated with compounds 1.36, 2.30, 3.1, 3.6, 3.8, 3.15, 3.17, 3.26, 3.30, 3.31, 3.34, 3.36, 3.47, 3.52, 3.56, 3.58, 3.59,

3.79, 3.117, 3.118, 3.163, 3.171, 4.36, 6.29, 7.6, 7.31 and 7.34 20% or less.

Example B-4: Action against Podosphaera leucotricha on apple shoots

Apple seedlings with fresh shoots approximately 15 cm long are sprayed with a spray mixture containing 0.06% active ingredient. After 24 hours, the treated plants are infected with a conidia suspension of the fungus and then placed in a controlled environmental chamber at a relative atmospheric humidity of 70% and a temperature of 20 ° C. The fungal infestation is evaluated 12 days after infection.

The compounds of Tables 1 to 7 show good activity. The following compounds are particularly potent: 1.36, 2.30, 3.1, 3.6, 3.8, 3.15, 3.17, 3.26, 3.30, 3.31, 3.34, 3.36, 3.47, 3.52, 3.56, 3.58, 3.59, 3.79, 3.117, 3.118, 3.163, 3.171,

4.36, 6.29, 7.6, 7.31 and 7.34 (0-5% attack).

Example B-5: Action against Plasmopara viticola on vines

a) Residual preventive action

Chasselas vine cuttings are grown in a greenhouse. 3 plants are sprayed at a concentration of 200 ppm at the 10 leaf stage. After the spray has dried on the plants, the underside of the plant leaves is evenly infected with the spore suspension of the fungus. The plants are then placed in a humid chamber for 8 days. After this time, the control plants clearly develop symptoms of the disease. The number and size of infected • sites on the treated plants are used to evaluate the efficacy of the test substances.

b) Curative effect

Chasselas grape cuttings are grown in a greenhouse and at the 10-leaf stage, the underside of the leaves is infected with a spore suspension of Plasmopara viticola. The plants are placed in a humid chamber for 24 hours and then sprayed with a liquid containing 200 ppm of active ingredient. The plants are then placed in a humid chamber for a further 7 days. After this time, symptoms of the disease can be observed on the control plants. The number and size of infected sites on the treated plants are used to evaluate the efficacy of the test substances.

The compounds of Tables 1 to 7 show good activity, in particular compounds 1.36, 2.30, 3.1, 3.6, 3.8, 3.15, 3.17, 3.26, 3.30, 3.31, 3.34, 3.36, 3.47, 3.52, 3.56, 3.58, 3.59, 3.79, 3.117, 3.118, 3.163, 3.171, 4.36, 6.29, 7.6, 7.31 and 7.34.

Example B-6: Action against Uncinula necator on vines

The vine shoots were sprayed with a 200 ppm solution prepared from a wettable powder formulation of the test compound. 24 hours later, the plants are infected with conidia from heavily infested vine leaves, which are shaken off to the test plants. The plants are then incubated at 26 ° C and 60% relative humidity. Assessment of fungal infestation is performed about 14 days after infection.

Compared to the control plants treated with the compounds of formula I, the compounds 1.36, 2.30, 3.26, 3.30, 3.31, 3.34, 3.36, 3.47

3.79, 3.117, 3.118, 3.163, 3.171,

7.34, 20% or less.

is assault plant care- from tables 1 to 7 eg - .1, 3.6, 3.8 , 3.15, , 3.17, 3.52, 3.56 3.58, 3.59, 4.36, 6.29 7.6, 7.31 a

• ·

Claims (9)

PATENTOVÉ YEARS ' 1. Compound of Formula I X (i) A is thienyl (including all three isomers), chiazolyl, pyridyl or pyridazinyl; X is an oxygen atom or a sulfur atom; Rx is hydrogen, halogen or trimethylsilyl; R ₂ is hydrogen, halogen or trimethylsilyl; at least one of R x and R ₂ is not hydrogen; R ₃ is C 1 -C 8 alkyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl that are unsubstituted or mono- to trisubstituted C 3 -C 6 cycloalkyl, halogen, alkoxy C 1 -C 6 or C 1 -C 6 haloalkoxy; C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl, halogen or (C 1 -C 6) alkoxy; N-C 1 -C 6 -alkyl; Or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety; R ₄ is C 1 -C 8 alkyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl that are unsubstituted or mono- to trisubstituted C 3 -C 6 cycloalkyl, halogen, cyano , (C 1 -C 6) alkoxy or (C 1 -C 6) haloalkoxy; nitro; -CO-alkyl having 1 to 6 carbon atoms in the alkyl moiety; (C 3 -C 6) cycloalkyl; or a phenyl group which is unsubstituted or mono- to trisubstituted by a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, cyano, nitro, amino, C 1 -C 6 monoalkylamino, C 1 -C 6 dialkylamino, C 1 -C 6 alkylthio, phenyl or phenoxy wherein the phenyl moiety is unsubstituted or mono-trisubstituted with halogen, (C 1 -C 6) alkyl, (C 1 -C 6) haloalkyl, (C 1 -C 6) alkoxy, or (C 1 -C 6) haloalkoxy. A compound of formula I according to claim 1, wherein A is a thienyl group, including all three isomers. A compound of formula I according to claim 2, wherein: 92 • · · · • · • · · · · · Ri is a hydrogen atom, a fluorine atom, chlorine atom, atom or bromine atom j odu; R ₂ is a hydrogen atom, a fluorine atom, chlorine atom, atom or bromine atom iodine; at least one of su R ₂ bstituentů a. Rp not an atom hydrogen; R ₃ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl which is unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl, halogen or (C 1 -C 4) alkoxy; N-C 1 -C 6 -alkyl; or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety; R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted by C 3 -C 6 cycloalkyl, halogen or alkoxy containing 1 to 4 carbon atoms; or a phenyl group which is unsubstituted or mono- to trisubstituted by a fluorine atom, a chlorine atom, a bromine atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkoxy group Phenyl or phenoxy, and wherein the phenyl moiety is unsubstituted or mono to trisubstituted by fluorine, chlorine, bromine, alkyl of 1 to 4 carbon atoms, haloalkyl of 1 to 4 atoms C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy. A compound of formula I according to claim 3, wherein R ₃ is an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, an alkynyl group having 2 to unsubstituted or a mono group containing 6 carbon atoms which are up to trisubstituted cycloalkyl of 3 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom or C 1 -C 4 alkoxy group; O-C 1 -C 6 -alkyl; An O-alkenyl group having 2 to 6 carbon atoms; O-alkynyl having 2 to 6 carbon atoms; N-C 1 -C 6 -alkyl; or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety; R ₄ is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl which are unsubstituted or mono to trisubstituted C 3 -C 4 cycloalkyl, fluoro, atom chlorine, bromine or C1-C4alkoxy; or a phenyl group which is unsubstituted or mono- to trisubstituted by fluorine, chlorine, bromine, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, haloalkoxy 94 ........... containing from 1 to 4 carbon atoms, phenyl or phenoxy, and wherein the phenyl moiety is unsubstituted or mono to trisubstituted with a fluorine atom, a chlorine atom or a bromine atom. A compound of formula I according to claim 4, wherein A is thienyl [2,3-d], X is an oxygen atom, R 1 is hydrogen, chlorine or bromine; R ₂ is hydrogen, chlorine or bromine; at least one of R ₂ and R ₂ is not hydrogen; R ₃ is C 3 -C 5 alkyl or C 1 -C 4 alkyl; R ₄ is C 2 -C 5 alkyl or phenyl which is unsubstituted or mono-tri-substituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl or phenoxy, and wherein the phenoxy group is unsubstituted or mono to trisubstituted by fluorine, chlorine or bromine. A compound of formula I according to claim 4, wherein A is thienyl [2,3-d], X is a sulfur atom, R 1 is hydrogen, chlorine or bromine; R ₂ is hydrogen, chlorine or bromine; at least one of R ₂ and R ₂ is not hydrogen; • • • 95 .......... R ₃ is C 3 -C 5 alkyl or C 1 -C 4 alkyl; R ₄ is an alkyl group containing. 2 to 5 carbon atoms or a phenyl group which is unsubstituted or mono-tri-substituted by fluorine, chlorine, atom, bromine, alkyl of 1 to 4 carbon atoms or phenoxy, and wherein the phenoxy group is unsubstituted or mono-trisubstituted by fluorine , chlorine or bromine. A compound of formula I according to claim 4, wherein A is thienyl [3,2-d], X is an oxygen atom, R 1 is hydrogen, chlorine or bromine; R ₂ is hydrogen, chlorine or bromine; at least one of R 1 and R ₂ is not hydrogen; R ₃ is C 3 -C 5 alkyl or C 1 -C 4 alkyl; R ₄ is C 2 -C 5 alkyl or phenyl which is unsubstituted or mono-tri-substituted by fluorine, chlorine, bromine, C 1 -C 4 alkyl or phenoxy, wherein the phenoxy group is unsubstituted or mono to trisubstituted by fluorine, chlorine or bromine. A compound of formula I according to claim 1, wherein A is a pyridyl group. A compound of formula (I) according to claim 1, wherein: A is a thiazolyl group. A compound of formula I according to claim 1, wherein A is pyridazinyl. An agent for controlling and preventing pests, wherein the active ingredient is according to claim 1 together with a suitable carrier. vvproduct compound2. Use of a compound of the formula I according to claim 1 for the protection of plants against attack by phytopathogenic microorganisms. 3. A method of controlling or preventing infestation of a crop plant by a phytopathogenic microorganism, which comprises applying a compound of formula I according to claim 1 to the plants, to parts thereof, or to the area of cultivation thereof. The method of claim 14, wherein the phytopathogenic microorganism is a fungal by the fact mikroorganisZpůsob preparing a compound of formula I according to claim 1, characterized in that it comprises a) converting the .alpha.-amino-.beta.-karboalkoxyheterocyklu formula II wherein R, _T and R ₂ has the same as defined for a compound of formula I and R is hydrogen, alkyl of 1 to 6 carbon atoms, COOR · 9 · using POCl ₃ in the presence of a solvent and R ₄ CONHR ₃ to an amidine of formula III, wherein R ₃ and R ₄ have the same meaning as given for formula I b) and treating the amidine in the presence of a solvent and, if necessary, in the presence of a base, and after ring closure to obtain a pyrimidin-4-one derivative of formula IV or wherein A, R _{1 #} R ₂ and R ₃ have the same with an orthoester ^R <t>^<0R5 R ^ R ₅ O- where R ₄ has the meaning steinv ~ i as oro c) reacting the aminocarboxylic acid amide of formula VI VI meaning as for formula I, XIII of formula I and R ₅ is an alkyl group having 1 to 5 carbon atoms, in the presence or absence of a solvent, in the presence or absence of an acid catalyst at 20 to 200 ° C, to obtain a pyrimidin-4-one derivative of formula IV; and (d) where intermediate VII NHR, By reacting a compound of formula VII in the presence of a solvent and, if necessary, in the presence of a base and after ring closure, to obtain a pyrimiain-4-one derivative of formula IV. 16. A compound of formula III NHR, FL III Ά is thienyl [2,3-d] or thienyl [3,2-d]; R @ 1 is hydrogen, halogen or trimethylsilyl; R _; is hydrogen, halogen or trimethylsilyl; and at least one of R ₃ and R is not hydrogen; R ₃ is C 1 -C 8 alkyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl that are unsubstituted or mono- to trisubstituted C 3 -C 6 cycloalkyl, halogen, alkoxy C 1 -C 6 or C 1 -C 6 haloalkoxy; O-C 1 -C 6 -alkyl, O-C 2 -C 6 -alkenyl, O-C 2 -C 6 -alkynyl which are unsubstituted or mono- to trisubstituted by C 3 -C 6 -cycloalkyl. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 9 · 9 9 · gg a carbon atom, a halogen atom or an alkoxy group having 1 to 6 carbon atoms; N-C 1 -C 6 -alkyl; or N = CH-alkyl having 1 to 6 carbon atoms in the alkyl moiety; R ₄ is C 1 -C 8 alkyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl that are unsubstituted or mono- to trisubstituted C 3 -C 6 cycloalkyl, halogen, cyano , (C 1 -C 6) alkoxy or (C 1 -C 6) haloalkoxy; alkoxyalkoxy having 1 to 4 carbon atoms in each alkoxy moiety; alkoxyalkylthio having 1 to 4 carbon atoms in the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety; nitro; -CO-alkyl having 1 to 6 carbon atoms in the alkyl moiety; (C 3 -C 6) cycloalkyl; or a phenyl group which is unsubstituted or mono- to trisubstituted by a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, nitro, amino, C 1 -C 6 monoalkylamino, C 1 -C 6 dialkylamino, C 1 -C 6 alkylthio, phenyl or phenoxy, and wherein the phenyl moiety is unsubstituted or mono-trisubstituted with halogen, (C 1 -C 6) alkyl, (C 1 -C 6) haloalkyl, (C 1 -C 6) alkoxy or (C 1 -C 6) haloalkoxy; and R is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.