FR2643224A1 - Use of aromatic and heterocyclic amine-containing compounds as agrochemical products - Google Patents

Abstract

The invention relates to the compounds of formula I: in which R1 and R2 form a group of formula IIg: or alternatively R2 denotes H, or an alkyl and R1 a group of formula IIa to IIf: R4 and R5 represent H or an alkyl group, R3 denotes H, alkyl, cycloalkyl or haloalkyl and R6 a group of formula IIIa to IIIe: or alternatively R1 represents a group of formula IIa to IIf and R2 and R3 form a (CH2)u group and the symbols R7 to R12, X, p, s, u, v, w, and Z have various meanings. These compounds can be used as agrochemical products.

Description

 The present invention relates to the use of aromatic and heterocyclic amines as drugs and agrochemicals, in particular as antifungals and fungicides, as well as pharmaceutical and agrochemical compositions containing them.

 The invention also relates to certain aromatic and heterocyclic amines and their preparation.

dans laquelle et et R2 forment ensemble , avec l'atome de carbone
auquel ils sont fiés, un groupe de formule IIg

In particular, the subject of the invention is, as medicaments and agrochemical products, the compounds of formula I

in which and R 2 together with the carbon atom
to which they are proud, a group of formula IIg

in which
p is 1, 2 or 3, or
R2 means hydrogen or a lower alkyl group and
R1 represents a group of formula IIa to IIf

dans lesquelles
R7 et R ont les significations données précédemment, signifie 2, 3, 4, 5 ou 6,
Z représente l'oxygène, le soufre ou NR3 ou R3 a la
signification donnée précédemment, et R12 représente un groupe alkyle , alcenyle, alcynyle,
cycloalkyle, cycloalkylalkyle, alcoxy inférieur,
alcoxycarbonyle inférieur, alkylthio inférieur,
phényle, phénylalkyle, trialkylsilyle, dialkyl
phénylsilyle ou un halogène, les groupes alkyle,
aîcényle, alcynyle, cycloalkyle, cycloalkylalkyle,
phényle et phénylalkyle pouvant être substitués
par des groupes phényle, alcoxy inférieur, alkyl
thio inférieur, phénylalcoxy, (alcoxy inférieur)
phényle, (alkyl inférieur )-phényle, halogéno
phényle, halogène ou un hétérocycle eventuellement
substitué, et pouvant éventuellement être fixés par
l'intermédiaire d'un groupe carbonyle, ou bien
R1 représente un groupe de formule IIa à IIf tel
que défini précédemment,
R2 et R3 forment ensemble un groupe -(CH2)-u où u
signifie un nombre entier de 1 à 8 et Rn, R5 et R6 ont les si-gnifications données précédem
ment, sous forme libre ou sous forme d'un sel d'addition d'acide pharmaceutiquement acceptable.in which
R7 and R8 represent, independently one of
the other, hydrogen, a halogen or a group
trifluoromethyl, lower alkyl or alkoxy
lower, R9 represents hydrogen, a halogen or a group
lower alkyl or lower alkoxy,
R10 and P ',' independently represent one of
the other, hydrogen, a halogen or a group
trifluoromethyl, lower alkyl, alkoxy
lower or lower alkylthio, one of the sympol es R10 and R11 to have a significant
tion other than hydrogen when the other sym
bole means hydrogen, a halogen or a
lower alkoxy group,
X represents oxygen, sulfur, an imino group,
lower alkylimin, -C-CH2- or -CH2-,
s is 3, 4 or 5,
v is 3, 4, 5 or 6,
one or two of the groups -CH2- in the formula IId
may be replaced by oxygen or sulfur,
R and R represent, independently of one another,
hydrogen or a lower alkyl group,
R3 represents hydrogen or an alkyl group, cyclo
alkyl or haloalkyl and
R6 represents a group of formula

in which
R7 and R have the meanings given above, means 2, 3, 4, 5 or 6,
Z represents oxygen, sulfur or NR3 or R3 has the
meaning previously given, and R12 represents an alkyl, alkenyl, alkynyl group,
cycloalkyl, cycloalkylalkyl, lower alkoxy,
lower alkoxycarbonyl, lower alkylthio,
phenyl, phenylalkyl, trialkylsilyl, dialkyl
phenylsilyl or halogen, alkyl groups,
alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,
phenyl and phenylalkyl may be substituted
by phenyl, lower alkoxy, alkyl groups
lower thio, phenylalkoxy, (lower alkoxy)
phenyl, (lower alkyl) -phenyl, halogen
phenyl, halogen or a heterocycle
substituted, and possibly
through a carbonyl group, or
R1 represents a group of formula IIa to IIf such
as defined previously,
R2 and R3 together form a group - (CH2) -u where u
means an integer from 1 to 8 and Rn, R5 and R6 have the meaning given above
in free form or in the form of a pharmaceutically acceptable acid addition salt.

The lower alkyl groups preferably contain 1 to 4 carbon atoms, especially 1 or 2 carbon atoms. The alkyl groups are in particular C 1 -C 12 alkyl, especially C 2 -C 8, more particularly C 2 -C 6, and more preferably C 2 -C 4. The alkenyl or alkynyl groups contain in particular from 3 to 6, especially 3 or 4 carbon atoms, and mean for example an allyl, propenyl or propynyl group. The groups mentioned above can be linear or branched. A preferred cycloalkylidene group of formula IIIb is a
Cyclohexylidene troupe. Cyclalkyl should be understood as encompassing polycycles such as bornyl or adamantyl groups, but preferably means cyclohexyl, cyclopentyl or cyclopropyl.

Advantageously, R7, R8 and R9 signify, independently of one another, hydrogen or a halogen. X advantageously means sulfur or a lower imino or alkyl-lower alkyl group.

 The heterocyls are, for example, saturated or unsaturated 5- or 6-membered rings containing one or more heteroatoms chosen from nitrogen, oxygen and sulfur, for example thiophene. They may contain one or more substituents such as those defined for R7.

R1 preferably means a group of formula Iic or IId, in particular of formula IIa or
IIb. R2 is preferably hydrogen and R3 is lower alkyl. R6 preferably means a group of formula IIIa. The values of p, s, u, v and w are advantageously chosen so as to form a 7 or preferably 6 or 5-membered ring. By halogen is meant fluorine, chlorine or bromine.

avec un composé de formule V

b) pour préparer les composés de formule Ia

on introduit un groupe R3, dans un composé de formule
Ib

c) i) pour préparer un compose de formule Ic

or fait réagir un composé de formule VI

The compounds of formula I can be prepared as follows: a) a compound of formula IV is reacted

with a compound of formula V

b) to prepare the compounds of formula Ia

a group R 3 is introduced into a compound of formula
Ib

(c) (i) to prepare a compound of formula Ic

or reacts a compound of formula VI

on fait réagir un composé de formule VIa

with a compound of formula VII
R6 - Me (VII) or ii) to prepare a compound of formula Id

a compound of formula VIa is reacted

on fait réagir un composé de formule VIb

avec un reactif de Wittig de formule IVb ou IVc

e) pour préparer un composé de formule If et Ig

cn réduit une base de Schiff de formule 1h ou Ii

ans les formules précédentes R, R2, R3, R4 , R5 et R6 ont les significations données pour la formule
l'un des symboles Y représente un groupe eliminable et l'autre un groupe -NH-R3, R3 représente un groupe cycloalkyle, halogénoaîkyîe ou alkyle inférieur, R représente un groupe alkyle inférieur,
Me représente l'équivalent d'un métal et R' represente un groupe de formule IIIf

oans laquelle
R13 , R14 et R15 représentent indépendamment l'hydrogène
ou un groupe alkyle inférieur, alcoxy inférieur,
pr-ényle, phénylalcoxy, (alcoxy inférieur)-phényle,
(alkyl inférieur)-phényle, halogénophényle, un
halogène ou un hétérocycle éventuellement substitué, et on récupère le composé ainsi obtenu sous forme libre ou sous forme d'un sel d'addition d'acide.with a compound of formula VIIa
R1 - Me (VIIa) d @ to prepare a compound of formula Ie

a compound of formula VIb is reacted

with a Wittig reagent of formula IVb or IVc

e) to prepare a compound of formula If and Ig

cn reduces a Schiff base of formula 1h or Ii

in the preceding formulas R, R2, R3, R4, R5 and R6 have the meanings given for the formula
one of Y is an eliminable group and the other is -NH-R3, R3 is cycloalkyl, halogeno or lower alkyl, R is lower alkyl,
Me represents the equivalent of a metal and R 'represents a group of formula IIIf

in which
R13, R14 and R15 independently represent hydrogen
or lower alkyl, lower alkoxy,
pr-enyl, phenylalkoxy, (lower alkoxy) -phenyl,
(lower alkyl) -phenyl, halophenyl, a
halogen or an optionally substituted heterocycle, and the compound thus obtained is recovered in free form or in the form of an acid addition salt.

 Process a) is carried out according to conventional methods for the preparation of tertiary amines by condensation. The process may be carried out in an inert solvent such as a lower alkanol, for example ethanol, optionally in admixture with water, an aromatic hydrocarbon, for example benzene or toluene, a cyclic ether, for example A dioxane is preferably a diakylamide of a carboxylic acid, for example dimethylformamide. Advantageously, the reaction is carried out at a temperature of between room temperature and boiling point of the reaction mixture, preferably at room temperature. The process is advantageously carried out in the presence of an acidic agent, for example an alkali metal carbonate such as sodium carbonate. The eliminable group is advantageously iodine or preferably chlorine or bromine or a sulphonyloxy group. organic compound containing from 1 to 10 carbon atoms, for example an alkylsulfonyloxy group, preferably containing 1 to 4 carbon atoms such as a mesyloxy group, or an alkylphenylsulfonyloxy group, preferably containing 7 to 10 carbon atoms such than a tosyloxy group.

Process b; can be carried out according to conventional methods for the alkylation of secondary amines, for example by direct alkylation with an alkylating agent, for example with a halide
Sulphate, or by reductive alkylation, especially by reaction with an appropriate aldehyde and simultaneous or subsequent reduction. The reductive alkylation can advantageously be carried out by reacting a compound of formula Ib in an inert solvent, for example in a lower alkanol such as methanol, with the corresponding aldehyde. The reduction can be carried out for example with a complex metal hydride such as NaBH4 or NaCNBH3 as reducing aeration.It can also be carried out using an aqueous solution of NaH2PO3
H. Loibner et al. Tetrahedron Letters 1984, 2535) or formic acid which can be used simultaneously as reducing agent and reaction medium.

 Process c) can be carried out according to the conventional methods for reactions involving organometallic compounds. It is preferably carried out in an inert solvent, for example in an ether, at a temperature between -20 and + 500C.

The process d) can be carried out according to the conventional methods for the Wittig reactions, preferably in an aprotic solvent such as a cyclic ether, for example tetrahydrofuran, or an aromatic hydrocarbon, for example toluene, between 20 C and the boiling point with reaction mixture
The reduction according to process e) can be carried out with a complex hydride such as NaBH4.

The procedure is preferably carried out in an inert solvent or, for example, in a lower alkanol such as methanol, at room temperature.

 The final products can be isolated and purified according to the usual methods. The compounds of this formula in the form of free bases can be converted into salts, and vice versa. Suitable acid addition salts are hydrochloride, hydrogen fumarate and naphthalene-1,5-disulfonate.

 The starting materials of formula VI and VIa can be prepared by reacting the corresponding amine of formula IV with formaldehyde and a lower alcohol of formula ROH.

avec un composé de formule VIII

dans lesquelles R1, R2, R4 et R6 ont les significations connées précédemment.The compounds of formula Ih can be prepared by reacting a compound of formula IVd

with a compound of formula VIII

in which R1, R2, R4 and R6 have the meanings previously known.

avec un composé de formule IX

The starting materials of formula II can be prepared by reacting a compound of formula IVe

with a compound of formula IX

 The other intermediate products are known or can be prepared analogously to the known processes or for example as described in the examples.

 Certain compounds of formula I are new and are also part of the present invention.

dans laquelle R, et R ont les significations données @@@@ @@@@@@@@ @4 @@ @5 @@@ @@@ @@@@@@@@@@@@@@ @@@@@@@ précédemment et R1," R2," R3" et R6" ont respectivement les mêmes significations que R1, R2, R3 et R6, avec les conditions que a, lorsque R1" représente un groupe naphtyle, R2, R3,
R4 et R5 représentent l'hydrogène et R6" représente
un groupe de formule IIIa dans laquelle R8 est l'hydro-
gène, alors R 12 et R7 ne signifient pas tous les deux
un halogène et R12 ne signifie pas un halogène ou
un groupe méthyle lorsque R7 est l'hydrogène, , lorsque Pl' représente un groupe de formule

dans lesquelles R7, et Rg représentent, independamment l'un de l'autre, l'hydrogène ou un groupe alkyle inférieur, alcoxy inférieur ou un halogène et s est le nombre 3, 4 ou 5, R represente l'hydrogène ou un roue alkyle inférieur, X représente l'oxygène, le soufre ou l'azote et R4 et R5 représentent l'hydrogène, alcrs R6" ne signifie pas un groupe de formule

These compounds correspond to the formula Ij

in which R 1 and R 2 have the meanings given in the following text. and R1, "R2," R3 "and R6" respectively have the same meanings as R1, R2, R3 and R6, with the conditions that a, when R1 "represents a naphthyl group, R2, R3,
R4 and R5 represent hydrogen and R6 "represents
a group of formula IIIa in which R8 is hydro-
gene, then R 12 and R7 do not mean both
a halogen and R12 does not mean a halogen or
a methyl group when R7 is hydrogen, when Pl 'represents a group of formula

in which R7, and Rg independently of one another are hydrogen or lower alkyl, lower alkoxy or halogen and s is 3, 4 or 5, R is hydrogen or a wheel lower alkyl, X represents oxygen, sulfur or nitrogen and R4 and R5 represent hydrogen, alcrs R6 "does not mean a group of formula

in which Z 'is oxygen or sulfur, R7
is hydrogen, R8 'is hydrogen, halogen or
a lower alkyl group and R12 'is hydrogen,
an alkyl, cycloalkyl or haloalkyl group
or halogen, in free form or in the form of an acid addition salt.

 The preferred compounds for use as antifungal and fungicidal agents are those of formula I 1 as defined above.

Other preferred compounds of formula I are those in which a, R 1 and P form a group of formula IIg together.
where p is 1,2 or 3, or R2 is hydrogen
gene or a lower alkyl group and R1 represents
a group that formulas IIa to IIf in which R7 and
R8 represent. independently of one another,
hydrogen, a halogen or a trifluoromethyl group,
lower alkyl or lower alkoxy and R 9 represents
hydrogen, a halogen or a lower alkyl group
or lower alkoxy, R10 and R11 represent, independently
with each other, hydrogen, halogen
or lower alkyl, trifluoromethyl, alkoxy
lower or lower alkylthio, one of the symbols
R10 and RIl must have a meaning other than
hydrogen when the other means hydrogen,
halogen or a lower alkoxy group, X represents
oxygen, sulfur or an imino group, alkylimino
lower or -CH2-, s means 3, 4 or 5 and v means
3, 4, 5 or 6, and in the group of formula IId one or
two of the CH2 groups can be replaced by oxygen
or sulfur, R4 and R5 represent, independently
from each other, hydrogen or an alkyl group
lower, R3 represents lthrogen or a cyclo group
alkyl, haloalkyl or alkyl and R6 represents
group of formulas IIIa to IIIe in which R7 and R8
have the meanings given above, w means
2, 3, 4, 5 or 6, Z means oxygen, sulfur or
an N-R3 or R3 group has the meaning given above,
and R12 represents an alkyl, alkenyl or alkynyl group,
cycloalkylalkyl, lower alkoxy, lower alkylthio,
phenyl, phenylalkyl, trialkylsilyl, dialkylphenyl-
silyl or halogen, alkyl, alkenyl,
alkynyl, cycloalkylalkyl, phenyl and phenylalkyl
may be substituted by alkoxy groups
lower, and can possibly be fixed by
via a carbonyl group, or b) R1 represents a group of formulas IIa to IIf such
that defined under a), R2 and R3 together form a
group - (CH2) U- where u is an integer from 1 to 8
and R4, R5 and R6 have the meanings given above.

Other preferred compounds of formula I are those wherein a) R 1 represents a group of formula IIa or IIb, b) R 2 represents hydrogen or a lower alkyl group,
in particular hydrogen, c) R3 represents hydrogen or an alkyl group,
particularly lower alkyl, and d) R6 represents a group of formula IIIa c
R7 and R8 @ represent, independently of one another,
hydrocene, halogen or a lower alkoxy roup, in particular hydrogen, X represents a group -O-CH 2, oxygen or sulfur, in particular sulfur,
R and R represent, independently of one another,
not
hydrogen or a lower alkyl group, in particular
hydrogen bond, R12 represents alkyl, alkenyl, alkynyl, cycloalkylalkyl, lower alkoxy, lower alkoxycarbonyl, lower alkylthio, phenyl, phenylalkyl, trialkylisilyl, dialkylphenylsilyl or halogen, alkyl, alkenyl, alkynyl, cyclalkylalkyl, phenyl and phenylalkyl groups; may be substituted by phenyl, lower alkoxy, lower alkylthio, phenylalkoxy, lower alkoxy, phenyl, lower alkylphenyl, halophenyl, halogen or optionally heterocycle
substituted, and may possibly be fixed by the terminus well carbonyl group.

Other preferred compounds of formula I are those in which R 1 and R together form a group of formula IIg wherein o is 1, 2 or 3, or R 2 is hydrogen or alkyl
lower and R1 represents a group of formula IIa,
IIb, IIc, IId or IIe in which R7 and R8 represent,
independently of one another, hydrogen, a halogen
cu trifluoromethyl, lower alkyl or alkoxy
lower and R9 represents hydrogen, a halogen or
lower alkyl or lower alkoxy, R10
and R1 represent, independently of one another,
hydrogen, a halogen or a lower alkyl group,
trifluoromethyl, lower alkoxy or lower alkylthio, one of the symbols R10 and R11 to be other than hydrogen when the other signifies hydrogen, a halogen or a lower alkoxy group, X represents oxygen, sulfur or a imino group, lower alkylimino, -O-CH2- or -CH2-, s is 3, 4 or 6 and v is 3, 4, 5 or 6, and one or both of the groups
CH 2 in the formula IId may be replaced by oxy- cene or sulfur, R4 and R5 represent, independently of one another, hydrogen or a lower alkyl group, R represents hydrogen or a cycloalkyl group , haloalkyl or alkyl and R6 represents a group that formula la, IIIb, IIIc, IIId or IIIe, in which
R7 and R8 have the meanings given above w @ means 2, 3, 4, 5 or 6, Z represents oxygen, ie sulfur or N-R3 where R3 is as defined above, and
R12 is as defined for formula I, or R1 represents a group of formula IIa to IIe, R2 and R3 together form a group - (CH2) u- where u is an integer from 1 to 8, and R4, R5 and R6 are as defined above.

 The compounds of formula I possess interesting chemotherapeutic properties and can therefore be used therapeutically as medicaments. In particular, they exert antifungal activity by local application or by oral administration. This activity has been demonstrated in various families and species of this fungi, eg Trichophyton spp., Aspergillus spp., Microsporum spp., Sporothrix schenckii and Candida spp., In vitro in serial dilution assays at concentrations ranging from 0.003 to 50 g / ml and in vivo in the experimental model of dermal mycosis in guinea-pigs and in the model of disseminated infection or intravaginal / intrauterine infection. In the experimental model of dermal mycosis, one rubs @ daily for 7 days the skin surface infected with the substance to be tested in polyethylene glycol. Anti-fungal activity is observed at concentrations of between 0.1 and 2%.

Oral activity was observed in vivo on guinea pig trichophytosis at doses between about 2 and 70 mg / kg.

 Thanks to these properties, the compounds of formula I can be used in therapeutics as medicaments, in particular as anti-fungals.

For this use, an appropriate daily dose will be between 70 and 2000 mg of active substance, advantageously administered in divided doses 1 to 4 times per day in unit dose form, or in sustained release form. Suitable unit doses, for example for oral administration, contain between 17.5 and 1000 mg of active substance.

 The compounds of formula I may be in the free base state or in the form of a pharmaceutically acceptable acid addition salt. These salts have the same order of activity as the corresponding free bases. Suitable salts are, for example, hydrochloride, hycrogenofumarate and naphthalene-1,5-disulphonate.

 The invention relates to the compounds of formula Ij and I, in free form or in the form of a pharmaceutically acceptable acid addition salt, for use respectively as medicaments and as systemic medicaments, in particular respectively as systemic anti-fungal and anti-fungal.

 The compounds of formula Ij and I may be used in the form of a pharmaceutical composition and a systemic pharmaceutical composition containing the active substance in combination with pharmaceutically acceptable carriers or diluents respectively. Such compositions, which are also subject to the invention, may for example be in the form of tablets, capsules, creams, tinctures or injectable preparations, intended to be administered orally, topically, intravenously, venous or parenteral.

Compounds of formula t, in free form or in the form of agriculturally acceptable salts or metal complexes, are also suitable for combating phytopathogenic fungi. This fungicidal activity has been demonstrated, inter alia, in in vivo tests against Uromyces appendiculatus (bean rust) on rye beans as well as against other rust fungi (for example Hemileia,
Puccinia), on coffee, wheat, flax and ornamentals (eg geranium and wolf mouths), and against Erisyphe cichoracearum on cucumber, as well as other powdery mildews (eg
E. Graminis f. sp. tritici, E. gram. f. sp. hordei, Podosphaera leucotricha, Uncinula recator) on wheat, barley, potatoes and grapes.

 The following examples illustrate the invention without in any way limiting its scope. In these examples, the temperatures are all indicated in degrees Celsius.

Example 1
N- (5,7-difluoro-1-naphthylmethyl) -N-methyl-4-tert-butylbenzylamine
To a mixture of 0.3 g of N-methyl-4-tert-butyl benzylamine; of 0.25 g of potassium carbonate and 5 ml of this anhydrous dimethylformamide, 0.5 g of 5,7-difluoro-1-bromomethylnaphthalene and gold are added dropwise. The mixture is stirred overnight at room temperature. The solvent is then removed under reduced pressure and the residue is partitioned between ether and water. After drying and evaporation of the organic phase, the product is chromatographed on silica gel (eluent: hexane / ethyl acetate 95: 5) to give the product in pure form as an oil.

Example 2
N- (4-tert-butyl-1-cyclohexenylmethyl) -1-napthylméthyla-ine
70 g of 4-tert.butyl-1-cyclohexenecarbaldehyde, 1.9 g of 1-naphthylmethylamine and 15 ml of toluene are heated for 4 hours with a molecular sieve. The solid product is washed with water and the filtrate is evaporated. The residue is dissolved in 30 ml of absolute methanol and 0.5 g of sodium porohydride is reacted for one hour with two parts each. The mixture is stirred for 2 hours at room temperature, evaporated and the residue is partitioned between water and dichloromethane.

The organic phase is dissolved in a little methanol, reacted with an excess of methanolic hydrochloric acid and evaporated to dryness. The residue is recrystallized from a mixture of isopropanol and ether.

By treatment with 1N caustic soda and extraction under nitrogen, the base of the title compound in pure form is obtained in the form of an oil; the hydrochloride melts at 153-155
Example 3
N- (4-tert-butyl-1-cyclohexenylmethyl) -N- (1-naphthylmethyl) methylamine
0.8 g of N- (4-tert.-butyl-1-cyclohexenylmethyl) -1-naphthylmethylamine are reacted with 13 ml of a 1N solution of NaH 2 PO 3 and the solution is introduced by adding 15 ml of dioxane. addition of 1.1 ml of a 37% formalin solution, the mixture is heated to 60 for half an hour, basified with caustic soda and extracted with ether, after drying and evaporation of the organic phase, the pure product is obtained in the form of an oil.

Example 4
N-methyl-N- (1-naphthylmethyl) -4- (2-phenyl-2-propyl) benzylamine
A Grignard reagent was prepared from 1 g of 2- (4-bromophenyl) -2-phenylpropane and 265 mg of magnesium in 25 ml of ether. 2.5 g of N-ethoxymethyl-N-methyl-1-naphthylmethylamine in 5 ml of ether are added dropwise at room temperature and with vigorous stirring and the mixture is refluxed for 12 hours. of a saturated solution of sodium chloride and stirring for half an hour, the aqueous phase is extracted with ether.

The combined organic phases are dried and the solvent is distilled off. By chromatography on a column of silica gel (eluent: toluene / ethyl acetate 95/5), the pure product is obtained in the form of an oil.

Example 5
N-methyl-N- (1-naphthylmethyl) -4 - [(1- (4-methoxyphenyl) ethenyl] benzylamine
The mixture is stirred at room temperature for 15 minutes with 1.37% methyltriphenylphosphonium bromide / sodium amide in 5 ml toluene. N-methyl-N- (1-naphthylmethyl) -4- (4-methoxybenzoyl) benzylamine (1 g) is then added and the mixture is heated at reflux for 1 hour and a half. After concentration, the residue is taken up in ether, filtered, the filtrate is concentrated and chromatographed on silica gel with toluene.

The title compound is thus obtained in the form of an oil.

By proceeding in a manner analogous to that described in Examples 1 to 5, the following formal compounds Ik are obtained:

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Starting products can be prepared as follows
A) C- (3-dithyl-1-butynyl) benzyl bromide (for
Example 6
The mixture is heated for 8 hours at reflux 3.35 g
4- (3,3-dimethyl-1-butynyl) toluene, 3.47 g of N-bromo
succinimide and 100 mg of dibenzoyl peroxide in
50 ml of carbon tetrachloride. We filter the mixture
and the solvent is removed in vacuo. The pure product
is obtained in the form of an oil after chromatography
on silica gel using hexane as eluent.

In a similar manner to method A), we obtain
the following compounds in the form of oils:
B) 4-bromomethyl-4'-methylbenzophenone (for example 29).

C) 2- (4-bromomethylphenyl) -2- (4-toluene) propane (for
Example 35).

D) 3-tert.-butylbenzyl bromide (for Examples 17 and 52): 2- (3,3-dimethyl-1-butynyl) benzyl bromide (for
Example 23).

F) 4- (2-methoxy-2-propyl) benzyl bromide (for
Example 25).

G) 3- (bromomethyl) -6-tert.-butylpyridine (for example)
72).

H) t-methyl-4-phenylbenzylamine (for example 7)
It is stirred overnight at room temperature
room temperature 10 g of 4-biphenylcarbaldehyde and 40 ml
of 33% ethanolic methylamine with a molecular sieve
range of 4 A. The reaction mixture is filtered
and concentrated under vacuum. The residue is treated
in 60 ml of ethanol per 2 g of sodium borohydride
sodium and stirred for 3 hours. We eliminate the
solvent in vacuo, the residue is partitioned between
ether and water, the organic phase is dried
and concentrates it. The pure base is obtained under
form of an oil after gel chromatography
silica with a 9/1 mixture of dichloromethane and
ethanol as eluent.

In a similar way to the method H), it is possible
obtain the following compounds in the form of an oil
I) N- (2,3-methylenedioxybenzyl) methylamine (for
Example 10).

J) 1- (naphthylmethyl) cyclopropylamine (for
Example 18).

K) N-methyl-2,3-dimethylbenzylamine (for the examples
60 and 61).

L) N-ethoxymethyl-N-methyl-1-naphthylmethylamine (for
Examples 4, 37, 50 and 71).

cut by cooling with ice, one
treats 2 μl of methyl-1-naphthylmethylamine and 9 g
of absolute ethanoi with 3.6 a of paraformaldehyde added
portionwise and stir the mixture for 1 hour
at room temperature. The reaction mixture is treated
dichloromethane, is filtered and
concentrated. The pure product is obtained under
form of a pale yellow oil after distillaition under
vacuum (1.3 mbar / 135-138).

M) N- (5,7-difluoro-1-naphthymethyl) methylamine (for the
examples 1 and 59)
a) 4 (2,4-difluorophenyl) -4-oxo-butyric acid
380 g are treated with 11.4 g of 1,3-difluorobenzene
and 28 g of aluminum chloride in 75 ml of
dichloromethane with 10 g of succinic anhydride
add in small portions and then heat
at reflux for 6 hours. Pour the mixture
in ice and hydrochloric acid,
it is treated with dichloromethane and stirred
for half an hour. The phases are separated,
the aqueous phase is extracted with dichloromethane
and the combined organic phases are stirred
diluted caustic soda. We wash the solution
aqueous alkaline with ether and acidify
with hydrochloric acid.
pite, wash it with water and dry it
(F 113-115).

b) 4- (2,4-Difluorophenyl) butyric acid
For 10 minutes, shake vigorously
50% zinc, 50 g mercury (II) chloride,
2.5 ml concentrated hydrochloric acid and 75 ml
of water. The liquid is separated by decantation and
treats zinc amalgam with 30 ml of water, 75 ml of acid
hydrochloric acid, 3ml of acetic acid and
15 9 of 4-1-2,4-diflorophenyl) -4dxo -buty acid
America. The mixture is heated at reflux for
Heures hours, 1G of concentrated hydrochloric acid
being added every 2 hours.It eliminates the
organic phase, decant the aqueous solution
To separate it from zinc, it is extracted
with toluene and wash the organic phases
When combined with water, they are dried and concentrated.

The residue is dissolved in an excess of soda
1N caustic, 200mg of palladium
activated charcoal and is hydrogenated for 36 hours at
at ambient temperature and under normal pressure.

The mixture is filtered, acidified and extracted
with ether. The crystalline crude product can
be purified by distillation in a bulb tube
at 0.13 mbar / 120; Mp 45-47 °.

(c) 5,7-difluoro-1-tetralone
60 to 120 g of polyphosphoric acid are obtained
and 2 g of phosphor pentoxide until
the mixture is homogeneous. Then add 43 g
4- (2,4-difluorophenyl) butyric acid,
stir the mixture for 1 hour and a half at 80,
it is then poured on a mixture of water and
ice and extracted with ether. The phases
organic compounds are washed with a solution
sodium carbonate and chloride solution
of sodium, dried, stirred with a little coal
active and evaporated. The gross product can be
Surified by silica gel chromatography
eluent: hexane / ethyl acetate 4: 1) or
sublimation under vacuum at 0.65 mbar / 100;
F = 89-91.

d) 5,7-difluoro-1-methyl-1-tetralol
Has a Grignard reagent prepared from
This magnesium and -2 g of methyl iodide
in ether add a solution of 2 g
5,7-difluoro-1-tetralone in 20 ml of ether.

laughs reflux heating for 2 hours and a half,
c pour the mixture on a mixture of ice and
this saturated solution of ammonium chloride and
shake it for half an hour. We extract the phase
aqueous with ether and purified. After
silica gel chromatography (eluent: toluene /
9: 1 ethyl acetate), the pure product is obtained
in the form of a colorless oil.

e) 5,7-difluoro-1-methylnaphthalene
Refluxed for 5 hours 2.5 g
of 5,7-difluoro-1-methyl-tetralol, 3.6 g of sorting
phenylmethanol and 2.6 g of trifluoro anhydride
acetic acid in 16 ml of trifluoroacetic acid.

Pour the mixture into water and ice and
extracted with dichloromethane. We wash
neutral organic phase with a solution of
sodium bicarbonate, it is dried and concentrated
be. The oily raw product can be purified
by chromatography on silica gel (evading
hexane).

f) 5,7-difluoro-1-bromomethylnaphthalene
Refluxed for four and a half hours
1.35 g of 5,7-difluoro-1-methylnaphthalene in
10 ml carbon tetrachloride with 1.4 g
t-bromosuccinimide and 50 mg peroxide
dibenoyle. After cooling the mixture,
it is filtered and the solvent is removed in vacuo.

The crystalline crude product is sufficiently pure
for the next reaction; Mp 74-76.5.

g) N- (5,7-difluoro-1-naphthylmethyl) methylamine
To 15 ml of a solution of methylamine etha
nolic a. 35, we slowly add drop to
drop, under cooling, 2.3 g of 5,7-difluoro
1-bromomethylnaphthalene dissolved in 10 ml of etha
nol. After 1 hour, we stop cooling and we
stir the mixture overnight at the temperature
room. The solvent is then removed under vacuum,
the residue is taken up in hydrochloric acid
2N, the aqueous phase is washed with ether and
alkanilizes with solid potassium carbonate.

By extraction with ether, the compound is obtained
the title in the form of a colorless oil;
the hydrochloride melts at 224-228.

N) 5,8-difluoro-1-bromomethylnaphthalene (for the example
19)
a) 5,8-difluoro-4-methyl-1-tetralol
5 g of 5,8-difluoro-4-methyl-1 are dissolved
tetralone in 75 ml of methanol and added by
small portions 1 g of sodium borohydride.

After 2 hours at room temperature,
concentrate the mixture and distribute the residue
between water and ether. We extract the phase
ether and dried and concentrated
combined organic phases. After recrystallization
in n-hexane, the pure product is obtained
form of colorless crystals; F = 73-75.

b) 5,8-difluoro-1-methylnaphthalene
It is heated for 5 hours under reflux 3 g
e 5,8-difluoro-4-methyl-1-tetralol with 1 g
Sulfur. The cold mixture is diluted with ether,
filtered and the solvent removed at 00. The product is
purified by silica gel chromatography
(eluent: hexane).

c) 5,8-dichloro-1-bromomethylnaphthalene
n proceeding in a similar way to that
described under lf), the pure product is obtained after
silica gel chromatography (eluent: hexane /
ethyl acetate 98/2).

O) (5-fluoro-1-naphthylmethyl) methylamine (for the examples
53 and 65)
a) 5-fluoro-1-naphthaldehyde
1.95 g of 5-fluoro-1-naphthonitrile are dissolved
in 40 ml of anhydrous toluene and cool the
solution to -30. At this temperature, we add
drip 11 ml of diisobutyl aluminum hydride
(20% in toluene) and continue shaking for
2 hours without cooling. We separate
phases, the aqueous phase is extracted with
toluene, the combined organic phases are dried
and concentrate them. After crystallization in
a mixture of ether and petroleum ether,
gets the product in pure form in the form of
colorless crystals; F = 93.

b) (5-fluoro-1-naphthylmethyl) methylamine
The compound is obtained in the form of an oil
colorless from 5-fluoro-1-naphthaldehyde
and methylamine, proceeding in a similar way
to that described in Example 2.

4- (Dimethylphenylsilyl) benzyl bromide (for
example 24)
a) 4- (dimethylphenylsilyl) toluene
Gold dissolves 5 g of bromotoluene in 30 ml of
tetrahydrofuran and treat slowly at -65
by an equimolar amount of butyllithium
in hexane. After 30 minutes at -65, we
add 5 g of dimethylphenyl dropwise
chlor-o-silane and stop cooling. After
2 hours at room temperature, pour the
mixture in a mixture of water and ice,
the extract with chloromethane and distilled
in a bulb tube (0.13 mbar / 95).

(b) 4- (Dimethylphenylsilyl) benyl bromide
The procedure is analogous to that described
under A), which gives a gross product that can
to be used without purification for the reaction
next.

Q) 1-phenyl-1- (4-bromomethylphenyl) ethylene (for
example 31)
a) 1-methoxy-1-phenyl-1-tolylethane
agate overnight 2 g of 1-phenyl-1
tolylethanol with 0.56 g of 80% NaH in 50 ml
this tetrahydrofuran is added 3.7 g of iodide
methylated and stirred for 6 hours
hours. The mixture is treated with aqueous HCl,
It is extracted with dichloromethane and
purifies the oily product on silica gel
with cyclohexane as eluent.

b) 1-phenyl-1- (4-bromomethylphenyl) ethylene
By proceeding in a manner similar to that described
under A, and using as product l-methoxy
1-phenyl-1-tolylethane, the compound of
title under an oil.

R) 5-chloro-2- (4-bromomethylbenzoyl) thiophene (for
example 32)
a) 5-chloro-2- (4-methylbenzoyl) thiophene
To a suspension of 5.17 g of AlCl3 in
1,2 1 this dichloromethane, add drop to
drop, under cooling, 3.84 g of 2-chloro
thiophene and 5% of p-toluyl chloride.

After shaking for 1 hour and a half at the
at room temperature, the mixture is treated with
or aqueous HOl, extracted with dichloro
ethane and the oily product is purified by
silica gel chromatography using
toluene as eluent.

b) 5-chloro-2- (4-bromomethylbenzoyl) thiophene
Proceeding in a similar way to that
described under A) and using as a product of
starting 5-chloro-2- (4-methylbenzoyl) thiophene,
the title compound is obtained as an oil.

S) 1- (4-Chlorophenyl) -1- (4-aminomethylphenyl) cyclopro
pane (for example 34)
a) 1- (4-Chlorophenyl) -1- (4-cyanophenyl) ethylene
Proceeding analogously to Example 5)
and using as starting material the 4-chloro
4'-cyanobenzophenone, an oily product is obtained
which can be used directly for the reaction
next.

b) 1- (4-Chlorophenyl) -1- (4-cyanophenyl) cyclopropane
600 mg of copper powder is treated with 10 mg
diode in 10 ml of toluene, 1.2 is added.
of diiodomethane and 500 mg of 1- (4-cyanophenyl) -1-
(4-chlorophenyl) ethylene, the mixture is heated
during 14G hours at reflux and then filtered
and the filtrate is concentrated. The oily residue
is chromatographed on silica gel using
toluene as eluent.

c) 1- (4-Chlorophenyl) -1- (4-aminomethylphenyl) cyclo
Prolan
To a suspension of 230 mg of lithium hydride
and aluminum in 10 ml of tetrahydrofuran,
234 mg of l- (4-chloro) are added dropwise
phenyl) -1- (4-cyanophenyl) cyclopropane in 5 ml
of tetrahydrofuran and the mixture is heated
18 hours at reflux. The hydrolysis is then
mixture with 1N HCl and extracted with
dichloromethane. The oily product obtained is
used directly for the next reaction.

T) N-methyl-3-tert.-butyl-2-methoxybenzylamine (for
examples 62 and 63)
a) 3-tert-butyl-2-methoxybenzyl bromide
By proceeding in a manner analogous to that described
under A) and using as starting material
2-tert.-butyl-6-methylphenyl oxide and
methyl, the title compound is obtained in the form of
of crude product suitable for the reaction sui
boasts.

b) N-methyl-3-tert-butyl-2-methoxybenzylamine
The procedure is analogous to that described
under M) g), which gives the product in form
a colorless oil.

U) 1-phenyl- [1- (4-aminomethyl) phenyl] cyclopropane
(for example 12)
n proceeding in a similar way to that
described under S) and using as a product of
starting 1-phenyl-1- (4-cyanophenyl) ethylene
the title compound is obtained in the form of a
oil.

Spectra NMR
Ex. Spectrum 1 7.9-8.1 sm, 1Hj; 7.6-7.8 (m, 1H); 7.2-7.6 (m, 6H); 6.98 (ddd, J
10.5 + 8.5 + 2.5Hz, 1H); 3.83 (s, 2H); 3.57 is, 2H); 2.19 (s, 3H); 1.31
(S, 9H).

8.0-8.25 (m, 1H); 7.65-8.0 (m, 2H); 7.30-7.65 (m, 4H); 5.55-5.80
(m, 1H); 4.18 (s, 2H); 3.26 (s, 2H); 1.55-2.30 (m, 5H); 1.50 (s, 1H);
1.0-1.4 (m, 2H); 0.87 (s, 9H).

8.2-8.45 (m, 1H); 7.65-7.95 (m, 2H); 7.30-7.65 (m, 4H); 5.55-5.75
im, 1H); 3.85 (s, 2h); 2.94 (s, 2H); 2.12 (s, 3H); 1.65-2.2 (m, 5H);
i.05-1.50 (m, 2Hi, 0.86 (s, 9H).

8.10-8.34 (m, 1H); 7.64-7.95 (m, 2H); 7.03-7.58 (m, 13H); 3.92 (s,
2H); 3.55 (s, 2H); 2.19 (s, 3H); 1.65 (s, 6H).

8.20-8.44 (m, 1H); 7.75-7.85 (m, 2H); 7.37-7.58 (m, 4H); 7.23-7.36
(m, 6H); 6.82-6.87 (m, 2H); 5.34-5.38 (m, 2H); 3.95 (s, 2H); 3.81 (s,
3H); 3.60 (s, 2H); 2.2i (s, 3H).

8.18-8.36 (m, 1H); 7.65-7.95 (m, 2H); 7.18-7.60 (m, 8H); 3.90 (s,
2H); 3.55 (s, 2H); 2.15 (s, 3H); 1.30 (s, 9H).

8.26-8.33 (m, 1H); 7.75-7.88 (m, 2H); 7.28-7.62 (m, 13H); 3.96 (s,
2H); 3.63 (s, 2H); 2.23 (s, 3H).

7.64-8.05 (m, 3H); 7.27-7.53 (m, 4H; 6.86 (s, 2H; 3.85 (s, 2H);
3.58 (s, 2H); 2.33 (s, 6H); 2.25 vs, 3H); 2.13 (s, 3H).

8.20-9.00 (br, 1H); 7.10-7.95 (m, 10H); 3.75-3.95 (m, 1H); 3.77 (d,
1H, J = 13.5 Hz); 3.00-3.25 (m, 1H); 2.80 (d, 1H, J = 13.5 Hz);
1.45-2.10 (m, 7H); 1.27 (s, 9H).

7.32 (s, 4H); 6.70-6.95 (m, 3H); 5.95 (s, 2H); 3.54 (s, 2H); 3.52 (s,
2H); 2.20 (s, 3H); 1.30 (s, 9H).

8.15-8.40 (m, 1H); 7.68-7.95 (m, 2H); 7.25-7.65 (m, 8H); 3.94 (s,
2H); 3.60 (s, 2H); 2.20 (s, 3H); 0.24 (s, 9H).

8.16-8.27 (m, 1H); 7.70-7.88 (m, 2H); 6.84-7.52 (m, 13H); 3.88 (s,
2H); 3.50 (s, 2H); 2.25 (s, 3H); 1.22-1.28 (m, 4H).

7.2-7.85 (m, 10H); 4.9 (dd, J = 7.5 + 4Hz, 1H); 3.95 (s, 2H); 3.74
(dd, J = 18 + 7.5Hz, 1H); 3.25 (dd, J = 18 + 4Hz, 1H); 1.7 (s, 1H);
1.30 (s, 9H).

7.2-7.8 (m, 10H); 5.0 (dd, J = 7.5 + 4Hz, 1H); 3.25-3.6 (m, 4H); 2.19
(s, 3H); 1.30 (s, 9H).

8.0-8.25 (m, 1H); 7.7-8.0 (m, 2H); 7.2-7.65 (m, 8H); 3.96 (s, 2H);
3.84 (qua, J = 6.5Hz, 1H); 2.15 (s, 3H); i.54 (d, J = 6.5Hz, 3H); 1.33
(s, 9H).

8.15-8.45 (m, 1H); 7.65-8.0 (m, 2H); 7.15-7.65 Cm, 13H); 7.1 (s,
2H); 3.95 (s, 2H); 3.6 (s, 2H); 2.2 (s, 3H).

7.15-7.5 (m, 8H); 3.54 (s, 2H); 3.49 (s, 2H); 2.21 (s, 3H); 1.34 (s,
9H); 1.32 (s, 9H).

7.95-8.2 (m, 1H); 7.6-7.95 (m, 2H); 7.1-7.6 (m, 8H; 4.1 (s, 2H);
3.73 (s, 2H); 1.7-2.05 (m, 1H); 1.32 (s, 9H); 0.1-0.4 μm, 4H).

8.0 (d, J = 8Hz, iHi; 7.76 (d, J = 7Hz, 1H); 7.52 (dd, J = 8 + 7Hz,
H ;; 7.25-7.35 AR'BB 'system, 4H); 7.0-7.13 (m, 2H); 4.11 (d, J
3Hz, 2H); 3.64 (s, 2H); 2.21 (s, 3H); 1.3 (s, 9H).

6.05-8.27 (m, 1H); 6.75-7.90 (m, 10H); 3.90 (s, 2H); 3.53 (s, 2H);
2.18 (s, 3H); 1.30 (s, 9H).

8.15-8.40 (m, 1H); 7.65-7.95 (m, 2H); 7.15-7.65 (m, 8H); 4.50 (dt,
J = 48 + 5.5 Hz, 2H); 4.12 (s, 2H); 3.70 (s, 2H); 2.84 (dt, J = 26 +
5.5Hz, 2H); 1.29 (s, 9H).

8.14-8.42 (m, 4H); 7.03 (s, 1H); 3.48 (s, 2H); 3.45 (s, 2H); 2.75-3.05
(m, 8H); 2.08 (s, 3H); 1.85-2.20 (m, 4H); 1.30 (s, 9H).

8.16-8.40 (m, 1H); 7.68-7.95 (m, 2H); 7.04-7.64 (m, 7H); 3.99 (s,
2H); 3.81 (s, 3H); 2.22 (s, 9H); 8.20-8.42 (m, 1H); 7.70-8.00 (m, 2H); 7.24-7.68 (m, 13H); 4.00 (s,
2H); 3.66 (s, 2H); 2.27 (s, 3H); 0.59 (s, 6H).

8.12-8.40 (m, 1H); 7.66-7.95 (m, 2H); 7.20-7.62 (m, 8H); 3.95 (s,
2H); 3.60 (s, 2H); 3.07 (s, 3H); 2.22 (s, 3H); 1.53 (s, 6H).

8.20-8.42 (m, 1H); 7.72-8.12 (m, 4H); 7.30-7.68 (m, 6H); 3.95 (s,
2H); 3.50 (s, 3H); 3.62 (s, 2H); 2.20 (s, 3H).

8.20-8.42 (m, 1H); 7.26-7.98 (m, 10H); 3.97 (s, 2H); 3.61 (s, 2H);
2.21 (s, 3H); 1.34 (s, 9H).

8.20-8.38 (m, 1H); 7.36-7.84 (m, 12H); 6.86-6.98 (m, 2H); 3.98 (s,
2H); 3.86 (s, 3H); 3.64 (s, 2H); 2.21 (s, 3H).

8.27-8.39 (m, 1H); 7.24-7.94 (m, 14H); 4.00 (s, 2H, 3.66 (s, 2H);
2.44 (s, 3H); 2.24 (s, 3H).

8.24-8.34 (m, 1H); 7.74-7.92 (m, 2H); 7.08-7.60 (m, 12H); 5.40 (s,
2H); 3.95 (s, 2H); 3.60 (s, 2H); 2.34 (s, 3H); 2.20 (s, 3H).

8.24-8.35 (m, 1H); 7.74-7.92 (m, 2H); 7.12-7.60 (m, 13H);
5.42-5.47 (m, 2H); 3.95 (s, 2H); 3.60 (s, 2H); 2.20 (s, 3H).

8.30-8.41 (m, 1H); 7.74-7.96 (m, 4H); 7.36-7.64 (m, 7H); 6.98-7.03
(d, J = 4 Hz, 1H); 4.02 (s, 2H); 3.68 (s, 2H); 2.26 (s, 3H).

8.24-8.28 (m, 1H); 7.72-7.85 (m, 3H); 7.34-7.52 (m, 7H); 6.74 (d,
J = 4 Hz, 1H); 6.64 (d, J = 4 Hz, 1H); 5.44 (s, 1H); 5.18 (s, 1H); 3.95
(s, 2H); 3.60 (s, 2H); 2.24 (s, 3H).

8.18-8.24 (m, 1H); 7.76-7.84 (m, 2H); 7.08-7.48 (m, 12H); 3.92 (s,
2H); 3.54 (s, 2H); 2.17 (s, 3H); 1.20-1.29 (m, 4H).

8.16-8.28 (m, 1H); 7.74-7.90 (m, 2H); 7.10-7.57 (m, 12H); 3.96 (s,
2H); 3.60 (s, 2H); 2.25 (s, 3H); 2.21 (s, 3H); 1.64 (s, 6H).

8.13-8.35 (m, 1H); 7.64-7.92 (m, 2H); 7.24-7.60 (m, 8H); 3.92 (s,
2H); 3.57 (s, 2H); 2.20 (s, 3H); 1.30 (s, 9H).

8.05-8.4 (m, 1H); 7.6-8.0 (m, 2H); 7.1-7.6 (m, 8H); 3.92 (s, 2H);
3.58 (s, 2H); 2.2 (s, 3H); 1.66 (qua, J = 7Hz, 6H); 0.64 (t, J = 7Hz,
9H); 8.20-8.35 (m, 1H); 7.70-7.92 (m, 2H); 7.36-7.60 (m, 4H); 7.05-7.35
(m, 4H); 3.90; s, 2H); 3.56 (s, 2H); 2.32 (s, 3H); 2.18 (s, 3H).

8.20-8.36 (m, 1H); 7.70-7.95 (m, 2H); 7.15-7.62 (m, 8H); 3.93 (s,
2H); 3.52 (s, 2H); 2.18 (s, 3H).

8.18-8.36 (m, 1H); 7.30-7.96 (m, 8H); 7.00-7.18 (m, 2H); 3.92 (s,
2H); 3.50 (s, 2H); 2.17 (s, 3H).

7.70-7.90 (m, 1H); 7.20-7.55 (m, 7H); 3.82 (s, 2H); 3.59 (s, 2H);
2.16 (s, 3H); 1.32 (s, 9H); 8.18-8.40 (m, 1H); 7.16-7.90 (m, 10H); 3.99 (s, 2H); 3.58 (s, 2H);
2.56 (that, 2H, J = 6.75 Hz, 1.28 (s, 9Hi, 1.10 (t, 3H, J = 6.75 Hz).

8.20-8.42 (m, 1H, 7.30-8.00 (m, 10H), 3.97 (s, 2H), 3.61 (s, 2H);
2.20 (s, 3H).

6.10-8.40 (m, 2H); 7.15-7.65 (m, 7H); 6.75 (d, J = 8Hz, 1H); 3.99 (s,
3H); 3.84 (s, 2H); 3.55 (s, 2H); 2.08 (s, 3H); 1.30 (s, 9H): 45.75-8.05 (m, 2H); 7.20-7.55 (m, 7H); 3.76 they, 2H); 3.56 (s, 2H);
2.12 (s, 3H); 1.31 (s, 9H); 7.65-7.90 (m, 1H); 7.20-7.55 (m, 8H); 3.82 (s, 2H); 3.60 (s, 2H);
2.18 (s, 3H); 1.31 (s, 9H); 7.76 (dd, J = 7 + 3Hz, 1H); 7.2-7.55 (m, 7H); 3.81 (s, 2H); 3.58 (s,
2H ;; 2.15 (s, 3H); 1.3 is, 9Hi.

7.95-8.2 (m, 1H, 7.65-7.95 (m, 2Hi, 7.10-7.6 (m, 8H), 4.23 (s, 2H);
3.68 (s, 2H); 2.9 (seven, i = 7Hz, 1H); 1.73 (s, 1H); 1.23 (d, J = 7Hz, 6h;

8.1-8.4 (m, 1H); 7.65-8.0 (m, 2H); 7.10-7.6 (m, 8H); 3.92 (s, 2H);
3.58 (s, 2H); 2.90 (sep, J = 7Hz, 1H); 2.2 (s, 3H); 1.24 (d, J = 7 Hz,
6H).

8.1-8.35 (m, 1H); 7.7-7.95 (m, 2H); 7.25-7.65 (m, 8H); 3.95 (s, 2H);
3.6 (s, 2H); 2.2 (s, 3H); 1.64 (qua, J = 7.5Hz, 2H); 1.26 (s, 6H); 0.66
(t, J = 7.5Hz, 3H).

7.63-7.7 (m, 1H); 7.15-7.45 (m, 7H); 3.59 (s, 2H); 3.55 (s, 2H); 2.22
(s, 3H); 1.32 (s, 9H).

8.2-8.45 (m, 1H); 7.65-8.0 (m, 2H); 7.10-7.6 (m, 8H); 3.92 (s, 2H);
3.61 (s, 2H); 2.22 (s, 3H); 1.33 (s, 9H).

53 7.9-8.15 (m, 2H); 7.0-7.6 (m, 8H); 3.9 (s, 2H); 3.56 (s, 2H); 2.19 (s,
3H); 1.3 (s, 9H).

6.73-7.48 (m, 8H); 5.75-5.85 (m, 1H); 4.70-4.85 (m, 2H); 3.52 (s,
2H); 3.28 (d, J = 1.5 Hz, 2H); 2.20 (s, 3H); 1.31 (s, 9H).

5.5 7.95-8.18 (m, 1H, 7.62-7.94 (m, 2H), 7.05-7.62 (m, 8Hi, 4.23 (s,
2H); 3.87 (s, 2H); 2.60 (tr, J = 7.5 Hz, 2H); 2.00 (s, 1H); 1.10-1.80
(m, 4H); 0.91 (tr, J = 7 Hz, 3H).

8.15-8.36 (m, 1H); 7.65-7.95 (m, 2H); 7.04-7.62 (m, 8H); 3.92 (s,
2H); 3.58 (s, 2H); 2.60 (tr, J = 7.5 Hz, 2H); 2.20 (s, 3H); 1.10-1.80
(m, 4H); 0.91 (tr, J = 7 Hz, 3H).

57 8.02-8.24 (m, 1H); 7.66-8.0 (m, 2H); 7.22-7.64 (m, 8H); 4.26 (s, 2H);
3.90 (s, 2H); 1.69 (s, 1H); 1.33 (s, 9H).

58 8.16-8.40 (m, 1H); 7.60-7.82 (m, 1H); 7.12-7.58 (m, 8H); 3.90 (s,
2H); 3.56 (s, 2H); 2.20 (s, 3H); 1.32 (s, 9H).

59 7.96-8.03 (m, 1H); 7.62-7.70 (m, 1H); 7.48-7.55 (m, 1H); 7.36-7.45
(m, 1H); 7.12-7.32 (m, 9H); 6.97 (ddd, J = 10.5 8.5 and 2.5 Hz,
1H); 3.62 (s, 2H); 3.54 (s, 2H); 2.19 (s, 3H); 1.67 (s, 6H).

7.00-7.45 (m, 7H); 3.52 (s, 2H); 3.50 (s, 2H); 2.27 (s, 6H); 2.13 (s,
(3H); 1.31 (s, 9H).

61 7.00-7.45 Cm, 12H; 3.52 (s, 2H); 3.50 (s, 2H); 2.30 (s, 3H); 2.27 (s,
3H); 2.15 (s, 3H); 1.70 (s, 6H).

62.92-7.60 (m, 7H); 3.78 (s, 3H); 3.61 (s, 2H); 3.52 (s, 2H); 2.19 (s,
3H); 1.40 (s, 9H); 1.31 (s, 9H).

6.50-7.60 (m, 12H); 3.78 (s, 3H); 3.61 (s, 2H); 3.51 (s, 2H); 2.19 (s,
3H); 1.68 (s, 6H); 1.40 (s, 9H).

7.74-8.02 (m, 1H); 7.12-7.45 (m, 12H); 3.79 (s, 2H); 3.56 (s, 2H);
2.15 (s, 3H); 1.66 (s, 6H).

7.90-8.15 (m, 2H); 7.02-7.60 (m, 13H); 3.90 (s, 2H); 3.55 (s, 2H);
2.19 (s, 3H); 1.66 (s, 6H).

7.65-7.86 (m, 1H); 7.15-7.55 (m, 13H); 3.82 (s, 2H); 3.59 (s, 2H);
2.18 (s, 3H); 1.68 (s, 6H).

67 7.10-7.60 (m, 12H); 3.67 (s, 2H); 3.58 (s, 2H); 2.22 (s, 3H); 1.68 (s,
6H).

7.46-7.56 (m, 1Hy; 7.25-7.40 (m, 5H1; 7.14-7.24 (m, 1H); 3.66 (s,
2H); 3.58 (s, 2H); 2.22 (s, 3H); 1.31 (s, 9H).

8.86 (d, J = 5Hz, 6.08-6.2 (m, 2H, 7.65-7.73 Cm, 1H);
7.46-7.56 (m, 2H); 7.25-7.40 (m, 4H); 3.93 (s, 2H); 3.62 (s, 2H);
2.25 (s, 3H); 1.32 (s, 9H).

8.25 (1, s, 1H, 7.70-7.77 (m, 1H), 7.05-7.40 (m, 8H), 3.73 (s, 2H);
3.53 (s, 2H); 2.22 (s, 3H); 1.32 (s, 9H).

8.20-8.25 (m, 1H); 7.74-7.84 (m, 2H); 7.07-7.47 (m, 12H); 3.93 (s,
2H); 3.92 (s, 2H); 3.55 (s, 2H); 2.29 (s, 3H); 2.18 (s, 3H).

8.44-8.60 (m, 1H); 8.16-8.42 (m, 1H); 7.70-7.96 (m, 2H); 7.20-7.68
(m, 6H, 3.98 (s, 2H), 3.56 (s, 2H), 2.22 (s, 3Hi, 1.35 (s, 9H).

 A 7.22-7.48 (m, 4H); 4.46 (s, 2H); 1.30 (s, 9H).

 B 7.10-7.80 (m, 8H); 4.48 (s, 2H); 2.26 (s, 3H).

 C, 7.20 (s, 4H); 7.10 (s, 4H); 4.45 (s, 2H); 2.27 (s, 3H); 1.62 (s, 6H).

 D 7.1-7.5 (m, 4H); 4.48 (s, 2H); 1.34 (s, 9H).

 E 7.15-7.50 (m, 4H); 4.67 (s, 2H); 1.37 (s, 9H).

 7.40 (s, 4H); 4.52 (s, 2H); 3.69 (s, 3H); 1.63 (s, 6H).

 G 8.50-8.66 (m, 1H); 7.20-7.80 (m, 2H); 4.50 (s, 2H); 1.35 (s, 9H).

 H, 7.20-7.70 (m, 9H); 3.75 (s, 2H); 2.42 (s, 3H); 1.80 (s, 1H).

 I 6.68 (s, 3H); 5.93 (s, 2H); 3.73 (s, 2H); 2.43 (s, 3H); 1.36 (s, 1H).

7.85-8.25 (m, 1H); 7.2-7.8 (m, 6H); 4.2 (s, 2H); 2.1 (which, J = 5Hz,
1H); 1.7 (s, 1H); 0.35 (d, J = 5Hz, 4H).

K, 6.95-7.25 (m, 3H); 3.70 (s, 2H); 2.50 (s, 3H); 2.28 (s, 3H); 2.25 (s,
3h ;; 1.1û (s, 1H).

L 8.05-8.35 (m, 1H); 7.15-8.0 (m, 6H); 4.15 (s, 4H); 3.48 (qua, J
7 Hz, 2H); 2.45 (s, 3H); 1.2 (t, J = 7 Hz, 3H).

M a) 7.98 (dt, J = 9 + 6.5 Hz, 1H); 6.8-7.1 (m, 2H); 5.8-6.8 (@, 1H);
3.2-3.4 (m, 2H); 2.8 (t, J = 6.5 Hz, 2H).

b) 7.15 (dt, J = 8 + 7 Hz, 1H); 6.7-6.9 (m, 2H); 2.68 (t, J = 7 Hz,
2H); 2.38 (t, J = 7 Hz, 2H); 1.75-2.1 (m, 2H).

cd 7.57 (ddd, J = 9, 2.5 + 1.5 Hz, 1H); 7.02 (ddd, J = 9.8 + 2.5 Hz,
1H); 2.93 (t, J = 6.5 Hz, 2H); 2.7 (t, J = 6.5 Hz, 2H); 2.0-2.3 (m,
2H).

d) 7.12 (dd, J = 9 + 2.5 Hz, 1H); 6.86 (ddd, J = g, δ + 2.5 Hz, 1H);
2.63-2.71 (m, 2H); 1.96 (s, 1H); 1.7-2.0 (m, 4H); 1.51 (s, 3H).

e) 7.8-8.0 (m, 1H); 7.3-7.5 (m, 3H); 6.98 (ddd, J = 10.5, 9 + 2.5 Hz,
1H); 2.6 (s, 3H).

f) 7.85-8.15 (m, 1H); 7.30-7.65 (m, 3H); 6.98 (ddd, J = 10.5, 9 +
2.5 Hz, 1H); 4.80 (s, 2H).

g) 7.80-8.15 (m, 1H); 7.15-7.65 (m, 3H); 6.90 (ddd, J = 10.5, 9 +
2.5 Hz, 1H); 4.02 (s, 2H); 2.48 (s, 3H); 1.38 (s, 1H).

N a) 6.8-6.95 (m, 2H); 5.03-5.1 (m, 1H); 3.09 (sext, J = 7Hz, 1H);
2.57 (dd, J = 7 + 3 Hz, 1H); 1.7-2.02 (m, 4H); 1.34 (dd, J = 7 +
1.5 Hz, 3H).

 b) 7.8-8.1 (m, 1H); 6.8-7.6 (m, 4H); 2.8 (d, J = 7.5 Hz, 3H).

 c) 7.8-8.2 (m, 1H); 6.85-7.6 (m, 4H); 5.05 (d, J = 2.5 Hz, 2H).

O a) 10.4 (d, J = 1 Hz, 1H); 9.03 (dt, J = 8.8 + 0.7 Hz, 1H); 8.41 (dqui,
J = 7.5 + 0.7 Hz 1H); 8.05 (dd, J = 7 + 1, 3Hz, iH;; 7.71 (dd, J =
7.5 + 7 Hz, 1H; 7.63 (ddd, J = 8.8 7.8 + 5.9 Hz, 1H); 7.27 (ddd, J =
10.4, 7.8 + 1.0 Hz, 1H).

b) 8.0-8.16 (m, 1H); 7.85-8.0 (m, 1H); 7.35-7.6 (m, 3H); 7.17 ddd,
J = 10.5, 8 + 1 Hz, 1H); 4.20 (s, 2H); 2.56 (s, 3H); 1.5 (s, 1H).

P a) 7.05-7.60 (m, 9H); 2.33 (s, 3H); 0.52 (s, 6H).

 b) 7.10-7.60 (m, 9H); 4.38 (s, 2H); 0.52 (s, 6H).

Q a) 7.10-7.40 (m, 9H); 3.10 s, 3H); 2.28 (s, 3H); 1.82 (s, 3H).

 b) 7.23 (s, 9H); 5.43 (s, 2Hi, 4.5 (s, 2H).

R a) 7.71 (d, J = 9 Hz, 2Hi, 7.39 (d, J = 4 Hz, 1H), 7.25 (d, J = 9 Hz,
2H); 6.95 (d, J = 4 Hz, 1H); 2.40 (s, 3Hi.

 bj 7.30-7.90 (m, 5H, 6.97 (d, J = 4 Hz, 1H), 4.50 (s, 2H).

S-aj 7.10-7.80 (m, 8H); 5.55 (s 2H).

 b) 7.15-7.70 (m, 8H); 1.30 (s, 4H).

 c) 7.15-7.30 (m, 8H); 3.80 (s, 2H, 1.80 (br s, 2H), 1.25 (s, 4H).

T a) 6.90-7.50 (m, 3H); 4.60 (s, 2H); 3.93 (s, 3H); 1.40 (s, 9H).

b) 6.85-7.40 (m, 3H); 3.80 (s, 5H); 2.46 (s, 3H); 1.50 (1, s, 1H); 1.39
(s, 9H).

U b) 7.00-7. G (m, 9H); 1.32 (s, 4H;

 c) 7.15-7.25 (m, 9H); 3.80 (s, 2H); 1.60 (1 s, 2H); 1.25 (s, 4H).

Claims (5)

1. - The compounds of formula I

 in which R1 and R2 together with the carbon atom  to which they are attached, a group of formula IIg

R2 is hydrogen or lower alkyl and @ is a group of formula IIa to IIf  p is 1, L or 3, or  in which

R represents a group of formula  alkyl or haloalkyl and R3 represents hydrogen or an alkyl group, cyclo  Hydrogen or a lower alkyl group,  may be replaced by oxygen or sulfur, and and R represent, independently of one another,  one or two of the groups -CH2- in the formula IId  v is 3, 4, 5 or 6,  s is 3, 4 or 5,  lower alkylimino, -O-CH2- or -CH2-,  X represents oxygen, sulfur, an imino group,  lower alkoxy group,  bole means hydrogen, a halogen or a  other than hydrogen when the other  symbols R10 and R11 must have a significant  lower or lower alkylthio, one of the  trifluoromethyl, lower alkyl, alkoxy  the other, hydrogen, a halogen or a group  R10 and R11 represent, independently of  lower alkyl or lower alkoxy,  P represents hydrogen, a halogen or a group  trifluoromethyl, lower alkyl or lower alkoxy,  the other, hydrogen, a halogen or a group R7 and R8 represent, independently one of  in which  use as agrochemicals.  free base or in the form of an agriculturally acceptable salt or metal complex  R4, R and R6 have the meanings given previously  means an integer from 1 to 8 and  R2 and R 3 together form a - (CH2) -u group at u  as defined previously,  R1 represents a group of formula IIa to IIf such  through a carbonyl group, or  substituted, and possibly  phenyl, halogen or optionally heterocycle  phenyl, (lower alkyl) -phenyl, halogen  thio Lower, phenylalkoxy, (lower alkoxy)  by phenyl, lower alkoxy, alkyl groups  phenyl and phenylalkyl which may be substituted  alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,  phenylsilyl or halogen, alkyl groups,  phenyl, phenylalkyl, trialkylsilyl, dialkyl  lower alkoxycarbonyl, lower alkylthio,  cycloalkyl, cycloalkylalkyl, lower alkoxy,  R12 represents an alkyl, alkenyl or alkynyl group,  meaning given above, and  L represents oxygen, sulfur or NR3 or R3 has the  w is 2, 3, 4, 5 or 6,  R7 and R8 have the meanings given above,  in which  2. The compounds of claim 1 for use in the fight against phytopatogens fungi.  3 .- An agrochemical composition, characterized in that it comprises a compound of formula I specified in claim I, in free form or in the form of a salt or an agriculturally acceptable metal complex, in combination with a diluent or vehicle acceptable in agriculture. IIb, IIc, IId or fIe wherein R7 and R8 are, independently of each other, hydrogen, halogen or trifluoromethyl, lower alkyl or alkoxy and Rg is hydrogen, halogen or halogen; lower alkyl or lower alkoxy, R10 and R11 represent, independently of one another.  (iii) R1 and R2 together form a group of formula IIg wherein p is 1, -2 or 3, or R2 is hydrogen or lower alkyl and R1 is a group of formula IIa,  given under (i),  and the other substituents have the significa  e) R4 and Rg represent hydrogen  d) X represents sulfur,  c) R7 and R8 represent hydrogen,  b) R3 represents a lower alkyl group,  (i @) aj R2 represents hydrogen,  carbonyl,  to be fixed through a group  replaced, and possibly  phenyl, a halogen or a heterocycle  phenyl, (lower alkyl) -phenyl, halogeno  lower, - phenylalkoxy, (lower alkoxy)  phenyl group, lower alkoxy, alkylthio  and phenylalkyl which may be substituted with  alkenyl, alkynyl, cycloalkylalkyl, phenyl  silyl or halogen, alkyl groups,  phenyl, phenylalkyl, trialkylsilyl, dialkylphenyl  lower carbonyl, lower alkylthio,  nyl, cycloalkylalkyl, lower alkoxy, alkoxy  R12 represents an alkyl, alkenyl, alky-  laughter, and  the other, hydrogen or a lower alkyl group  R4 and R5 represent. independently one of  X represents -O-CH 2 -, oxygen or sulfur,  lower alkoxy,  the other, hydrogen, a halogen or a group  R7 and R8 represent, independently one of  or  d) R6 represents a group of formula IIIa  (c) R3 represents hydrogen or an alkyl group  inferior  b) R2 represents hydrogen or an alkyl group  4. The use according to claim 1 or 2 or a composition according to claim 3, characterized in that in formula I (i) a) R1 represents a group of formula IIa or IIb R12 is as defined for formula I, or R1 represents a group of formula IIa to IIe, R2 and R3 together form a group - (CH2) u- where u is an integer from 1 to 8, and R4, R5 and R6 are as defined above.  sulfur or N-R3 where R3 is as defined above..and  W is 2, 3, 4, 5 or 6, Z is oxygen, R and R have the meanings given above  alkyl, haloalkyl or alkyl and R6 represents a group of formula la, IIIb, IIIc, IIId or IIIe, in which  R3 represents hydrogen or a cyclo group  from each other, hydrogen or a lower alkyl group  gene or sulfur, R4 and R5 represent, independently  CH2 in formula IId can be replaced by oxy  means 3, 4, 5 or 6, and one or both of the groups  lower, -O-CH2- or -CH2-, s means 3, 4 or 6 and v  oxygen, sulfur or an imino group, alkylimino  halogen or a lower alkoxy group, X represents  hydrogen when the other means hydrogen. a  Jn symbols R10 and R11 to be other than  trifluoromethyl, lower alkoxy or lower alkylthio,  hydrogen, a halogen or a lower alkyl group,  5. The use according to claim 1 or 2 or a composition according to claim 3, characterized in that in formula I a) R1 represents a naphthyl group,  R2, R3, R4 and R5 represent hydrogen and  R6 represents a group of formula IIIa,  in which  R8 represents hydrogen and  R7 and R12 have the meanings given to the revenge  1, R7 and R12 can not mean all  two a halogen and R12 having a meaning  other than one. halogen or a methyl group  when R7 is hydrogen, or b) R; represents a group of formula IIa, IIb, IIc or IId  in which  R8 represents hydrogen,  R7 and R9 represent, independently of  the other, hydrogen, a halogen or a group  lower alkyl or lower alkoxy,  R2 represents hydrogen or a lower alkyl group,  X represents oxygen, sulfur or an imino group,  R4 and R5 represent hydrogen and  R6 has the meaning given in claim 1. R12 represents hydrogen, a halogen or an alkyl, cycloalkyl or haloalkyl group. R8 is hydrogen, halogen or lower alkyl, and R7 represents hydrogen, R6 can not mean a group of formula IIIa or IIId in which Z represents oxygen or sulfur,