FR2788764A1 - Preparation of indanones and thioindanones by Friedel Crafts acylation of a benzene in the presence of hydrofluoric acid, and cyclization using sulfuric acid - Google Patents

Abstract

Process for preparing indanones and thioindanones, especially 5-chloroindanone and 5,6-dimethoxyindanone, in a 2-stage process, comprises: (1) acylation, in the presence of HF and optionally BF3, of a (substituted) benzene (I) to add a side chain of at least 3 C atoms and with carbonyl or thiocarbonyl group alpha to the benzene ring; and (2) cyclization of the product in the presence of sulfuric acid. Process for preparing indanones and thioindanones, especially 5-chloroindanone and 5,6-dimethoxyindanone, in a 2-stage process, comprises: (1) acylation, in the presence of HF and optionally BF3, of a (substituted) benzene of formula (I) to add a side chain of at least 3 C atoms and with carbonyl or thiocarbonyl group alpha to the benzene ring; and (2) cyclization of the product in the presence of sulfuric acid. R = H, halogen, pseudohalogen, or an electron-donor, or two groups R may form a 5 or 6-membered carbocycle or heterocycle; and n = 0 - 4, preferably 1 or 2 The acylating agent is preferably of formula Z'-C(=Y')-R5 (II) Y' = O or S; R5 = -C(R1)(R2)-C(R3)(R4)-X; R1 - R4 = H or 1-6C alkyl; X = halogen; Z = halogen, -O-C(O)-R5, or -OR'; and R' = 1-6C alkyl. T The preparation of 3,4'-dichloropropiophenone and 3-chloro-3',4'-dimethoxypropiophenone is especially preferred. The reaction mixture may distilled to eliminate, at least partially, the HF and BF3 and, without further purification, is treated with 95 - 99.9% sulfuric acid in the molar ratio 1 : 1 - 30, especially 1 : 5 - 20, and heated at 30 - 120 (preferably 80 - 100 deg C) to effect cyclization and give (IV)

Description

PROCESS FOR THE PREPARATION OF AN INDANONE-LIKE COMPOUND

OR THIOINDANONE.

  The subject of the present invention is a new process for preparing a compound of indanone or thioindanone type from a compound

  optionally substituted benzene.

  The invention relates more particularly to the preparation of 5-

  chloroindanone from monochlorobenzene and 5,6-

  dimethoxyindanone from veratrole.

  5-chloroindanone which corresponds to the following formula is used in the phytosanitary field: O ClX It is obtained according to a process described in PCT / US / 96/20151 published

  under n 96/20151 which consists of bringing the 3,4'- into contact

  dichloropropiophenone with a catalyst which can be sulfuric acid or

a solid catalyst.

  When the solid catalyst is used, the reaction takes place at

  high temperature between 200 and 425 C.

  The reaction carried out in the presence of sulfuric acid takes place between 90 and

   C and in an inert organic solvent.

  In this case, the reaction yield is around 60 - 70%.

  Another particularly interesting indanone compound is

  5,6-dimethoxyindanone used in the health field.

  It is obtained according to Tetrahedron 37, 24, pp. 4199-4202 (1996) according to a process which consists in reacting veratrole and N, Ndimethylacrylamide,

in the presence of triflic anhydride.

  The reaction yield is only 42%.

  Not only does this process use an expensive reagent, but it uses triflic anhydride which is not easily accessible. In addition, the

  reaction generates a base that consumes triflic anhydride.

  The objective of the present invention is to provide a process which is easily implemented, making it possible in particular to access 5-chloroindanone from 3,4'-dichloropropiophenone obtained from monochlorobenzene and to, 6-dimethoxyindanone from of 3-chloro-3 ', 4'-dimethoxypropiophenone

  obtained from veratrole, without separation of intermediate products.

  It has now been found, and this is what constitutes the object of the present invention, a process for the preparation of an indanone or thioindanone type compound from an optionally substituted benzene compound characterized in that it comprises the following steps: - (1) an acylation step which consists in reacting a benzene compound optionally substituted with an acylating agent so that a benzene compound carrying a side chain comprising at least 3 atoms is obtained of linearly chained carbon, a carbonyl or thiocarbonyl group in position a with respect to the carbon atom of the benzene ring to which the chain is connected and a reactive functional group; the reaction being carried out in the presence of an effective quantity of hydrofluoric acid and optionally of boron trifluoride, - (2) a step which consists in carrying out the cyclization of the product obtained

  in the presence of an effective amount of sulfuric acid.

  In accordance with the invention, the preparation of a compound of indanone or thioindanone type is carried out according to a process which consists in preparing in

  the first stage a product which is cyclized in the second stage.

  The product which is cyclized in order to obtain the indanone or thioindanone type compound is obtained from a benzene compound optionally

  substituted according to an acylation reaction carried out under certain conditions.

  Thus, the object of the invention is a process which links the acylation reaction of the benzene compound and the cyclization reaction of the product.

  obtained, without separation of the intermediate product.

  The starting substrates involved in the process of the invention are optionally substituted benzene compounds which more particularly correspond to the following formula (I): (R) n

N1 (1)

  in said formula (I): - R represents a hydrogen atom, a halogen atom, a pseudohalogen group or an electron-donor group, - two R groups can be linked together to form a cycle comprising 5 or 6 atoms ,

  - n is a number equal to 0.1, 2, 3 or 4, preferably equal to 1 or 2.

  When n is greater than or equal to 2, two R groups carried by two vicinal carbon atoms can be linked together by a bridge of the alkylenedioxy type having 1 or 2 carbon atoms. Thus, two R groups can

  represent a methylenedioxy or ethylenedioxy group.

  The starting substrates which can be used in the process of the invention can be compounds corresponding to formula (I) in which the benzene nucleus carries one or more substituents which can

  be a halogen atom, a pseudohalogen group or an electro-

  giver. The group R may represent a halogen atom, preferably a chlorine or bromine atom; a pseudohalogen group and in particular a trifluoromethoxy, trifluorothiomethoxy, pentafluoroethoxy, pentafluorothioethoxy group.

  The group R can also be an electron donor group.

  In the present text, the term “electro-donor group” is understood to mean a group as defined by H.C. BROWN in the work of Jerry MARCH - Advanced Organic Chemistry, 4th edition, John Wiley and Sons, 1992, chapter 9, pp.

273 - 292.

  As more specific examples of R groups, there may be mentioned inter alia: - a hydroxyl group, - a linear or branched alkyl group, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, - an alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, - a methylenedioxy or ethylenedioxy group, - a alkylamide group having from 1 to 6 carbon atoms, preferably 1

to 4 carbon atoms.

  The preferred substrates of the process of the invention correspond to formula (I) in which R represents: - a chlorine atom, - a hydroxyl group, - a methyl or ethyl group, - a methoxy or ethoxy group,

- an acetamide group.

  As benzene compounds corresponding to formula (I) used

  preferably, mention may be made of monochlorobenzene and veratrole.

  According to the invention, the benzene compound and an acylation reagent which reacts with the CO or CS group and the reactive functional group are reacted. The acylation reagent may be of a different nature. It can be an acid

  carboxylic or derivative, halide, ester or anhydride.

  It more particularly responds to the formula (II) Z% ó Y (II) in said formula (II) - Y symbolizes an oxygen or sulfur atom, - represents a chain of two carbon atoms comprising a reactive functional group, - Z represents: a halogen atom, preferably a chlorine or bromine atom, a group - O - CO - in which has the meaning given above, 20. a group - O - R 'in which R' represents a alkyl group having 1

  with 6 carbon atoms, preferably from 1 to 4 carbon atoms.

  A first variant which is preferred, consists in choosing as reactive functional group, a halogen atom which is preferably a chlorine atom, which is located on the carbon atom in position f relative to the group

CO or CS.

  Another variant consists in replacing the halogen atom with a hydroxyl group. Finally, another variant consists in using, as a reactive functional group, a double bond located in position a, 3 relative to the

CO or CS group.

  Thus in formula (II), the functional group can represent: - a group R1 gR2

_C- C-X

I I

R3 R4 (la) - a group Ri R2

- C- C-OH

I I

R3 R4 (lb) - one group

C -C-R4 (IC)

  In these different functional groups, R1, R2, R3, R4, which may be identical or different, represent a hydrogen atom or an alkyl group which may be linear or branched and which generally comprises from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms. R1, R2, R3, R4 identical or different preferably represent a hydrogen atom or a group

methyl or ethyl.

  In the functional groups of formula (la) or (lib), preference is given to those which have at least one hydrogen atom having a of the carbon atom carrying X or OH. Thus, at least one of the groups R1 and R3 is a hydrogen atom. The acylation reagents preferably chosen correspond to formula (11) in which: - Y represents oxygen, - & represents a group of formula (la) as previously described, - Z represents: 25. a chlorine atom, a group - O - CO - l in which le represents a group of formula (la) as previously described,

  a group - O - R 'in which R' is a methyl or ethyl group.

  Among the acylation reagents, use is preferably made of reagents

acylation in halide form.

  As examples of acylation reagents preferably used in the process of the invention, there may be mentioned in particular: - 3-chloropropionyl chloride, - acryloyl chloride, - 2chloropropionyl chloride, - methyl ester 3-chloropropionic acid, the methyl ester of acrylic acid, - the methyl ester of 2-chloropropionic acid, - the anhydride of 3-chloropropionic acid, the anhydride of the acid acrylic,

  - 2-chloropropionic acid anhydride.

  Among these reagents, the chloride of 3- is chosen more particularly

  chloropropionyl. In accordance with the process of the invention, the benzene compound preferably corresponding to formula (I) is acylated in the presence of an effective amount of hydrofluoric acid and optionally boron trifluoride. The quantity of hydrofluoric acid expressed relative to the starting benzene compound preferentially corresponding to formula (I) is such that the molar ratio between hydrofluoric acid and the benzene compound varies

  between 1 and 30, preferably between 10 and 20.

  The quantity of boron trifluoride expressed relative to the starting benzene compound preferentially corresponding to formula (I) is such that the molar ratio between the boron trifluoride and the benzene compound varies

  between 0 and 3.0, preferably around 1.0.

  As regards the amount of acylation reagent, it is most often close to stoichiometry. Thus, the ratio between the number of moles of benzene compound and the number of moles of acylation reagent can go

  from 1 to 3, and is preferably between 1 and 2.

  According to a preferred embodiment of the method of the invention, charging is

  the benzene compound and the acylation reagent.

  The reaction mixture is cooled to a low temperature ranging from

preferably between -10 C and 0 C.

  The hydrofluoric acid and optionally the boron trifluoride are charged.

  When using an acid chloride as acylation reagent, it is preferable to introduce hydrofluoric acid, to degas hydrochloric acid formed by reaction of the acylation reagent and the acid hydrofluoric

  then optionally to introduce boron trifluoride.

  The temperature at which the acylation reaction is carried out is chosen more particularly between 0 ° C. and 100 ° C., preferably between 15 ° C. and C. Generally, the reaction is carried out under autogenous pressure of the reactants. According to a preferred variant of the process of the invention, the process of the invention is carried out under a controlled atmosphere of inert gases. We can establish an atmosphere of rare gases, preferably argon but it is more

  economical to use nitrogen.

  The duration of the reaction is generally of the order of 1 hour to 8 hours.

  Thus, we obtain a product which is then cyclized in the next step,

  without separation of the reaction medium.

  The product obtained following the first reaction is a benzene compound which carries a side chain which has 3 characteristics: - a number of carbon atoms of 3 chained linearly in order to form a ring with 5 carbon atoms by involving the 2 atoms of the benzene ring carbon, - a carbonyl group CO or CS in position a with respect to the carbon atom of the benzene ring on which the chain is connected,

- a reactive functional group.

  According to a preferred variant of the invention, the benzene ring carries at least one substituent which can be a halogen atom, a group

  pseudohalogen or an electron donor group.

  Thus, the product which is cyclized in the second step can be symbolized by the following formula: (R) n Y 0111) in said formula (111): - R represents a hydrogen atom, a halogen atom, a group pseudohalogen or an electron-donor group, - two R groups can be linked together to form a cycle comprising 5 or 6 atoms, - t represents a chain of two carbon atoms comprising a reactive functional group, - Y symbolizes an atom of oxygen or sulfur,

  - n is a number equal to 0.1, 2, 3 or 4, preferably equal to 1 or 2.

  More specifically, the benzene compound of formula (111) carries a side chain comprising a carbonyl group CO or thiocarbonyl CS in position a relative to the carbon atom of the benzene ring which carries it and whose other characteristic is to have a number of carbon in the linear chain

  sufficient to form the cycle in C5, during cyclization.

  Thus, the side chain is a linear chain comprising 3 carbon atoms. Another characteristic of the side chain is to include a functional group t capable of reacting in order to form the ring which can be a halogen atom, a hydroxyl group or a double bond located in

  position a, i with respect to the group CO or CS.

  Indeed, and without limiting the invention to this interpretation, there is reason to believe that cyclization using a benzene compound carrying a carbonylated or thiocarbonylated side chain and carrying a halogen atom or d '' a hydroxyl group, goes through an intermediate stage of dehydrohalogenation or dehydration thus leading to the formation of a double bond and to obtaining a compound with side chain of the same

type as the third variant.

  Among the compounds corresponding to formula (111), the raw material of

  choice used in the process of the invention is 3,4'-

  dichloropropiophenone or 3-chloro-3 ', 4'-dimethoxypropiophenone.

  According to the method of the invention, the cyclization of the product obtained, preferably corresponding to formula (III), is carried out in a second step in the presence of an effective quantity of sulfuric acid, without separation of the product.

intermediate of formula (Ill).

  A concentrated sulfuric acid solution is generally used.

  The sulfuric acid concentration advantageously varies between 95 and 99.9% by weight. We preferentially use the commercial solution which

titer 98%.

  The amount of acid expressed by the ratio between the number of moles of acid and the number of moles of starting substrate to be cyclized, preferably corresponding to formula (111) varies between 1 and 30 and is preferably situated,

between 5 and 20.

  Said acid can optionally be deposited on a solid support.

  In this case, use is made of a support which is inert under the reaction conditions. As preferred examples of supports, there may be mentioned

especially silica.

  It is also possible according to the process of the invention to add an organic solvent which is compatible with the sulfuric acid used and which is

  inert under the reaction conditions.

  Advantageously, an aprotic organic solvent is used.

  As more specific examples, there may be mentioned aliphatic, cycloaliphatic, aromatic hydrocarbons, halogenated or not such as by

  example, n-pentane, hexane, heptane, octane, cyclohexane, 1,2-

  dichloroethane, trifluoromethylbenzene, 1,2-dichlorobenzene, toluene.

  The amount of solvent used can be variable. One can for example, put a quantity representing from 1 to 5 times the volume of sulfuric acid. The cyclization reaction of the starting substrate takes place at a temperature which is advantageously between 30 C and 120 C, preferably between 80 C

and 1 00 C.

  From a practical point of view, the reaction is simple to carry out.

  The sulfuric acid solution is brought to the reaction temperature

desired, by heating.

  The medium comprising the product to be cyclized, preferably corresponding to formula (111), is gradually added to this solution.

  in solution in an organic solvent as mentioned above.

  During the reaction, care must be taken to ensure that the reactor is surmounted by a condenser, the temperature of which is regulated so that the volatile compounds, in particular HF, can be evacuated and that any

  organic solvent remains at the bottom of the reactor.

  At the end of the reaction, the cyclized product is obtained which preferably corresponds to the following formula (IV):

(R) Y

(Rn "" R1 R3 R2

R4 (IV)

  in said formula (IV), R, R1, R2, R3, R4, Y and n have the meaning given above. The indanone or thioindanone type compound is recovered according to the

  classical techniques used in the technical field.

  It is in particular possible to carry out a hydrolysis with water, preferably with ice used at the rate for example of 1 to 1.5 kg of ice per liter of concentrated sulfuric acid as specified. A solid is obtained which is separated according to conventional techniques of

  solid / liquid separation, preferably by filtration.

  The desired product is thus obtained.

  The process of the invention is particularly suitable for the preparation of -chloroindanone from monochlorobenzene and 5,6-

  dimethoxyindanone from veratrole.

  The conversion of intermediate compounds, namely 3,4'-

  dichloropropiophenone and 3-chloro-3 ', 4'-dimethoxypropiophenone is total.

  An exemplary embodiment of the invention is given below.

  illustrative and not limiting.

  The reaction yield is defined as follows: The yield (RR) corresponds to the ratio between the number of moles of

  product formed and the number of moles of substrate used.

Example 1

  In this example, the preparation of 5-chloroindanone from

monochlorobenzene.

  In a 250 ml reactor, stirred by a turbine agitator, equipped with a dropping funnel, a thermometer, a reflux condenser and maintained under a nitrogen atmosphere: - 14.2 g ( 0.126 mol) of monochlorobenzene,

  - 17.45 g (0.139 mol) of 3-chloropropionyl chloride.

  The mixture is cooled to 0 ° C. and 48.6 g (2.43 mol) of acid are charged

  hydrofluoric and 8.7 g (0.128 mol) of boron trifluoride.

  The mixture is stirred at 350 rpm and heated at 20 ° C. for 4 h 30 min. This reaction medium is transported in a controlled and slow manner (4 h) in another reactor containing 140 ml of 98% by weight sulfuric acid brought to a

temperature 83 C.

  It should be noted that volatile species, in particular HF, can be recycled. 5-Chloroindanone is obtained with an RR reaction yield of%.

Claims (22)

  1 - Process for preparing a compound of indanone or thioindanone type from an optionally substituted benzene compound characterized in that it comprises the following steps: - (1) an acylation step which consists in reacting a benzene compound optionally substituted with an acylating agent so that a benzene compound bearing a side chain comprising at least 3 carbon atoms chained linearly, a carbonyl or thiocarbonyl group in position a relative to the carbon atom of the benzene ring to which the chain is connected and a reactive functional group; the reaction being carried out in the presence of an effective quantity of hydrofluoric acid and optionally of boron trifluoride, - (2) a step which consists in carrying out the cyclization of the product obtained   in the presence of an effective amount of sulfuric acid.   2 - Method according to claim 1 characterized in that the compound   benzene corresponds to the following formula (I): (R) n ()   in said formula (I): - R represents a hydrogen atom, a halogen atom, a pseudohalogen group or an electron donor group, - two R groups can be linked together to form a cycle comprising 5 or 6 atoms ,   - n is a number equal to 0.1, 2, 3 or 4, preferably equal to 1 or 2.   3- A method according to claim 2 characterized in that the benzene compound corresponds to the following formula (I) in which the group R represents: - a halogen atom, preferably, a chlorine or bromine atom, - a pseudohalogen group, preferably a trifluoromethoxy, trifluorothiomethoxy, pentafluoroethoxy, pentafluorothioethoxy group, - a hydroxyl group, - a linear or branched alkyl group, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, - an alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, - a methylenedioxy or ethylenedioxy group, - an alkylamide group having from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms.   4 - Method according to one of claims 2 and 3 characterized in that the group R represents: - a chlorine atom, - a hydroxyl group, - a methyl or ethyl group, - a methoxy or ethoxy group, - an acetamide group.   - Method according to claim 1 characterized in that the compound   The benzene of formula (I) is monochlorobenzene and veratrole.   6- A method according to claim 1 characterized in that the acylation reagent corresponds to formula (II): ZYb (II) in said formula (II) Y symbolizes an oxygen or sulfur atom, -t represents a chain of two carbon atoms comprising a reactive functional group, - Z represents: a halogen atom, preferably a chlorine or bromine atom, 30. a group - O - CO - in which tb has the meaning given above, a group - O - R 'in which R' represents an alkyl group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, 7- A method according to claim 6 characterized in that the reactant d acylation corresponds to formula (II) in which t represents a chain of two carbon atoms comprising a reactive functional group chosen from a halogen atom, a hydroxyl group or a double bond located in position a, 3 with respect to the group CO or CS.   8 - Method according to one of claims 6 and 7 characterized in that the   acylation reagent corresponds to formula (II) in which corresponds to one of the formulas: - a group R1 R2 C- C-X I I R3 R4 (la) - a group Ri R2 1 12 C- C-OH R3 R4 (I lb) - one group I I2   C- C-R4 (11c) in said formulas (11a) to (11c), R1, R2, R3, R4 identical or different represent a hydrogen atom or an alkyl group, linear or branched, comprising from 1 to 6 atoms carbon, preferably from 1 to 4 carbon atoms. 9- A method according to claim 8 characterized in that the functional group t corresponds to one of the formulas (la) to (11c) in which R1, R2, R3, R4 identical or different, represent a hydrogen atom or a methyl or ethyl group.   - Method according to claim 8 characterized in that the functional group corresponds to one of the formulas (lia) and (lib) in which at least   one of the groups R1 and R3 is a hydrogen atom.   11- A method according to claim 6 characterized in that the reagent   of acylation corresponds to the formula (II) in which Y represents oxygen.   12- A method according to claim 6 characterized in that the acylation reagent corresponds to formula (II) in which Z represents: 10. a chlorine atom, a group - O - C O - in which represents a group of formula   (la) described in one of claims 6 to 10,   a group - O - R 'in which R' is a methyl or ethyl group.   13- A method according to claim 6 characterized in that the acylation reagent used is chosen from: - 3chloropropionyl chloride, - acryloyl chloride, - 2chloropropionyl chloride, - methyl ester of l 3-chloropropionic acid, the methyl ester of acrylic acid, - the methyl ester of 2-chloropropionic acid, - the anhydride of 3-chloropropionic acid, the anhydride of acrylic acid,   - 2-chloropropionic acid anhydride.   14- A method according to claim 6 characterized in that the reagent   acylation is 3-chloropropionyl chloride.   15 - Method according to one of claims 1 to 14 characterized in that the   quantity of hydrofluoric acid expressed relative to the starting benzene compound preferentially corresponding to formula (I) is such that the molar ratio between hydrofluoric acid and the benzene compound varies between 1 and 30, preferably between 10 and 20.   16 - Method according to one of claims 1 to 15 characterized in that the   quantity of boron trifluoride expressed relative to the starting benzene compound preferentially corresponding to formula (I) is such that the molar ratio between the boron trifluoride and the benzene compound varies between 0 and   3.0, preferably around 1.0.   17 Method according to one of claims 1 to 16 characterized in that the   temperature at which the acylation reaction is carried out is chosen   between 0 C and 100 C, preferably between 15 C and 50 C.   18- Method according to one of claims 1 to 17 characterized in that   the benzene compound and the acylation reagent are charged, the reaction mixture is cooled to low temperature, preferably between -10 ° C. and 0 ° C., which is charged with hydrofluoric acid and optionally the boron trifluoride, which brings the reaction mixture to the temperature of the acylation reaction.   19- Method according to one of claims 1 to 18 characterized in that   at the end of the acylation reaction, a benzene compound carrying a side chain is obtained, the number of carbon atoms chained linearly is 3 in order to form a ring with 5 carbon atoms by involving the 2 atoms benzene ring carbon; which carries a carbonyl group CO or CS in position a with respect to the carbon atom of the benzene ring on which the chain is branched: side chain which also carries a reactive functional group.   - Method according to claim 19 characterized in that the benzene compound carrying a side chain comprising at least one carbonyl or thiocarbonyl group and a reactive functional group corresponds to the general formula (111): (R) n YW (111) in said formula (111): - R represents a hydrogen atom, a halogen atom, a pseudohalogen group or an electron donor group, - two R groups can be linked together to form a cycle comprising 5 or 6 atoms , - t represents a chain of two carbon atoms comprising a reactive functional group, - Y symbolizes an oxygen or sulfur atom,   - n is a number equal to 0.1, 2, 3 or 4, preferably equal to 1 or 2.   21 - Process according to claim 20 characterized in that the benzene compound carrying a side chain comprising at least one carbonyl or thiocarbonyl group and a reactive functional group corresponds to the general formula (111) in which R, t2, Y and n have the meaning given in one from claims 2 to 4, 6 to 12.   22- A method according to claim 20 characterized in that the compound   of formula (111) is 3,4-dichloropropiophenone or 3-chloro-3 ', 4'- dimethoxypropiophenone   23- Method according to one of claims 1 to 22 characterized in that   the product obtained is cyclized, preferably corresponding to formula (111),   without separation, in the presence of sulfuric acid.   24- A method according to claim 23 characterized in that the sulfuric acid concentration varies between 95 and 99.9% by weight and is equal preferably 98%.   - Method according to one of claims 23 and 24 characterized in that   the amount of acid expressed by the ratio between the number of moles of acid and the number of moles of starting substrate to be cyclized, preferably corresponding to formula (111), varies between 1 and 30 and is preferably situated, between 5 and 20.   26 - Method according to one of claims 23 to 25 characterized in that   the cyclization reaction of the starting substrate takes place at a temperature which is   between 30 C and 120 C, preferably between 80 C and 100 C.   27 - Method according to one of claims 23 to 26 characterized in that   The sulfuric acid solution is brought to the desired reaction temperature, by heating, which is gradually added to this solution with the medium comprising the product to be cyclized, preferably corresponding to the formula (111).   28- A method according to claim 1 characterized in that the cyclized product corresponds to the following formula (IV): R3 (R) n 'RR3 R2 R4 (IV)   in said formula (IV), R, R1, R2, R3, R4, Y and n have the meaning given   in one of claims 2 to 4, 6 to 12.   29- A method according to claim 28 characterized in that the compound   of formula (I) is 5-chloroindanone or 5,6-dimethoxyindanone.