GB2145082A

GB2145082A - Process for the preparation of 2,3-dihydro-[4H)-1 -benzopyran-4-one and 2,3,5,6,7,8- hexahydro-(4H)-1-benzopyran-4,5-dione derivatives

Info

Publication number: GB2145082A
Application number: GB08419581A
Authority: GB
Inventors: Lucio Merlini; Anna Arnoldi
Original assignee: Farmitalia Carlo Erba SRL
Current assignee: Pfizer Italia SRL
Priority date: 1983-08-15
Filing date: 1984-08-01
Publication date: 1985-03-20
Also published as: FI842972L; GB8419581D0; FI842972A0; DK389484A; CA1262139A; DK389484D0; IT8422058A0; GB2145082B; ATA258784A; IT1179508B; GB8321943D0; FI842972A7

Abstract

Compounds of formula (I> <IMAGE> wherein each of R1 and R2 independently is hydrogen or C1-C10 alkyl; or R1 and R2, taken together, form a C5-C7 cycloalkyl ring; R3 is hydrogen, C1-C10 alkyl or phenyl; R4 is hydrogen or C1-C6 alkyl; R5 is -OR9 or -SR9, wherein R9 is hydrogen or C1-C6 alkyl; each of R6, R7 and R8 independently is hydrogen, C1-C12 alkyl or phenyl; and their salts with bases; may be prepared by: a) reacting a compound of formula (II> <IMAGE> with a compound of formula (III> <IMAGE> or a reactive derivative thereof, so obtaining a compound of formula (IV> <IMAGE> and, if desired, alkylating a compound of formula (IV), so obtaining a compound of formula (V> <IMAGE> wherein R'4 is C1-C6 alkyl, and then aromatizing a compound of formula (IV) or (V) and, if desired, converting the compound of formula (I) thus obtained into a salt thereof with a base. The compounds of formula (I) have central nervous system activity and are useful intermediates.

Description

SPECIFICATION Process for the preparation of 2,3-dihydrobenzopyranone derivatives 2, 3-Dihydrobenzopyran derivatives, in particular 5-hydroxy-2, 3-d ihyd ro-[4H]- 1 -benzopyran-4ones, are known to be useful as such or as intermediates for the preparation both of other useful compounds (US Patent 3,467,676, UK published Patent Application GB 2120247A, US Patent 3,636,058 and Belgian Patent 844943) and of natural products . Am. Chem. Soc., 89 (23), 5934(1967)].

They are generally prepared by reacting suitable resorcinols with a, ssunsaturated carboxylic acids, in the presence of an acid or a Lewis acid catalyst, e.g. boron trifluoride etherate, or AICI3, without a solvent or in a solvent, e.g. diethyl ether, carbon disulphide or nitrobenzene, at a temperature ranging from about 20"C to about 180"C.

Although Friedel Crafts acylation is the most used reaction for the synthesis of these compounds, the yields obtained are unsatisfactory: in fact the reaction e.g. of olivetol (A) with 3methylcrotonic acid (B), in the presence of boron trifluoride etherate at 125"C, leads to the synthesis of several products, from which, in particular, two products may be isolated, i.e.

compound (C), 50% yield and compound (D), 22% yield, the remaining 20-25% being undesired secondary products.

The ratio of these products depends clearly on the reaction temperature, in fact it can be reversed by using boron trifluoride etherate at 25"C, so obtaining compound (C) with 23% yield and compound (D) with 63% yield. Moreover the subsequent separation of compound (C) from the isomeric compound (D) and especially from the undesired secondary products is difficult and yields are low.

The present invention relates to a new process for the preparation of 2,3-dihydrobenzopyran derivatives and also to certain new 2,3,7, 8-tetrahydrn-4H]-1 -benzopyran-4, 5[6 H]-diones, useful as intermediate products for their synthesis.

The new process of this invention has the important advantage over the prior art of allowing to obtain the desired products in very good yields (from about 53% to about 80%) without any need of separation of isomeric compounds and especially of separating them from the considerable amount of by-products.

Furthermore the new process is very cheap, since all the starting compounds are either commercially available products or easily obtainable by simple methods, known in organic chemistry.

The 2,3-dihydrobenzopyran derivatives, which can be obtained through the new process are, in particular, compounds having formula (I)

wherein each of R1 and R2, being the same or different, is hydrogen or C,-CI0 alkyl; or R1 and R,,., taken together, form a C5-C7 cycloalkyl ring; R3 is hydrogen, C1-C10 alkyl or phenyl; R4 is hydrogen or C1-C6 alkyl; R5 is -ORg or -SR9, wherein R9 is hydrogen or C1-C6 alkyl; each of R6, R7 and R8, being the same or different is hydrogen, C1-C12 alkyl or phenyl; and the salts thereof with bases; which, as said above, are both drugs having central nervous system activity and intermediates useful for the synthesis of drugs and of natural products.

Salts of the compounds of formula (I) may be both salts with inorganic, e.g. alkali metal, especially lithium, sodium or potassium, bases or alkaline-earth metal, especially calcium or magnesium, bases or with organic bases, e.g. alkylamines, preferably triethylamine. In the compounds described in the present invention the alkyl, alkoxy and alkylthio groups may be branched or straight chain groups.

When one or more of R1, R2 and R3 is Cl-Clo alkyl, it is preferably C1-C7 alkyl, in particular methyl, ethyl, propyl, butyl, pentyl or hexyl.

When R1 and R2, taken together, form a C5-C7 cycloalkyl ring, it is preferably cyclopentyl orcyclohexyl. When the radical -OR9 is C1-C6 alkoxy, it is preferably a C1-C4 alkoxy group, in particular methoxy, ethoxy, propoxy or isopropoxy.

When the radical -SRgis C1-C6 alkylthio, it is preferably a C1-C4 alkylthio group, in particular methylthio, ethylthio, propylthio or isopropylthio.

When one or more of R6, R7 and R8 is C1-C12 alkyl, it is preferably C2-C10 alkyl and more preferably ethyl, propyl, butyl, tert-butyl, pentyl, hexyl, 1,1-dimethylheptyl or 1,2-dimethylheptyl.

According to the new process, which is the first object of this invention, the compounds of formula (I) can be obtained by a process comprising a) reacting a compound formula (II)

wherein R6, R7 and R8 are as defined above, with a compound of formula (III)

wherein R1, R2 and R3 are as defined above, or a reactive derivative thereof, so obtaining a compound of formula (IV)

wherein R,. R, R,, Rb. R and R.;; are as defined above, and, if desired, alkylating a compound of formula (IV). so obtaining a compound of formula (V)

wherein R1, R2, R3, R6, R7 and R9 are as defined above and R'4 in C,-C6 alkyl, and then b) aromatizing a compound of formula (IV) or (V), thus obtaining a compound of formula (I), wherein R1, R2, R3, R6, R7 and R8 are as defined above and R'4 in C,-C6 alkyl, and then b) aromatizing a compound of formula (IV) or (V), thus obtaining a compound of formula (I), wherein R1, R2, R3, R6,R7 and R8 are as defined above, R5 is hydroxy and R4, according to the starting product of formula (lV) or (V), is hydrogen or C,-C6 alkyl, and, if desired, converting a compound of formula (I), thus obtained, into another compound of formula (I), and/or if desired, converting a compound of formula (I) into a salt thereof with a base, and/or, if desired, converting a salt into a free compound.

A reactive derivative of a compound of formula (III) is for example an acyl halide, an anhydride, a mixed anhydride, an azide, a reactive ester. A reactive ester may be for example a p-nitrophenyl ester, a 2,4-dinitrophenyl ester, a pentalchlorophenyl ester,a N-hydroxysuccinimide ester or a N-hydroxyphthalimide ester. Preferably a reactive ester of a compound of formula (III) is an acyl halide, in particular the chloride.

The reaction between a compound of formula (II) and a compound of formula (II) and a compound of formula (III), or a reactive derivative thereof, is carried out, either in a suitable organic solvent or without any solvent; in the presence of a Lewis acid, such as AlCI3, TiCI4, BF3, FeCI3, snCl4, ZrCI4 or ZnCl2, preferably TiCI4 or SnCl4, at temperatures ranging from about 0 C to about 120"C, and, if necessary, under cooling to keep the reaction temperature ranging from about 15"C to about 35"C. Then the reaction mixture is hydrolyzed with water and/or a diluted inorganic acid, such as hydrochloric acid: the subsequent working up, e.g. crystallization, distillation and chromatography, is carried out according to well known procedures. Examples of preferred solvents, in which the Friedel Crafts reaction is performed, are alkanes, alkyl halides, aromatic hydrocarbons, alkylbenzenes and nitrobenzene, more preferably aromatic hydrocarbons, in particular benzene, toluene and xylene, and alkyl halides, in particular, the chlorides, e.g. dichloromethane, 1, 2-dichloroethane and 1 1 ,2,2-tetrachloroethane.

The aromatization of a compound of formula (IV) or (V) may be carried out by a brominationdehydrobromination process. The bromination of a compound of formula (lV) or (V) may be performed through a suitable brominating agent, such as N-bromosuccinimide, in a suitable organic solvent, e.g. chloroform or carbon tetrachloride, with or without the presence of a radical initiator, such as dibenzoyl peroxide or bis-azodiisobutyronitrile. Other suitable brominating agents may be, for instance bromine in acetic acid, bromine in dimethylformamide or pyridinium perbromide.The bromination reaction is immediately followed, in the same reaction medium, by a dehydrobromination step consisting in heating the obtained reaction, mixture, in the presence of a suitable, base. e.g. diethylaniline, dimethylaniline, collidine or triethylamine, at temperatures ranging from about 60"C to the reflux temperature.The aromatization of a compound of formula (IV) or (V) may be alternatively performed by heating, at temperatures ranging from about 150"C to about 250"C, in a high-boiling solvent, chosen e.g. from diethyleneglycol dimethylether, diphenylether and decalin; or by heating at reflux temperature, either in the same high-boiling solvent maintained above or in a hydrogen acceptor solvent, such as cyclohexene, in the presence of sulphur, palladium black, palladium on carbon or palladium on other substrates, or in the presence of another noble metal, such as rhodium or ruthenium.

Alternatively the aromatization of a compound of formula (IV) or (V) may be performed by heating with chloranyl or dichlorodicyanobenzoquinone (DDQ) or other active quinones in boiling benzene or in another suitable solvent, e.g. dioxane, acetic acid, or toluene.

Also after the aromatization of a compound of formula (IV) or (V), the subsequent working up, e.g. filtration and evaporation of the solvent, is carried out according to well known procedures.

The compounds of formula (II) and (III) are known compounds, which are either commercially available products or easily obtainable by simple methods well known in organic chemistry. The optional alkylation of a compound of formula (IV) to obtain a compound of formula (V), as well as the optional alkylation of a compound of formula (I), wherein R4 is hydrogen, to obtain another compound of formula (I), wherein R4 is C,-C6 alkyl, may be carried out in a conventional way, for example by reaction with NaH or NaN H2 in dry dioxane or dimethylformamide or toluene and alkylating the obtained anion with an alkyl sulphate.

As example of another optional conversion of a compound of formula (I) into another compound of formula (I), a compound of formula (I), wherein R6 is hydroxy may be converted into another compound of formula (I), wherein R5 is a -SH group, by following known methods, for example according to the procedure of H. Wolfers, U. Kraatz. F. Korte, Synthesis, 1971, page 43.

Furthermore a compound of formula (i), wherein R is a -OH or -SH group, may be converted into another compound of formula (I), wherein Rs is C1-C6 alkoxy or C,-C6 alkylthio, respectively. Said etherification may be performed by reaction with a suitable alkyl halide, in the presence of a base such as NaOH, KOH, Na2CO3, K2CO3, NaH, Nans2, sodium methoxide or sodium ethoxide in a solvent selected from the group consisting, for example, of methanol, ethanol, dioxane, acetone, dimethylformamide, hexamethyl-phosphorotriamide, tetrahydrofuran, water and their mixtures at a temperature ranging preferably between about O"C and about 150"C. Furthermore, when R5 is an etherified hydroxy group, it may be converted into a free hydroxy group, for example by treatment with pyridine hydrochloride or with a strong acid such as HBr or HI, or with a Lewis acid such as AIR13 or BBr3 or with an alkaline salt of a thiol.

Also the optional salification of a compound of formula (I) as well as the conversion of a salt into the free compound may be carried out by conventional methods. The compounds covered by the general formulae (IV) and (V) may be summarized by the general formula (Vl)

wherein R1, R2, R3, R4, R6. R7 and R8 are as defined above. As previously stated, object of this invention are also certain new 2,3, 7,8-tetrahydro-[4H]-1 -benzopyran-4, 5-[6 H]-diones having the general formula (Vla)

wherein R1, R2, R3 and R4 are as defined above and one of R'6, R'7 and R'8 is C2-C,2 alkyl or phenyl and the others, which may be the same or different, are hydrogen, C,-C6 alkyl or phenyl.

The invention also provides a process for the preparation of a compound of formula (Vl), which process comprises reacting a compound of formula (ill):

wherein R6, R7 and R8 are as defined above, with a compound of formula (III)

wherein R1, R2 and R3 are as defined above, or a reactive derivative thereof, so obtaining a compound of formula (Vl) in which R4 is hydrogen, represented by the formula (IV):

wherein R1, R2, R3, R6, R, and R6 are as defined above, and, if desired, alkylating a compound of formula (IV), so obtaining a compound of formula (Vl), in which R4 is C,-C6 alkyl, reprsented by formula (V)::

wherein R1, R2, R3, R6, R7 and R6 are as defined above and R'4 is C1-C6 alkyl.

The following Examples ilustrate but do not limit the present invention.

Example 1 5-Pentyl-1,3-cyclohexane-1,3-dione (2.18 g) was added portionwise to a solution of titanium tetrachloride (1 .6ml) in dichloromethane (40 ml) at 0 C, under nitrogen. A red oil precipitated from the solution. After 0.5 h, 3,3-dimethylacrylic acid chloride (1.72 g) was dropped and the solution was stirred again for 20 h, till a yellow precipitate was obtained. The mixture was poured into a chilled 2 M HCI solution (50 ml). The phases were separated, the aqueous one was extracted twice with chloroform, the organic extracts were washed with water, dried and concentrated. The crude residue was crystallized from ethyl ether. 2,2-Dimethyl-7-pentyl-2,3,7,8-tetrahydro-[4H]-1-benzopy- ran-4,5-[6H]-dione was obtained as pale yellow needles, m.p. 88-89 C, 2.06 g, 83% yield.By proceeding analogously the following compounds were prepared: 2,2-dimethyl-2,3,7,8-tetrahydro-C4H]-l -benzopyran-4, 5-[6 H]-dione, m .p. 97-98 C, (from toluene); 2,2.7-trimethyl-2,3,7,8-tetrahydro-[4H]- -benzopyran-4, H]-dione, m . p.134- 135 C; 2-methyl-2, 3,7, 8-tetrahydro-[4H]-1 -benzopyran-4,5-[6 H]-dione, m. p. 89 C; 2-methyl-7-pentyl-2, 3,7, 8-tetrnhydro-[4H]- 1 -benzopyran-4, 5-[6 H]-dione, yellow oil:: M+250;'H NMR(CDCI3)8(ppm) 0.9(3H,t,CH3CH2), 1.1-1 .35(8H), 1 .4(3H,d,CH3-2), 1.9-2.9 (7H), 4.25-4.9 (1 H,m,CH-2); 2-pentyl-2, 3, 7. 8-tetrahydro-[4H]-l -benzopyran4, 5-[6 H]-dione, oil; 2,2-dimethyl-7-phenyl-2,3,7,8-tetrahydro-[4H]-1 -benzopyran-4, 5-6 HJ-dione, m p. 96-97 C (from toluene); 2-methyl-7-phenyl-2, 3,7 ,8-tetrahydrn-[4H]-1 -benzopyran-4, 5-i6H]-dione; and 2-pentyl-7-methyl-2,3,7,8-tetrahydro-[4H]- 1 -benzopyran-4, 5-[6 H]-dio ne.

Example 2 2, 2-Dimethyl-7-phenyl-2, 3, 7. 8tetrahydro-[4H]-l -benzopyran-4, 5-[6 H]-dione (1 g) was refluxed for 7 h in 20 ml of diethyleneglycol dimethylether in the presence of 50 mg of 10% Pd/C. The cold mixture was filtered, diluted with ethyl acetate and washed several times with water. After column chromatography, 2, 2-di methyl-5-hydroxy-7-phenyl-2, 3-d ihydro-[4H]- 1 -benzopyran-4-one was obtained as a yellow solid, m.p. 126-128"C, 0.52 g.

By proceeding analogously the following compounds were obtained: 2, 2-dimethyl-5-hydroxy-2, 3-dihydrnI4H]- 1 -benzopyran-4-one, m p. 75-77"C; 2,2,7-trimethyl-5-hydroxy-2, 3-dihydrn-[4H]- 1 -benzopyran-4-one, m.p. 23-25 C; 2-methyl-5-hydroxy-2,3-dihydro-[4H]- 1 -benzopyran-4-one, m . p. 30 C; 2-methyl-5-hydroxy-7-pentyl-2, 3-dihydro-[4H]- 1 -benzopyran-4-one, oil, M + 248; 1H N M R(CDCI3): #(ppm) 0.9(3H,t,CH3), 1.0-1.7(6H), 1.5(3H,d,J6, Ch3-2), 2.4-2.8(6H), 4.3-4.8(1 H,m,H-2), 6.2-6.4(2H,H6 and H-8), 11.6(1 H,s,OH); 2-pentyl-5-hydroxy-2, 3-dihydro-[4 H]- 1 -benzopyran-4-one: 2-methyl-5-hydroxy-7-phenyl-2,3-dihydro-[4H]- 1 -benzopyran-4-one; 2-pentyl-5-hydroxy-7-methyl-2,3-dihydro-[4H]-1 -benzopyran-4-one, yellow oil; and 2,2-dimethyl-5-hydroxy-7-pentyl-2, 3-dihydrn-[4H]-1 -benzopyran-4-one, b. p. 100-105"C (0.01 mmHg).

Example 3 2,2-Dimethyl-7-pentyl-2,3,7,8-tetrahydro-[4H]- -benzo-pyran-4, H]-d ione (2.4 g), N-bromosuc cinimide (2 g) and dibenzoyl peroxide (100 mg) were refluxed for 2 h in carbon tetrachloride (25 ml).

The solution was filtered and concentrated. The crude residue was added with N,N-diethylaniline (3 ml) and warmed for 3 h on a steam bath. The mixture was diluted with ethyl acetate and washed with 5N HCI, then with water. After drying and evaporation of the solvent, 2,2-dimethyl-5-hydroxy-7 pentyl-2, 3-dihydro-[4HJ-1 -benzopyran-4-one was obtained by distillation, b.p. 100-105"C (0.01 mmHg), 2.359, 98% yield.

By proceeding analogously the following compounds were obtained: 2, 2-dimethyl-5-hydroxy-7-phenyl-2, 3-dihydro-[4H]- 1 -benzo-pyran-4-one, m. p. 126-128 C; 2,2,7-trimethyl-5-hydroxy-2,3-dihydro-[4H]- -benzopyran-4-one, m p. 23-25"C; 2,2-dimethyl-5-hydroxy-2,3-dihydro-[4H]-1 -benzopyran-4-one, m . p. 75-77 C; 2-methyl-5-hydroxy-2, 3-dihydro-[4HJ- 1 -benzopyran-4-one, m p. 30"C; 2-methyl-5-hydroxy-7-pentyl-2,3-dihydro-[4H]-1 -benzopyran-4-one, oil; 2-pentyl-5-hydroxy-2, 3-dihydro-[4H]- 1 -benzopyran-4-one; 2-methyl-5-hydroxy-7-phenyl-2, 3-dihydro-[4H]- 1 -benzopyran-4-one; and 2-pentyl-5-hydroxy-7-methyl-2,3-dihydro-[4H]-1 -benzopyran-4-one, yellow oil.

Example 4 2,2-Dimethyl-5-hydroxy-7-pentyl-2,3-dihydro-[4H]-1-benzopyran-4-one (1 g) was dissolved in tetrahydrofurane (12 ml) and treated with the stoichiometric amount of NaH.

The reaction mixture was evaporated, leaving 2,2-dimethyl-5-hydroxy-7-pentyl-2,3-dihydro-[4H]-1 - benzopyran-4-one, sodium salt, as a residue; m.p. > 250 C.

Example 5 2,2-Dimethyl-7-phenyl-2,3,7,8-tetrahydro-[4H]-1 -benzopyran4, 5-[6 H]-one (1.08 g) was refluxed 1.5 h in 10 ml of toluene in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.9 g). The mixture was filtered and concentrated. After column chromatography, 2,2-dimethyl-5-hydroxy-7 phenyl-C$H1-l -benzoyran-4-one was obtained as a yellow solid, m.p. 126-128 C, 0.98 g (90% yield).

The following compounds were analogously prepared: 2,2, 7-trimethyl-5-hydroxy-2, 3-dihydro-[4H]-1 -benzopyran-4-one, m. p. 23-25 C; 2,2-dimethyl-5-hydroxy-2,3-dihydro-14H]- -benzopyran-4-one, m.p. 75-77 C; 2,2-dimethyl-5-hydroxy-7-pentyl-2,3-dihydro-[4H]-1 -benzopyran-4-one, b. p. 100-105 C (0.01 mmHg): 2-methyl-5-hydroxy-2, 3-dihydro-[4H]-1 -benzopyran-4-one; 2-methyl-5-hydroxy-7-pentyl-2, 3-dihydro-[4H]- 1 -benzopyran-4-one, oil; 2-pentyl-5-hydroxy-2, 3-dihydro-[4H]- 1 -benzopyran-4-one; 2-methyl-5-hydroxy-7-phenyl-2, 3-dihydro-[4H]- 1 -benzopyran-4-one; and 2-pentyl-5-hydroxy-7-methyl-2, 3-dihydro-[4H]- 1 -benzopyran-4-one, yellow oil.

Example 6 2,2-dimethyl-2,3,7,8-tetrahydro-[4H]-1-benzopyran-4,5-[6H]-dione (1 g) was dissolved in 10 ml of dry tetrahydrofurane, the mixture cooled at - 20"C, added with 0.5 g of sodium hydride (80% suspension in paraffine oil), the mixture left two hours at room temperature, then added with 0.75 g of methyl iodide and refluxed three hours. Evaporation, taking up with water, extraction with ethyl acetate and evaporation of the solvent gave a crude mixture. Chromatography of this product on silica gel afforded 0.24 g of 2,2, 3-trimethyl-2, 3,7' 8-tetrahydro-4H]- 1 -benzopyran-4, 5-[6 H]-dione, as a low melting solid.

Claims

1. A process for the preparation of compound of formula (I]

wherein Each of R, and R2, being the same or different, is hydrogen of C,-C10 alkyl; or R1 and R2, taken together, form a C5-C7 cycloalkyl ring; R3 is hydrogen, C1-C10 alkyl or phenyl; R4 is hydrogen or C1 -C6 alkyl; R6 is -ORg or -SR9, wherein R9 is hydrogen or C1 -C6 alkyl; each of R6, R7 and R6, being the same or different is hydrogen, C1 -C12 alkyl or phenyl; and the salts thereof with bases; said process comprising: a) reacting a compound of formula (II)

wherein R6, R7 and R6 are as defined above, with a compound of formula (III)

wherein R1, R2 and R3 are as defined above, or a reactive derivtive thereof, so obtaining a compound of formula (IV)

wherein R1, R2, R3, R6, R7 and R6 are as defined above, and, if desired, alkylating a compound of formula (IV), so obtaining a compound of formula (V)

wherein R1,R2,R3,R6, R7 and R6 are as defined above and R'4 is C,-C6 alkyl, and then b) aromatizating a compound of.formula (IV) or (V), thus obtaining a compound of formula (I), wherein R1, R2, R3, R6, R7 and R6 are as defined above, R6 is hydroxy and R4, according to the starting product of formula (IV) or (V), is hydrogen or C1-C6 alkyl, and, if desired, converting a compound of formula (I), thus obtained, into another compound of formula (I), and/or, if desired, converting a compound of formula (I) into a salt thereof with a base, and/or, if desired, converting a salt into a free compound.

2. 2,2-Dimethyl-5-hydroxy-7-pentyl-2,3-dihydro-(4iH]-1-benzopyran-4-one when prepared by a process as claimed in claim 1.

3. A compound of formula (Vla)

wherein R1, R2, R3 and R4 are as defined in claim 1 and one of R'6, R'7 and R'8 is C2-C,2 alkyl or phenyl and the others, which may be the same or different, are hydrogen, C1-C5 alkyl or phenyl.

4. A compound of formula (Vla), as claimed in claim 3, when obtained by part a) of the process described in claim 1.

5. A compound of formula (Vla), as claimed in claim 3, selected from 2,2-dimethyl-7-pentyl 2,3,7 ,8-tetrahydrn-4H]-1 -benzopyran-4, 546 H]-dione, 2-methyl-7-pentyl-2, 3,7,8-tetrahydro- [4H]-1 -benzopyran-4, 5-16 H]-dione and 2,2-dimethyl-7-phenyl-2,3,7,8-tetrahydro-[4H]- 1 -benzo pyran-4,5-[6H]-dione.

6. A process for the preparation of a compound of formula (I) as defined in claim 1 or a salt thereof, said process being substantially as hereinbefore described in any one of Examples 2 to 5.

7. A process for the preparation of a compound of formula (Vl)

wherein R1, R2, R3, R4, R6, R7 and R6 are as defined in claim 1, which process comprises reacting a compound of formula (II)

wherein R6, R7 and R6 are as defined in claim 1, with a compound of formula (III)

wherein R1, R2 and R3 are as defined in claim 1, or a reactive derivative thereof, so obtaining a compound of formula (Vl) in which R4 is hydrogen, represented by the formula (IV): :

wherein R1, R2, R3, R6, R7 and R6 are as defined in claim 1, and, if desired, alkylating a compound of formula (IV), so obtaining a compound of formula (Vl), in which R4 is C1 -C6 alkyl, represented by formula (V):

wherein R1, R2, R3, R6, R7 and R6 are as defined in claim 1 and R'4 is C1 -C6 alkyl.

8. A process according to claim 7 in which, in the compound of formula (II), one of R6, R7 and R6 is C2-C12 alkyl or phenyl and the others, which may be the same or different, are hydrogen, C1-C6 alkyl or phenyl.

9. A process for the preparation of a compound of formula (Vi) as defined in claim 7, said process being substantially as hereinbefore described in Examples 1 or 6.