DE2145319A1 - SUBSTITUTED BENZOPYRAN DERIVATIVES AND PHARMACEUTICAL PREPARATIONS CONTAINING SUCH BENZOPYRANE DERIVATIVES - Google Patents

Description

¹¹ Substituted benzopyran derivatives and pharmaceutical preparations containing such benzopyran derivatives "

Priority: September 10, 1970, Great Britain, Mr. 43 347/70 May 11, 1971, Great Britain, No. 14 225/71

The invention relates to new heterocyclically substituted benzopyran derivatives, which contain an aromatic 5-membered heterocyclic group in the 4-position of the benzopyran ring. The invention also relates to pharmaceutical preparations containing such derivatives.

British Patent 1,162,784 discloses pyridyl-substituted ones Benzopyran derivatives of the following general formula are known:

-S

OH

(D

R,

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in which R-, an alkyl group having 1 to 6 carbon atoms and R2 represents an alkyl group having 1 to 20 carbon atoms ". Some of these known compounds are said to have activity with respect to the central nervous system. In this Patent specification also describes a process for the preparation of compounds having the formula I given above.

Surprisingly, it has now been found that benzopyran derivatives, which instead of a pyridyl group in the 4-position a aromatic 5-membered heterocyclic ring, exhibits favorable pharmacological activity.

Accordingly, the invention relates to substituted benzo- / " pyran derivatives of the general formula below, as well as their salts

(II)

in which R-, a hydrocarbon group with 1 to 6 carbon atoms, R2 is a saturated or unsaturated alkyl group having 1 to 20 carbon atoms or a cycloalkyl-lower alkyl group with 3 to 8 carbon atoms in the cycloalkyl part and with 1 to 6 carbon atoms in the lower alkyl part, R, an aromatic Sgüedrigen heterocyclic ring and X is a Hydroxyl group or a salt, ester or salt derived therefrom Ether group means.

The groups R- ^ can be saturated or unsaturated, straight-chain or branched. For example, it can be the

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Act as methyl, ethyl, propyl, isopropyl, vinyl, allyl, butenyl, hexyl or phenyl groups. Ira are within the scope of the invention Compounds preferred in which R- ^ represents the methyl group.

Rp can be straight-chain and branched-chain alkyl groups, for example lower alkyl groups such as those given above for R- ^. In addition, Rp can also have the meaning of an n-heptyl, 3-methyl-2-octyl, 2-octyl and n-heptadeelyl group. In the context of the invention, “cycloalkyl-lower alkyl groups” are understood to mean combinations of alkyl and cycloalkyl groups. For example, Rp. a cyclopropyl, cyclobutyl, 2-methyl-cyclobutyl, cyclohexyl, 4-ethyl-cyclohexyl, cyclooetyl, cyclohexylpropyl or methyl-cyclohexylpropyl group. In the context of the invention, preference is given to compounds in which Rg is the 3-methyl-2-octyl group.

R ^ ₅ means an aromatic 5-membered heterocyclic ring. For example, R ₅ can be the puryl, thienyl, thiazolyl, pyrryl, isoxazolyl, oxazolyl, imidazolyl or pyrazolyl group. These heterocyclic groups can be linked to the benzopyran portion of the molecule by means of any ring carbon atom. In addition, the heterocyclic group can also contain lower alkyl groups as substituents. In the context of the invention, preference is given to compounds in which R is a 2-thienyl, 3-thienyl, 2-thiazolyl, 5-furyl, ^ - (1-methyl) pyrazolyl or 2-pyrry! group has.

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X has the meaning of a hydroxyl group or one derived therefrom Salt group, such as a lithium, sodium or potassium salt, e.g. In addition, the hydroxyl group can also be etherified or esterified. Esterified hydroxyl groups can differ from inorganic ones Acids, such as phosphoric acid, and of organic acids, such as acetic acid, Derive lactic acid, citric acid or amino acids. In addition, the hydroxyl group, by means of alkyl groups or aralkyl groups be etherified, which ones you want if you want May have substituents, for example amino groups.

The invention encompasses both the tautomeric forms and specific stereoisomers or geometric isomers of compounds of the formula II given above.

The inventive substituted -. - ·

Benzopyran derivatives of the above formula II leave sicii produce by using a substituted chromanone of the general formula III below

OX

(III)

in which Rj. " R? ¹ ^ ¹ * ^{1 X} ^ ^{e YOrs} "t ^eiienä - have the meaning given, treated in an inert medium with a compound R ^ Y, in which R * has the meaning given above and Y means an alkali metal or a metal halogen group, and that one optionally split off from the intermediate product V / water initially formed.

The reaction is preferably carried out by means of a compound R, Y carried out, in which Y lithium or the group MgCl, MgBr

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or MgJ means.

The temperatures used for the preparation of the organometallic compounds and their further reaction depend on the stability of the compounds in question, and in some cases one will therefore work at or below room temperature, while in other cases elevated temperatures are more favorable

man

are. When using lithium compounds can -beispielsweise in the temperature range of '+ 4O ⁰ C .to -80 C to work, although under certain circumstances, even higher temperatures are possible. In general, is with the use of G-rign ν ö- compounds at slightly higher temperatures work as if one lithium derivatives verv / ends. Certain stable Grignard compounds are in some cases converted at temperatures which are just as high or even higher than the reflux temperature of tetrahydrofuran, if only by using such higher temperatures the _{conversion can be} carried out in reasonable periods of time.

Suitable solvents for the above-mentioned reaction are aprotic solvents, as they are usually used in reactions with organometallic compounds, e.g. ether, for both lithium and magnesium compounds or ethers or hydrocarbon solvents such as hexane for lithium compounds.

The organometallic used in the inventive reaction Compounds R-zY can by means of methods known per se getting produced. For example, the lithium compounds in question can be obtained by reacting n-butyl

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lithium with a Rz halogen compound, such as 3-bromothiophene or with a compound R * H, such as furan, obtained in an apr ο ti sham solvent, generally working at low temperature. Grignard compounds are obtained by reacting magnesium with a compound R ₇ halogen in an aprotic solvent at low temperatures, at room temperature or at higher temperatures, the choice of the reaction temperature in question depending on the reactivity of the R 2 halogen bond.

In the production process, an organometallic intermediate compound represented by the following general formula is first used V obtained, which then in situ in an aqueous reaction medium to the desired hydroxy compound of the following

general formula IV is added. . i

HO R, ^x

(V) (IV). .

For example, 1 η-sulfuric acid, aqueous ammonium chloride or other agents are suitable for this decomposition reaction, as they are commonly used for such decomposition reactions.

If the compound of formula IV thus obtained is relatively unstable is, a spontaneous elimination of water with formation of the desired compound with the general formula II can be accomplished

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gen. Such dehydration is favored if the for the
/ Decomposition of the intermediate with the formula V required acid concentration increased, or if the reaction mixture is heated.

In some cases it can be beneficial to connect first to isolate with the formula IV and then to carry out the elimination of water in a further process stage. In again in other cases it may prove expedient to Change the reaction medium for carrying out the dehydration stage.

. The dehydration can be carried out using customary methods, by, for example, the compound of formula IV alone., or heated in a solvent, or by treating with a dehydrating agent such as a strong acid.

If you want to perform dehydration by using the. If undissolved compound of the formula IV is heated, temperatures in the range from 25 to 250 G are required depending on the nature of the substituents R- ^, R ₂ , Rz and X, v / whether the substituent R * in particular has an influence . The elimination of water can in some cases be facilitated by using the chromanol of the formula IV in finely divided form and / or by heating it under reduced pressure.

. For this dehydration stage, inert solvents can be used if desired, hydrocarbons such as benzene "paü'TöluöI ^ or alkene oils, such as butanol and pentanol or halogenated compounds, such as tetrabromethylene and chlorobenzene can also be used. The solvent in question only has to have the chroma

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Solve nol of the formula IV sufficiently and have a higher boiling point * than corresponds to the temperature at which the elimination of water from the chromanol takes place.

In general, an acid catalyst is used for the elimination of water is also used, since the reaction is then much deeper Temperatures expire as if no acid is used with. For example, most of the chromanols in the for-

mel IV in the presence of sulfuric acid at temperatures of 100 C or less can be converted very easily and quickly into the corresponding compound with the formula II. For example, takes place the elimination of water in most of the chromanols of the formula IV when heated in a water bath, if this chromium. manols as solutions in ethanol, which contain sulfuric acid,. or as solutions in benzene which contain / use p-toluenesulphonic acid. If more dehydrating catalysts

- are used »the conversion takes place even when the

. drigeren temperatures, for example, the ^ water-. cleavage by means of p - '^ oluenesulfonyl chloride in pyridine also does Perform at room temperature. If X is a basic group

- Is, acid addition salts of the compounds of . general formula II can be prepared by this ge. optionally reacts with an acid. Such acid. . However, addition salts are formed automatically if an acid catalyst is also used during the elimination of water.

If desired, from the inventive Final products the free base can be obtained by adding this with a basic compound such as sodium carbonate or ammonium hydroxide; treated.

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Acid addition salts can by means of mineral acids, such as hydrochloric acid, Hydrobromic acid, sulfuric acid or phosphoric acid, -and also obtained by means of organic acids such as acetic acid, lactic acid, citric acid, tartaric acid or toluenesulfonic acid will. If the benzopyran derivatives of the formula II in question are used as active ingredients in pharmaceutical preparations however, the acid used for salt formation must be pharmacologically acceptable.

The compound of the formula III used as a reaction component in the preparation process ?, ^^ according to that of K.E. Fahrholtz, M. Lurie and ß.W. Kierstead in "J. Amer. 'Chem. Soc." (1967), 89, 5934 described method will.

The pharmacological activity of the benzopyran derivatives according to the invention has been tested on animals and this has been shown to have very good psychodynamic activity and can be used in particular as a means of depression.

Accordingly, the invention also relates to pharmaceutical preparations which are composed of a compound of the general formula II exist as an active ingredient and optionally customary pharmacologically acceptable carriers and diluents. Such pharmaceutical preparations can be in the form of pills, tablets or capsules, or for oral administration parenteral administration in the form of injection solutions in sterile water or as suppositories.

The examples illustrate the invention.

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Example 1 ·>

2,2-dimethyl-7- (3-methyl-2-octyl) -4- (2-thienyl) -2H-chromen-5-ol

4.89 g (0.03 mol) of 2-bromothiophene in 10 ml of dry ether are added dropwise over 50 minutes to a stirred. Suspension of 0.72 g (0.03 mol) of magnesium in 10 ml of dry ether was added, the reaction being initiated by adding an iodine crystal. In this way a solution of 2-ihienylmagnesium bromide is obtained. After a further 20 minutes, a solution of 3.18 g (0.01 mol) of the compound 2,2-dimethyl-5-hydroxy-7- (3-methyl-2-octyl) -ehroman is added in the course of 15 minutes -4-one in 10 ml of dry ether is added to the solution of the Grignard reagent and this mixture is stirred for three hours. Room temperature. The reaction complex is then decomposed by adding .5 η hydrochloric acid and extracted with ether. "The ether extract is washed with water and dried over magnesium sulfate. The ether is then evaporated in vacuo and 3.65 g of a brown-colored oil is obtained, which is heated to 100 ° C. for 1/2 hour in vacuo to / in the ^{4- (2- 2} hienyl) -4- contained in the reaction product

water
chromanol / split off .. The crude chromene obtained in this way is purified by chromatography on a column of 160 g of silica gel. ; When eluting with a mixture of benzene and light gasoline in a ratio of 1: 4, traces of oils are first obtained and then 285 g (yield 74 percent) of the desired oil product in the form of a light yellow oil, the purity of which is indicated by gas. Liquid chromatography is determined to be 95 percent.

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"Ρΐΐτ · Γ ¹ TT Π CJ ·
-ι- * · * ■ - * · * ^ O v1 ^^ ζ O ^ * ^ O * ^ · - ■ 11 -. 0; H 3; 2U5319 analysis Theory: C. 9; 8th, 5; S. found 75 8th, $ 8.3> 75 8.2 ^

Example 12 2,2-Dimethyl-7- (3-methyl-2-octyl) -4- (3-t-menyl) -2H-chromene-5-ol

8.43 g (0.05 mol) of 3-bromothiophene in 25 ml of dry ether are added dropwise over 1 1/4 hours under a protective layer of nitrogen at -70 ° to a stirred solution of 3.6 g (O _t O56 mol) of n-butyllithium in 18 ml of hexane are added

of 3-Thi2: i;, 'llithium ₀

stirs this solution / for a further 45 minutes at -70 G and sets then a solution of 3.18 g (0.01 mol) of the compound 2,2-dimethyl-5-hydroxy-7- (3-methyl- Add 2-octyl) -ehroman-4-one in 15 ml of dry ether.

The reaction mixture is then for 2 1/2 hours at -70 ⁰ C,

ο
Stirred for 11/2 hours at -40 ° C and finally 11/2 hours at -10 ° C. After neutralization with 5 η sulfuric acid, the organic layer is separated off and the aqueous layer is extracted twice with ether. The combined ether extracts are washed with water, dried over magnesium sulfate and then the solvent is evaporated off. The following is obtained _: 3.8 g of a black oil which, according to thin-sheet chromatography analysis, is a non-separable mixture of the desired chromenol together with the chromanone used as the starting material. This crude product is therefore dissolved in 15 ml of pyridine and then 2 g of hydroxylamine hydrochloride are added. This solution is heated for 6 hours on a water bath _r then poured into water and extracted three times with ether. The combined ether extracts are mixed with 5n salt

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washed acid and with water, dried over magnesium sulfate then evaporated \ whereupon the solvent. This gives ⁸⁰ 3.7 g of a black oil which contains the desired chromenol

. represents that only traces of the raw material used Contains chromanone and chromanone oxime. This oil will

- Purified by chromatography on a column of silica gel. By Eluting with a mixture of benzene and light gasoline in the ratio 1: 4 gives 1.80 g (yield 47 percent) of the

. desired end product in the form of a brown oil, its degree of purity is found to be 94.5 percent by gas-liquid chromatography.

Analysis for θ £ 4 ^Η 32 ° 2 ^SGHS

Theory 75.0; 8.3; 8.3 #; found 74.7; 8.6; 7.9 #.

Example 3 2,2-Dimethyl-7- (3-methyl-2-octyl) -4- (2-thiazolyl) -2H-chromene-5-

ol.

dry ether 8 »43 g (0.05 mol) of 2-bromothiazole in 25 ml / are in the course of

. 1 1/4 hours under a protective layer of nitrogen

. -70 C dropwise to a stirred solution of 3.6 g

. (0.056 mol) of n-butyllithium in 18 ml of η-hexane were added. To this

. Way, a solution of the compound 2-lithiothiazole is obtained,

. Then add to this stirred solution over a period of 30 minutes.

. utes at -70 C a solution of 3.18 g (0.01 mol) of the compound

. formation of 2,2-dimethyl-5-hydroxy-7- (3-methyl-2-octyl) -chroman-4-one

. in 12 ml of dry ether and stir for a further 3 hours

. - 70 C. This solution is then left in the course of 1 hour assume a temperature of -10 C. The black one obtained in this way

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Solution is neutralized with 5 η sulfuric acid and the precipitating black solid is filtered off and discarded, "The aqueous layer is also separated and twice extracted with ether. The combined ether extracts are washed with water, dried over magnesium sulfate and then is ■ the solvent evaporated. A black colored one is obtained in this way solid fabric. By recrystallizing twice from an ether-light gasoline mixture with the addition of activated charcoal 0.81 g (yield 20 percent) of the compound 2,2-diraethyl-7- (3-methyl-2-octyl) -4- (2-thiazolyl) -cnroman-4,5-diol are obtained in the form of a colorless solid substance with a melting point of 142-143 ° C.

Analysis for O ₂ ^ H, ^ NO, S! Theory: found:

1.3 g (0.003 mol) of the diol thus prepared and 0.12 g of p-toluenesulfonic acid monohydrate in 25 ml of benzene are refluxed for 45 minutes. Then it is poured into water. The organic layer is separated, dried over magnesium sulfate and the solvent is removed. One obtains so _; a yellow colored oil. Chromatographic purification on a column of silica gel using a mixture of benzene and light gasoline in a ratio of 3: 7 as eluant gives the desired compound in the form of a yellow oil (0.9 g, yield 72 percent), the purity of which is gas-liquid -Chromatography is found to be 97.5 percent.

C. , 5; H 2; N 5; S. 68 , 3; 8th, 2; ' 3, 5; 7, 68 8th, 3, 8th,

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for O ₂₃ H ₃₁ MO ₂ S. -'14 MB C. 7; H 05; H 2145319 analysis Theory: 71 4; 8th, 5; 3 S. found 72, 8th, 3 , 6; 8.3? Fc , 3; 8.3;

• Example 4 2,2-Dimethyl-7- (2-octyl) -4- (2-thienyl) -2H-chromen-5-ol

4.89 g (0.03 mol) of 2-bromothiophene in 10 ml of dry ether dropwise over 30 minutes to a stirred suspension of 0.72 g (0.03 mol) of magnesium in 10 ml of dry Ether added, the reaction being started by adding an iodine crystal. That way you get a solution of 2-thienyl magnesium bromide. After another 20 minutes 3.04 g (0.01 mol) of the compound 2,2-dimethyl-5-hydroxy-7- (2-oetyl) -chroman-4-one are added dropwise over the course of 12 minutes in 10 ml of dry ether is added to this Grignard reagent and the reaction mixture is stirred for 4 hours long at room temperature. The reaction complex is then decomposed with aqueous ammonium chloride and extracted with ether. The ether extract is washed with water and over magnesium sulfate dried. Evaporation of the solvent in vacuo gives 3.90 g of a brown-colored oil, which on a column of 160 g of silica gel is purified by chromatography. By eluting with a mixture of benzene and mineral spirits in a ratio of 1: 4, traces of an oil are first obtained and then the desired compound in the form of a pale yellow oil (3 »36 g, yield 89 percent), by means of gas-plus chromatography the degree of purity is determined to be 99 percent. , ■

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Analysis for

C. , 6; H i; 2145319 ■ co C ₂₃ H ₃₀ O ₂ S: 74 ,8th: 8th, 4; 8.65 ^; Theory: 74 8th, 8.9 "K found:

Example 5 2,2-dimethyl-7- (n-heptadecyl) -4- (2-thienyl) -2H-chromen-5-ol

According to the method of Fahrholtz and coworkers, the compound is 2,2-dimethyl-7- (n-heptadecyl) -5-hydroxychroman-4-one with a melting point of 73 to 74 ° C. in 38 percent yield from 5 n-heptadecylresorcinol monohydrate and 3,3-dimethylacrylic acid.

Analysis for C ₂₈ H 1 O ₃ ; CH

Theory:. 78.1; 10.7j6; found: 78.1; 10.8ίί.

A solution of 190 mg (0.00044 mol) of this chromanone in 6 ml of dry ether is added dropwise over 5 minutes

stirred
added to a / solution of 0.066 moles of 2-thienylmagnesium bromide in 10 ml of dry ether, which according to the method of

Example 1 has been prepared. This solution becomes / ^.

Stirred for 2 3/4 hours and heated to boiling under reflux. Further working up is carried out according to Example 1. ^Man: thus obtains 216 mg of a green colored oil, which is purified by chromatography on a column of 8 g of silica gel. By eluting with a mixture of benzene and light gasoline in a ratio of 1: 4, fractions of 20 ml each are obtained. Fractions 4 and 5 contain 22 mg of a low-melting substance which is recrystallized from light petrol ^{at 0 ° C.} 14 mg (yield 6 percent) of the desired are obtained in this way.

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End product in the form of colorless crystals with a pp. From 55.5 to 56 ⁰ C.

Analysis for C 52 ^H 48 ^O 2 ^{S 'c H} Theory: 77.4 °;? $ 9.7; Found: $ 77.2; 9.85ε.

Example 2 .2,2-Dimethyl-4- (2-furyl) -7- (3-methyl-2-octyl) -2H-chromen-5-ol

2.72 g (0.04 mol) of furan in 10 ml of dry ether are im'Ver- ^; added dropwise to a stirred solution of 2.56 g (0.04 mol) of n-butyllithium in 17 ml of hexane over a period of 10 minutes under a protective layer of nitrogen at a temperature of -20 C. In this way a solution of 2-puryllithium is obtained. This solution warmed up. over the course of 20 minutes to room temperature and then heated to 35 to 40 ^° C. for 2 1/2 hours.

To this stirred solution of 2-furyllithium are employed in the course of 10 minutes at a temperature of 35 to 40 ⁰ C was added dropwise a solution of 3.18 g (0.01 mol) of the compound. 2,2-dimethyl-5 ~ hydroxy-7- (3-methyl-2-octyl) -CHR oman-4-one in 10 ml ether Mnzu and holds a further 2 1/2 hours under '■ stirring. the specified temperature. The reaction mixture is then cooled and neutralized with dilute hydrochloric acid. The organic layer is then separated and dried over magnesium sulfate. After evaporation of the solvent, the compound 2,2-dimethyl-4- (2-furyl) -7- (3-methyl-2-octyl) -chroman-4,5-diol is obtained as the crude product. Chromatographic treatment of this compound to Süicagel .and

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Elution with a mixture of benzene and light gasoline in a ratio of 1: 1 results in the elimination of water. This gives 1.32 g (yield 36 percent) of the desired end product in the form of a colorless oil which, however, darkens very quickly in the air. The degree of purity of the oil is determined to be 95.5 percent by gas-liquid chromatography. Analysis for C ₂₄ H ₅₂ O * CH

Theory: 78.2; ö

found: 78.2; 9

Example 7

2,2-Dimethyl-7- (3-methyl-2-octyl) -4- (1-methyl-2-pyrryl) -2H-chromen-5-ol

A solution of 3.24 g (0.04 mol) of 1-methylpyrrole in 10 ml of anhydrous ether is converted under a protective layer of nitrogen in the course of 10 minutes to a stirred solution of 2.56 g (0.04 mol) of n-butyllithium added in 17 ml of hexane. This solution is stirred then for 20 'hours at 40 ⁰ C. In this way, one obtains a solution of 2-lithio-l-methylpyrrole. Are then added to this stirred solution over 10 minutes at 40 ⁰ C was added dropwise a solution of 3.18 g (0.01 mol) of the compound 2,2-dimethyl-5-hydroxy-7- (3-methyl-2-octyl) -chromen-4-one in 10 ml of dry ether are added stirred for a further 6 hours at the specified temperature.

After cooling, the reaction mixture is neutralized with dilute hydrochloric acid, separate the organic layer and dry it over magnesium sulfate. By evaporating the solvent the compound 2,2-dimethyl-7- is obtained as the crude product

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(3-methyl-2-octyl-4- (1-methyl-1-2-pyrryl) chroman-4,5-diol, which is 1 hour long ernitzt in vacuo to 15O ⁰ C. The oil obtained is purified by chromatography on Purified a column of silica gel, using a mixture of benzene and light gasoline in a ratio of 1: "1 as the eluant. In this way, 1.90 g (50 percent yield) of the desired end product, whose degree of purity by gas-liquid, is obtained -Chromatography is found to be 99 percent.

Analysis for C ₂₅ H ₃₅ NO ₂ ; CHN theory: 7d, 7; 9.25; 3 found: 78.3; 9.5; 3

Example 8

2,2-Dimethyl-7- (3-methyl-2-octyl) -4- (1-methyl-5-pyrazolyl) -2H-chromen-5-ol

A solution of 3.28 g (0.04 mol) of 1-methylpyrazole in 20 ml of dry ether is converted into a stirred solution of 2.56 g (0.04 mol) over the course of 10 minutes under a blanket of nitrogen at 20 ° C. n-Butyllithium in 17 ml of hexane was added. This suspension is then kept under stirring at a temperature of 10 to 2O ⁰ C for 3 3/4 hours. In this way a solution of 5-lithio-1-methylpyrazole is obtained.

It is then added to this stirred over the course of 10 minutes Solution of the lithium compound dropwise a solution of 3.18 g (0.01 mol) of the compound 2,2-dimethyl-5-hydroxy-7- (3-methyl-2-octyl) -ehroman-4-one in 10 ml of anhydrous ether. The yellow precipitate that initially separates out dissolves gradually dissolve to form a red solution. This lo-

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solution is stirred for 17 1/2 hours at room temperature and then neutralized with dilute hydrochloric acid.

The organic layer is extracted three times with 100 ml of 5 η hydrochloric acid each time, then washed with water and dried over magnesium sulfate. Evaporation of the solvent gives 3.22 g of a brown, rubber-like substance which, when rubbed with ¹ light gasoline, 1.45. g of a yellow pest. Recrystallization from light gasoline gives 0.96 g (25 percent yield) of the compound 2,2-dimethyl-7- (3-methyl-2-octyl) -4- (1-methyl-5-pyrazolyl) -chroman-4 »5-diol with a Pp ₁ of 154 to 157 ° C.

Analysis for C ₂₄ H ₅ ^ N ₂ O ₃ : Theory: found:

4.0 g of this diol are heated ^{to 180 to 190 ° C. in vacuo for 40 minutes.} In this manner the desired end product, which has, after recrystallization from light petroleum Fp.von a 149 Ms 150 ⁰ C is obtained.

C. 0; H i; N 72, 2; 9, 3i 7, 72, 9, 7,

analysis for ^C 24 ^H 34 ^N 2 ° 2 ^; C. 35; H 0; B. Theory: 75 6; 9, i; 7, found 75 9, 7,

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Claims (7)

Claims before Substituted benzopyran derivatives of the following general menen formula and their salts R, (II) in which R- ^ is a hydrocarbon group with 1 to 6 carbon atoms, Rp © ine saturated or unsaturated alkyl group having 1 to 20 carbon atoms or a cycloalkyl-lower alkyl group with 3 to 8 carbon atoms in the cycloalkyl part and with 1 to 6 carbon atoms in the IT-lower alkyl part, R-, a aromatic 5-membered heterocyclic ring and X is a hydroxyl group or a salt, ester or ether group derived therefrom. 2. Substituted benzopyran derivatives according to claim 1, formula II, in which R _{1 is} the methyl group, R _{2 is} a straight-chain or branched aliphatic group with 5 to 17 carbon atoms, R ^ is an aromatic 5-membered heterocyclic ring and X is a hydroxyl group or a salt derived therefrom . 3. Substituted benzopyran derivatives according to claim 1, formula II, in which R- * is an optionally substituted furyl, Thienyl, thiazolyl, pyrryl, isoxazolyl, oxazolyl, imidazolyl or pyrazolyl group. 309831/12 4 8 "" ²¹ ~ 2H5319 4. Substituted benzopyran derivatives according to claim 3, formula II, .in which R * the 2- or 3-thienyl, 2-thiazolyl, 5-furyl, 5- (1-methyl) pyrazolyl, 2-pyrryl or 1-methyl-2-pyrazolyl group means. 5. Substituted benzopyran derivatives according to claim 1, formula II, in which R _{2 is} a saturated straight-chain or branched alkyl group with 7, 8 or 9 carbon atoms. 6. Substituted benzopyran derivatives according to claim 1 of the following general formula OH in which a) R ₂ the 3-methyl-2-octyl group and R, the 2-thienyl, 3-thienyl, 2-thiazolyl, 2-furyl, l-methyl-2-pyrryl or l-methyl-2- pyrazolyl group, or b) R _{2 is} the 2-octyl group and R ^ is the 2-thienyl group, or c) R _{2 is} the n-heptadecyl group and R is the 2-thienyl group. 7. Pharmaceutical preparations consisting of a compound of the general formula II according to claim 1 as an active ingredient and optionally customary pharmacologically acceptable carriers and diluents. 309831/1248