DE2537891A1 - NEW BENZOFURANES AND METHOD FOR MAKING THEM - Google Patents

Description

PATENT LAWYERS

Dlp! - lng. P. WIRTH Dr. V. SCHMIED-KOWARZIK DipL-lng. G. DANNENBERG Dr. P. WEINHOLD Dr. D. GUDEL

281134 6 FRANKFURTAM MAIN

TELEPHONE (0611J ^ _{7014 GB} ESCHENHEIMER STHASSE 39

SK / SK

BA. No. 38818 /? ^ -

Fisons Limited

Fison House, 9 _f Grosvenor Street

London WlX OAH / England

Repentance Benzofurans and "Methods of Making Them."

The present invention relates to the following chemical compounds of formula I and process for their preparation:

in which IL and Rp, which can be the same or different, each represent hydrogen or an alkyl group, in particular a lower alkyl group with 1-6 carbon atoms, such as methyl, ethyl or propyl, or R ₁ and R _? together form an alkylene chain, for example with 2-5 carbon atoms; R 1 and R 1, which can be the same or different, each stand for a lower alkyl group or R ₁ and R 1 → together with the nitrogen atom form a heterocyclic ring; the above compounds are suitable as intermediates for the preparation of herbicides. It has been proposed to convert these compounds by reacting the corresponding enamine, ie a compound of the general formula II:

609812/0968

2 b 3 7 8 9 1

- 2 -

with benzoquinone. However, the herbicidal compounds prepared from the compounds of the formula I by this process were not entirely satisfactory in that the solution of the herbicidal compounds developed precipitate on standing. It was found that these precipitates are caused by the presence of hydroquinone derived materials and that surprisingly the presence of an aldehyde of the formula R ₁ R ₂ CHO during the reaction of benzoquinone and Knamin reduced the amount of hydroquinone materials in the product. Thus, herbicidal compounds of the formula III can be prepared:

III

CXM

in which R .. and R ^ have the above meaning and in particular for methyl or ethyl; M is a lower alkyl group, preferably with 1-6 carbon atoms, such as methyl, ethyl, propyl or isopropyl, and R- for an alkyl group, preferably with 1-6 carbon atoms, such as methyl, ethyl, Propyl, those having less than 1 mole $ of hydroquinone derived impurities are contaminated.

The present invention thus provides on the one hand compounds of the formula I or IIKand herbicidally active derivatives of the compound of formula III, which thereby are characterized in that the compound has less than 1 mole # of hydroquinone contains derived impurities.

The hydroquinone-derived impurities present in an amount less than 1 mol-i are hydroquinone itself in the case of the compounds of formula I and a compound of the formula:

609812/0968

R ₅ SO ₂ -O

R ₅ SO ₂ -O

in the case of the compounds of formula III. The impurities x-earth in the Compounds of formulas I and III easily by gas / liquid chroniatography established. The impurities are preferably present in an amount below 0.5 mol- «.

Furthermore, the present invention provides a method for producing the Compounds of formula I and their derivatives, which is characterized by that one reacts benzoquinone with a compound of the formula II, the reaction being carried out in the presence of a compound of the formula R.RoCHCHO becomes, in which R., and Rn have the above meaning.

The method according to the invention is particularly suitable for the production of compounds of formula I, in which R .. and Rg for the same lower alkyl group in particular methyl or ethyl, and the group -NRoHj, for a piperidino-, Morpholino or pyrrolidino group. In this case the connection is of the formula RjRgCHCHO an aliphatic aldehyde, in particular isobutyraldehyde.

The process according to the invention is usually carried out in the presence of a liquid Medium. Liquid media suitable according to the invention include aromatic hydrocarbons, such as benzene, toluene or xylene; aliphatic hydrocarbons, such as cyclohexane or petroleum ether; halogenated hydrocarbons; and aliphatic ketones such as acetone and methyl ethyl ketone. If necessary, it can

liquid medium supplied in whole or in part by the twisting RJRpCHCHO e.g. when isobutyraldehyde is used. However, it is preferred

609812/0968

such a liquid medium used in which the compound of formula I and water are only sparingly soluble or miscible. Such. Liquid media are e.g. the aromatic hydrocarbons.

Benzoquinone and compound of the formula II are advantageously used in the form of solutions or Aufschlanmungen in one of the above liquid media, and the reaction is preferably carried out with stirring at a temperature of-60 C -io, for example 0-5O ^ ⁰ C, although lower or higher temperatures, e.g. 3. can be used up to the return temperature of the reaction mixture. V. ^r the reaction enn not untsr reflux occurs, it may be appropriate that

Reaction mixing in the final stages to support a complete Reaction e.g. to 100-120 ° C. to heat.

The amount of the compound of formula R ₁ R ₂ CHCHO present is preferably at least 10, for example 10-200, mol- £, based on the amount of the compound of formula II, and is usually between 20-100 Μοί-, ο. The presence of the compound R ₁ R ₂ CHCHO can be achieved by adding the compound separately to the reaction mixture or by using the compound as a solvent or carrier for one or both of the other reactants. However, a convenient method of incorporating the compound R ₁ R ₂ CHCHO is to use the reaction mixture in which the compound of Formula II is prepared. For example, the clogging of the formula II can be produced by reacting a compound H-NRoRj ₁₊ with an excess, for example 10-200 mol $, in particular 2C-100 mol $, of the compound R ₁ R ₂ CHCHO and the reaction product used directly in the process according to the invention without purification, although it is usually necessary to remove water therefrom, for example by distillation. The present invention therefore also provides a process for the preparation of compounds of the formula I or their derivatives, which is characterized in that a compound of the formula H-NR-R ^ with an excess of a compound of the formula R ₁ R ₂ CHCHO to form a reaction mixture is implemented, which is a

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2 b 37 8 ^C J 1

bond of the formula II and the compound R.R ^ CHCHO, whereupon this reaction mixture is reacted with benzoquinone.

Although the preparation of the compound of formula I by adding a Solution of the enamine of the formula II to a solution or slurry of the benzoquinones It has been found that the product can be obtained from this reaction may be discolored due to side reactions and that surprisingly these side reactions are suppressed when the snaniin for the most part or the entire reaction time is present in more than a stoichiometric amount, as is necessary for the reaction with the benzoquinone.

The presence of the necessary amount of enamine in the reaction mixture can e.g. by adding the benzoquinone all at once or progressively over a period of time to a reaction mixture which contains the desired amount of enarnine; or by adding benzoquinone and snamine in the desired proportions to a continuously operated process. The total used Amine excess is preferably 1-10, especially 1- ^ 4-, mol-iC, although if applicable, and during the initial stages of a batch process, when benzoquinone is progressively added to the enamine and much larger excesses occur, higher excesses are used can.

Thus, the present invention also provides a process for the preparation of compounds of the formula I or their derivatives, which is characterized in that a compound of the formula H-NRJt ^ with an excess of a compound of the formula R ₁ R ₂ CHCHO in the presence of an organic Reacts solvent to form a reaction mixture which contains a "compound of the formula II, whereupon this reaction mixture is reacted with benzoquinone, the compound of the formula II in the reaction mixture practically to each.

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2 b 3 7 8 9 1

• _ 6 -

Time is present in more than stoichiometric amount, as is necessary for the reaction with the benzoquinene present in the reaction mixture. The invention also provides a process for the preparation of a compound of the formula I or its derivatives by reacting benzoquinone with a compound of the formula II, which is characterized in that the reaction takes place in the presence of a compound of the formula R 1, R ₂ CHCHO, and that is practical at any time during the reaction the compound of the formula II is present in more than the stoichiometric amount, as is necessary for the reaction with the benzoquinone present in the reaction mixture.

The processes according to the invention can be carried out batchwise or continuously, and the product of formula I can be prepared by conventional methods, for example by filtration the reaction mixture in which it was formed to recover the solid Product and subsequent washing, are obtained. V / o the connection of the Formula I, however, is used as an intermediate in the preparation of other compounds, it need not be necessary to separate them from the reaction mixture.

The compounds of the formula I are particularly suitable for the preparation of herbicides Compounds of formula III.

The preparation is expediently carried out by reacting the compound of formula I with a compound R ^ SO ₂ Hal (where Hai stands for halogen, in particular chlorine) to convert the 5-OH group into a 5-SOoR ₁ group, and convert the 2 -NRoR ^ group into a -OM group by hydrolysis and alkoxylation. These conversions can be performed in any order.

The present invention also provides a process for the preparation of the compounds of the formula IV: R _-1

IV

609812/0968

₇ _ 2b37891

in which R. and R ₉ , which are identical or different, each represent an alkyl group, M denotes an alkyl group, and R ^ denotes _{hydrogen or a group R 1 -SO 9} -, in which R _r denotes an alkyl group ,

characterized in that one

(a) Benzoquinone with an "inanine of the formula II

in which R ^ and R _{9 have} the above meaning and R ^ and R ^, which can be the same or different, each stand for a lower alkyl group or R ^ and R ^ together with the nitrogen atom form a heterocyclic ring, in the presence of a compound of the formula RR ₉ CHCH0, the enamine being present at practically every point in time of the reaction in more than stoichiometric amounts than is necessary for the reaction with the benzoquinone, whereby a compound of the formula I is obtained:

(b) a compound of formula V

NR ₃ R ₄

with an acid defined below and a compound of the formula KOM, in which K has the above meaning, preferably converts in a single stage, whereby a compound of formula I or a derivative thereof is formed.

In step (b) of the above process, the compound of formula V (which is the same the compound of formula I or, as described below, a derivative thereof may be) by treatment with an acid and an alkanol hydro-

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lysed and alkoxylated. Stage (b) is preferably carried out in one and one = n stages using a mixture of acid and alkanol.

The acid mentioned here in relation to step (b) means a strong acid, which can be a mineral or organic acid, does not take part in harmful side reactions during step (b) of the process (except for the formation of a salt with the during the Process released amine HNR-R ^) and which dissociates in water preferably with the formation of at least 1 g equivalent H ⁺ per g- ^ lol acid. Thus, acids suitable according to the invention include hydrochloric, sulfuric and phosphoric acid, but not nitric acid, which can oxidize the reactants and / or product. The acid can be used in the form of an aqueous solution or in an anhydrous form. The mineral acid used according to the invention is preferably hydrochloric acid, which expediently provides not less than 20 parts by weight of HCl per 80 parts of water in the reaction mixture.

The connection HOM is, as indicated in the preferred connections to be established, preferably a lower alkanol, especially methanol, ethanol, propanol or isopropanol.

Step (b) is preferably carried out in a liquid medium, which can simply be an excess of the alkanol reagent. However, the process is expediently carried out by adding the solution of the compound of formula I formed in step (a) of the process to a mixture of acid and alkanol with stirring to form a two-phase reaction mixture. The addition can take place in one or more stages or continuously if the process is operated continuously. The reaction can take place at elevated temperatures, although the use of temperatures below 40 ^° C. is preferred.

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It was found that the relative proportions of acid, alkanol and compound of formula I affect the yield and quality of the product. According to the invention, more than 1.5 molar proportions of alkanol and more than 1.2 molar equivalent parts of acid per molar part of the compound of formula I are used. Although the process is practically anhydrous Conditions can take place, e.g. using ^ SO ^ as acid, water with some acids, e.g. in the presence of HGl, is preferred. In in this case, more than 0.35 parts by weight of HCl per part of water are preferably used used in the reaction mixture.

The reaction mixture is preferably stirred; refer of course all weights and ratios apply to the entire reaction mixture and not just on the organic or aqueous phase.

In addition to the reactants and solvents, the reaction mixture can contain small amounts of other non-harmful materials. The compound of the formula II does not need to be in pure form, but rather can be used as a reaction product from an earlier process stage, as explained below.

The compound of the formula V can also be obtained from the reaction mixture, by separating the mixture into an organic and aqueous phase leaves, the organic layer is removed and the product is removed therefrom, e.g. by distillation (to remove excess alkanol and optionally present solvent) wins, washes with a mild alkali, such as sodium carbonate and to remove residual amounts of solvent, preferably under reduced pressure, distilled again. The isolated product can then be cleaned in the usual dry manner.

609812/0 96 8

As shown by formula IV, the preparation according to the invention can have a 5-OH group or a derivative thereof in the 5-position. However, the 5-position is preferably in the form of an Rj-SO ₀ group. This group is preferably a CH ₀ SOoO group, which is converted into the intermediate of the formula I, preferably by reacting this compound with HaISOoRi- in the presence of an acid acceptor (where Hai stands for halogen, in particular chlorine) between steps (a) and (b ) is introduced. The group R ₁ SO ₉ O- can also be introduced by reacting a compound of the formula V, in which R / is H, with after step (b) according to the invention has been carried out.

When a compound of formula I or V is reacted with HaISO ₂ Ri-, the reaction takes place in the presence of an acid acceptor, such as, for example, a tertiary amine, in particular trialkylamine, such as trimethylamine or triethylamine; tertiary aromatic amine, e.g. dimethylaniline, and pyridine and its homologues. Although the reactants can be used in practically stoichiometric amounts, a small excess, for example up to 20 mol-jo, of the compound R ₁ -SO ₂ Hal, based on the compound of the formula I or V, and an excess of, for example 10- 50 M0I- / 6 of the acid acceptor, based on the theoretical amount of H-Hal to be released, is preferred.

The reaction can be carried out by simply mixing RJSO ₂ Hal and the compound of the formula I or V simultaneously or in succession and in one or more stages. The reaction temperature is expediently below 100 ^° C., preferably between 30-80 ° C. To support a uniform reaction, however, it is preferably carried out in an organic solvent as the reaction medium or in an excess of the acid acceptor. Suitable solvents include non-polar organic solvents such as benzene, toluene, xylene or hexane.

609812/0968

When the reaction is practically complete, as shown by analysis of a sample which has little or no residual starting compound of formula 1 or V, the product can be recovered in a conventional manner. However, where the compound bond has not been subjected to step (b) according to the invention, ie where it is a compound of the formula V, the product is preferably not isolated, but the halogen salt of the acid acceptor is simply extracted from the reaction mixture by water extraction, and the compound The organic layer containing the formula V is separated off in the manner described above for use in the preparation of the compound of the formula IV in which Rg is R ₁ —SO _{2 -.}

As can be seen, the steps of the method of the invention can be as follows can be summarized:

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Level $

, α ία ίο

Level 2

Level 3A R ₅ SOJIaI + acid acceptor

Acid + alkanol

Level 3B

^R 5 ^SO 2 °

Level kk

Acid + alkanol

step

IUSCLHaI + acid acceptor

60981 2/0368

2 b 3 7 8 9 Ί

The above process steps can be carried out as individual and separate steps, However, as stated above, they are particularly suitable for successive work, in that the reaction products from one stage are carried out directly in a later stage Level can be used. In addition, excess reactants can be used and recover solvent for reuse. So can the acid acceptor from the aqueous phase of stage 3A or ^ B by treating the Recovered halogen salt with alkali, e.g. NaOH, and subsequent distillation will; the organic phase of the reaction mixtures from stage 3B and / or 4a can be fractionally distilled to recover alkanol and solvent and the aqueous phases can be used to recover alkanol

possibly
and, / acid are distilled, the residue then with alkali

is treated to liberate the amine NHNRoRk and the acid acceptor which have been transferred to the organic phase from stage 3A in stage 4A. This residue is then fractionally distilled and provides amine for use in stage 1 and acid acceptor for use in stage 3A. or ² JB.

The following examples illustrate the present invention without it to restrict. Unless otherwise stated, all parts and percentages are given Parts by weight and wt .- ^.

Example 1

Production of the enamine

To a mixture of 332 parts of isobutyraldehyde (excess of 100 mol $) with 867.5 parts of toluene, 200.5 parts of morpholine were added with stirring. The temperature rose from 20 ° C. to M ⁰ C. The mixture was heated to reflux with constant separation and removal of the aqueous phase from the refluxing solvent stream. To complete the water removal, the final stages were carried out using a fractionation column. The total reflux time was 4.8 hours.

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Preparation of 2,3-dihydro-3,3-diraethyl-5-hyciroxy-2-morpholinobenzofuran

54 parts techn. Benzoquinone was added to 5 × 5 parts of toluene; to this slurry sufficient enamine solution prepared above was added to a 4 ^ molar excess of enamine in relation to the technical. To yield benzoquinone. The addition time was 0.7 hours and the reaction temperature during the addition was 40-4-5 ° C. After a further 0.7 hours, the reaction mixture was brought to the boiling point and refluxed for 0.25 hours. After cooling to 25 ^° C., the insoluble product was filtered off, washed with toluene and air-dried to constant weight; 2,3-dihydro-3i3-dimethyl-5-hydroxy-2-morpholino-ben aofur an was obtained in this way.

The yield of 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinobenzofuran was $ 89.3, based on the starting benzoquinone material; the purity was according to analysis 98.7 4>. The contamination of the product with hydroquinone was $ 0.2 .

Comparative example

The above steps were repeated, except that the amine solution was fractionally distilled to remove unreacted isobutyraldehyde, so that no significant amount of isobutyraldehyde was present during the reaction of enamine with benzoquinone. The formed, in this case 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinbenzofuran was obtained in a yield of 89.2 4> and having a purity of 96.1%. The hydroquinone content was 1.6 %.

Example 2

The procedure of the comparative example was repeated with isobutyraldehyde being added in an equimolar amount based on the finamine used as a separate charge to the reaction vessel in which the 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinobenzofuran was prepared became. The product was obtained in 90% yield with a purity of 97.8 % and a hydroquinone content of 0.2 %.

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2 b 3 7 8 9 1

example

To a mixture of 332 parts of isobutyraldehyde (100 mol # excess) with 867.5 parts of toluene were added to 200.5 parts of morpholine with stirring.

The temperature rose from 20 ° C. to 41 ° C. The mixture was heated to reflux with constant separation and removal of the aqueous phase from the refluxing solvent stream. To completely remove water, the final stages were done using a fractionation column. The total reflux time was 1.8 hours. A total of 238.2 parts of techn. Benzoquinone ($ 95.7 mol, based on the morpholine, assuming a € 100 conversion to enamine) was added within 1.2 hours. The temperature was kept at 35- ^ 5 ° C. during the entire addition by heating or cooling as required. When no further heat of reaction was detected, the reaction mixture was brought to the boiling point and refluxed for 0.5 hours. After cooling to 25 ° C. the insoluble product was filtered off, washed with 670 parts of toluene and air-dried to constant weight; 505.1 parts of 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinobenzofuran were obtained in a yield of 91.7 #, based on the technical grade used. Benzoquinone.
Example ^

To a slurry of 108 parts of benzoquinone in 10 ^ parts of toluene, 0.52 molar equivalents of the enamine prepared in a manner similar to the enamine solution of Example 3, dissolved in toluene and isobutyraldehyde, was added. The addition time was 0.75 hours and the reaction temperature 40-V5 ° C. The reaction mixture was stirred for 16 hours before adding an additional 0.52 molar equivalents. Enamine solution were added. After refluxing the reaction mixture and isolating the product as in Example 1, 208.3 parts of product were obtained, which corresponds to a yield of 83.6 %, based on the technical grade used. Benzoquinone.

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While the product of Example 3 is slightly yellowish. the product of this example was gray.
Example 5_

Preparation of 2,3-dihydro-3,3 "dimethyl-2-morpholino-benzofuran-5-yl methanesulfonate

112.5 parts of the product from Example 1 were slurried again in 350 parts of toluene and heated to 40 ° C. with stirring. heated. 56.5 parts of methanesulfonyl chloride and 50.5 parts of triethylamine were added separately, but at the same time, to the reaction mixture, and the mixture was kept at 40-46 ° C. for 0.35 hours. held. A further 5 parts of triethylamine and then 110 parts of water were then added first. The two-phase reaction mixture was heated to 50-55 ° C. and then allowed to separate. The lower triethylamine hydrochloride layer was removed. The upper organic layer was evaporated to dryness giving solid 2,3-dihydro-3,3-dimethyl-2-morpholinobenzofuran-5-yl-methanesulfonate.

Production of 2,3-dihydro-3,3-diniethyl-2-ethoxyben2ofuran-5-ylmethanesulfonate

24.9 parts of the product from the above step were suspended in 50 parts of water and 22.4 parts of anhydrous hydrochloric acid. The suspension was heated quickly to 90-100 ° C. and then cooled after 2 minutes. The crude product was extracted 3 times into 60 parts of ether each time and the extracts were washed 2 times with 50 parts of water each time. The egg acts were dried with sodium sulfate and evaporated to a gum which crystallized and gave 2,3-dihydro-3,3-dinßthyl-2-hydroxy-benzofuran-5-yl-methanesulfonate crystals. The crystals were dissolved in ethanol containing 2 drops of sulfuric acid and refluxed for 1 hour. The mixture was then cooled, neutralized with triethylamine and evaporated to about a quarter of its volume. Water was added to precipitate 2,3-dihydro-3,3-dimethyl-2-ethoxylaenzof uran-5-yl-methanesulfonate. This product contained 0.4 % dimesylquinol as an impurity compared to $ 2 in a product that

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was derived from the material of the comparative example. Example 6

(a) Preparation of the enamine and its conversion into a compound of formula I.

To a mixture of 332 parts of isobutyraldehyde (100 molar excess) with 86.5 parts of toluene, 200.5 parts of morpholine were added with stirring. The temperature rose from 20 ^° C. to ¹ H ^° C. The mixture was heated to reflux with constant separation and removal of the aqueous phase from the returning solvent stream. To completely remove water, the last stages were carried out by means of a fractionation column. The total reflux time was 4-8 hours.

For the enamine solution thus obtained, a total of 238.2 parts of technical. Benzoquinone added within 1.2 hours. The temperature was increased as needed Maintained heating or cooling at 35- ^ 5 C. As no more heat of reaction was found, the reaction mixture was brought to the boiling point and Refluxed for 0.5 hours. After cooling to 25 ° C. it became insoluble Product filtered off, washed with 670 parts of toluene and brought to a constant Weight air dried; 505.1 g of 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholino-benzofuran® were obtained in this way Yield 91.7 # »based on that used techn. Benzoquinone.

(b) Preparation of the compound of Formula V and its conversion into one Compound of formula IV

Preparation of 2,3-dihydro-3,3-dimethyl-2-morpholino-benzofuran-5-yl-methanesulfonate (Level 3A)

505.1 parts of the product from step (a) were slurried again in 1083 parts of toluene and ^{heated to 2} K) ⁰ ° C. with stirring. At the same time, but separately, 258 parts of methanesulfonyl chloride and 228 parts of triethylamine were added and the reaction mixture was kept at kO-k6 ° C. for 0.35 hours. held. Then were

afterward
a further 23 parts of triethylamine and 585 parts of water were added. The two-

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- 18 -

phase reaction mixture was heated to 50-55 ° C. and then allowed to separate. The lower triethylamine hydrochloride layer was removed and the upper organic layer passed to step kA .

Production of 2,3-dihydro-3,3-dimethyl-2-ethoxybenzofuran-5-yl-methanesulfonate (stage kA)

To the solution from stage 3A were 350 parts of ethyl alcohol, 4-3 parts of water and Parts of 30% w / w hydrochloric acid were added. The temperature rose to 4-7 G. The two-phase reaction mixture was cooled to 20 ° C. for 16 hours. stirred, and after settling, the lower aqueous layer was removed.

The upper solvent layer was distilled to remove most of the unreacted ethyl alcohol and washed with sodium carbonate solution to remove traces of hydrochloric acid. The solution was then distilled to remove residual toluene and gave 564 parts of product in a yield of $ 87.5, based on the technical grade used in stage (a). Benzoquinone.
Example 7 \

Alternative method for carrying out step (b) in Example 6 Preparation of 2 _l , 3-dihydro-3,3-dimethyl-5-hydroxy-2-ethoxybenzofuran (step 3B)

97 parts of 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinobenzofuran (prepared as in step (a) of Example 6) were allowed to air-dry after filtration and added to 513 parts of ethyl alcohol and 32.5 parts of water added. For this purpose 72 parts of conc. Sulfuric acid was added and the mixture was refluxed for k hours.

The reaction mixture was cooled and poured into 3200 parts of ice water; so an oil was obtained which solidified after inoculation with the previously prepared product. This product was filtered off and air dried; yield

57.7 parts, purity according to glc 95 ^r k which corresponds to a molar yield of 67.5 %

609812/0968

corresponded. Its continuous ether extraction of the filtrate showed that a further 5 % of product had remained in solution.

Step 4b - Preparation of 2,3-dihydro-3,3-di5iethyl-2-ethoatybenzofuran-5-yl-methane sulf onate

8.32 parts of the product from stage 3B were dissolved in 20 parts of toluene and 6 parts of triethylamine. For this purpose, 6.3 parts of methanesulfonyl chloride was added within 0.2 hours with the temperature to ^ '- 0-45 ⁰ C. was maintained. With stirring, 15 parts of v / ater were added and after the lower layer had been separated off and evaporated to dryness, 11.7 parts of product were obtained with a purity according to glc of 91 $, which corresponds to a molar yield of 98 <p .

In the present application, the term "alkyl group" preferably means a lower alkyl group, i.e. one with 1-6, especially 1-4, carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc. The same applies to the term "alkoxy group". "Halogen" stands for chlorine, Bromine, iodine or fluorine, preferably chlorine, and "alkylene group" especially for ethylene, propylene, butylene and pentylene.

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Claims (1)

2 b 3 7 8 9 1 Patent pending 1.- Process for the preparation of compounds of the formula I: HO. NR ₃ R ₄ in which _{R.- and R 9} , which can be identical or different, each represent hydrogen or an alkyl group, preferably a lower alkyl group; or R. and R ₂ together form an alkylene chain; R- and R ^, which can be the same or different, each stand for a lower alkyl group or together with the nitrogen atom they form a heterocyclic ring, preferably a morpholino, piperidino or pyrrolidino group, or their derivatives, characterized in that benzoquinone with a compound of the formula II: R ₁ R ₂ C = CH-NR ₃ R ^ II ^; in which R. to R ^ have the above meaning, in the presence of a compound of the formula R.RpCHCHO, preferably isobutyraldehyde, in which R. and R «have the above meaning, the compound R ₁ R ₉ CHCHO preferably in a Amount of at least 10, preferably 10-200, mol $, based on the compound of the formula II, is present. 2. - Process according to claim 1, characterized in that a compound of the formula II is used which is obtained by reacting a compound of the formula NHRJIl. with an excess of the compound R ₁ R ₂ CHCHO to form a reaction mixture which contains the compounds of the formula II and R ₁ R ₂ CHCHO, whereupon this reaction mixture is reacted with benzoquinone, preferably after prior removal of the water . 3.- The method according to claim 1 and 2, characterized in that in the reaction between benzoquinone and the compound of the formula II, the latter is present practically at any point in time in more than a stoichiometric amount, as it is 609812/0968 . ₂₁ _ 2b 3 7 8 91 required for reaction with the benzoquinone present in the reaction mixture is. k.- Process for the preparation of a compound of the formula I or a derivative thereof, characterized in that a compound of the formula H-NR-R ₂ , with an excess of a compound of the formula R ^ RgCHCHO in the presence of an organic solvent to form a reacting a compound of the formula II containing reaction mixture and this reaction mixture reacts with benzoquinone, wherein the compound of the formula II is present in the reaction mixture practically at any time in more than stoichiometric amount over the reaction with the benzoquinone present in the reaction mixture and preferably the water is removed from the reaction mixture containing the compound of formula II before it is reacted with benzoquinone. 5. - Process according to claim 2 or k, characterized in that the compound of formula II is used in a total excess of 1-10 mol $. 6.- Process for the preparation of a compound of the formula: III: R, Rt-SO ₉ O in which R. and Rg, which can be identical or different, each represent H or an alkyl group, or R. and R2 together form an alkylene chain; M stands for an alkyl group with 1-6 carbon atoms and R, - stands for an alkyl group, characterized in that the compound of the formula I or a derivative thereof, prepared by a process according to claims 1 to 5 »with a compound of the formula RJBO ₂ Hal implemented and the -NR "R ^ group is hydrolyzed and alkoxylated, the hydrolysis and alkoxylation preferably being carried out before the reaction with the compound R ₄ -SO ₉ Hal. 609812/0968 7.- Process for the preparation of a compound of the formula IV: IV in which IL and Rg, which can be the same or different, each represent H or an alkyl group, or R. and Ro together form an alkylene chain; M is an alkyl group and R ^ is hydrogen or a group RJSO ₅ -, where R ^ is an alkyl group, characterized in that one
(a) Benzoquinone with an enamine of formula II: in which R- and R ^ have the above meaning and R "and R ₂ ,, which can be the same or different, each stand for a lower alkyl group or R ^ and R ^, together with the nitrogen atom, form a heterocyclic ring, in the presence a compound of the formula R ₁ R ₂ CHCHO, the snarain preferably being present at practically every point in time during the reaction in more than the stoichiometric amount required for the reaction with the benzoquinone, whereby a compound of the formula I is obtained: (b) a compound of Forms IV:
R ₆ O- NR ₃ R ₄ rait an acid and a compound of the formula HCM, in which M the above Has meaning, preferably in a mixture with one another, resulting in a compound of the formula IV or a derivative thereof. 8.- The method according to claim 7, characterized in that the compound of the formula IV, preferably in the presence of an acid acceptor, with a compound of the formula RJElO ₉ Hal to a compound of the formula: is implemented. 9 - Process for the preparation of a compound of the formula: CILSO ₀ O C (CH ₃ ) or a derivative thereof, characterized in that p-benzoquinone with a total molar excess of 1-Λ '$> of an enamine (CH _O ) _O C = CN 0 in the presence of 10-200 mol ^ isobutyraldehyde, based on the 3namin, in an aromatic hydrocarbon medium converts the reaction product with CH0SO2CI in the presence of an acid acceptor and the product off this reaction with a mixture of ethyl alcohol and a mineral acid from the group of sulfuric, hydrochloric and phosphoric acid. 10. Compounds of formula 6098 12/0968 - Zk - and their derivatives, in which R and IL ,, which can be the same or different, each represent H or an alkyl group, preferably a lower alkyl group, or IL and R ^ together form an alkylene chain; R ^ _{0 represents} a group OM or NRoRk; R ... is a group R ₁ -S (^ or hydrogen;! M represents a lower alkyl group having 1-6 carbon atoms, preferably a methyl, ethyl or propyl group, group} Ro and _R1 ^ are the same or can be different, each stand for a lower alkyl group or together with the nitrogen atom form a heterocyclic ring, preferably a morphdino, piperidino or pyrrolidino group, and R ₁ denotes an alkyl group, preferably a lower alkyl group, the compounds and their derivatives are contaminated with less than 1 mole percent hydroquinone-based impurities. 11. 2,3-Dihydro-3t3- <iimethyl-2-ethoxy-benzofuran-5-yl-methanesulfonate, which with less than 1 mole of dimesylquinol is contaminated. The patent attorney: 6098 12/0968