DE1543573C - Process for the preparation of 2,3 dihydro 2,2 dimethyl 7 benzofuranol - Google Patents

Description

¹ 2

The invention relates to a process for the preparation of decomposed diazo oxide formation. Now that the

of 2,3-dihydro-2,2-dimethyl-7-benzofuranol. penultimate stage of the process according to the invention

. In Belgian patent specification 649 260, a diazonium salt formed is also an o-diazonium

Process for the preparation of 2,3-dihydro-2,2-dime- ether, it was to be expected that this too

thyl-7-benzofuranol described, in which one would split these 5 accordingly. So it couldn't

Compound, starting from pyrocatechol mono- can easily be foreseen that such

methallyl ether, by rearrangement and cyclization cleavage does not occur here and during hydrolysis that

obtained, or you can also from a corresponding corresponding 7-benzofuranol in good yield

o-halophenyl ether and hydrolysis of the cyclized will hold. "

7-Halogenbenzofurans.das 2,3-Dihydro-2,2-dimethyl- io The first stage of the process is by heating

7-benzof uranol obtained. . o-nitrophenol with a methallyl halide in counter-

Since the necessary production of the starting material is carried out using an acid acceptor. As an acid

rials, namely the corresponding etherification of the acceptors are z. B. Alkalimethallyldroxyde

Catechol, which is difficult, is the well-known carbonate and carbonate. Methallyl chloride is used as a reaction

drive uneconomically and there is an overall 15 component preferred for economic reasons,

Yield of only 21.7% · It can under atmospheric pressure at the boiling point

There has now been a process for the preparation of the mixture, usually at 60 to 125 ⁰ C, or at

2,3-Dihydro-2,2-dimethyl-7-benzofuranol found, pressures above atmospheric pressure and temperature

that the disadvantages of the known processes are not worked up to temperatures of up to 150 ° C or above,

has and gives significantly higher yields. 20 Furthermore, organic solvents such as metha-

The inventive method for the preparation of nol, dioxane and dimethylformamide, acetone or

of 2,3-dihydro-2,2-dimethyl-7-benzofuranol is used as methyl ethyl ketone or the Um- r

characterized in that settlement can be carried out in an aqueous medium.

a) o-nitrophenol with a methallyl halide in. The rearrangement of the l-methallyloxy-2-nitrobenzene is implemented in a manner known per se, ^ ™ ' ^d ™ S-nitro-o-methallylphenol takes place at 150 bis

b) the l-methallyloxy-2-nitrobene formed according to a) ²⁰ ° ^{C and} preferably at 175 to 190 ° C C into the isomeric 2-nitro- atmospheric pressure or under reduced pressure

6-methallylphenol rearranged, then g ^ ^{1 we} _u ^rd . ^en · Preferably without a solution

c) the above isomers in known manner worked in 3 ° ^m i ^tte although high-boiling-Losungs presence of an acid catalyst to 2,3-di ^{mi "eI 'w} o-dichlorobenzene can if hydro-2 are used, 2-dimethyl-nitrobenzofuran 7-cyclized, P * cyclization yon 2-nitro-6-methallylphenol or b stages) and c) in an ^becomes} \ ψ ^^ ^e _'u ^{n it s} _u ^acids catalyst, such as operation then carries out pyndine hydrochloride, phosphoric acid, formic acid,

d) the 2,3-dihydro-2,2-dimethyl-7-nitro-iron (III) chloride and magnesium chloride obtained, passed through benzofuran in a manner known per se, preferred ^f ^ ^Tt : ^ ¹ ^ catalysts cause the cyclization Reduced with hydrogen in the presence of a hydrogen at a temperature of about 100 to 200 C and pre-, drier catalyst, to 7-amino-2,3-dihydro- preferably at 150 to 19O ⁰ C Preferred catalysts 2,2-dimethylbenzofuran, are iron (II) chloride and magnesium chloride

e) the 7-amino-2,3-dihydro-2,2-dimethylbenzofuran * ° ^The ^ ¹¹ ™ ^ can be converted into a 7-diazonium by adding the 2,3- dihydro-2,2-dimethylbenzofuran salt converts cyclization catalyst during the rearrangement

j reaction will be carried out. / ■

f) the diazonium salt obtained according to e) at elevated ₊ Reduction of 2,3-dihydro-2! 2-dimethyl-7-ni ^ temperature with stirring in water in the counter "trobenzofuran to 7-amino-3- 2 dihydro-2,2-dimethyl · waiting a non-volatile mineral acid or hydrolyzed by ^ ^{ηζο ί υ} / ^ka ™ ^{"n by} hydrogenation in the presence of copper sulphate as catalyst, where ^e i ^{nes u} _D ^{bl 'chen} Hydnerungskatalysators, preferably

the formed 2,3-dihydro-2,2-dimethyl-7-benzo- ^a palladium-on-carbon catalyst, at space

furanol is removed from the reaction mixture. temperature or slightly elevated temperatures and

.50 under atmospheric pressure or increased pressure

The method according to the invention has been carried out over the. The reduction can also be on

known method has the advantage that it is in a simple chemical way, ζ. -Β. by means of a diluted

and technically useful manner from o-nitrophenol, acid such as aqueous hydrochloric acid, and a metal such as

a technically easily accessible material, the metallic iron or tin.

2,3-Dihydro-2,2-dimethyl-7-benzofuranol to a considerable extent. The diazotization is also carried out in the usual manner

lent gives higher yields. So the total is carried out. This reaction can easily be found in

yield according to the example of the temperature according to the invention or below instead. Preferably the

Process 36.4% compared to a yield of reaction mixture cooled below room temperature,

21.7% with the known method. This is equivalent to reducing side reactions. At temperatures

an increase in yield of 67% ^6o above about 40 ° C results in undesirable decomposition

Furthermore, the course of the reaction takes place in the last transfer of the product.

driving stage is surprising in that it is, for example, the conversion of the diazonium salt into the 2,3-di-

wise from the work of M. L. Crossley and hydro-2,2-dimethyl-7-benzofuranol is increased at

Staff in the Journal of the American Chemical Temperatures in the Presence of Water or a

Society, Vol. 69 (1947), p. 1160, it was known that o-di- 65 aqueous mineral acid carried out,

azonium ether, e.g. B. o-Methoxybenzoldiazoniumchlo- To accelerate the reaction and improve

rid, in the presence of water, replacing the conversion can be a catalyst, e.g. B.

Methoxy group through a hydroxy group and under a non-volatile mineral acid such as phosphoric and

Sulfuric acid or copper (II) sulfate can be used. Copper (II) sulfate is preferably used as the catalyst. The quick removal of the product from the reaction mixture is desirable. This can be done by continuous steam distillation or can be achieved by continuous solvent extraction of the reaction mixture.

The process according to the invention is illustrated by the following examples. '

For example

600 ecm of water and 60 g (2 mol) of sodium hydroxide pellets were placed in a 2 liter reaction vessel which was provided with a heater, paddle stirrer, feed line for flushing nitrogen, reflux condenser, thermometer and dropping funnel. 278 g (2 mol) of o-nitrophenol were added to the warm solution. The mixture was heated until solution occurred at a temperature of 70 ° C. To the solution was added 236 g (2 mol) of methallyl chloride over a period of 20 minutes with gentle stirring and moderate reflux. The heat was controlled so that the reaction temperature rose as slowly as the etherification proceeded. After 5 hours, a temperature of 88 to 90 ° C was reached, and the mixture was then cooled to 3O ⁰ C, it first with pentane and then with a mixture of 25% benzene in pentane, and finally with a mixture of 50% benzene in Pentane extracted. The organic phases were combined and concentrated to give 356 g of a crude product remained which g in the distillation 320 l-methallyloxy-2-nitrobenzene, bp. 86 _Oil returned to 107 ⁰ C. The yield was 83% of theory.

193 g (1 mol) of the l-methallyloxy-2-nitrobenzene prepared above and 2 g of anhydrous magnesium chloride were placed in a reaction vessel, and the mixture was ^{heated to a temperature of 180 °} C. over the course of 30 minutes in a nitrogen atmosphere with stirring. This was taken as the starting point for determining the proportion of rearrangement and cyclization product. Samples of the reaction mass were then taken at intervals and subjected to gas chromatographic analysis. The course of the reaction can be seen from the table below.

time temperature ether phenol
connection Benzofuran
connection hours ⁰ C Mole percent 16 0 181 " 100 ___ 40 1 183 to 187 60 24 59.5 2 178 to 184 44 16 94 3 185 33 7.5 94 6th 180 to 185 > 5 <1 7th 185 > 5 <1

After 7 hours the reaction mixture was cooled and the mass solidified. Vacuum distillation of the reaction mixture yielded 135 g (0.695 mol) of 2,3 - dihydro - 2,2 - dimethyl - 7 - nitrobenzofuran from Kp _-015,109 to 120 ^0C per mole of the crude starting material (yield = 69.5% of theory) . A portion of this product was recrystallized once from methanol. The compound had a melting point of 65 to 67 ^° C.

25 g (0.13 mol) of the above recrystallized 2,3-dihydro-2,2-dimethyl-7 ^: nitrobenzofurans, 230 ecm of absolute ethanol and 250 mg of a 5% palladium-on- Coal catalyst given. The flask was purged of atmospheric gases and pressurized to 3.52 kg / cm ² with hydrogen. The whole was then continued for 1 hour while maintaining the hydrogen pressure at a temperature of 25 to

ίο 45 ⁰ C stirred. The decrease in pressure caused by the uptake of hydrogen was 2.46 kg / cm ² . Subsequent distillation of the reaction mixture gave 20.1 g (95% yield) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran with a boiling point of _0> 160 ° C., nl ³ = 1.5590.

In a 100 cc beaker containing 25 ecm of water and 3 g of concentrated sulfuric acid, 5 g (0.030 mol) of the 7-amino-2,3-dihydro-2,2-dimethylbenzofuran obtained above were added at room temperature. The solution was cooled to 1O ⁰ C and added 1.5 g of concentrated sulfuric acid with stirring. Then a cold solution of 2.2 g (0.032 mol) of sodium nitrite in 10 ecm of water was added within a few minutes. cooled to ⁰ C 2 amine sulfate solution with stirring. The maximum temperature reached in the course of the reaction was 12 ° C. After all of the sodium nitrite solution had been added, the test with potassium iodide starch paper indicated the presence of nitrous acid. The solution is now allowed to warm to 2O ⁰ C, after which the test was still positive on nitrous acid. The subsequent addition of 0.1 g of urea to the solution gave a negative nitrous acid test.

The 50 ecm of the yellow-brown solution of the diazonium sulfate prepared above were now added dropwise placed in a 250 cc reaction vessel containing 125 cc of a boiling, stirred, saturated copper sulfate solution , through which superheated steam was passed in an amount of about 600 g per hour.

It took 35 minutes to add all of the diazonium sulfate. Then the steam distillate was extracted with benzene. The benzene extract was concentrated in vacuo, 3.5 g (70% of the amine used) of a thin brown liquid of «? _i5 = 1.5385, which consisted of 95% 2,3-dihydro-2,2-dimethyl-7-benzofuranol, was obtained.

The total yield of 2,3-dihydro-2,2-dimethyl-7-benzofuranol was 36.4%, based on the o-nitrophenol used.

Example2

Modified stage f)

40 g of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran (purity 97.7%), obtained as indicated in Example 1, were stirred in dilute sulfur

'acid (37.5 g concentrated sulfuric acid in 200 g water) and used to prepare the diazonium sulfate solution. The solution was cooled and kept at a temperature below 8 ^° C., during which a solution of 17.4 g of sodium nitrite in 60 g of water was added with stirring over the course of about 15 minutes. The temperature of the solution was then ^{increased to 20 °} C. in the course of 40 minutes and the solution was stirred at this temperature for 2 hours. In a 3-liter three-necked flask equipped with a stirrer, a reflux condenser and a device for taking up the distillate, the lighter organic phase in the reaction

To allow the mixture to flow back and separate the water, a mixture of concentrated sulfuric acid (415 g), sodium sulfate (344 g), water (300 g) and pseudocumene (300 g) was heated to reflux. Added to the refluxing acid mixture over a period of about 1 hour wurde'die Diazoniumsulfatlösung slowly, the temperature of which was kept by continuous azeotropic removal of water to 120 ⁰ C.

After a further hour at reflux, the hydrolysis was complete and the 2,3-dihydro-2,2-dimethyl-7-benzofuranol was complete was extracted with pseudocumene. The overall yield in the 2-step reaction was 35 g (88% based on the amine added).

Claims (1)

Claim:. Process for the preparation of 2,3-dihydro-2,2-dimethyl-7-benzofuranol, characterized in that one a) converts o-nitrophenol with a methallyl halide in a manner known per se, b) after a) formed L-methallyloxy-2-nitrobenzene in a known manner at a temperature of 150 to 200 ⁰ C in the isomeric 2-nitro-6-methaIlylphenol rearranges, then c) the above isomer in a known manner in the presence of an acidic catalyst 2,3-Dihydro-2,2-dimethyl-7-nitrobenzof uran cyclized or that steps b) and c) in carries out one operation, then d) the 2,3-dihydro-2,2-dimethyl-7-nitrobenzofuran obtained in a manner known per se, preferably with hydrogen in the presence of a hydrogenation catalyst, to give 7-amino-2,3-dihydro-2,2-dimethylbenzofuran reduced, e) the 7-amino-2,3-dihydro-2,2-dimethylbenzofuran in a known manner in a 7-diazonium-2,3-dihydro-2,2-dimethylbenzofuran salt transferred and f) the diazonium salt obtained according to e) at elevated temperature with stirring in water in the presence of a non-volatile mineral acid or copper sulfate as a catalyst hydrolyzed, the 2,3-dihydro-2,2-dimethyl-7-benzofuranol formed is removed from the reaction mixture.