NO145693B - 2-PHENYL-INDOL DERIVATIVES AS STABILIZERS FOR POLYMERS AND COPOLYMERS OF VINYL CHLORIDE. - Google Patents

Description

The present invention relates to 2-phenyl-indole derivatives with the general formula:

where R 1 and R 2 , which are the same or different, each means a branched or linear alkyl group containing from 1 to 12 carbon atoms, a cyclohexyl radical, a branched or linear alkyloxy group containing from 1 to 12 carbon atoms, a benzyloxy radical, a hydroxy radical or and R 2 means together an alkylenedioxy radical containing from 1 to 3 carbon atoms, and R, means a hydrogen atom or a methyl or methoxy radical, with the proviso that at least one of the substituents R 1 or R 2 does not mean an alkyl radical.

The compounds of formula I can be prepared according to Fischer's indole synthesis by reacting a substituted acetophenone derivative of the formula: wherein R1, R2 and R3 have the same meanings as in formula I, with phenylhydrazine to form a substituted acetophenone-phenylhydrazone with the formula:

where R1#R2 and R3 have the same meanings as in formula I, and ring-closing the compounds of formula III either with a dehydrating agent, such as for example sulfuric acid, polyphosphoric acid or zinc chloride, or by thermolysis to form the desired 2-phenyl -indole derivative of formula I.

The compounds of formula I can alternatively be prepared

in accordance with Bischler's indole synthesis, by reacting a substituted acetophenone derivative of the formula:

where R^, R2 and R^ have the same meanings as in formula I and X means, a halogen atom, preferably bromine or chlorine, with aniline to form the desired 2-phenyl-indole derivative of formula I.

The compounds of formula I, where at least one of the substituents R^, R-, and R^ means a branched or linear alkyloxy group containing from 1 to 12 carbon atoms, can alternatively be prepared by reacting the corresponding hydroxylated 2-phenyl-indole derivative, where said hydroxylated derivative has been prepared by one of the two general methods described above, with a branched or linear alkyl halide containing from 1 to 12 carbon atoms, in the presence of sodium methylate and optionally N,N-dimethylformamide.

The compounds of formula I, where at least one of the substituents R-1 and R2 means a hydroxy radical, can alternatively be prepared by demethylating a corresponding methoxy-substituted 2-phenyl-indole derivative, where said derivative has been prepared by one of the two general methods described above, using aluminum chloride or pyridine hydrochloride, optionally in the presence of benzene.

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The compounds of formula II are already known or can be prepared by known methods.

The compounds of formula IV are either known or they can be prepared by reacting a suitable compound of formula II with a halogen, preferably bromine or chlorine.

It has been found that the 2-phenyl-indole derivatives according to the invention are good stabilizers for polymers and copolymers of vinyl chloride, such as for example polyvinyl chloride, polyvinyl chloride - polyvinyl acetate and polyvinyl chloride - polyvinylidene chloride.

They have been found to be particularly valuable as stabilizers for polymers and copolymers intended to be molded by extrusion molding, blow molding and calendering, mainly, but not exclusively, for the purpose of making food and beverage containers, such as bottles for wine, oil, vinegar and mineral water.

The compounds according to the invention listed below are new and must be protected as such: 2-(2',4<1->dihydroxy-phenyl)-indole (stabilizer 1) 2-(3'- methoxy-4'-hydroxy-phenyl)-indole (stabilizer 2) 2-(3',5'-dimethoxy-phenyl)-indole (stabilizer 3) 2-(2'-hydroxy-4'-methoxy-phenyl)- indole (stabilizer 4) 2-(2'-hydroxy-4'-methyl-phenyl)-indole (stabilizer 5) 2-(2'-methyl-4'-hydroxy-phenyl)-indole (stabilizer 6) 2-( 2'-methoxy-4'-methyl-phenyl)-indole (stabilizer 7) 2-(3'-methyl-4'-methoxy-phenyl)-indole (stabilizer 8) 2-(2',4'-dimethoxy- phenyl)-indole (stabilizer 9) 2-(2'-methyl-4'-methoxy-phenyl)-indole (stabilizer 10) 2-(2'-methoxy-5'-methyl-phenyl)-indole (stabilizer 11) 2-(3'-methyl-4'-hydroxy-phenyl)-indole (stabilizer 12) 2-(3'-hydroxy-4'-methoxy-phenyl)-indole (stabilizer 13) 2-(3'-dodecyl- 4'-methoxy-phenyl)-indole (stabilizer 14) 2-(3'-isopropyl-4'-methoxy-phenyl)-indole (stabilizer 15) 2-(3'-cyclohexyl-4'-methoxy-phenyl)- indole (stabilizer 16) 2-(3',5'-dim ethyl-4'-methoxy-phenyl)-indole (stabilizer 17) 2-(3',5'-dimethyl-4'-ethoxy-phenyl)-indole (stabilizer 18) 2-(3'-dodecyl-4'- hydroxy-phenyl)-indole (stabilizer 19) 2-(3'-isopropyl-4'-hydroxy-phenyl)-indole (stabilizer 20) 2-(3'-cyclohexyl-4'-hydroxy-phenyl)-indole (stabilizer 21) 2-(3',5'-dimethyl-4'-hydroxy-phenyl)-indole (stabilizer 22) 2-(3'-methoxy-4'-ethoxy-phenyl)-indole (stabilizer 23) 2-(3' -methoxy-4'-dodecyloxy-phenyl)-indole (stabilizer 24) 2-(3'-methoxy-4'-butyloxy-phenyl)-indole (stabilizer 25) 2-(3'-methoxy-4'-propyloxy- phenyl)-indole (stabilizer 26) 2-(3'-methoxy-4'-isopropyloxy-phenyl)-indole (stabilizer 27) 2-(3',4'-diethoxy-phenyl)-indole (stabilizer 28) 2- (3'-Benzyloxy-4'-methoxy-phenyl)-indole (stabilizer 29) 2-(3'-methyl-4'-dodecyloxy-phenyl)-indole ('stabilizer 30) 2-(3'-methoxy-4 '-benzyloxy-phenyl)-indole (stabilizer 31) 2-(3'-methyl-4'-benzyloxy-phenyl)-indole (stabilizer 32) 2-(3',4'-methylenedioxy-phenyl)-indole (stabilizer 33) 2-(3',4'-ethylenedioxy-phenyl)-indole (stabilizer 34) 2-(3'-methyl-4'-ethoxy-phenyl)-indole (stabilizer 35)

In contrast, the compounds listed below are already known, but are being considered as new stabilizers for polymers and copolymers of vinyl chloride: 2-(3',4'-dimethoxy-phenyl)-indole (stabilizer 36) 2-(3 ',4',5'-trimethoxy-phenyl)-indole (stabilizer 37) 2-(2'-hydroxy-5'-methyl-phenyl)-indole (stabilizer 38) 2-(3',4'-dihydroxyphenyl) indole (stabilizer 39) . It is known that vinyl resins deteriorate under the influence of heat, and it is necessary to add a stabilizer to these masses of synthetic materials in order to prevent the thermal degradation and thus postpone the coloring of the resin.

Among the organic stabilizers until now, 2-phenyl-indole is one of the most valuable because of its good stabilizing power and its low toxicity. It is also widely used in the plastics industry to stabilize vinyl polymers and copolymers, especially those that are to be used for the production of containers for food and drink.

But although good stabilizing power is necessary, it is not the only property required for a good stabilizer. The following properties are also of great importance:

- thermostability in the stabilized resin

- bonding of the stabilized resin

- behavior during extrusion of the stabilized resin

- behavior when blowing the stabilized resin

- sublimation of the stabilizer

- thermostability of the stabilizer itself.

And finally, in the case of food and beverage containers, the ability of the food and beverage present in the container to extract the stabilizer must be carefully considered.

With regard to one or more of the above properties, the stabilizers according to the invention have been found to be better than 2-phenyl-indole, while the preferred stabilizer, namely 2-(3<1->methoxy-4'-hydroxy-phenyl )-indole, has been shown to be better than 2-phenyl-indole from every point of view.

The toxicity of the stabilizers according to the invention was first investigated, and the satisfactory results obtained were such that it justified continuing with the research.

A. Acute toxicity

Acute toxicity study (LDC^) for stabilisa-DU

The tests listed below were performed by determining the dose of compound which caused the death of 50% of the treated animals.

A gummy suspension of the compound under investigation was administered orally to groups of at least 10 mice, and the following results were obtained:

The maximum non-lethal dose (LDq) was also determined for the stabilizers listed below, using the same method.

The following results were obtained:

B. Thermostability in stabilized resin

The stabilizing power of the compounds according to the invention was investigated from two points of view:

a) Static thermostability

b) Dynamic thermostability

These investigations were carried out with five different

compositions of vinyl resins (hereinafter referred to as mixtures).

Mixture A

Mixture B

Mixture C

Mixture D

Mixture E.

The following ingredients are defined below:

SL 2016: solution of zinc 2-ethyl hexanoate in a mixture of hydro- carbons that boil between 158 and 184°C.

Chelating agent 1832: 67 parts by weight diphenyldecyl phosphite and 33

parts by weight of a solution of 10% zinc octoate in diisobutyl phthalate.

a) Static thermostability

The different mixtures were mixed together and calendered in a mixer in which the cylinders were heated to 160°C.

The rigid sheets thus obtained were then heated in an oven to a temperature between 180 and 215°C until carbonization begins.

An oven with rotating drums, ventilated and equipped with a thermostat, was used for this. In the experiments described below, the behavior of a sheet containing the stabilizer to be investigated is tested in comparison with a sheet of the same composition but containing 2-phenyl-indole as stabilizer.

The comparison may be made by one of two methods, namely: 1) The coloring of the sheets sampled from the furnace at fixed intervals was compared with a standard scale of coloring known as the GARDNER scale, and the coloring was expressed by using reference numbers on the GARDNER scale.

Comparisons were made with a GARDNER scale comparator which contains 18 colored glass filters and which allows for observation through transparency and in a limited field of view, both the sheet and the reference filters.

It may happen that the color of the sheets is so far from the color of the GARDNER scale that the comparison is difficult, if not impossible.

The following results were obtained:

• 2-(3'-Methoxy-4'-hydroxy-phenyl)-indole

Mixture B was used, and the resulting sheets exhibited the following properties:

The superiority of stabilizer 2 over 2-phenyl-indole is clearly apparent after 21 minutes, since after this period of time the comparison sheet is completely burned while the test sheet has a color formation of only 11° GARDNER.

2-(3'-Methoxy-4'-hydroxy-phenyl)-indole Mixture A was used.

Also with compound A, stabilizer 2 was found to be better than 2-phenyl-indole.

2-(3'-methoxy-4'-benzyloxy-phenyl)-indole Mixture A was used.

2) It is also possible to use a simplified method which is faster and by which durable results are also obtained: A reference scale is set up for sheets of thermally treated polyvinyl chloride, for which the color formations have been precisely determined by GARDNER gradings which above.

A GARDNER sub-scale is thus obtained on polyvinyl chloride sheets, which can be compared directly with the sheets to be tested, without the use of the comparator.

The following results were obtained with the aforementioned simplified method: 2-(3'-methoxy-4'-hydroxy-phenyl)-indole Mixture C was used.

Temperature: 210°C

The color formations were quite far from the GARDNER scale and the color intensity was therefore difficult to assess. But here too it can be seen that stabilizer 2 is a better stabilizer than 2-phenyl-indole.

2-(3'-Methoxy-4'-hydroxy-phenyl)-indole Mixture D was used.

Temperature: 185°C

It is clear that stabilizer 2 in this case is clearly better than 2-phenyl-indole at 0, 10 and 20 minutes, primarily with regard to the color imparted to the copolymer.

2-(3',5'-dimethoxy-phenyl)-indole

Mixture A was used.

Temperature: 210°C

As early as after 9 minutes, stabilizer 3 proved to be clearly better than 2-phenyl-indole. Moreover, the sheet containing 2-phenyl-indole was burnt along its side edges after 15 minutes, while this was not the case with the test sheet.

2-(3'-hydroxy-4'-methoxy-phenyl)-indole Mixture A was used.

Temperature: 210°C

Stabilizer 13 was clearly better than 2-phenyl-indole.

The results indicated in the following table were obtained with mixture A at a temperature of 210°C.

b) Dynamic thermostability

The dynamic thermostability of resins containing respectively 2-(3'-methoxy-4'-hydroxy-phenyl)-indole and 2-phenyl-indole as stabilizers was compared using the following numbered mixtures: No. 609: Mixture C with 2-phenyl-indole as stabilizer No. 676: Mixture C with stabilizer 2

No. 633: Mixture E with 2-phenyl-indole as stabilizer No. 674: Mixture E with stabilizer 2.

The test was carried out on a plastograph working at a temperature of 190°C, rotating at a speed of 60 rev/m. and contains an addition of 30 g of gelatinized material.

Two curves were drawn, namely:

- A splitting curve that gives the values for the resistance twisting moment (m kg) in relation to time.

From this curve, two important results can be obtained: it

minimum resistance torque and the splitting time.

- A curve that gives the self-heating time in relation to the temperature. The self-heating time is defined as the time it takes for the temperature in the sheet to exceed the temperature of the plastograph (190°C).

The results indicated in the following table were

obtained from these curves:

Although the minimal resistance twisting moments and splitting times are comparable, it should be pointed out that the sheets containing stabilizer 2 show better results with regard to the self-heating time.

C. Bonding of the stabilized material

Mixtures Nos. 609 and 676 were placed in a mixer of the type previously used to investigate static thermostability, with cylinders at a fixed temperature of 210°C. They were subjected to alternating periods of 3 minutes of mixing and 3 minutes of rest.

Mixture No. 674, unlike Mixture No. 609, did not stick to the cylinders after 19 minutes, showing that the sheet containing Stabilizer 2 is better than the sheet containing 2-phenyl-indole in terms of sticking.

D. Behavior during extrusion of the stabilized material

Blends Nos. 609 and 676 were extruded with an extruder fitted with a 45 mm diameter thread. Unlike blend #609, blend #676 extruded perfectly.

E. Behavior when blowing

Bottles were cast with Mixtures Nos. 609, 674, 633 and 676, and it was observed that Mixtures Nos. 674 and 676 produced much more transparent bottles than those obtained with Mixtures Nos. 633 and 609.

Also in this test it was quite clear that stabilizer 2 was clearly better than 2-phenyl-indole.

F. Sublimation of the stabilizers according to the invention

It is well known that 2-phenyl-indole carries with it the disadvantage that it sublimes when it is processed in powder form, during the formation of the mixture and during the extrusion of the latter. This relatively extensive sublimation constitutes a main disadvantage because, in addition to a not inconsiderable loss of stabilizer, it causes pollution of the atmosphere in the workplaces where the various operations are carried out.

The propensity to sublimate was investigated for 2-(3'-methoxy-4'-hydroxy-phenyl)-indole (stabilizer 2) in comparison with that for 2-phenyl-indole.

A sample of the compound to be examined was introduced into a test tube and heated under reduced pressure. The fraction with sublimed compound was recovered on a moving cold wall.

After a certain period of time, the sublimated compound was weighed, and the result was expressed as a percentage by weight of the starting material.

The results obtained can only be of relative value and enable comparisons to be made between two products that are tested under the same conditions.

The percentages of sublimed compound were respectively: 2-phenyl-indole: 26.9%

Stabilizer 2: 1.2%.

The ratio between the sublimation percentages for stabilizer 2 and for 2-phenyl-indole shows that the sublimation of stabilizer 2 is 20 times less than that of 2-phenyl-indole.

G. Thermostability of the stabilizers

The thermostability of stabilizer 2 and of 2-phenyl-indole was investigated by differential thermoanalysis and by thermogravimetric analysis.

a) Differential thermoanalysis

Diagrams of differential thermoanalysis were recorded

by studying 2 mg of sample material placed in a non-airtight container, and the rate of temperature rise was 2°C/minute and the sensitivity was 4 mcal/sec.

Diagrams were made for 2-phenyl-indole (i) and for stabilizer 2 (ii), and this enabled the following conclusions to be drawn: (i) 2-phenyl-indole sublimes at 140°C and especially from 185-190 °C (melting point). There was no loss of water at 100°C. Cleavage appears to begin at around 210-220°C.

It is very difficult to determine the decomposition temperature with accuracy because it is not possible to separate the thermolysis effect from the sublimation effect. (ii) There was no loss of water. Melting takes place at 160°C and cleavage begins at 235-240°C, followed by a series of exothermic waves.

b) Thermogravimetric analysis

This analysis necessitates that two be carried out

series of experiments, under air and under inert gas (argon), to eliminate any possible effect of oxygen. The results obtained were identical.

The temperature increased at a rate of 80°C/hour.

For the experiments under air, thermograms were drawn for both 2-phenyl-indole (i) and for stabilizer 2 (ii), and this enabled the following conclusions to be drawn": (i) Weight loss begins at around 190-195° C. It is due to both sublimation and incipient decomposition. In the case of the experiments carried out under air, a yellowish residue was actually obtained at 210°C, which constitutes evidence of the decomposition. Although the sample was not held at 210°C , it can be confidently stated that if this temperature had been maintained for an extended period of time, the sample would have been extensively decomposed, at least in the presence of air. (ii) Weight loss begins at about 235-240°C, which corresponds to the beginning of the cleavage.

The results of the thermogravimetric analysis confirm the results of the differential thermoanalysis, and thus show that stabilizer 2 has better thermostability than 2-phenyl-indole.

This fact is very important since the production and processing of the resin often involves temperature ranges from 180 to 220°C, in some cases for several minutes.

H. The extractability of the stabilizers

The stabilizers according to the invention can be used to stabilize polymers from which it is intended to produce packaging materials and containers for food and drink, and it was therefore necessary, despite their low toxicity, to determine their ability to be extracted by solvents that can mimic food and drink.

This study was conducted in accordance with the requirements of the Food and Drug Administration (U.S.A.).

The extractions were carried out in semi-rigid bottles, prepared with mixtures no. 609 and 676, and with the following solvents: water, an aqueous solution of acetic acid (3%), ethanol-water 50/50 and heptane.

The ratio between the surface of the plastic material exposed to extraction and the volume of the solvent was about 1 to 100 ml of solvent, taking into account the geometric characteristics of the bottles.

Operating conditions

Temperature: 49 C

Heating: An oven with thermostat for non-flammable solvents (water and acetic acid),

a water bath with a thermostat for flammable solvents (alcohol and heptane).

Duration of

the extractions: These are indicated under each result.

In each case, they are intentionally longer than those that would have given stable maximum values.

The amount of stabilizer examined was determined by colorimetric tests using p-dimethylaminobenzaldehyde, in accordance with the method described in Analytical Chemistry 36, 425-26 (1964).

A blank was run with a mixture of the same composition as the Nos. 609 and 676 mixtures, but without any stabilizer. A purely negative result was obtained. All results are listed in the table below. The amount of stabilizer in the experiments is expressed in ^ug per liters of extraction solvent or, which is the same, per 1000 cm^ of surface exposed to extraction.

Other tests were carried out with mixture A containing the various stabilizers listed below and the following results were obtained:

These results show that the stabilizers 2, 14, 19, 24 and 30 are clearly less extractable than 2-phenyl-indole with respect to water, aqueous ethanol and heptane.

In the case of dilute acetic acid, the extracted amounts are approximately the same, but it is difficult to draw any conclusions because the amounts are below the sensitivity threshold of the test method.

With regard to water, it is clear that stabilizer 2 is clearly better than 2-phenyl-indole since its extractability is at least 10 times less than that of 2-phenyl-indole. This discovery is important because it is closely related to the problem of providing containers for mineral water, seen in the context of possible contamination of the mineral water by the constituents of the stabilized polymer.

The stabilizers covered by the present invention are introduced into the thermoplastic material in an amount of 0.1 to 1% by weight.

The following examples provide a non-limiting illustration of the methods for preparing the compounds covered by the invention:

Example 1

2-(2'-hydroxy-4'-methoxy-phenyl)-indole

a) Preparation of 2-hydroxy-4-methoxy-acetophenone-phenylhydrazone In a solution of benzene containing 166 g (1 mol)

2-hydroxy-4-methoxy-acetophenone, 94 g (1 mol) of phenylhydrazine and a catalytic amount of acetic anhydride were introduced, and

the mixture was refluxed for one hour. The solvent was then evaporated and the crude 2-hydroxy-4-methoxy-acetophenone-phenylhydrazone obtained was directly used in the subsequent step.

By the procedure described above, but using the appropriate starting compounds, the compounds listed below were prepared: 2-hydroxy-5-methyl-acetophenone-phenylhydrazone

2-methyl-4-methoxy-acetophenone-phenylhydrazone

2- hydroxy-4-methyl-acetophenone-phenylhydrazone

3- methyl-4-methoxy-acetophenone-phenylhydrazone

2.4- dimethoxy-acetophenone-phenylhydrazone

3-n-dodecyl-4-methoxy-acetophenone-phenylhydrazone

3-isopropyl-4-methoxy-acetophenone-phenylhydrazone

3-cyclohexy-3-methoxy-acetophenone-phenylhydrazone 3.5-dimethyl-4-methoxy-acetophenone-phenylhydrazone

3,5-dimethyl-4-ethoxy-acetophenone-phenylhydrazone

b) Preparation of 2-(21-hydroxy-4'-methoxy-phenyl)-indole

To 450 g of a mixture of orthophosphoric acid/phosphoric anhydride (1/1), heated to a temperature between 140 and 180°C, 230 g (1 mol) of 2-hydroxy-4-methoxy-acetophenone-phenylhydrazone were slowly added, and the temperature was kept at the same level for 1 hour.

The reaction medium was poured into 1 liter of water, and the substance that precipitated was taken up in ether. The ether phase was washed with water until neutral and then dried.

After purification of the solution with activated charcoal and evaporation of the ether, a greenish oil was obtained which crystallized to provide the crude product.

After recrystallization from benzene, 60 g of 2-(2'-hydroxy-4'-methoxy-phenyl)-indole were obtained.

Melting point: 195°C. Dividend: 25%.

By the same procedure, but using the appropriate starting compounds, the compounds listed below were prepared:

ttKsempex

2-(2'-methyl-4'-methoxy-phenyl)-indole

By the method described in example 1, but using a temperature of 110-120°C and starting from 2-methyl-4-methoxy-acetophenone-phenylhydrazone, after recrystallization from ethanol 95 g of 2-(2 '-methyl-4<1->methoxy-phenyl)-indole.

Melting point: 131°C. Yield: 40%.

Example 3

2-(3'-n-dodecyl-4'-methoxy-phenyl)-indole

A quantity of 50 g of polyphosphoric acid was prepared by

mix one part orthophosphoric acid with one part phosphoric anhydride and heat the mixture to 100°C. To this mixture was slowly added 40.8 g (0.1 mol) of 3-n-dodecyl-4-methoxy-acetophenone-phenyl-

hydrazone, prepared as described in example 1, and reaction

the medium was held at about 100 to 110°C for one hour. After off-

cooling to 80°C, the mixture was poured into ice-water, and the indolic precipitate formed was filtered off and washed with water until neutral, and then dried and washed with hexane.

After recrystallization from ethanol under nitrogen

atmosphere, 9 g of 2-(3'-n-dodecyl-4'-methoxy-phenyl)-

indole.

Melting point: 111°C. Yield: 23%.

By the same method, but using the appropriate starting compounds, the following compounds were prepared:

Example 4

2-(3'-Methoxy-4'-hydroxy-phenyl)-indole

a) Preparation of 3-methoxy-4-hydroxy-acetophenone-phenylhydrazone A mixture containing 8.3 g (0.05 mol) 3-methoxy-4-hydroxy-acetophenone, 5.4 g (0.05 mol) phenylhydrazine , 20 ml of ethanol and a drop of acetic acid, was refluxed for 6 hours and then kept at a temperature of about 5°C overnight.

The precipitated substance was centrifuged, washed with a minimal amount of benzene and dried under vacuum at room temperature to give 10.5 g of 3-methoxy-4-hydroxy-acetophenone-phenylhydrazone. Melting point: 131°C. Yield: 82%.

b) Preparation of 2-(3'-methoxy-4'-hydroxy-phenyl)-indole

40 g of orthophosphoric acid was poured into 7.68 g (0.03 mol)

3-Methoxy-4-hydroxy-acetophenone-phenylhydrazone and the mixture was heated to 130°C for one hour and then to 180°C for ten minutes. After standing for 30 minutes at room temperature, the reaction medium was taken up in 200 ml of water and the aqueous solution was extracted several times with methylene chloride. The combined organic phases were washed with water, dried over anhydrous magnesium sulfate and then filtered through an alumina column.

The solution was evaporated to dryness and 5.1 g of impure product was obtained. After recrystallization from toluene, 4.8 g of 2-(3'-methoxy-4'-hydroxy-phenyl)-indole were obtained.

Melting point: 165°C. Yield: 67.3%.

Example 5

2-(3',4'-dimethoxy-phenyl)-indole

a) Preparation of 3, 4-dimethoxy-acetophenone-phenylhydrazone

A mixture of 60 g (0.3 mol) of 3,4-dimethoxy-acetophenone, 33 ml of phenylhydrazine, 100 ml of ethanol and 1.5 ml of acetic acid was refluxed under nitrogen for 10 hours.

The alcohol was evaporated and the residue was recrystallized from toluene to give 56.8 g of crystals. By concentrating the mother liquor, 28.2 g of impure product was also recovered, and this was added to the 56.8 g of crystals that had already been obtained.

The thus obtained 85 g of impure 3,4-dimethoxy-acetofenone-phenylhydrazone was directly used in the following step.

By the method described above, but using the appropriate starting compounds, the following compounds were prepared: 3,5-dimethoxy-acetophenone-phenylhydrazone and 3,4,5-trimethoxy-acetophenone-phenylhydrazone.

b) Preparation of 2-(3', 4'-dimethoxy-phenyl)-indole

While stirring and maintaining a temperature of

around 170-185°C, 67.5 g (0.25 mol) of 3,4-dimethoxy-acetophenone-phenylhydrazone was added to 450 g of polyphosphoric acid, prepared as in example 1.

The temperature was then maintained at 180°C for 10 minutes, and the mixture was then allowed to stand at room temperature for 10 minutes.

The reaction medium was taken up in one liter of water and stirred until the oily phase disappeared. After cooling to room temperature, the aqueous suspension was extracted several times with ether, and the combined ether phases were washed with water, dried over anhydrous sodium sulfate and filtered through a neutral alumina column. After recrystallization from toluene, 22 g of 2-(3',4'-dimethoxy-phenyl)-indole were obtained.

Melting point: 188°C. Yield: 35%.

By the procedure described above, but using the appropriate starting compounds, the following compounds were prepared:

Example 6

2-(3'-hydroxy-4'-methoxy-phenyl)-indole

a) Preparation of 3-hydroxy-4-methoxy-acetophenone-phenylhydrazone A solution of 500 ml of benzene containing 60 g (0.36 mol) of 3-hydroxy-4-methoxy-acetophenone was stirred. 20 g (0.2 mol) of phenylhydrazine and 5 ml of acetic anhydride refluxed for one hour. The benzene solution was concentrated by evaporation under reduced pressure to give impure 3-hydroxy-4-methoxy-acetophenone-phenylhydrazone, which was directly used in the next step.

b) Preparation of 2-(3'-hydroxy-4'-methoxy-phenyl)-indole

During 20 minutes, 20 g (0.12 mol) of 3-hydroxy-4-methoxy-acetophenone-phenylhydrazone was added to 100 g of a mixture of phosphoric acid/phosphoric anhydride (60/40) and the reaction medium was heated to 110°C in 30 minutes after finishing the addition. The mixture was poured into ice-water and the indolic derivative was extracted with ether.

The ether phase was washed, dried and concentrated under reduced pressure. The crude product obtained was recrystallized from a mixture of toluene-ethanol (80/20) and 14.3 g of 2-(3'-hydroxy-4<1->methoxy-phenyl)-indole was obtained.

Melting point: 217°C. Yield: 50%.

Example 7

2-(2', 4'-dihydroxy-phenyl)-indole

a) Preparation of 2, 4-dihydroxy-acetophenone-phenylhydrazone

A mixture of 15.2 g (0.1 mol) of 2,4-dihydroxyacetophenone, 50 ml of ethanol, 10 ml of phenylhydrazine and 3 drops of acetic acid was refluxed for 2 hours and then placed in an ice bath for 30 minutes. The crystals obtained were centrifuged and washed with 100 ml of hexane to give 21 g of 2',4'-dihydroxy-acetophenone-phenylhydrazone in the form of brown crystals.

Melting point: 159°C.

b) Preparation of 2-(2', 4'-dihydroxy-phenyl)-indole

12.2 g (0.05 mol) were added to 60 g of orthophosphoric acid.

2,4-dihydroxy-acetophenone-phenylhydrazone and the reaction medium were heated to 130°C for one hour and then to 180°C for 10 minutes. While stirring, the mixture was poured into one liter of ice-water and extracted with ethyl acetate. The organic phase was washed with 100 ml of water, was dried and the solvent was evaporated. The residue was chromatographed on a silica column with a mixture of ethyl acetate/ether (10/90) as eluent. The solvent

was eliminated and the residue recrystallized from a mixture of toluene-methanol to give 4.60 g of 2-(2<1>,4<1->dihydroxy-phenyl)-indole. Melting point: 188°C. Yield: 40%.

Example 8

2-(3'-Methoxy-4'-hydroxy-phenyl)-indole

Over a period of 15 minutes, 20 g (0.1 mol) of CO-chloro-3-methoxy-4-hydroxy-acetophenone was added to 32.5 g (0.35 mol) of boiling aniline and the temperature was maintained at 180 °C for 20 minutes.

The mixture was then poured into a dilute aqueous solution of hydrochloric acid, and the indolic derivative was extracted with ether. The ether phase was washed, dried and concentrated under reduced pressure. The crude product was moistened with toluene and centrifuged.

After recrystallization from a mixture of toluene-ethanol (80/20), 4.8 g of 2-(3'-methoxy-4'-hydroxy-phenyl)-indole were obtained.

Melting point: 165°C. Dividend: 20%.

By the same method, but using the appropriate starting compound, the following compound was prepared:

Example 9

2-(3',4'-dimethoxy-phenyl)-indole

A mixture of 372 g (4 mol) aniline and 215 g (1 mol) C 1 -chloro-3,4-dimethoxy-acetophenone was refluxed for one hour. The reaction medium was cooled to about 50°C and poured into ice-water to which 50 ml of concentrated hydrochloric acid had been added. The reaction medium was extracted with chloroform and the organic phase was washed with water, dried and concentrated under reduced pressure.

After recrystallization from ethanol, 100 g of 2-(3<1>,4'-dimethoxy-phenyl)-indole were obtained.

Melting point: 190-192°C. Yield: 40%.

Example 10

2-(2'-methoc.sy-5'-methyl-phenyl)-indole

To a solution of 223 g (1 mol) 2-(2<1->hydroxy-5<1->methyl-phenyl)-indole, prepared as in example 1, in 1200 ml of N,N-dimethyl-formamide, was at a temperature of 90°C, 65 g (1.2 mol) of sodium methylate and then 170 g (1.2 mol) of methyl iodide were added dropwise.

After completion of the addition, the mixture was heated to 100°C for 3 hours. The reaction medium was allowed to cool, and the impure product was precipitated by the addition of water. The eluate was taken up in ether, washed and dried. The ether was evaporated and the product was purified by chromatography on a silica column eluting with benzene to give 150 g of 2-(2'-methoxy-5'-methyl-phenyl)-indole.

Melting point: 119°C. Yield: 59%.

Example 11

2-(2'-Methoxy-4'-methyl-phenyl)-indole

At a temperature of 25°C, 54 g (1 mol) of sodium methylate and 170 g (1.2 mol) of methyl iodide were added to a solution of 223 g (1 mol) of 2-(2*-hydroxy-4'-methyl-phenyl) )-indole, prepared as in example 1, in 1200 ml of N,N-dimethylformamide. The solution was then stirred for 2 hours and the impure product was precipitated by the addition of water. After recrystallization from benzene, 166 g of 2-(2'-methoxy-4'-methyl-phenyl)-indole were obtained.

Melting point: 125°C. Yield: 70%.

Example 12

2-(3'-Methoxy-4'-ethoxy-phenyl)-indole

To a mixture of 50 ml of N,N-dimethylformamide and 1.23 g (0.022 mol) of potassium hydroxide was added 4.8 g (0.02 mol) of 2-(3<1->methoxy-4<1->hydroxy -phenyl)-indole, prepared as described in example 4, and the reaction medium was heated to a temperature of 50°C. In the course of 10 minutes, 4.68 g (0.03 mol) of ethyl iodide were added and everything was heated to 60°C for 2 hours. After cooling, the reaction medium was poured into water and extracted with ether. The ether phase was washed with water until neutral, and was dried and concentrated under reduced pressure.

After recrystallization from toluene, 3.06 g of 2-(3'-methoxy-4'-ethoxy-phenyl)-indole were obtained.

Melting point: 177°C. Yield: 60%.

Example 13

2-(3'-Methoxy-4'-n-dodecyloxy-phenyl)-indole

In the course of 15 minutes, 23.9 g (0.1 mol) of 2-(3'-methoxy-4'-hydroxy-phenyl)-indole, prepared as described in Example 8, was added to a mixture of 120 ml of N, N-dimethylformamide and 6.75 g (0.125 mol) sodium methylate. The mixture was stirred for 15 minutes, after which 25.6 g (0.1 mol) of 1-chloro-dodecane was added over 15 minutes. The reaction medium was then heated to a temperature of 130°C and was stirred at this temperature for 3 hours. After cooling, the reaction medium was poured into water, and the slurry that formed was filtered out and washed with water until neutral.

After two successive recrystallizations from ethanol, 20 g of 2-(3'-methoxy-4'-n-dodecyloxy-phenyl)-indole were obtained. Melting point: 104°C. Yield: 50%.

By following the same procedure, but using the appropriate starting compounds, the following compounds were prepared:

Example 14

2-(2'-methyl-4'-hydroxy-phenyl)-indole

A solution of 1800 ml of benzene containing 2 37 g

(1 mol) of 2-(2'-methyl-4'-methoxy-phenyl)-indole, prepared as in Example 2, and 300 g (2.25 mol) of aluminum chloride were refluxed for 2 hours. The reaction medium was cooled and extracted with ether. The ether phase was washed until neutral and then dried over anhydrous sodium sulfate.

The ether was evaporated, and after recrystallization from benzene, 167 g of 2-(2'-methyl-4'-hydroxy-phenyl)-indole were obtained. Melting point: 106°C. Yield: 75%.

By the above procedure, but using the appropriate starting compounds, the following compounds were prepared:

Claims (1)

New 2-phenyl-indole derivatives as stabilizers for polymers and copolymers of vinyl chloride, characterized in that they are 2-phenyl-indole derivatives with the general formula: where and R^, which may be the same or different, each means a branched or linear alkyl group containing from 1 to 12 carbon atoms, a cyclohexyl radical, a branched or linear alkyloxy group containing from 1 to 12 carbon atoms, a benzyloxy radical, a hydroxy radical or R^ - and R 2 together means an alkylenedioxy radical containing from 1 to 3 carbon atoms, and R 1 means a hydrogen atom or a methyl or methoxy radical, with the proviso that at least one of the substituents R 1 or R 2 does not mean an alkyl radical. 2. • Stabilizer as stated in claim 1, characterized in that it is 2-(3'-methoxy-4<1->hydroxy-phenyl)-indole.