DK144009B - 2-PHENYL-INDOLIDATE DERIVATIVES TO USE AS HEAT STABILIZERS FOR POLYMERS AND COPOLYMERS - Google Patents

Description

(19) DENMARK (wj

(jP (12) PUBLICATION WRITING (11) H4009B

DIRECTORATE OF THE PATENT OE THE TRADEMARK TRADE

"'' '*'" '"' 'I" I ....... "Ill. 1 III' .1 '' nil) - ......... '| mu mi (21) Application No. 2520/75 (61) tattt «Q 07 D 209/12

(22) Submission day 4 Jun. 1975 C 07 D 405 / 0A

(24) Race day 4 Jun. 1975 C 08 K 5/34 (41) Aim. available Dec. 6; 1975 (44) Presented 16 Nov. 1981 (86) International Application No. - (86) International Filing Day - (85) Continuation Day - (62) Master Application No. -

(30) Priority 5 Jun. 1974, 7419504, FR

(71) Applicant SANOFI, 75008 Paris, FR, (72) Inventor Marie-Madelelne Chandavoine, FR: Paul de Cointet de

Branch, FR: Souli Nanthavong, FR: Charles Pigerol, FR.

(74) Prosecutor of Danish Patent Office ApS.

.......... "" .............. III · .— ....... ^ now). U — IW, 1.11) 1..1. ............. m. . "(54) 2-Phenyl indole derivatives for use as heat stabilizers for polymers and copolymers of vinyl chloride.

The present invention relates to 2-phenyl-indole derivatives for use as heat stabilizers for polymers and copolymers of vinyl chloride.

The 2-phenyl-indole derivatives of the invention are characterized in that they have the general formula R1 R2 R3 in CU-5; - 12 wherein R and R, being the same or different, each represent a branched or straight chain alkyl group of 1-12 carbon atoms, a cyclohexyl group, a branched or straight chain alkyloxy group of 1-12 1 2

carbon atoms, a benzyloxy group, a hydroxy group e, or R and R

2 144009 x together means an alkyl endoxy group of 1-3 carbon atoms, Ir is a hydrogen atom, a methyl or methoxy group, however, at most one of the substituents R1 or R2 is an alkyl or cyclohexyl group and R and R are not methoxy when they are 3f and 4 'substituted in the phenyl ring or when R is a 5' methoxy group and does not mean a hydroxy and methyl group when in the 2 'and 5' positions, respectively in the phenyl ring.

Vinyl resins are known to degrade under the influence of heat, and it is necessary to add a stabilizer to these masses of synthetic materials to delay thermal degradation and thus stain of the resin.

Although good stabilizing ability is required, it is not the only property required by a stabilizer. The following properties of the stabilized material are also of great importance: thermostability, adhesion, extrusion behavior and blowing behavior. Furthermore, the sublimation and thermostability of the stabilizer are of great importance.

Finally, as far as food and beverage containers are concerned, extraction of the stabilizers from the food and beverage containers in the container must be carefully investigated.

It is known that 2-phenyl-indole is one of the most valuable organic stabilizers due to its good stabilizing ability and its low toxicity. It is widely used in the plastics industry to stabilize vinyl polymers and copolymers, especially those used to accommodate food and beverages.

Further, from the disclosure of French Patent No. 2,198,939, it is known to use certain alkyl or cycloalkyl-substituted 2-phenyl-indole derivatives as a stabilizer for vinyl chloride polymers. While these known substituted 2-phenyl-indole derivatives have a lower solubility in water and a higher sublimation temperature, they also have a significantly poorer stabilization effect over 2-phenyl-indole.

It has been found that the 2-phenyl-indole derivatives of formula (I) having a substituent bonded over a heteroatom have a significantly better stabilizing effect than 2-phenyl-indole and those from the disclosure of French Patent No. 2,198 above. .939 known substituted 2-phenyl-indole derivatives and similarly good properties in water solubility and sublimation temperature as the known substituted 2-phenyl-indole derivatives. In particular, according to the invention 2- (3'-methoxy-4'-hydroxy-phenyl) -indole has particularly good properties in this regard.

Fnrh-infrels fimp of formula (I) can be prepared according to Fischer's indole synthesis by reacting a substituted acetophenone derivative of formula 0 C-CH 3 6 3 · wherein R, R and R above, with phenylhydrazine to form a substituted acetophenone-phenylhydrazone of the formula / -NH-N = C-CH 3

I III

Wherein R, R and R 2 are as defined above and cyclize the compounds of formula III either with a dehydrating agent such as sulfuric acid, polyphosphoric acid or zinc chloride, or by thermolysis to give the desired 2 -phenyl-indole derivative of formula I.

Alternatively, the compounds of formula I may be prepared following the Bischler indole synthesis by reacting a substituted acetophenone derivative of formula 0 in XV

R * - N. "C-CH? X

R2-IV

V

Wherein R, R and R are as defined above and X is a halogen atom, preferably bromine or chlorine, with aniline to form the desired 2-phenyl-indole derivative of formula I.

1 2

The compounds of formula I, wherein at least one of the substituents R, R and R R is a branched or straight chain alkyloxy group of 1-12 carbon atoms, can alternatively be prepared by reacting the corresponding hydroxylated 2-phenyl-indole derivative prepared by one of the two general procedures described above, with a branched or straight chain alkyl halide of 1-12 carbon atoms, in the presence of sodium methylate and optionally R, ΪΓ-dime t he If ormami d.

Alternatively, the compounds of formula I wherein at least one of the substituents R 1 and 2 R is a hydroxy group can be prepared by demethylating the corresponding methoxy-substituted 2-phenyl-indole derivative prepared by one of the above-described two general processes, using aluminum chloride or pyridine hydrochloride, optionally in the presence of benzene.

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

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

The 2-phenyl-indole derivatives of the general formula (i) are to be used as heat stabilizers for polymers and copolymers of vinyl chloride such as polyvinyl chloride, polyvinyl chloride-polyvinyl acetate, polyvinyl chloride-polyvinylidene chloride.

They have been found to be particularly valuable as stabilizers for vinyl chloride polymers and copolymers to be formed by extrusion molding, blow molding and calendaring, mainly but not exclusively for the manufacture of food and beverage containers such as bottles for wine, oil, vinegar and mineral water.

Examples of novel 2-phenyl-indole derivatives of the invention are: 2- (21,4'-dihydroxy-phenyl) -indole (stabilizer 1) 2- (3'-methoxy-4'-hydroxy-phenyl) -indole ( stabilizer 2) 2- (31'-5'-dimethoxy-phenyl) -indole (stabilizer 3) 2- (2'-hydroxy-4f-methoxy-phenyl) -indole (stabilizer 4) 2- (2'-hydroxy-4) 2-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 $ 1) 2- (3 »-cyclohexyl-4» -methoxy-phenyl) -indole (stabilizer 16) 2- (3f-dimethyl-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-4f) isopropyloxy-phenyl) -indole (stabilizer 27) 2- (3 'AT-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- (31-methyl-4'- benzyloxy-phenyl) -indole (p tabulator 32) 2- (3β, 4β-methylenedioxy-phenyl) -indole (stabilizer 33) 2- (3β, ethylenedioxy-phenyl) -indole (stabilizer 34) 2- (3β-methyl-4'-ethoxy) phenyl) -indole (stabilizer 35) 6 144009

The toxicity of the compounds of formula (i) was first investigated and the results obtained were so satisfactory that they justified the continuation of the study.

A. Acute toxicity.

The acute toxicity (LD 2) of the stabilizers listed below was investigated by determining the dose of drug that caused death of 50 µg of the treated animals.

A rubber suspension of the compound to be examined was administered orally to groups of at least ten mice and the following results were obtained:

Stabilizer LD ^ q (mg / kg) Toxic symptoms 2> 2000 none 3> 2000 none 14> 3000 none 15> 3000 none 2-phenyl-indole> 3000 none

The maximum dose that does not induce death (LDq) was also determined for the stabilizers listed below using the same method.

The following results were obtained: 7 144009

Stabilizer LDq (mg / kg) Toxic symptoms 17> 3000 none 23> 500 none 25> 3000 none 27> 3000 none 29> 500 none 31> 500 none 33> 3000 none 34> 3000 none B. Thermostability of the stabilized resin.

The stabilizing ability of the compounds of the invention was investigated from two points of view: a) Static thermostability b) Dynamic thermostability

These studies were performed with five different formulations of vinyl resins (hereinafter called compounds).

Compound A

Ingredients Weight Parts

Polyvinyl chloride resin 100

Anti-shock resin 9

Epoxidized soybean oil 2

Calcium-12-hydroxy stearate 0.2 SL 2016 0.1

Stabilizer 0.3

Compound B

Ingredients Weight Parts

Polyvinyl chloride resin 100

Anti-shock resin 9

Epoxidized soybean oil 2

Chelating agent 1832 0.25

Solution of 2-ethyl-potassium hexanoate containing 10 # potassium 0.025 8 144009

Pure stearyl alcohol 0.5

Glyceryl 12-trihydroxy stearate 0.5

Glycerol trimontanate 0.2 C alc ium-mont anat 0.1 SL 2016 0.1

Stabilizer 0.3

Compound C

Ingredients Weight Parts

Polyvinyl chloride resin 100

Anti-shock resin 12

Epoxidized soybean oil 3

Chelating agent 1 & 32 0.25

Solution of potassium 2-ethyl hexanoate containing 10% potassium 0.025

Zinc-calcium stearate 0.2

Calcium stearate 0.2

Glyceryl 12-trihydroxy stearate 1

Glycerol trimontanate 0.3

Acrylic resin 0.5

Stabilizer 0.3

Compound D

Ingredients Weight Parts

Polyvinyl chloride resin 90

Vinyl chloride-vinylidene chloride copolymer 10

Anti-shock resin 7

Acrylic Resin 2

Epoxidized soybean oil 0.5 3- (2'-Phenyl-phenyl) -1,2-epoxy-propane 0.6

Organotin Stabilizer 0.5

Calcium stearate 0.2

Hydrogenated rapeseed oil 0.5

Methyl dihydroxy stearate 0.2

Micronized silica 0.2

Antioxidant 0.1

Stabilizer 0.3 9 144009

Compound E

Ingredients Weight Parts

Polyvinyl chloride resin 100

Anti-shock resin 12

Epoxidized soybean oil 3

Glyceryl 12-trihydroxy stearate 1

Glycerol trimontanate 0.3 A c ryl resin 0.5

Stabilizer 1

The following ingredients are defined below: SL 2016: solution of zinc-2-ethyl-hexanoate in a mixture of hydrocarbons boiling between 1 ° C and 14 ° C.

Chelating agent 1832: diphenyl decyl phosphite: 67 parts by weight; solution of 10 # zinc octoate in diisobutyl phthalate: 33 parts by weight.

a) Static thermostability.

The various compounds became. mixed and calendered in a mixer whose rollers were heated to 160 ° C. The stiff plates thus obtained were then heated in an oven to a temperature between 160 ° C and 215 ° C, until incipient charring.

A rotary drum furnace, ventilated and equipped with a thermostat, was used for this process. In the experiments described below, the behavior of plates containing one of the stabilizers to be tested was compared to the behavior of plates of the same composition but containing 2-phenyl-indole as a stabilizer.

Comparison can be made by one of two methods, namely: 1) The staining of the plates, of which samples were removed from the oven at certain intervals, was compared with a standard color scale known as the Gardner scale and expressed as the reference number of the Gardner scale .

10 144009

Comparisons were made with a Gardner-scale comparator containing 13 stained-glass filters, which allows both the plate and the reference filters to be viewed in transparency and in a limited field of view.

It may appear that the color of the plates is far from the Gardner scale, in which case a comparison is difficult, if not impossible.

The following results were obtained: 2- (3T-Methoxy-4T-hydroxy-phenyl) -indole

Compound B was used and the plates obtained had the following characteristics:

Initial thickness of the control plate 0.9 mm

Initial thickness of the test plate 1 mm

Oven temperature 210 ° C

Stabilizers ______________ 0 3 6 9 12 15 18 21 2-phenyl-indole 1 1 2 3 4 7 9> 18 2 1123469 11

The superiority of stabilizer 2 over 2-phenyl-indole is clear after 21 minutes, as the control plate is completely burned after this time, while the test plate has a staining of only 11 ° GARDNER.

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

Compound A was used.

Initial thickness of the control plate 0, S mm

Initial thickness of the test plate 0.9 mm

Temperature 210 ° C

Stabilizers _ Time in minutes_ 0 3 6 9 12 15 18 2-phenyl-indole 1234 9 12 13 2 1 1 1.5 2 5 9 11

Also with Compound A, stabilizer 2 proved to be superior to 2-phenyl-indole.

2- (3 T-Methoxy-4T-benzyloxy-phenyl) -indole

Compound A was used.

Initial thickness of the control plate 0.9 mm

Initial thickness of the test plate 0.9 mm

Temperature lS5 ° C

Stabilizers _ Time in minutes____ 0 6 12 id 24 30 36 42 46 54 60 2-phenyl-indole 1 2 4 9 11 15 15 16 16 18 roasted 31 1 1 2 6 9 10 11 11 15 15 roasted 2) It is also possible to use a simplified method that is faster and with valid results:

A reference scale is set up with sheets of thermally treated polyvinyl chloride, the staining of which is exactly determined in GARDNER degrees as above.

Thus, a GARDNER sub-scale is available in polyvinyl chloride sheets, which can be directly compared with the panels to be tested, without the use of a comparator.

The following results were obtained by said simplified method: 2- (3T-Methoxy-4t-hydroxy-phenyl) -indole

Compound C was used.

Temperature: 210 ° C.

Stabilizers _ Time in minutes_ 0 10 20 30 40 50 55 60 2-phenyl-indole 1 1.5 2 <3 3> 3 3.5> 4 2 <L 1 1, 5 2 2.5 <3 3 <4

The colors are quite far from the GARDNER scale, so the intensity of the color is difficult to assess. However, it can also be seen here that stabilizer 2 is 2-phenyl-indole superior as a stabilizer.

2- (31-Methoxy-4 * -hydroxy-phenyl) -indole

Compound D was used.

Temperature: L85 ° C.

Stabilizers Time 1

OudUJ.liod.uUX ΰΧ ___ Ο 10 20 30 2-phenyl-indole 1 1 <2 2 2 «1 <1 1« 2

Obviously, in this case, stabilizer 2 is 2-phenyl-indole markedly superior at 0, 10 and 20 minutes, especially with respect to the staining of the copolymer.

2- (3 *. 5 ^ Dimethoxy-phenyl) -indole Compound A was used.

Temperature: 210 ° C.

Stabilizers Time in minutes ~ 3 O 9 6 2 2 5 2-phenyl-indole 1 2 3 S 11 13 3 1 1 2 3 S 11 As early as the ninth minute, stabilizer 3 was found to be 2-phenyl-indole superior In addition, the plate containing 2-phenyl-indole was burned along its edges after 15 minutes, it was not the test plate.

2- (3 * -Hydroxy-4T-methoxy-phenyl) -indole

Compound A was used.

Temperature: 210 ° C.

Time in minutes

Stabilizers ___; ___ O 3 6 9 12 15 18 2-phenyl-indole 1 1 2 5 9 13 burned 13 1 1 1 4 7 10 burned

Stabilizer 13 is 2-phenyl-indole clearly superior.

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

13 U4009 —— Time in minutes

Stabilizers -g-3-g-9-fg-Γ5 T§ ~ 14 112 5 S 10 16 2-phenyl-indole 11 2 9 11 13 burnt 15 112411 13 burnt 2-phenyl-indole 1 1 3 10 12 13 burnt 16 1123 9 13 roasted 2-phenyl-indole 1 1 3 4 12 14 roasted 17 1113 6 S 12 2-phenyl-indole 1 1 1 4 10 12 roasted IS 1 1 2 3 10 11 13 2-phenyl-indole 1 1 2 S_9 10 roasted 19 1 1 3 6 6 11 16 20 1 1 3 6 10 11 roasted 2-phenyl-indole 1 1 2 9 11 13 roasted 23 1 1 2 2 3 9 roasted 2-phenyl-indole 1 1 310 12 13 roasted 24 1 1 1 4 10 13 roasted 29 1 1 1 4 10 13 roasted 2-phenyl-indole 1 1 3 6 14 14 roasted 25 1123 912 roasted 25 1 1 2 2 10 13 roasted 2-phenyl-indole 1 1 3 4 12 14 roasted 26 1 1 1 2 3 4 10 27 1 1 1 3 4 9 13 2-phenyl-indole 1_1_1 4 10 12 roasted 30 1135 613 roasted 32 1 1 4 4 11 13 roasted 2-phenyl-indole 113 5_6 13 roasted 21 1123 S 12 14 35 1 1 2 5 5 11 12 2-phenyl-indole 1_1_2 S_9 10 burnt 33 1 1 2 5 11 13 burnt 34 1 1 2 5 10 13 burnt 2-phenyl-indole 1 1 3 11 13 14 burnt 14 144009 b] Dynamic thermostability.

The dynamic thermostability of resins containing 2- (3'-methoxy-4T-hydroxy-phenyl) -indole and 2-phenyl-indole, respectively, as stabilizers was compared using the following compounds:

No. 609: Compound C with 2-phenyl-indole as stabilizer

No. 676: Compound C with stabilizer 2

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

No. 674: Compound E with stabilizer 2.

The experiments were carried out on a plastograph operating at a temperature of 190 ° C, rotating at a speed of 60 rpm. per minute and contained a charge of 30 g of gelled material.

Two curves were drawn, namely: - a decomposition curve indicating the value of resistance torque (m * kg) in relation to time.

Two important results are obtained from this curve: the minimum resistance torque and the decomposition time.

- a curve indicating the self-heating time in relation to the temperature.

The self-heating time is defined at the moment when the temperature of the material exceeds the temperature of the plastograph (190 ° C).

From these curves, the results given in the following table were obtained:

Compounds Measurements ------ 609 676 633 674

Minimum resistance torque 1.1 1.1 0.96 0.95 torque in m * kg

Decomposition time in min. 23.5 23 43.5 44.5

Self-heating time in min. 6 S 9 22.5 15 U4009

Although the minimum resistance torque and decomposition times are comparable, it should be emphasized that the plates containing stabilizer 2 provide a better result in self-heating time.

C. Adhesion of the stabilized material.

Compound Nos. 609 and 676 were placed in a mixer of the type previously described for static thermostability testing, with rollers at a constant temperature of 210 ° C. They were subjected to alternating periods of 3 minutes mixing and 3 minutes rest.

In contrast to Compound No. 609, Compound No. 674 did not adhere to the rollers after 19 minutes, demonstrating the superiority of the stabilizer-containing material2 relative to the adhesive-containing 2-phenyl-indole.

D. Behavior in extrusion of the stabilized material.

Compound Nos. 609 and 676 were extruded with an extruder fitted with a screw having a diameter of 45 ram · Unlike Compound No. 609, Compound No. 676 was extruded perfectly.

E. Blasting behavior.

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

Also with this test, the superiority of stabilizer 2 over 2-phenyl-indole was very pronounced.

F. Sublimation of the compounds of the invention.

It is well known that 2-phenyl-indole has the disadvantage that it sublimates when handled in the form of powder, forming the compound and during extrusion of the latter. This relatively significant sublimation poses a significant disadvantage because, besides providing a not insignificant loss of stabilizer, it causes pollution of the air in the rooms where the various operations are performed.

16 144009

The tendency to sublimate with 2- (3'-methoxy-4'-hydroxy-phenyl) -indole (stabilizer 2) was compared with the same trend of 2-phenyl-indole.

A sample of the compound to be tested was introduced into a test tube and heated under reduced pressure. The fraction of sublimated compound was captured on a mobile cold wall.

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

The results obtained can only be of relative value and enable a comparison between two products tested under the same conditions.

Trial conditions (selected arbitrarily).

Heating temperature 120 ° C

Cold wall temperature 13 ° C Pressure 15 mm Hg

Heating duration 150 minutes

Starting weight 150 mg

The percentage of sublimated compound was, respectively: 2-Phenyl-indole $ 26.9

Stabilizer 2 $ 1.2

The ratio of the sublimation rate of stabilizer 2 to 2-phenyl-indole shows that the sublimation of stabilizer 2 is twenty times less than the sublimation of 2-phenyl-indole.

G. Thermostability of the Stabilizers.

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

a) Differential thermal analysis.

Differential thermal analysis charts were drawn by studying 2 mg samples of the material placed in a non-airtight container where the temperature increase rate was 2 ° C / minute and the sensitivity 4 mcal / sec.

Diagrams were prepared for 2-phenyl-indole (i) and compound 2 (ii) and allowed to draw the following conclusions: 17 144009

(i) 2-Phenyl-indole sublimates at 140 ° C and especially from 1S5-190 ° C

(melting point). There is no loss of water at 100 ° C. Decomposition seems to begin at 210-220 ° C.

It is very difficult to accurately determine the decomposition temperature because it is not possible to distinguish the thermolysis effect from the sublimation effect.

(ii) There is no loss of water; melting occurs at 160 ° C and decomposition begins at 235-240 ° C, followed by a series of exothermic waves.

b) Thermogravimetric analysis.

This analysis necessitated two series of experiments performed under air and under inert gas (argon) to eliminate any possible effect of oxygen. The results obtained were identical.

The temperature increase rate was SO ° C / hr.

Thermograms were plotted for both 2-phenyl-indole (i) and for stabilizer 2 (ii) under air and allowed to draw the following conclusions: (i) Weight loss begins at about 190-195 ° C. This is due to both sublimation and incipient decomposition. In fact, in the case where the experiment was conducted under air, a yellow residue was obtained at 210 ° C which is evidence of decomposition. Although the sample was not kept at 210 ° C, it can reasonably be assumed that if this temperature had been maintained for an extended period of time, the sample would have undergone extensive degradation at least in the presence of air.

(ii) Weight loss begins at about 235-240 ° C, which corresponds to the onset of de-composition.

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

This relationship is very important, since the preparation and processing of the resin often involves temperatures of from 10 ° C to 220 ° C, sometimes for several minutes.

18 144009 H. Extractability of the Stabilizers.

The compounds of the invention can be used to stabilize polymers intended for the manufacture of packaging and containers for food and beverages, and therefore, despite their low toxicity, it was necessary to determine their extractability with solvents simulating food and beverages.

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

The extractions were carried out with semi-rigid vessels prepared with Compound Nos. 609 and 676 and with the following solvents: water, an aqueous solution of acetic acid (3%) ethano 1- · water 5Ο / 5Ο, heptane.

The bottles had the following specifications:

Diameter 62 mm Height 170 mm

Capacity 375 ml Weight 2 S g

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

Experimental conditions.

Temperature 49 ° C

Heating An oven with thermostat for the non-combustible solvents (water and acetic acid). A water bath with thermostat for the flammable solvents (alcohol and heptane). The extraction This is given under each result. In each case, the duration is intentionally longer than those that would have given stable maximum values.

The amount of stabilizer extracted was determined by colorimetric analysis using p-dimethylaminobenzaldehyde according to the method described in Analytical Chemistry 36, 425-26 (1964).

19 144009

A blank test was performed with a compound of the same composition as Compound Nos. 609 and 676, but without any stabilizer. A purely negative result was achieved. All the results are given in the tables below. The amount of stabilizer found is expressed in pg per day. liter of extraction solvent or, what is the same, per liter. 1000 cm surface exposed to extraction.

Solvents Compounds No. 609 no. 676

Water 40 (6 days) <3 (10 days) 3% aqueous acetic acid solution <3 (20 days) <3 (20 days)

Aqueous ethanol 50/50 100 (9 days) <10 (9 days)

Heptane 875 ($ 4 hours) 175 (48 hours)

Other experiments were performed with compound A containing the various stabilizers listed below and the following results were obtained:

stabilizers

Solvents __ 14 19 24 30

Water 23 <3 <3 <3 (10 days) (10 days) (10 days) (10 days) 3 ^ aqueous solution of <3 <3 <3 <3 vinegar (20 days) (20 days) ) (20 days) (20 days)

Aqueous ethanol <10 <10 <10 <10 50/50 (9 days) (9 days) (9 days) (9 days)

Heptane 175 175 175 175 (46 hours) (48 hours) (48 hours) (48 hours)

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

In the case of dilute acetic acid, the amounts extracted are approximately the same, but it is difficult to draw a conclusion as these quantities are below the sensitivity threshold of the assay method.

20 164009

With regard to water, it is clear that stabilizer 2 is 2-phenyl-indole markedly superior, since the former's extractability is at least 10 times less than the latter. This result is important as it is closely related to the problem of finding containers for mineral water and the possible contamination of the latter from the container of stabilized polymer.

The compounds of the invention are introduced into the thermoplastic material in an amount of from 0.1% to 1% by weight.

The following examples illustrate the processes for preparing the 2-phenyl-indole derivatives of formula (i).

Example 1 2- (2T-Hydroxy-1-methoxy-phenyl) -indole.

a) Preparation of 2-hydroxy-4-methoxy-acetophenone-phenylhydrazone.

Into a solution of benzene containing 166 g (1 mole) of 2-hydroxy-4-methoxy-acetophenone is introduced 94 g (1 mole) of phenylhydrazine and a catalytic amount of acetic anhydride and the mixture is refluxed for 1 hour. The solvent is then evaporated and the crude 2-hydroxy-4-methoxy-acetophenone-phenylhydrazone obtained is used directly for the following step.

By analogy, the following compounds are prepared: 2-methyl-4-methoxy-acetophenone-phenylhydrazone 2-hydroxy-4-methyl-acetophenone-p-phenylhydrazone 3-methyl-4-methoxy-acetophenone-phenylhydrazone 2,4-dimethoxy-2 acetophenone-phenylhydrazone 3-n-dodecyl-4-methoxy-acetophenone-phenylhydrazone 3-isopropyl-4-methoxy-acetophenone-phenylhydrazone 3-cyclohexyl-4-methoxy-acetophenone-phenylhydrazone 3, 5-dimethyl-4-methoxy-acetophenone phenylhydrazone 3.5 ”dimethyl-4-ethoxy-acetophenone-phenylhydrazone b) Preparation of 2- (2T-hydroxy-4T-methoxy-phenyl) -indole.

To 450 g of a mixture of orthophosphoric acid / phosphoric anhydride (l / l), heated to a temperature between 140 ° C and 10 ° C, 234 g (1 mole) of 2-hydroxy-4-methoxy-acetophenone are added slowly. -phenylhydrazone, and the temperature is kept at the same level for 1 hour.

The reaction medium is poured into 1 liter of water and the precipitated substance is taken up in ether. The ether phase is washed with water until neutrality and dried.

After purification of the solution with activated charcoal and evaporation of the ether, a greenish oil is obtained which crystallizes and gives a crude product.

After recrystallization from benzene, 60 g of 2- (2, -hydroxy-4, -nethoxy-phenyl) -indole are obtained, m.p. 195 ° C. Yield: $ 25.

By analogy, the following compounds are prepared:

Compound Melting point

2- (2f-hydroxy-4T-methyl-phenyl) -indole 191 ° C

2- (3 T-methyl-4R-nonhoxy-phenyl) -indole 210 ° C

2- (2 ', 4'-dimethoxy-phenyl) -indole 143 ° C

Example 2 2- (2 t-Methyl-4t-methoxy-phenyl) -indole.

By the procedure described in Example 1, but at a temperature of about 110 ° C-120 ° C and starting from 2-methyl-4-methoxy-acetophenone-phenylhydrazone, 95 g of 2- (2, -methyl-4, -methoxy) are obtained. -phenyl) -indole after recrystallization from ethanol. Mp. 131 ° C. Yield: $ 40.

Example 3 2- (3 T-n-Dodecyl-4T-methoxy-phenyl) -indole.

A quantity of 50 g polyphosphoric acid is prepared by mixing 1 part orthophosphoric acid with 1 part phosphoric acid anhydride and the mixture is heated to 100 ° C. To this mixture is slowly added 40.8 g (0.1 mole) of 3-n-dodecyl-4-methoxy-acetophenone-phenylhydrazone, prepared as described in Example 1, and the reaction medium is maintained at about 100 to 110 ° C for 1 hour. After cooling to 80 ° C, the mixture is poured into ice water and the indole bottom filter is filtered off and washed with water until neutrality, dried and washed with hexane.

22 H4009

After recrystallization of ethanol under a nitrogen atmosphere, 9 g of 2- (3'-n-dodecyl 3 '- methoxy-phenyl) -indole are obtained. Mp. 111 ° C. Yield: 21%.

By analogy, the following compounds are prepared:

Compounds Melting point

2- (3 T-isopropyl-4T-methoxy-phenyl) -indole 160 ° C

(benzene, then ethanol)

2- (3 T-cyclohexyl-4f-methoxy-phenyl) -indole 176 ° C

(Benzene)

2- (3β, 5T-dimethyl-4, -methoxy-phenyl) -indole 175 ° C

(ethanol, then acetone)

2- (3 ', 5, -dimethyl-4T-ethoxy-phenyl) -indole 134 ° C

(chromatography on a silica column with benzene as the eluent)

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

a) Preparation of 3-methoxy-4-hydroxy-acetophenone-phenylhydrazone.

A mixture consisting of S, 3 g (0.05 mole) of 3-methoxy-4-hydroxy-aceto-phenone, 5> 4 g (0.05 mole) of phenylhydrazine, 20 ml of ethanol and a drop of acetic acid is refluxed for 6 hours and is then kept at a temperature of about 5 ° C for 16 hours.

The precipitate is centrifuged, washed with a minimum of benzene and dried under vacuum at room temperature to give 10.5 g of 3-methoxy-4-hydroxy-acetophenone-phenylhydrazone. Mp. 131 ° C. Yield: & 2%.

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

40 g of orthophosphoric acid are poured onto 7.68 g (0.03 mole) of 3-methoxy-4-hydroxy-acetophenone-phenylhydrazone and the mixture is heated to 130 ° C for 1 hour and then to 10 ° C for 10 minutes. After being allowed to stand for 30 minutes at room temperature, the reaction medium is taken up in 200 ml of water and the aqueous solution is extracted several times with methylene chloride. The combined organic phases are washed with water, dried over anhydrous magnesium sulfate and then filtered through a column of alumina.

23 144009

The solution is evaporated to dryness to give 5.1 g of crude product. After two recrystallizations of toluene, c, 3 g of 2- (3T-methoxy-A * -hydroxy-phenyl) -indole is obtained. Mp. L65 ° C. Yield $ 67.3 *

Example 5 2- (3T, 5β-Dimethoxy-phenyl) -indole.

a) Preparation of 3,5-dimethoxy-acetophenone-phenylhydrazone.

A mixture of 60 g (0.3 mol) of 3,5-dimethoxy-acetophenone, 33 ml of phenylhydrazine, 100 ml of ethanol and 1.5 ml of acetic acid is refluxed under nitrogen for 10 hours.

The alcohol is evaporated and the residue is recrystallized from toluene to give 56.3 g of crystals. Concentrating the mother liquor also gives 23, in g of crude product, which is added to the 56.3 g of crystals already obtained.

The 35 g of crude 3,5-dimethoxy-acetophenone-phenylhydrazone thus obtained is used directly in the following step.

b) Preparation of 2- (3T> 5'-dimethoxy-phenyl) -indole.

While stirring and maintaining a temperature of about 170 ° C-135 ° C, 67.5 g (0.25 mol) of 3,5-dimethoxy-acetophenone-phenylhydrazone is added to 150 g of polyphosphoric acid prepared as in Example 1.

The temperature is then kept at 130 ° C for 10 minutes and the mixture is allowed to stand for 10 minutes at room temperature.

The reaction medium is taken up in 1 liter of water and stirred until the oily phase disappears. After cooling to room temperature, the aqueous suspension is extracted several times with ether and the combined ether phases are washed with water, dried over anhydrous sodium sulfate and filtered through a column of neutral alumina. After recrystallization from toluene, 26.4 g of 2- (3 ', 5'-dimethoxy-phenyl) -indole are obtained. Mp. 124 ° C.

Yield: 42%.

24 1460-0--9

Example 6 2- (3f-Hydroxy-4 * -methoxy-phenyl) -indole.

a) Preparation of 3-hydroxy-4-methoxy-acetophenone-phenylhydrazone.

With stirring, a solution of 500 ml of benzene containing 60 g (0.36 mol) of 3-hydroxy-4-methoxy-acetophenone, 20 g (0.2 mol) of phenylhydrazine and 5 ml of acetic anhydride is refluxed for 1 hour. The benzene solution is concentrated by evaporation under reduced pressure to give crude 3-hydroxy-4-methoxy-acetophenone-phenylhydrazone, which is used directly in the following step.

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

Over 20 minutes, 20 g (0.12 mol) of 3-hydroxy-4-methoxy-acetophenone-phenylhydrazone are added to 100 g of a phosphoric / phosphoric anhydride (60/40) mixture and the reaction medium is heated to 110 ° C for 30 minutes. minutes after completion of addition. The mixture is poured into ice-water and the indole derivative is extracted with ether.

The ether phase is washed, dried and concentrated under reduced pressure. The crude product obtained is recrystallized from a mixture of toluene-ethanol (30/20) to give 14.3 g of 2- (3T-hydroxy-4T-methoxy-phenyl) -indole.

Mp. 217 ° C. Yield: $ 50.

Example 7 2- (21.1'-Dihydroxy-phenyl) -indole.

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

A mixture of 15.2 g (0.1 mole) of 2,4-dihydroxy-acetophenone, 50 ml of ethanol, 10 ml of phenylhydrazine and 3 drops of acetic acid is refluxed for 2 hours and then left in an ice bath for 30 minutes. The obtained crystals are centrifuged and washed with 100 ml of hexane to give 21 g of 2 ', 4T-dihydroxy-acetophenone-phenylhydrazone in the form of brown crystals. Mp. 159 ° C.

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

To 60 g of orthophosphoric acid are added 12.2 g (0.05 mole) of 2,4-dihydroxy-acetophenone-phenylhydrazone, and the reaction medium is heated to 130 ° C for 1 146009 hours and then to 180 ° C for 10 minutes. With stirring, the mixture is poured into 1 liter of ice water and extracted with ethyl acetate. The organic phase is washed with 100 ml of water, dried and the solvent is evaporated. The residue is chromatographed on a silica column with a mixture of ethyl acetate / ether (10/90) as the eluent. The solvent is removed and the residue is recrystallized from a mixture of toluene-methanol to give 4> 60 g of 2- (2 ', 4f-dihydroxy-phenyl) -indole. Mp. L88 ° C. Yield: 40%.

Example 8 2- (3 t-Methoxy-4t-hydroxy-phenyl) -indole.

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

The mixture is poured into a dilute aqueous solution of hydrochloric acid and the indole derivative is extracted with ether. The ether phase is washed, dried and concentrated under reduced pressure. The crude product is wetted 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 are obtained. Mp. L65 ° C. Yield $ 20.

By analogy, the following compound is prepared:

Compound Melting point

2- (3'-isopropyl-4T-methoxy-phenyl) -indole at 160 ° C

Example 9 2- (2β-Methoxy-5-t-methyl-phenyl) -indole.

To a solution of 223 g (1 mol) of 2- (2'-hydroxy-5T-methyl-phenyl) -indole, prepared as in Example 1, in 1200 ml of N, N-dimethylformamide is added at a temperature of 90 ° C 65 Sodium methylate (1.2 g) and then 170 g (1.2 mol) methyl iodide dropwise.

After the addition is complete, the mixture is heated to 100 ° C for 3 hours. The reaction medium is allowed to cool and the crude product precipitates by addition of water. The precipitate is taken up in ether, washed and dried. The ether is evaporated and the product is purified by chromatography on a silica column with benzene as eluent to give 150 g of 2- (2f-methoxy-5'-methyl-phenyl) -indole. Mp. 119 ° C. Yield: 59%.

Example 10 2- (2T-Methoxy-4H-methyl-phenyl) -indole.

At a temperature of 25 ° C, 54 g (1 mole) of sodium methylate and 170 g (1.2 mole) of methyl iodide are added to a solution of 223 g (1 mole) of 2- (2f-hydroxy-4'-methyl-phenyl) - indole, prepared as in Example 1, in 1200 ml of N, N-dimethylformamide. The solution is then stirred for 2 hours and the crude product is precipitated by the addition of water. After recrystallization from benzene, 166 g of 2- (2T-methoxy-4R-methyl-phenyl) -indole are obtained. Mp. 125 ° C. Yield: 70%.

Example H

2- (3 T-Methoxy-1-ethoxy-phenyl) -indole.

To a mixture of 50 ml of N, N-dimethylformamide and 1.23 g (0.022 mol) of potassium hydroxide is added 4, 5 g (0.02 mol) of 2- (3, -methoxy-4, -hydroxy-phenyl) -indole, prepared as described in Example 4 and the reaction medium is heated to a temperature of 50 ° C. Over a period of 10 minutes, 4.68 g (0.03 mole) of ethyl iodide is added and the whole is heated to 60 ° C for two hours. After cooling, the reaction medium is poured into water and extracted with ether. The ether phase is washed with water until neutrality, dried and concentrated under reduced pressure.

After recrystallization from toluene, 3.06 g of 2- (3'-methoxy-4T-ethoxy-phenyl) -indole are obtained. Mp. 177 ° C. Yield: 60%.

Example 12 2- (3R-Methoxy-4, -n-dodecyloxy-phenyl) -indole.

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

27 144009

After two successive recrystallizations in ethanol, 20 g of 2- (3T-methoxy-4f-n-dodecyloxy-phenyl) -indole is obtained. Mp. 104 ° C. Yield: $ 50.

By analogy, the following compounds are prepared:

Compounds Melting point

2- (3, -Methoxy-4f-n-butyloxy-phenyl) -indole 140 ° C

(Ethanol)

2- (3'-Methoxy-4R-n-propyloxy-phenyl) -indole 138 ° C

(ethanol, then acetone)

2- (3, -methoxy-4'-isopropyloxy-phenyl) -indole 139 ° C

(ethanol, then acetone)

2- (3T, 4'-diethoxy-phenyl) -indole 163 ° C

(benzene, then ethanol)

2- (3T-benzyloxy-4T-methoxy-phenyl) -indole 174 ° C

(Ethanol)

2- (3-methyl-4T-n-dodecyloxy-phenyl) -indole 112 ° C

(Hexane)

2- (3, -methyl-4, -benzyloxy-phenyl) -indole 184 ° C

(ethanol, then acetone)

2- (3, -methoxy-4T-benzyloxy-phenyl) -indole 157 ° C

(Toluene)

2- (3T, 4'-methylenedioxy-phenyl) -indole 191 ° C

(Methanol)

2- (3T, 4f-Ethylenedioxy-phenyl) -indole 190 ° C

(Methanol)

Example 13 2- (2'-Methyl-it'-hydroxy-phenyl) -indole.

A solution of 1800 ml of benzene containing 237 g (1 mole) of 2- (2f-methyl-4T-methoxy-phenyl) -indole, prepared as in Example 2 * and 300 g (2.25 mole) of aluminum chloride, is refluxed for 2 hours. The reaction medium is cooled and extracted with ether. The ether phase is washed until neutrality and dried over anhydrous sodium sulfate.

The ether is evaporated and after recrystallization of benzene 167 g of 2- (2f-methyl-4r-hydroxy-phenyl) -indole are obtained. Mp. 106 ° C. Yield: $ 75.

By analogy, the following compounds are prepared:

Compound Melting point

2- (3T-methyl-4'-hydroxy-phenyl) -indole 222 ° C

(recrystallization from ethanol-water 95/5)