Polypropylene stabilizing anti-oxidant 2,3-dihydrobenz-4-oxa-1-thiin derivatives, compositions and method of use therefor

2,3-Dihydrobenz-4-oxa-1-thiins of the general formula I ##STR1## where R.sup.1, R.sup.2 and R.sup.3 are each hydrogen, methyl or methoxy, and R.sup.2 and R.sup.3 together may furthermore be a fused benzene ring, R.sup.4 is hydrogen or an m-valent aliphatic hydrocarbon radical which may be interrupted by sulfur and /or carry thiol groups as substituents, or is halogen when n is zero, X is --O--, --S-- or --O--CO--, m is 1 or 2 and n is zero or 1, are useful as antioxidants for organic materials.

The present invention relates to 2,3-dihydrobenz-4-oxa-1-thiins of the 
general formula I 
##STR2## 
where R.sup.1, R.sup.2 and R.sup.3 are each hydrogen, methyl or methoxy, 
and R.sup.2 and R.sup.3 together may furthermore be a fused benzene ring, 
R.sup.4 is hydrogen or an m-valent aliphatic hydrocarbon radical which may 
be interrupted by sulfur and/or carry thiol groups as substituents, or is 
halogen when n is zero, X is --O--, --S-- or --O--CO--, m is 1 or 2 and n 
is zero or 1. 
The present invention furthermore relates to the preparation of the 
compounds of the formula I and their use as antioxidants for organic 
materials, and to organic materials which contain the compounds I. 
Compounds of the type I' 
##STR3## 
R=H, organic radical ie. those which contain the structural unit of the 
chroman 
##STR4## 
are well known antioxidants. For example, alphatocopherol (vitamin E) is 
derived from chroman, and various chroman derivatives are described in, 
inter alia, European Laid-Open Application Nos. 0,036,160, 0,036,169 and 
0,057,427. 
It is an object of the present invention to provide industry with 
antioxidants which are even more effective than the chroman derivatives I 
known to date. 
We have found that this object is achieved by the dihydrobenzoxathiins 
defined at the outset. 
The novel compounds I differ from the known chroman derivatives in 
principle only in that they have a sulfur atom instead of a --CH.sub.2 -- 
group in the 4-position of the chroman skeleton; surprisingly, however, 
their activity as antioxidants is superior to that of the correspondinng 
chroman compounds. 
The compounds I are obtainable by conventional methods, in which the 
essential synthesis step is the condensation of a quinone II 
##STR5## 
with a thioglycol III 
##STR6## 
in which cyclization takes place. 
This condensation reaction involving cyclization takes place readily at 
40.degree.-150.degree. C., preferably 50.degree.-110.degree. C., 
preferably in the presence of an acid, with simultaneous elimination of 
water. Particularly suitable acids are mineral acids, such as hydrochloric 
acid and phosphoric acid, their concentration advantageously being such 
that the reaction mixture has a pH of less than 1. 
In general, it is preferable to carry out the reaction of II with III in 
the presence of a solvent or diluent, water being preferred. Other 
suitable solvents are water-soluble solvents such as alcohols, 
tetrahydrofuran and dioxane, as well as mixtures of these with water. 
Water-immiscible solvents, such as toluene, petroleum ether and 
chlorobenzene, may also be used. 
Those compounds I in which R.sup.4 is one of the hydrocarbon radicals 
conforming to the definition can be synthesized by the above procedure by 
first preparing one of the other compounds I in which m is 1, ie. a 
compound containing the side chain group --CH.sub.2 --OH, --CH.sub.2 --SH 
or --CH.sub.2 --Hal (where Hal is halogen, in particular Cl or Br), and 
then reacting the compound obtained, in a conventional manner, with a 
compound IV 
EQU R.sup.4 Y.sub.m IV 
where Y is a functional group capable of linking the hydrocarbon radical 
R.sup.4 to the group --CH.sub.2 --X.sub.n -- in conformity with the 
definition. 
If it is intended to prepare, for example, compounds I containing an ether 
or thioether group, a compound I possessing a side chain group (--CH.sub.2 
--OH) or (--CH.sub.2 --SH) is reacted with, for example, a halogen 
compound IV (where Y is halogen) or an olefinic compound IV (where Y is 
CH.sub.2 .dbd.CH--), or, conversely, a compound I containing the side 
chain group --CH.sub.2 --Hal is reacted with an alcohol or thiol IV (where 
Y is HO-- and HS--, respectively). 
Compounds I containing the ester group --CH.sub.2 --O--CO-- can be 
prepared, for example, by esterification or transesterification 
(Y=.vertline.--COOH.vertline., .vertline.--CO Hal.vertline., 
.vertline.--CO--O--CH.sub.3 .vertline.). 
If the coupling reactions take place with elimination of acids, eg. a 
hydrohalic acid, it is advisable to bind these by means of a base, such as 
sodium hydroxide solution, pyridine or trimethylamine. If the reaction is 
one of the other reactions, such as addition at an olefinic group or the 
esterification of an alcohol with an acid, the presence of a strong acid, 
such as p-toluenesulfonic acid, or of an acidic ion exchanger is 
advantageous. 
In other respects, the stated coupling reactions are standard operations in 
preparative chemistry, so that further description can be dispensed with 
here. 
If the group (--X.sub.n --R.sup.4) is halogen, it is also possible to 
halogenate the corresponding hydroxy compound. 
Starting compounds II are known, or are obtainable in a conventional manner 
(cf., for example, Houben-Weyl, Methoden der Organischen Chemie, 4th 
edition, volume 7/3a, pages 23-112). The same applies in the case of the 
thioglycols III (Houben-Weyl, 4th edition, volume 9, pages 22-23) and the 
monofunctional and bifunctional compounds IV. 
Since the compounds I are by their very nature sensitive to oxidation, it 
is advantageous to carry out all operations under a protective gas 
atmosphere, for example under nitrogen. 
Preferred compounds I are those in which R.sup.1, R.sup.2 and R.sup.3 are 
each methyl, R.sup.4 is an aliphatic C.sub.2 -C.sub.18 -hydrocarbon 
radical and n is 1. It has furthermore been found that sulfur, in the form 
of a thioether or thiol functional group, reinforces the antioxidative 
effect; hence, preferred radicals R.sup.4 are the sulfur-containing 
hydrocarbons conforming to the definition. Examples of such radicals are 
--CH.sub.2 --SH, --CH.sub.2 CH.sub.2 --S--CH.sub.2 CH.sub.3 and 
--CH(SH)--CH.sub.3. 
The novel compounds I are very useful as antioxidants for stabilizing 
organic materials to oxidation and thermal oxidation. Examples of such 
materials are plastics, foodstuffs, animal feeds and particularly 
sensitive substances such as dyes, vitamins, unsaturated fats and 
pharmaceutical, veterinary and cosmetic active ingredients and 
formulations. 
The concentration of I in the organic materials is in general from 0.005 to 
50% by weight. In the case of plastics, foodstuffs and animal feeds, 
concentrations from 0.005 to 1% by weight are usually sufficient. In 
contrast, the concentrations in the case of vitamins and similar highly 
sensitive substances may be up to 50% by weight. 
In the case of plastics, especially polypropylene, the compounds I 
substantially increase not only the resistance to aging but also the 
stability to processing. 
We have furthermore found that the antioxidative effect of the compounds I 
is reinforced by aliphatic and cycloaliphatic polyols, which act as 
synergistic agents. Examples of such polyols, which should contain not 
less than 2, preferably 3-6, free alcoholic hydroxyl groups in the 
molecule, are ethylene glycol, glycerol, trimethylolpropane and in 
particular sugars and hydrogenated sugars, such as sorbitol. Some of the 
hydroxyl groups of the polyols may furthermore be etherified with alkanols 
or esterified with fatty acids. 
The concentration of the polyols in the organic materials is from 0.005 to 
90% by weight, and the sum of the concentrations of I and the polyols may 
be as high as 99% by weight. In the case of less sensitive materials, such 
as plastics, foodstuffs and animal feeds, the concentration of I is about 
0.001-0.3% by weight, and the ratio of the concentration of I to that of 
the polyols is preferably from 1:1 to 1:10. 
The compounds I also provide further possible methods for synthesizing 
tocopherol-like substances.

EXAMPLES 
Below, the radical 
##STR7## 
is referred to as radical A, and the radical 
##STR8## 
is referred to as radical B. 
EXAMPLE 1 
Preparation of A--CH.sub.2 --OH 
150 g (1.0 mole) of molten trimethylquinone was added to a solution of 151 
g (1.4 moles) of propane-1,2-diol-3-thiol, 1 l of water and 25 ml of 
concentrated hydrochloric acid under a nitrogen atmosphere at 50.degree. 
C., and the mixture was heated at the boil for 2.5 hours. When the mixture 
was subsequently cooled, the above compound was obtained in the form of 
pale beige crystals. 
The crystals were separated off, washed with warm water and cold water, 
dried over calcium chloride and recrystallized from 500 ml of acetonitrile 
to give 177 g of product. A further 46 g of the product were obtained from 
the mother liquor, so that the total yield was 92%. Mp. 
118.degree.-120.degree. C. 
EXAMPLE 2 
Preparation of A--CH.sub.2 --Br 
48 g (0.2 mole) of the product of Example 1 were added a little at a time 
to a brominating reagent prepared from 55 g (0.21 mole) of 
triphenylphosphine, l of dry methylene chloride and 34 g (0.212 mole) of 
bromine. The dark brown solution was heated at the boil (about 40.degree. 
C.) for 3 hours and then stirred into 1 L of a 5% strength by weight 
sodium bicarbonate solution. 
Thereafter, the organic phase was separated off, washed with dilute NaCl 
solution, dried with Na.sub.2 SO.sub.4 and evaporated down under reduced 
pressure in a rotary evaporator. The residue was taken up with 250 ml of 
diethyl ether, triphenylphosphine oxide separating out. The remaining 
organic phase was evaporated down, the residue was taken up with 200 ml of 
a mixture of 3 parts by volume of cyclohexane and 1 part by volume of 
ethyl acetate, and the solution was filtered over silica gel and eluted 
with about 2 L of the same solvent. Evaporation of the filtrate gave the 
above bromine compound in the form of brownish crystals, which had a 
melting point of 87.degree.-88.degree. C. after extraction by boiling with 
petroleum ether. Yield: 75%. 
EXAMPLE 3 
Preparation of B--CH.sub.3 --OH 
34.4 g (0.2 mole) of powdered 2-methyl-1,4-naphthoquinone were added a 
little at a time to a solution of 30.2 g (0.28 mole) of 
propane-1,2-diol-3-thiol, 200 ml of water and 5 ml of concentrated 
hydrochloric acid at 50.degree. C. under a nitrogen atmosphere, and the 
mixture was heated at the boil for 2 hours. Thereafter, the aqueous phase 
was separated off at 70.degree. C. and the remaining melt was washed twice 
with the same volume of water, at this temperature. The subsequent 
suspension in cold water gave the product as a pale gray crystalline mass, 
which was separated off, dried over CaCl.sub.2 and then recrystallized 
from 200 ml of acetonitrile to give pale gray to colorless crystals of 
melting point 142.degree.-144.degree. C. Yield: about 70%. 
EXAMPLE 4 
Preparation of A--CH.sub.3 
This compound was prepared in 60% yield from trimethylquinone and 
propan-2-ol-1-thiol in the manner described in Example 1. Mp. 
86.degree.-87.degree. C. 
EXAMPLE 5 
Preparation of (A--CH.sub.2 --O--CO--CH.sub.2 --CH.sub.2 --).sub.2 S 
24 g (0.1 mole) of the product from Example 1 were heated together with 8.9 
g (0.05 mole) of thiodipropionic acid and 0.5 g of p-toluenesulfonic acid 
in 50 ml of toluene under a nitrogen atmosphere, the water being separated 
off. After 3 to 4 hours, the mixture was cooled, and some of the product 
was precipitated. The mixture was brought into solution again with 
methylene chloride, and the solution was extracted by shaking with dilute 
NaHCO.sub.3 solution, washed with water, dried, treated with 2 g of active 
carbon and evaporated down under reduced pressure in a rotary evaporator. 
The residue was recrystallized from about 50 ml of isopropanol. Yield: 
62%; mp. 81.degree.-83.degree. C. 
EXAMPLE 6 
Preparation of A--CH.sub.2 --O--CO--CH.sub.2 --SH, 
24 g (0.1 mole) of the product from Example 1 were heated together with 
10.1 g (0.11 mole) of thioglycolic acid and 0.5 g of p-toluenesulfonic 
acid in 50 ml of toluene under a nitrogen atmosphere, with removal of the 
water. When the reaction mixture was worked up in a conventional manner, 
the above compound was obtained in the form of a pale brown oil, in a 
yield of 95%. 
EXAMPLE 7 
Preparation of A--CH.sub.2 --O--CO--C.sub.17 H.sub.35 
This compound was prepared in a yield of 61% from the compound A--CH.sub.2 
--OH and stearic acid by a method similar to that desired in Example 6. 
Mp. 69.degree.-71.degree. C. 
EXAMPLE 8 
Preparation of B--CH.sub.2 --O--CO--C.sub.17 H.sub.35 
This compound was prepared in a yield of 77% from the compound B--CH.sub.2 
--OH and stearic acid by a method similar to that described in Example 3, 
beige crystals of melting point 54.degree.-56.degree. C. being obtained. 
EXAMPLE 9 
Stabilizing effect of various antioxidants in lard 
Lard containing in each case 0.02% by weight of various antioxidants was 
subjected to the peroxide test (Oil and Soap, 15 (1938), 184). In this 
test, the samples were stored in the presence of air at 80.degree. C. 
until the peroxide number (PON) reached 50. The longer this time t, the 
more effective is the antioxidant. 
The test results, which speak for themselves, are shown in Table 1. 
TABLE 1 
______________________________________ 
Peroxide test for Lard according to Example 9 
According 
Test Antioxidant to Example 
t [days] 
______________________________________ 
For comparison 
1 V alpha-tocopherol -- 1 
2 V 2,5,7,8-tetramethyl-2- 
-- 5 
(2-hydroxyeth-1-yl)-5- 
hydroxychroman 
3 V as for 2 V, but esterified 
-- 4 
in the side chain with 
stearic acid 
According to the invention 
1 A--CH.sub.2 --OH 1 7 
2 B--CH.sub.2 --OH 3 12 
3 (A--CH.sub.2 --O--CO--CH.sub.2 CH.sub.2).sub.2 
5 13 
4 A--CH.sub.2 --O--CO--CH.sub.2 --SH 
6 10 
5 B--CH.sub.2 --O--CO--C.sub.17 H.sub.35 
8 9 
______________________________________ 
EXAMPLE 10 
Stabilizing effect of various antioxidants in dry canthaxanthin powder 
Canthaxanthin, which is used as an additive in feeds for layers, was mixed 
with 4% by weight of the antioxidant A--CH.sub.2 --O--CO--C.sub.17 
H.sub.35 according to Example 7, and the mixture was processed in a 
conventional manner with gelatine to give a dry powder. This powder was 
then mixed with a commercial feed for layers so that the concentration of 
active ingredient was 200 ppm. After storage for 8 weeks at 40.degree. C. 
and 70% relative humidity, the residual canthaxanthin content was 66% of 
the initial concentration. 
In a comparative test without the addition of an antioxidant, no 
canthaxanthin was detectable. When the antioxidant according to test 3 V 
in Table 1 was used, the residual content of active ingredient was only 
43%. 
EXAMPLE 11 
Stabilization of polypropylene to processing 
Pure polypropylene powder having a mean molecular weight of 10,000 was 
mixed, in each case, with 0.1% by weight of an antioxidant or of a mixture 
of various antioxidants, and the mixture was extruded at 250.degree. C. 
and then converted to granules. Extrusion and granulation were repeated 
several times, the melt flow index MFI of the particular granular sample 
being measured at 190.degree. C. in accordance with DIN 53,135 after the 
1st, 3rd, 5th and 8th passes. The higher the melt index, the greater is 
the degradation of the polypropylene as a result of the thermal load 
during extrusion, and the lower is the stability to processing. 
The color of the material after the 8th extrusion pass was also determined. 
The results of the tests are shown in Table 2. 
EXAMPLE 12 
Stabilization of polypropylene: long-term stability 
The material described in Example 11 was subjected to oven aging according 
to DIN 53,383 and then processed first to granules at 220.degree. C. and 
then to 20.times.20.times.1 mm.sup.3 panels at 220.degree. C. The panels 
were stored at 140.degree. C. in a through-circulation oven with a supply 
of fresh air. 
In this test, the panels became brittle, and the time t taken in each case 
to reach a certain degree of embrittlement, identical for all tests, was 
determined. This time is not only a direct measure of oven aging but also 
an indirect measure of the long-term stability. 
The results of these tests are likewise shown in Table 2. 
TABLE 2 
__________________________________________________________________________ 
Stabilization of polypropylene according to Examples 11 and 12 
Test 
Antioxidant 
Synergistic MFI after passes 
Oven aging 
No. 
according to Example 
agent q.sup.1 
Color.sup.2 
1 3 5 8 t .vertline.h.vertline. 
__________________________________________________________________________ 
For comparison 
1 V 
-- sorbitol 
-- 
0 7 13 20 30 
2 
2 V 
see 3 V from Table 1 
-- 0 3 4 6 7 8 
200 
3 V 
" sorbitol 
2 3 4 5 6 7 
200 
4 V 
" " 4 2 5 6 9 11 
150 
According to the invention 
1 Example 7 -- 0 3 5 6 8 10 
400 
2 " sorbitol 
2 3 5 6 7 9 
290 
3 " " 4 2 5 5 6 7 
200 
4 " " 6 2 5 6 7 10 
--.sup.3 
__________________________________________________________________________ 
.sup.1 ratio of synergistic agent to antioxidant 
.sup.2 between 0 (colorless) and 6 (brown) 
.sup.3 not measured