DERIVES DE 3,5-DICARBOXYDIHYDROPYRIDINE

3,5-DICARBOXY DIHYDROPYRIDINE DERIVATIVES

Abrégé anglais

ABSTRACT OF THE DISCLOSURE
The invention is concerned with new 3,5-dicarboxy
dihydropyridine derivatives having the general formula:
<IMG> (I)
wherein the radicals R1 are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to 16
carbon atoms, a butenyl radical, a phenyl radical or a benzyl
radical, the radicals R2 are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to 4
carbon atoms, an allyl radical, a propargyl radical, an
.omega. -halogenoethyl group, a benzyl radical, a benzyl radical
substituted on the ortho- or para-position by a halogen atom or
a methyl radical, a cinnamoyl radical, a phenyl radical, a
phenyl radical substituted on the para-position by a halogen
atom or a methyl radical, a radical of the formula R4-O-(CH2)N-,
where n n is 1, 2, 3 or 4 and R4 represents a branched- or
straight-chain alkyl group containing from 1 to 4 carbon atoms,
unsubstituted or substituted on the .omega.-position by a halogen
atom, or R4 represents a phenyl group, and R3 represents a
hydrogen atom or a branched- or straight-chain alkyl group
containing from 1 to 7 carbon atoms, with the proviso that when R1
represents a methyl radical and R3 a hydrogen atom, R2 does not
represents an alkyl or phenyl radical. The compounds of the
invention are useful as stabilizers for vinyl resins.

Revendications

The embodiments of the invention in which an
exclusive property or privilege is claimed are defined as
follows:
1. 3,5-Dicarboxy dihydropyridine derivatives
having the general formula:
<IMG> I
wherein the radicals R1 are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to
16 carbon atoms, a butenyl radical, a phenyl radical or a
benzyl radical, the radicals R2 are the same and each
represents a branched- or straight-chain alkyl group con-
taining from 1 to 4 carbon atoms, an allyl radical, a
propargyl radical, an .omega.-halogenoethyl group, a benzyl radical,
a benzyl radical substituted on the ortho- or para-position
by a halogen atom or a methyl radical, a cinnamoyl radical,
a phenyl radical, a phenyl radical substituted on the para-
position by a halogen atom or a methyl radical, a radical of
the formula R4-O-(CH2)n-, wherein n is 1, 2, 3 or 4 and R4
represents a branched- or straight-chain alkyl group con-
taining from 1 to 4 carbon atoms, unsubstituted or substituted
on the .omega.-position by a halogen atom, or R4 represents a
phenyl group, and R3 represents a hydrogen atom or a branched-
or straight-chain alkyl group containing from 1 to 7 carbon
atoms, with the proviso that when R1 represents a methyl
radical and R3 a hydrogen atom, R2 does not represent an
alkyl or a phenyl radical, and excluding:
2,6-dimethyl-3,5-dicarbobenzyloxy-1,4-dihydropyridine,
2,6-dimethyl-3,5-dicarbocinnamyloxy-1,4-dihydropyridine,
2,6-dimethyl-3,5-dicarbomethoxy-4-phenyl-1,4-dihydropyridine,
37

2,6-diphenyl-3,5-dicarboethoxy-1,4-dihydropyridine,
2,6-dimethyl-3,5-di-(2'-carbomethoxy-ethoxy)-l,4-dihydropyri-
dine,
2,6-dimethyl-3,5-di-(2'-carboethoxy-ethoxy)-1,4-dihydropyri-
dine,
2,6-dimethyl-3,5-di-(2'-carbobutoxy-ethoxy)-,4-dihydropyridine,
2,6-dimethyl-3,5-di-(2'-carbophenoxy-ethoxy)-1,4-dihydropy-
ridine, and
2,4,6-trimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine.
2. Derivatives according to claim 1, wherein R3
represents a hygrogen atom.
3. 2,6-Dimethyl-3,5-dicarboallyloxy-1,4-dihydro-
pyridine.
4. 2,6-Dimethyl-3,5-dicarbopropargyloxy-1,4-
dihydropyridine.
5. Process for the preparation of the compounds
of general formula I:
<IMG> (I)
wherein the radicals R1 are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to
16 carbon atoms, a butenyl radical, a phenyl radical or a
benzyl radical, the radicals R2 are the same and each
represents a branched- or straight-chain alkyl group con-
tainlng 1 to 4 carbon atoms, an allyl radical, a propargyl
radical, an .omega.-halogenoethyl group, a benzyl radical, a benzyl
radical substituted on the ortho- or para-position by a
halogen atom or a methyl radical, a cinnamoyl radical, a
phenyl radical, a phenyl radical substituted on the para-
38

position by a halogen atom or a methyl radical, a radical of
the formula R4-O(CH2)n-, wherein n is 1, 2, 3 or 4 and R4
represents a branched- or straight-chain alkyl group con-
taining from 1 to 4 carbon atoms, unsubstituted or substituted
on the .omega.-position by a halogen atom, or R4 represents a
phenyl group, and R3 represents a hydrogen atom or a branched-
or straight-chain alkyl group containing from 1 to 7 carbon
atoms, with proviso that when R1 represents a methyl radical
and R3 a hydrogen atom, R2 does not represent an alkyl or a
phenyl radical, wherein a compound of the general formula:
<IMG> (II)
wherein R1 and R2 have the same meanings as in claim 1, is
reacted with an aldehyde of the general formula:
<IMG> (III)
Wherein R3 has the same meanings as in claim 1, and with
ammonia.
6. Process according to claim 5, wherein use is
made of an aldehyde of the formula (III) in which R3 represents
a hydrogen atom.
7. Process for stabilizing a vinyl resin, wherein
a compound of general formula I:
<IMG> (I)
wherein the radicals R1 are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to
16 carbon atoms, a butenyl radical, a phenyl radical or a
benzyl radical, the radicals R2 are the same and each
represents a branched- or straight-chain alkyl group con-
39

taining from 1 to 4 carbon atoms, an allyl radical, a
propargyl radical, an .omega.-halogenoethyl group, a benzyl radical,
a benzyl radical substituted on the ortho- or para-position
by a halogen atom or a methyl radical, a cinnamoyl radical,
a phenyl radical substituted on the para-position by a halogen
atom or a methyl radical, a radical of the formula R4-O-(CH2)n-,
wherein n is 1, 2, 3 or 4 and R4 represents a branched- or
straight- chain-alkyl group containing from 1 to 4 carbon
atoms, unsubstituted or substituted on the .omega.-position by a
halogen atom, or R4 represents a phenyl group, and R2
represents a hydrogen atom or a branched- or straight-chain
alkyl group containing from 1 to 7 carbon atoms, with proviso
that when R1 represents a methyl radical and R3 a hydrogen
atom, R2 does not represent an alkyl or a phenyl radical, is
introduced into a polymer or copolymer of vinyl chloride.
8. Process according to claim 7, wherein, in the
compound of the formula I, R3 represents a hydrogen atom.
9. Process according to claims 7 or 8, wherein the
compound of the general formula I is introduced into the vinyl
resin in a proportion of 0.01 to 1 part by 100 parts of resin
by weight.
10. Process according to claims 7 or 8, wherein
the compound of the general formula I is introduced into the
vinyl resin in a proportion of 0.01 to 0.5 part by l00 parts
of resin by weight.
11. Process according to claims 7 or 8, wherein
the vinyl resin is polyvinyl chloride.
12. Process according to claims 7 or 8, wherein the
vinyl resin is a vinyl chloride-vinyl acetate copolymer.

13. Process according to claims 7 or 8, wherein
the vinyl resin is a vinyl chloride-vinylidene chloride
copolymer.
14. Polymers and copolymers of vinyl chloride
containing as stabilizer at least one compound of general
formula I:
<IMG>
wherein the radicals R1 are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to
16 carbon atoms, a butenyl radical, a phenyl radical or a
benzyl radical, the radicals R2 are the same and each repre-
sents a branched- or straight-chain alkyl group containing
from 1 to 4 carbon atoms, an allyl radical, a propargyl
radical, an .omega.-halogenoethyl group, a benzyl radical, a benzyl
radical substituted on the ortho- or para-position by a
halogen atom or a methyl radical, a cinnamoyl radical, a phenyl
radical, a phenyl radical substituted on the para-position by
a halogen atom or a methyl radical, a radical of the formula
R4-O(CH2)n-, wherein n is 1, 2, 3 or 4 and R4 represents a
branched- or straight-chain alkyl group containing from 1 to
4 carbon atoms, unsubstituted or substituted on the .omega.-position
by a halogen atom, or R4 represents a phenyl group, and R3
represents a hydrogen atom or a branched- or straight-chain
alkyl group containing from 1 to 7 carbon atoms with proviso
that when R1 represents a methyl radical and R3 a hydrogen
atom, R2 does not represent an alkyl or a phenyl radical.
15. Polymers and copolymers of vinyl chloride
according to claim 14, wherein said at least one compound of
general formula I as defined in claim 14, is contained in a
41

proportion of 0.01 to 1 part by 100 parts of resin by weight.
16. Polymers and copolymers of vinyl chloride
according to claim 14, wherein said at least one compound of
general formula I as defined in claim 14, is contained in a
proportion of 0.01 to 0.5 part by 100 parts of resin by weight.
17. Polymers and copolymers of vinyl chloride
according to claim 14, further containing calcium and calcium-
zinc salts, as primary stabilizers, said at least one compound
of general formula I acting as secondary stabilizer.
18. Plastified polymers and copolymers of vinyl
chloride aceording to claim 14, further containing barium-
cadmium and calcium-zinc salts as primary stabilizers, said
at least one compound of general formula I acting as secondary
stabilizers.
42

Description

-
9176
This invention relates to new additives for plastic
materials and, more particularly, to new stabilizers for
vinyl resins such as, for insta`nce, polyvinyl chloride and
its copolymers.
The new additives for plastic materials with which
the present invention is concerned are 3,5-dicarboxy
- dihydropyridine derivatives having the general formula:
H R
R O-C ~ C-OR
~ ~ 2
Rl N l `
wherein the radicals Rl are the same and each represents a
branched- or straight-chain alkyl group containing from 1 to
16 carbon atoms, a butenyl radical, a phenyl radical or a
benzyl radical, the radicals R2 are the same end each
represents a branched- or straight-chain alkyl group containing
from l to 4 carbon atoms, an allyl radical, a propargyl
radical, an ~-halogenoethyl group, a benzyl radical substituted
on the ortho- or para-position by a halogen atom or a methyl
radical, a cinnamoyl radical, a phenyl radical, a phenyl
radical substituted on the para-position by a halogen atom
or a methyl radical, a radical of the formula R4-O-(CH2)n-,
wherein n is 1, 2, 3 or 4 and R4 represents a branched- or
stralght-chain alkyl group containing from 1 to 4 carbon
atoms, unsubstituted or substituted on the w-position by a
halogen atom, or R4 represents a phenyl group, and R3
rcprcscnts a hydrogcn atom or a brancllcd- or strai~ht-chain
alkyl group containing from 1 to 7 carbon atoms, with the
proviso that when Rl represents a methyl radical and R3 a
hydrogen atom, R2 does not represent an alkyl or a phenyl
radlcal.
~31 - 1- ~

`: 111~17~i
A particularly preferred class of compounds
having the general formula I is represented by those compounds
of the formula I in which R3 is hydrogen. These dihydro-
pyridines bearing no substituents in position-4 show a
greater stabilizing power than the corresponding 4-substituted
dihydropyridines.
Some compounds of formula I are new. Among these
new compounds, invention can be made of the following,
preferred compounds:
2,6-Dimethyl-3,5-dicarboallyloxy-1,4-dihydropyridine (1)
2,6-Dimethyl-3,5-dicarbopropargyloxy-1,4-dihydropyridine (2)
2,6-Dimethyl-3,5-di-(2'-carbochloro-ethoxy)-1,4-dihydropyridine
(3)
2,6-Dimethyl-3,5-di-(4'-carbomethoxy-benzyloxy)-1,4-dihydro-
pyridine(4)
2,6-Dimethyl-3,5-di-(2'-carbochloro-benzyloxy)-1,4-dihydro-
pyridine (5)
2,6-Dimethyl-3,5-di-(2'-carbomethyl-benzyloxy)-1,4 dihydro-
pyridine (6)
2,6-Dimethyl-3,5-di-(4'-carbochloro-benzyloxy)-1,4-dihydro-
pyridine (7)
2,6-Dimethyl-3,5-dicarbomethoxy-4-hexyl-1,4-dihydropyrldine
(8)
2,6-Dimethyl-3,5-dicarbomethoxy-4-propyl-1,4-dihydropyridine ..
(9)
2,4,6-Trimethyl-3,5-dicarbophenoxy-1,4-dihydropyridine (10)
2,4,6-Trimethyl-3,5-di-(4'-carbomethylphenoxy)-1,4-dihydro-
pyridine (11)
2,4,6-Trimethyl-3,5-dicarbobenzyloxy-1,4-dihydropyridine (12)
2,4,6-Trimethyl-3,5-dicarboallyloxy-1,4-dihydropyridine (13)
2,4,6-Trimethyl-3,5-di-(4' carbochloro-benzyloxy)-1,4-
dihydropyridine(14)
' ' ', ' ' ,

111~176
2,6-Dimethyl-3,5-dicarbomethoxy-4-(1-propenyl)-1,4-dihyd~o-
pyridine (15)
2,6-Dibenzyl-3,5-dicarbethoxy-1,4-dihydropyridine (16)
2,6-Di-(3-butenyl)-3,5-dicarbomethoxy-1,4-dihydropyridine
(17)
2,6-Diphenyl-3,5-dicarbomethoxy-1,4-dihydropyridine (18)
- 2 a -

` ` ` 1~191~6
2,6-Dimethyl-3,5-di(2" -carbochloro-2' ethoxy-ethoxy)-1,4~ ~;
dihydropyridine (19)
2,6-Ditridecyl-3,5-dicarbomethoxy-1,4-dihydropyridine (20)
Some other compounds of fo~mula I are already known.
These known compounds that are ~isted hereunder have never-
the less to be considered as new stabilizers of polyvinyl
chloride: . ;
2~6-dimethyl-3~5-dicarbobenzyloxy-1~4-dihydrOpyridine (21) ~'
2,6-dimethyl-3,5-dicarbocinnamyloxy-1,4-dihydropyridine (22)
,2,6-dimethyl-3,5-dicarbomethoxy-4-phenyl-1,4-dihydropyridine ~:
,~23) -:~
2,6-diphenyl-3,5-dicarboethoxy-1,4-dihydropyridine (24) ~,-
2,'6-dimethyl-3,5-di-(2'-carbomethoxy-ethoxy)-1,4-dihydro- ~' -
pyridine (25)
2,6-dimethyl-3,5-di-(2'carboethoxy-ethoxy)-1,4-dihydro- ,
pyridine (26) -:
2,6-dimethyl-3,5-di-(2'-carbobutoxy-ethoxy)~1,4~dihydro-
pyridine (27) ' '~
2,6-dimethyl-3,5-di-(2'carbophenoxy-ethoxy)-1 ! 4-dihydro- ''
pyridine (28), and ~ ,
2,4,6-trimethyl-3,5-dicarbomethox,y-1,4-dihyd~opyridlne (29)
The invention also rela,tes to the process of prepa, .
ratlon of the compounds of form~la I.
The compounds of the invention may be prepared
according to the HANTZSCH synthesis, d,e,scribed in Chemical
Revlews 72, I, 1972, by reacting a compound of the general
ormula:
o
Rl-C-CT~2-COOR2 II
- 30 wherein Rl and R2 have the same meanings as in formula I,
with an aldehyde of the general formula~
:E3
'. ' ' ' . ; '-' ' " .: ,
,-

L76
R3CH III
wherein R3 has the same meanings as in formula I and with
ammonia.
- 3 a -
:

~1191~6
The compounds of formula II, wherein Rl represents
a methyl radical, can be prepared by one or the other of the
following methods:
1) By reacting compound of the formula H2 C=C-0\ with
CH2 -C=O
an alcohol of the general formula :
R2OM IV
wherein R2 has the same meanings as in formula I, as
described in Journal of Chemical Society, 854-60, 1954 and
in Organic Synthesis 42, 28, 1962;
2) By transesterifying in a known manner methyl acetoacetate
O O
Il . :
of the formula CH3-C-CH2-C-OCH3 by means of an alcohol of
the above formula IV.
The compounds of general formula II, wherein Rl
represents an alkyl chain containing from 2 to 16 carbon atoms
may be prepared by reacting a halogenated derivative of the
general formula :
R5X V
wherein R5 has the same meanings as Rl as defined above but
having one carbon atom less, with a compound of formula II
wherein Rl represents a methyl group, as described in Journal
of American Chemical Society 4, 6702-6704, 1970 and in Bulletin
de la Société Chimique de France, 945-51, 1964.
Vinyl resins are known to deteriorate under the
influence of heat and it is necessary to add a stabilizing
agent to these masses of synthetic materials in order to
retard thermodegradation and thus delay coloration of the resin.
Vinyl resins are also known to deteriorate under the
influence of sunlight and a change in the original coloration
may result therefrom.
This problem is particularly important where contain-
ers for food and drink are concerned. It is readily appreciated
: - 4 -

~119176
that food and drink could not be packed in containers of which
the coloration may change in course of time.
The problem is the same with regard to floor-coverings,
of which the coloration must also remain stable for a long
period of time.
That is why stabilizers which are both thermostabil-
izers and photostabilizers are specially recommanded for vinyl
resins.
Amongst the organic stabilizers there are already
known the 1,4-butanediol- bis amino crotona e, the methyl
aminocrotonate and the aminocrotonate of alcohols containing
from 16 to 18 carbon atoms, compounds which have been described
in "Les Matières Plastiques dans l'Industrie Alimentaire" by
R. LEFAUX, C.F.E. Paris (1972).
2-Phenyl-indole, however, is especially valuable due
both to its good stabilizing power and to its low toxicity.
It is, moreover, widely used in the plastic industry to
stabilize vinyl polymers and co-polymers, especially those which
are to be used for containing food and drink.
The compounds of the invention have many advantages
over the aminocrotonates hereabove mentioned and also over
2-phenyl-indole.
For instance, the compounds of the invention already
show a good stabilizing power when they are introduced into
a vinyl resin in the proportion of 0.01 to 0.2 part per hundred
parts of re~in (p.h.p.r.), whereas the aminocrotonates and 2-
phenyl-indole are to be used in a minimum proportion of 0.2
p.h.p~r. Moreover, the compounds of the invention are also
superior to 2-phenyl-indole when used in a proportion of 0.2
to 1 p.h.p.r. This means that the stabilizers according to
the invention can be used in lower proportions than well-known
stabilizers.
_ 5 --

~119176
This possibility of using lower proportions of
stabilizers is a definite asset as far as plastic containers
for food and drink are concerned. Besides the lower cost-
price obtained, it should be remembered that when the concentra-
tion in stabilizer is lower, the amount of stabilizer extracted
by the food or drink will also be lower. -
Moreover, the compounds of the invention present a
photostabilizing power which is far from negligible resulting
in a better resistance of the resin to sunlight, i.e. in a
reduced tendency to darken.
In addition, in resins requiring the use of a dye,
which is very frequent in bottles for mineral water, the
dihydropyridines according to the invention improve the basic
colour and markedly increase the stability of the coloration. -~
Finally, the dihydropyridines of the invention possess
valuable antioxidant properties, which are superior to those of ;~
the phenols, which are the most widely used antioxidants in vinyl
resins (for instance, 2,6-diterbutyl-4-methyl-phenol).
When compared more particularly, to 2-phenyl-indole,
the dihydropyridines according to the invention also present ;
the following advantages:
- ~etter transparency of the resin;
- The colorations which are obtained do not affect the trans-
parency of the resin and are perfectly stable; '!' ",
- Absence of yellowish tinges which are very common in vinyl
resins. This enables the use of blue-tinting agents to be
avoided;
r - When the dihydropyridines of the invention are used as
secondary stabilizers in resins containing as primary
stabilizer~ calcium and calcium-zinc salts, they enable, when
compared to 2-phenyl-indole used under the same conditions,
the content of zinc in the resin to be diminished without
- 6 -

.
1~19176
affecting the thermostability of the latter. This is important
since it is known that too much zinc causes defects in resin;
- When the compounds of the invention are used as secondary
stabiliæers in a plastified resin, i.e. a resin containing
as primary stabilizers barium-cadmium and calcium-zinc salts,
they enable the content in cadmium, a very expensive and very
toxic product, to be diminished while improving appreciably
the basic colour and increasing thermostability.
Amongst the compounds of the invention, the stabilizers
listed hereunder have been found to be particularly valuable:
2,6-Dimethyl-3,5-dicarboallyloxy-1,4-dihydropyridine (1)
2,6-Dimethyl-3,5-dicarbopropargyloxy-1,4-dihydropyridine (2)
2,6-Dimethyl-3,5-dicarbobenzyloxy-1,4-dihydropyridine (21)
2,4,6-Trimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine (29)
The stabilizers of formula I are incorporated in vinyl
resins in a proportion of 0.01 to 1 p.h.p.r. and preferably
of 0.01 to 0.5 p.h.p.r.
The toxicity of the stabilizers of the invention was
studied first and the satisfactory results obtained were such
as to justify continuation of the investigation.
A. Acute toxicitv
The acute toxicity of the stabilizers of the invention
was measured by determining the dose of substance which
pro~oked the death of 50% of the treated animals (LD50~.
A LD50 superior to 2g/kg was found in both mice and
rats, no toxic symptoms being observed after 15 days.
B. Studv of thermostabilizin~ power
The study of the thermostabilizing power of the
compounds of the invention was extremely thorough.
Its covers several phases, each of which is important
from the point of view of the use of these stabilizers.
1) Statlc thermostability_
-- 7 --

- \
11~9~76
This study was carried out according to the GARDNER
method, described in British Patent N 1,489,685.
The reference substance was 2-phenyl-indole, a well-
known and widely used stabilizer.
The stabilizer (dihydropyridine or 2-phenyl-indole)
and the other usual ingredients were mixed with powdered vinyl
resins and the mixtures were calendered at a temperature of
160C to give rigid sheets.
The sheets were then heated in a thermostated oven
(185C or 210C) for different intervals of time until incipient
carbonization.
The coloration of the samples was compared to a
standard scale of coloration, known as the GARD~ER scale and
wa~ expressed in terms of the reference figures of the GARDNER
scale.
This study was carried out with the following resin:
Inaredients Parts b~ weiqht
Polyvinyl chloride resin 100
Anti-shock resin 9
Epoxide soja bean oil 2
Calcium-12-Hydroxy-stearate 0.2
SL 2016 0.1
Stabilizer 0.3 or 1.55.10 3 mol
SL 2016 is a solution of zinc-2-ethyl-hexanoate in a
mixture of hydrocarbons boiling between 158C and 184C.
The first trial was carried out at 210C with a
resin containing 0.3 part by weight of stabilizer, the sheets
being removed from the oven every three minutes over a period
of 21 minutes.
The following results were obtained :

1~19176
. . Time in minutes
Stablllzer
O 3 6 9 12 15 18 21
1 1 1 2 4 7 Burnt
21 1 1 2 35 . 5 14 Burnt .
2-Phenyl-
indole 1 2 2 10 11 16 Burnt
4 1 1 2 4 6 11 Burnt
23 1 2 3 13 14 15 Burnt
29 1 2 3 6 7 10 10. 5 Burnt
8 1 2 3 6 8 10. 5 11 Burnt
~-Phenyl-
indole 1 2 3 . 510 . 513 14 Burnt
6 1 1 1.5 3 4 7 Burnt
2-Phenyl-
indole 1 1 3 8 13 13 Burnt
,....
1 1 2 3 6 10. 5 Burnt
2-Phenyl-
indole . 1 3 3 4 11 13 Burnt
22 1 1 2 4 11 Burnt
2-Phenyl-
indole 1 2 2 9 11 Burnt
:'
3 1 1 3 4 5 10 . 5 Burnt :
2-Phenyl- 1 1 3 510 . 5 11 Burnt
,
2 1 1 1 4 8 12 Burnt
indole 1 2 3 11 14 18 Burnt
7 1 1 2 410. 5 14 Burnt
2-Phenyl-
30indole 1 1 2 6 14 14 Burrt
_ 9 _
.: .

~9~76
Time in minutes
Stabilizer
0 3 6 9 12 15 18 21
17 1 1 2 8 9Burnt
2-Phenyl-
indole 1 1 2 11 13 16 Burnt
16 1 l 3 4 ll 18 Burnt
2-Phenyl-
indole l l 3 9 14 18 Burnt
l 1 1 1 l 4 11 17
2-Phenyl-
indole 1 2 2 5 2.5 10 13 16Burnt
26 1 l 1 1 1.5 3 llBurnt :
18 l l 2 2 2 3 6Burnt
1 l 1.5 2 22.5 4 7
2-Phenyl-
indole 1 1 1 2 2 4 10.5 11
19 1 1 1 2 3 10 13Burnt
202~PihnednoYle~ 1 1 1 2 4 11 13Burnt
27 1 1 l 2 5 14 Burnt .
2-Phenyl
indole 1 1 2 3 5 14 17Burnt
28 l l l 3 4 5 10Burnt
2-Phenyl-
indole 1 1 1 3 5 11 13Burnt
The above results show a marked superiority of the
thermostabilizing power of the dihydropyridines over 2-phenyl-
indole, at least up to 12 minutes.
The coloration of the reqins stabilized with compound~
1,2, 4, 5 and 21 is considerably less over the period from 0
to 3 minutes.
-- 10 _

11~9176
Compounds 1, 2, 3, 16 and 17 have proved to be
greatly superior to 2-phenyl-indole.
A second trial was performed at a temperature of
185C, with a resin containing 0.3 part of stabilizer, the
samples being removed from the oven every 6 minutes over a
period of 24 minutes, then every 3 minutes until the 42nd
minute (or until carbonization).
The results given hereunder were obtained:
. -
Time in minutes
Stabilizer _ _
0 612 18 24 27 30 33 36 39 42
21 1 1 2 10 12 12 13 14 Burnt
4 1 1 2 8 13 14 17 18 Burnt
1 1 2 9 11 11 13 14 14 Burnt
6 1 1 2 9 11 11 13 14 Burnt
2-Phenyl-
indole 1 1 3 5 13 14 15 15 L6 16 3urnt
1 1 1 3 3 5 7 10 10.5 11 16 Burnt
2 1 1 2 4 6 7 8.5 9 10.5 12 18
2-Phenyl-
indole 1 1 4 9 13 14 14 14 14 15 15
_ , i,
3 1 1 5 8 10 10. 13 14 18 18 Burnt
2-Phenyl-
indole 1 1 5 10.5 11 13 14 14 15 16 18
_ _ _
The above results taken as a whole show the super-
iority of the dihydropyridines over 2-phenyl indole during
30 minutes.
Finally, a trial was performed at 185C, with resins
containing equimolecular quantities of the dihydropyridines or
of 2-phenyl-indole, namely 1.55 x 10 3 mol. In this case too,
the samples were removed from the oven every 6 minutes over a

11~91~i
period of 24 minutes and then every 3 minutes until the 42nd
minute (or until carbonization).
The following results were obtained :
. . _
. . Time in minutes
St abl 11 zer _ _ _
0 6 12 18 24 27 3033 36 39 42
_ _
21 1 1 1 4 6 8 11 15 Burnt
4 1 1 1 4 6 8 11 15 Burnt
1 1 1 510 11 13 14 15 Burn
6 1 1 2 410 13 s.
2-Phenyl-
indole 1 2 3 1013 14 14 14 16 16 Burnt
The dihydropyridines, when used in an equimolecular
quantity to 2-phenyl-indole, show up to the 30th minute a
thermostabilizing power superior to that of this latter compound.
2) Study of tke_duratlon of thermostabilization
This study was carried out with vinyl resins which
are used for manufacturing bottles for mineral water, namely
resin~ containing calcium and zinc stearates, epoxy soja bean
oil and either 2-phenyl-indole or a dihydropyridine of the
invention (compound 1).
The following trials were carried out with various
resins :
1) The resin was mixed in a cylinder-mixer and the following
parameters were measured:
- The stability of the colour, i.e. the time which elapsed
between the start of the mixing and the first visible change
in the colour of the resin.
- The thermostability, i.e. the time which elapsed between
the start of the mixing and the carbonization of the resin.
With a resin containing 0.2% of stabilizer, it wa~
found, after mixing at 220C, that the resin containing 2-
phenyl-indole as stabilizer changed colour after 3 minutes and
- 12 -

1119~76
carbonized after 13 minutes, whereas the resin containing
2,6-dimethyl-3,5-dicarboallyloxy-1,4-dihydropyridine (Compound
1) changed colour after five minutes and carbonized after 13.3
minutes.
2) Examination of the colour of the resin after each passage
(3 in all) in a blower-extruder, the mould being a 250 ml
cylindrical flask.
Four resins were tested, the first containing 0.2%
of 2-phenyl-indole and the others 0.2%, 0.03% and 0.015% of
compound 1 respectively.
After the first passage the flask presented, with
all four resins, a brilliant sky-blue colour.
After the second passa~-e, the flask made with the
rèsin containing 2-phenyl-indole presented a blue colour tending
towards green, whereas the other three flasks had kept the
same colour.
After the third passage, the flask corresponding to
the resin stabilized with 2-phenyl-indole had become greenish-
blue, whereas the other three flasks still had the same
brilliant sky-blue colour.
Two conclusions may be drawn from the above findings:
- In equal concentrations, Compound 1 provides vinyl resin
with a stability of colour which is markedly superior to
that obtained with 2-phenyl-indole.
- At a concentration of 0.015%, Compound 1 is at all times
superior to 2-phenyl-indole used at a concentration of 0.2%.
Trials were also carried out with resins containing
a larger quantity of zinc stearate.
The various proportions of calcium and zinc stearate
and of the stabilizers are given in the following table:
- 13 -

76
Additiv ~ Quantity of stabilizer
,
N of the 1 2 ¦ 3 4 5 6 7 8 9
_
Calcium
stearate 0.29 0.29 0.29 0.29 0.29 0.29 0.29 0.29 0.15
Zinc stearate 0.32 0.32 0.32 0.32 0.32 0.32 0.15 _ 0.32
2-Phenyl-
indole 0.15 _ _ _ _ _ _ _ _
Compound 1 _ ~ 0 075 0.05 0 03 0 015 ~ 0.15 0.075
The same trials as hereabove were carried out and the
following results were obtained (mixing at 220C)
Resin
6 7 8 9
in min. 2 to 3 5 4 4 3 3 3 ~1 3
Tbeillmtoyta-
in min. 9 8.5 8 8 8 8 15 < 7 5
. _ _
The results show that the improvement of the
8tability of the colour with compound 1 is very good, this
latter compound being 10 to 15 times more effective than 2-
phenyl-indole.
Compound 1 does not directly influence thermostability
but it enables, by preserving the colour, the amount of zinc
stearate to be recuded and also thermostability to be increased.
Examination of the colour of the resin after each
passage through the blower-extruder, clearly showed the
excellent behaviour of the resins containing compound 1.
3) Study of the stabilization of ~lastified vinyl_resins
This study was carried out by pressing plates from
_ 14 -
.

-
~9176
sheets which had been mixed for 5 minutes at 180C, the pressing
also lasting 5 minutes but at 170C.
The same parameters as hereabo~e were studied, namely
the duration of~the stability of the colour, the duration of
the thermostability and the colour of the pressed plate.
The following resins were used :
Ingredients Parts by weight
r i~ 1 _ ~ - 5 6 ~ _ _
Polyvinyl
chloride
resin 100 100 100 100 100 100 100 100 100
Wax E 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3
Dioctylic
Phthalate 50 50 50 50 50 50 50 50 50
Barium
stearate_ 0.375 i ~ 0.375 0.375 0.375 0.375 0.375 0.375
Cadmium
stearate_ _0.375 0.375 0.375 0~15 0.150.050.05
Compound 1 _ ~ _ ~ 0 _ 0.05 _ 0.05
The following results were obtained :
T 'al N of the resin
r1 _ 2 3 ¦ 4 5 6 7 6 _
Stability of
the colour
in min. ~5 <5 25 35 50 30 45 20 35
Thermosta-
bility in min. (5 5 25 35 50 30 55 25 50
_ _ _ _
It can be noted that Compound 1 has a favourable
influence on the stability of the plate in plastified resin
since it :
- incr~aseg the time elapsing between the start of the treatment
and the first visible change of colour ,

11.~917 Ei
- increases the time elapsing between the start of the treatment
and the carboniæation of the resin.
Examination of the colour of the various resins shows
that the addition of Compound 1 has a favourable influence on the
basic colour,lthis latter approaching the colourless.
4) Studv of the stabilization of vinyl co-polymers
The study of the static thermostability of vinyl co-
polymers was carried out according to the GARDNER method described
above and, also in a more detailed manner in British Patent
Specification N~ 1,489,685.
a) Rigid co-polymer vinyl chloride-vinyl acetate
The following compound was prepared :
Inaredient Parts bv weiqht
Co-polymer vinyl chloride-vinyl acetate 80
Vinyl chloride resin 20
Calcium stearate 0.5
Stabilizer 0 or 0.1
The sheets were heated in a ventilated oven at 185~C
and the following results were obtained :
Time in min. _
0 2 4 6 810 12 14
Stabilize~?~-__
_ _
None 1.5 2 4 11.5 15 17 18 18.5
j28 ~ 1 4 10 12 13 15 17
The above results clearly show the thermostabilizing
properties of Compound 28.
b) Flexible co-polymer vinyl chloride-vinyl acetate.
The following compound was prepared :
Inqredient Parts by weiqht
Co-polymer vinyl chloride-vinyl acetate 100
Dioctylic phthalate 60
- 16 -

Melamine 2
; Calcium stearate 2
Stabilizer 0 or 0.2
The resin was allowed to gel for 5 minutes at 120C
and the sheets were heated at 160C in a Metrastat oven.
The following results were obtained :
Time in min.
0 30 40 50 60
Stabiliwer ~~~~~
10 None 1 6 13 14 17
28 1 2 6 12 15
2l 1 1 6 12 l5
c) Flexible co-polymer vinyl chloride-vinyl acetate
The following compound was prepared :
InqredientParts bv weiaht
Co-polymer vinyl chloride-vinyl acetate 100
Dioctylic phthalate 40
Calcium stearate 2
Melamine 2
Stabilizer 0 or 0.3
The sheets were heated in a Metrastat oven at 160C
and the following results were obtained :
j Time in min.
0 10 20 30 40 50 60
Stabilizer
None 1 1 5 8 12 13 13
28 1 1 2 5 7 10 12
21 1 1 2 5 6 7 12
1 1 1 2 4 5.~ 6 7
.:
. .

! -
1~19~7~
d) Rigid co-polymer vinyl chloride-vinylidene chloride
The following compound was prepared :
Inaredient Parts bv weiaht
Vinyl chloride resin 90
Co-polymer vinyl chloride-vinylidene chloride 10
Anti-shock agent 8
Epoxide soja bean oil 4
Calcium stearate 0.2
Zinc stearate 0.1
hydrogenated rape-seed oil 1.2
Glyceryl trimontanate 0.4
Stabilizer 0 or 0.3
The sheets were heated in a ventilated oven at 210C.
The following results were obtained :
.-
Time in min. _
~ 0 3 6 9 12 15
Stabilizer ~
. ~
None 2 2 5 10.5 14 16
21 1.5 2 2 3 7 15
28 1.' 2 3 3.5
e) Rigid co-polymer vinyl chloride-vinylidene chloride
The following compound was prepared :
InaredientParts bv weiaht
Vinyl chloride resin 90
Vinyl chloride-vinylidene chloride co-polymer 10
Anti-shock agent 8
Epoxide soja bean oil 4
Calcium stearate 0.2
Zinc stearate 0.1
Hydrogenated rape-seed oil 1.2
Glyceryl trimontanate 0,4
Stabilizer 0 or 0.3
- 18 -

1~19~6
The sheets were heated in a ventilated oven at 210C
and the following results were obtained :
_ . . _ ,
in min. 0 3 6 9 12
Stabilizer \
~ 1.5 ~ 2.5 ~ 4.5 1
It is clear from tests b, c, d and e that the
compounds of the invention have a marked stabilizing action on
vinyl chloride co-polymers.
5) Com~arison of the compounds of the invention with ~-amino-
crotonate derivatives.
a) Comparison with 1,4-butanediol-~-aminocrotonate and with
methyl-~-aminocrotonate.
The following rigid co-polymer was prepared :
Inaredients Parts by weiqht
Co-polymer vinyl chloride-vinyl acetate
containing 15% of acetate 80
Vinyl chloride polymer 20
Calcium stearate 0,5
Stabilizer 0.5
The sheets were heated in a ventilated oven at
185C and the following results were obtained :
_-
me in min.
Stabiliz ~ 0 2 4 6 8 10 12
_
1,4-butanediol-~-
aminocrotonate 1 1 4 10 13 15 18
Methyl-~-amino-
crotonate 1 1 5 12 14 17 18
Compound 21 1 1 4 6 11 13 17
Compound 28 1 1 5 7 11 13 17
-- 19 --

1J~917~
b) Comparison with stabilizer G 1
Stabilizer G 1 is a mixture of 1,4-butanediol-~-
aminocrotonate and of ~-aminocrotonate of alcohols containing
from 16 to 18 carbon atoms.
The following rigid co-polymer was prepared :
In~redients Parts bY weiaht
Co-polymer vinyl chloride-vinyl acetate 80
containing 15% of acetate
Vinyl chloride polymer 20
Calcium stearate 0.5
Stabilizer 0~5
The sheets were heated in a ventilated oven at
185C and the following results were obtained :
. Time in min. _ _ _
i 0 2 4 6 8 10 12
~ Stabilizer \ .
_ ~ .,
G 1 1 1 4 11 12.5 16 18.5
2 1 1 1. 5 10 12 16
1 1 1 2 6 0 13 17
G 1 1 1 2. ¦ 11 13.5 17 18.5
. 27 1 1 4 7 12.5 17 _
_ _ _ ,
Another comparison was made with the following
rigid co-polymer :
Inaredients Parts by weiqht
Co-polymer vinyl chloride-vinyl acetate
containing from 12.5 to 13.5% of acetate 100
Glyceryl tribehenate 0.4
Calcium stearaté 0.5
Stabilizer 0.5
~,, 30 The sheets were heated in a ventilated oven at 185C
and the following results were obtained :
,j

1119~76
: ~ Time in min. _ _ _ _ _ _
~ 0 2 ~ 6 8 10 12 14
Stabilizer ~
_ _~ _
G 1 1 2 3 4 9 12 18 _
2 1 1 2 3 4 8.5 13 17
1 1 1 2 3 7 12 18 _
_ _
A test was also carried out with the following
compound :
nqredients Parts by weiqht
Co-polymer vinyl chloride-vinyl acetate
containing 15% of acetate 80
: Vinyl chloride resin 20
Calcium stearate 0.5
Stabilizer 0-3
The sheets were heated in a ventilated oven at 185~C
and the following results were obtained :
_
e in min 0 2 46 8 10 12 14
Stabiliz ~ _
20 G 1 1 1 23 6 10 12.516
28 1 1 24 5 9 11 13
, ' . _ _
G 1 1 1 26 11.5 16 18Burnt
21 1 1 24 7 12 16 18
Another test was made with the same resin but
containing 0.1 part of stabilizer.
The sheets were also heated in a ventilated oven at
185C and the following results were obtalned :
Time in min. _ _ _ _ _
~~ O 2 46 8 10 1214
Stabilize~~~--_
_
G 1 1 1 67 11 12 1416
- 21 -

~l9~76
2 1 1 2 4 8 10 12 13
1 1 1 2 4 3 11 12 13
G 1 1 1 2 6 13 16 18 _
21 1 1 2 4 11 13 17 _
c) Comparison with 2-phenyl-indole
A comparative test was made using the following
compound :
Inqredients Parts by weiqht
Co-polymer vinyl chloride-vinyl acetate
containing 15% of acetate 80
Vinyl chloride resin 20
Calcium stearate 0.5
Stabilizer 0.3
The sheets were heated in a ventilated oven at 185C
and the following results were obtained :
Time in min. _
0 2 4 6 8 10 12 14
Stabilizer ~
_ _
202-Ph~nyl-indole 1 1 2 3 8 12 14 17
21 1 1 2 3 7 10 12 16
A second test was made using the following compound:
Inqredients Parts by weiaht
Vinyl chloride resin 90
Co-polymer vinyl chloride-vinylidene chloride
containing 70% of vinylidene chloride 10
Antishock agent 8
Epoxide soja bean oil 4
Calcium stearate 0.2
Zinc stearate 0.1
~Iydrogenated rape-seed oil 1.2
Glyceryl trimontanate 0.4
- 22 -

1~19176
Stabilizer 0-3
The sheets were heated in a ventilated oven at
210C and the following results were obtained :
_ ..
Time in min.
~~~ O 3 6 9 12 15
Stabilizer ~
_ _ .
2-phenyl-indole 2 2 5 8.5 14 16
21 1.5 2 2 3 7 15
28 1.5 2 3 3.5 7 15
~ _ , ~
2-phenyl-indole 1 I 4 10 15 _
1 1 1 2 4 10 _
The above results clearly show that the dihydro-
pyridines of the invention have a stabilizing action on vinyl
co-polymers which is markedly superior to that of well-known
stabilizers, such as the ~-aminocrotonate derivatives and
2-phenyl-indole.
C. Studv of photostabilizinq power -
1) Vinyl ~olY_ers_
The photostabilizing power of the compounds of the
invention was studied by exposing to the sun polyvinyl chloride
plates which had been stabilized either by a dihydropyridine
of the invention or by 2-phenyl-indole, or again by 2-(3'-
methoxy-4'-hydroxy)-indole. This last product is an extremely
valuable thermostabilizer for thermoplastic resins and is
described in British Patent N 1,489,685.
The resin given hereunder was prepared by mixing
on cylinders at 160C :
InqredientsPart by weiqht
Polyvinyl chloride resin 100
~nti-shock resin 8
- 23 -

l~l9i76
Epoxide soja bean oil 4
Acrylic resin 0-5
; Trinonylphenyl phosphate 0.3
SL 2016 0.25
Calcium behenate 0.4
Hydrogenated castor oil 0.2
Glyceryl trimontanate 0.4
Stabilizer 0.3
The plates of stabilized polyvinyl chloride, together
with a plate which had not been stabilized, were stood in the
sun under ~he same conditions and at the ~ame time. Their
colour was measured after 6 hours ànd 12 hours of exposure.
The coloration of the plates was determined according
to two methods :
- On the plates themselves, following the GARD~ER scale, as
- .
in the sect~on on thermostability,
, - On a solution of these plates in tetrahydrofuran, the colora-
tion of the solution being measured according to the French
Pharmacopeia (IXth edition, II-338).
~, 20 The following results were obtained :
Coloration of Coloration of the plate,~ .
the plates FRENCH PHARMACOPEIA
, Stabilizer GARD~ER
Time of exposu-
re to sun Time c ,f exposure to sun
. . 0 6h 12h 0 6h 12h
Standard 3+ 3+ 3+ J5 J5 J5
2-(3'-Methoxy-
4'-hydroxy-phe- 1 4 8 B5 B4 ~o JB4 B3 to JB
nyl)-indole _
2-Phenyl-indole 2 3 5+ J6 J5 J4
Compound 1 1 1 1.5 J6 J5 J5
Compound 2 1 1 1.5 ~V6 JV6 JV5
- 24 -

176
.
Compound 21 ¦ 1 1 1.5 JV6 ~ JV6 ~ JV5
Compound 29 2 3 5 JV6 JV5 JV4
The sign + means that the coloration lies between the
lower unit and the upper half-unit. Thus, 3~ means that the
coloration lies between 3 and 3.5. Similarly, the sign - means
that the coloration lies between the lower half-unit and the
upper unit.
It may be concluded from the above results that the -
dihvdropyridines according to the invention have a photo-
stabilizing power on vinylpolymers which is markedly superior
to that of 2-phenyl-indole and of its derivative.
2) Vinyl _o-polYmers
The sheets were exposed to the sun and their colora-
tions were also determined according to the GARDNER method.
a) Co-polymer vinyl chloride-vinyl acetate
The following compound was prepared :
InaredientsParts ~y we'iqht
Co-polymer vinyl chloride-vinyl acetate
conbaining 15% of acetate 100
Dioctylic phthalate 40
Calcium ~tearate 2
Melamine 2
Wax
Stabilizer 0.3
The following results were obtained :
Time in hours Colour in GARDNER degrees
Stabilizer Time 0 After 24 hours
2-Phenyl-indole 1 6
~, . `' :

~` 1119~76
.
-~b~ L-indole ~ 1 ~
b) Rigid co-polymer vinyl chloride-vinylidene chloride
The following compound was prepared :
Inqredients Parts by weiqht
10Vinyl chloride resin 90
Co-polymer vinyl chloride-vinylidene chloride
containing 70% of vinylidene chloride lO
Anti-shock agent 8
Epoxide soja bean oil 4
Calcium stearate 0.2
Zinc stearate 0.1
Hydrogenated rape-seed oil 1.2
Glyceryl trimontanate 0.4
Stabilizer 0.3
The following results were obtained:
Time in hours Colour in GARD~ER degree
Stabilizer Time 0 After 24 hours
21 1 5 3.5 :;~
28 1.5 3.5
. _
2-Phenyl-indole 1 13
The above results clearly show the marked superiority
of the compounds of the invention over 2-phenyl-indole with
regard to the stabilization of vinyl co-polymers.
D. Study of antioxidant Power
- 26 -
... ~ :

~9176
The value of the antioxidant power of the 1,4-
dihydropyridines o~ the invention was demonstrated by two
differents methods :
- ~y a polarographic study of their oxidation potential, compared
to well-known antioxidants such as 2,6-diterbutyl-4-methyl-
phenol, 2-terbutyl-4-methoxy-phenol, 4-methoxy-phenol and
hydroquinone.
- By direct comparison, on a polyvinyl chloride resin, of the
anti oxidant power of Compound 1 of the invention and that
of an anti-oxidant known as one of the most valuable and
frequently used in polyvinyl chloride, namely 2,6-diterbutyl-
4-methyl-phenol.
1) Polaroqraphic studY of the oxidation potential
a) O~eratina conditions
E_e=c=t==des
Reference electrode : Calomel electrode containing a
saturated solution of anhydrous
lithium perchlorate as bridge liquid.
Workina electrode : Vitrous carbon rotating electrode
(2,500 r. p.m.)
Counter-electrode : Platinum electrode
=he-m=Lca=l=~2=od=u=c=t==
- Acetonitrile containing less than 0.1% of water and
presenting no polarographic waves between -2.5 V and
+2.5 V.
- Anhydrous lithium perchlorate containing less than 1%
of water.
Re=a=ct=nt
A 0.1 M solution of lithium perchlorate in acetonitrile,
treated and preserved on a 4 A molecular sieve.
Pg_==~o~==pb-= ==o=n=d=t===o=n_
Tension : 10 m V
- 27 -

1119176
Initial potential : 0 V
Amplitude of exploration : 0 to 2 V
Speed of exploration : 10 a V/second
Sensitivity : 1.25 ,u A to 50 ,u A
Mean concentration : about 0.3 x 10 3 mol/litre
Precautions
Between each measurement, the vitrous carbon electrode
and the platinum electrode were carefully cleaned with
Joseph paper.
Results
Substance Oxidation potential in volts
1 0.75 + 0.01
21 0.73 + 0.01
2 0.80 + 0.01
2,6-Diterbutyl-4-methyl-phenol 1.11 + 0.02
2-Terbutyl-4-methoxy-phenol 0.81 + 0.01
Hydroquinone 0.83 + 0.01 '
4-Methoxy-phenol 0.89 + 0.01
The above results show that the dihydropyridines
are more reducing than the substance usually used as anti-
oxidants.
2) Trial on a polyvinyl chloride resin
The antioxidant power of Compound 1 was compared to
that of 2,6-diterbutyl-4-methyl-phenol (Compound 2) by using
the following resin :
, Inaredients Parts by weiqht
Polyvinyl chloride resin 100
Anti-shock agent 10
Acrylic resin 0,5
Epoxide soja bean oil 3
SL 2016 0.1
Zinc and calcium stearates 0.2
- 28 -

"` lli~1~6
Hydrogenated castor oil 1.5
Polyethylene wax 0.3
Antioxidant from 0.05 to 1
The study was carried out according to the GARD~ER
method, the samples being removed from an oven at 185C every
10 minutes over a period of 80 minutes.
The following results were obtained :
!Concentra- Anti- Tim~ ! ln minutes _
prartls oxidant 0 0 20 30 40 50 60 7080
0.05 Compound Z ~1 1+ 2 5+ >6 7 7 83urnt
Compound 1 1 1 1+ 3+ 4 6+ 7 8 B
. _ _
0.1 Compound Z >11+ 2 ~5 ~6 7 7 8 B
Compound 1 1 1 1+ <2 3+ 5+ 7 7 B
0.2 Compound Z ~ 11+ 2+ 5 ~6 7 7 8 B
, Compound 1 1 1 1 1+ 2 3 5 ~6 B
,; _ _ _
0.3 Compound Z ~1+ 1+ ~2 6 78 8 8+ B
Compound 1 1 1 1 1 2~2 8 8 B
0.4 Compound Z ~1+ >1+ 3 ~6 89 9 9 B
Compound 1 1 1 1 1 1+ ~2+ 4 8 B
_ _ _ _ _
0.5 Compound Z <1+ ~1+ 3~6 >7 8 8 8 B
Compound 1 1 1 1>1 1+ ~2+ 4 8 B
_
1.0 Compound Z 1+ 2 ~38 8 8 9 9 B
Compound 1 1 1 11 1+ 4 8 B -
The signs + and - have the same meanings as in the
previous table and > 2 means that the coloration lies between
2 and 2+.
The following conclusions can be drawn from the above
table : up to 50 minutes in the oven at 185C , Compound 1
- 29 -

1~1917~;
proved to be superior to Compound Z at every concen~ration.
Moreover, no concentration in Compound Z gives the
best results obtained with Compound 1.
The same trials were carried out in a Metrastat oven
at 210C.
The following results were obtained :
Concentra . Time in minutes
tion part Antl-
per 100 oxidant0 to 10 to 20 to 25 tc 30 to 35 to
parts 10 20 25 30 35 40
Compound Z 2 2 3 4+ 10 ~ 10
0.05 B/38'
Compound 1 1 1 1 1 5 B~/4~'
0.1 Compound Z 2 2 3 4+ 11 B~/39'
Compound 1 1 1 1 1 5 BC/3l8,
Compound Z 2 2 3 4+ 11 ~ 11
o.2 B/39'
Compound 1 1 1 1 1 5 ~ 9
B/39'
0.3 Compound Z ~ 1 2 3 3 9 B~/309'
. Compound 1 1 1 1 1 3+ ~ 9
~/19'
Compound Z 2 2 3 3+ 10 > 10
0.4 B/38'
Compound 1 1 1 1 1 4 6-
B/38'
_
0.5 Compound Z 2 2 3 3+10+ B/38'
Compound 1 1 1 1 1 3+ B/38
Compound Z 2 2 3 5 11 > 11
1.0 B/38'
Compound 1 1 1 1 1 2+ > 2+
_ B/37'
- 30 -

176
As in the previous trial, Compound 1 was found to
be markedly superior to Compound Z. Moreover, all the samples
containing Compound Z gave, from the time zero, pink-coloured
sheets, which is another disadvantage as compared to the
dihydropyridine of the invention.
The following Examples provide a non-limitative
illustration of the process of preparation of the compounds
of the invention.
EXAMPLE 1
PreDaration of 2 6-dimethyl-3,5-dicarboallyloxy-1,4-dihydro-
Pvridine
Into a reactor cooled in an ice-bath were introduced
28.4 g (0.2 mol) of allyl acetoacetate and 0.2 g of diethyl-
amine.
The solution was cooled to 0C and 7.5 g (0.1 mol)
of a 40% aqueous solution of formic aldehyde was introduced
drop-by-drop in 90 minutes, care being taken to maintain the
temperature below or equal to 10C.
The reaction medium was maintained at 0C for 6
hours, and then at room-temperature for 40 hours.
The solution was decanted and the aqueous phase was
extracted with ether. The ethereal phase was added to the
oily phase and was dried over anhydrous sodium sulphate.
The solution was filtered, the ether eliminated and
the oily residue diluted with one part of methanol.
Ammonia was bubbled through the solution obtained,
the temperature heing maintained at 0C, and the solution
saturated with ammonia was allowed to stand at room-temperature
for 12 hours.
The solution was filtered on a Buchner funnel and
the solid residue so obtained was recrystallized from acetone
to give 2,6-dimethyl-3,5-dicarboallyloxy-1,4-dihydropyridine.
- 31 -

~19~76
Yield : 75%.
Melting point : 167C.
By the method described above but using the appropriate
starting-products, the following compounds were prepared :
Compound Yield % Meltina point C
2,6-Dimethyl-3,5-dicarbopropar-
gyloxy-1,4-dihydropyridine 60202-203
(acetone)
2,6-Dimethyl-3,5-di-(2'-carbochloro-
ethoxy)-1,4-dihydropyridine 31 153
(acetone)
2,6-Dimethyl-3,5-di(4'-carbomethoxy-
benzyloxy)-1,4-dihydropyridine 18 143
(benzene 55~C)
2,6-Dimethyl-3,5-dicarbobenzyloxy-
1,4-dihydropyridine 57 122
(benzene)
2,6-Dimethyl-3,5-dicarbocinnamyloxy-
1,4-dihydropyridine 37 156
(benzene then acetone)
2,6-Dimethyl-3,5-di-(2'-carbochloro-
benzyloxy)-1,4-dihydropyridine 44 190
(acetone)
2,6-Dimethyl-3,5-di-(2'-carbomethyl-
benzyloxy)-1,4-dihydropyridine 47 149
(acetone)
EXAMPLE 2
Preparation of 2,6-dimethyl-3 5-dicarboproparqyloxy-1l4-
dihydropYridine
Into a reactor were introduced 14g (0.1 mol) of
propargyl acetoacetate, 10.5g (0.075 mol) of tetramine hexa-
methylene, 2.9g (0.033 mol) of ammonium acetate, 36g of
methanol and 5g of water.
Under a light flow of nitrogen, the reaction medium
was refluxed for one hour and was allowed to cool to room-
temperature and was then poured into a mixture of water and ice.
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1~19176
The precipitate which formed was filtered off and was
washed with hot acetone in order to eliminate the excess of
tetramine hexamethylene.
The precipitate was dried to constant weight and
washed with hot acetone to give 2,6-dimethyl-3,5-dicarbopropar-
gyloxy-1,4-dihydropyridine.
Yield : 75%
Melting Point : 206C.
By the above procedure but using the appropriate
starting-product, the following compounds were prepared :
Compound Yield % Meltinq Point C
2,6-Dimethyl-3,5-dicarboallyloxy-
1,4-dihydropyridine 86 168
(washing with hot
acetone)
2,6-Dimethyl-3,5-di-(4'-carbochloro-
benzyloxy~l,4-dihydropyridine 82 171
(acetone) ~`
2,6-Dimethyl-3,5-dicarbobenzyloxy-
1,4-dihydropyridine 75 120
(methanol)
2,6-Dimethyl-3,5-di-(2'-carbobutoxy-
ethoxy)-1,4-dihydropyridine 40 95
(methanol)
2,6-Dimethyl-3,5-di-(2'-carbometho~y-
ethoxy)-1,4-dihydropyridine 70 107
(methanol)
2,6-Dimethyl-3,5-di-(2'-carboethoxy-
ethoxy)-1,4-dihydropyridine 65 109
(methanol then
acetone)
2,6-Dimethyl-3,5-di-(2'-carbophenoxy-
ethoxy)-1,4-dihydropyridine 55 132
(acetone)
2,6-Diphenyl-3,5-dicarbethoxy-1,4-
dihydropyridine 10 142
(ethylic ether)
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- 1119176
2,6-Dibenzyl-3,5-dicarbethoxy-1,4-
dihydropyridine 51 118
` (methanol)
2,6-Di-3-butenyl-3,5-dicarbomethoxy-
1,4-dihydropyridine 46 79
(benzene/pentane
10/30)
2,6-Dimethyl-3,5-di-(2"-carbochloro-
2'-ethoxy-ethoxy)-1,4-dihydropyridine 79 110
(methanol)
2,6-Diphenylethyl-3,5-dicarbomethoxy-
1,4-dihydropyridine 59 156
(methanol-acetone
80/20)
2,6-Ditridecyl-3,5-dicarbomethoxy-
1,4-dihydropyridine 73 61
(acetone)
EXAMPLE 3
Preparation of 2,4 6-trimethyl-3,5-dicarbomethoxv-1,4-
dihydropvridine
Into a reactor were introduced 232g (2 mols) of methyl
acetoacetate and 160g of methanol. While stirring, 44g (1 mol)
of freshly distilled acetaldehyde were added drop-by-drop,
at 15C.
Temperature and stirring were maintained for 15
minutes under a light flow of nitrogen and 90g of a 20%
ammonium hydroxide solution (l.lS mol) were added at room-
temperature. The temperature rose to 45C and the mixture
wa~ heated to the methanol reflux temperature for one hour.
After cooling, the reaction medium was poured into
a water-ice mixture and the precipitate which formed was
filtered off on a Buchner funnel.
The precipitate wa~ thoroughly washed with water and
wa9 recrystallized from methanol to give 2,4,6-trimethyl-
3,5-dicarbomethoxy-1,4-dihydropyridine.
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76
Yield : 69 %
Melting point : 155-156C.
By the above procedure but using the appropriate
starting-product, the following compounds were prepared :
Compound ~ield % Meltinq Point C
2,6-Dimethyl-3,5-dicarbomethoxy-
4-hexyl-1,4-dihydropyridine 70 100
(cyclohexane)
2,6-Dimethyl-3,5-dicarbomethoxy-
4-propyl-1,4-dihydropyridine 57 140
(acetone)
; - 2,4,6-Trimethyl-3,5-di-(4'-carbo-
methylphenoxy)-1,4-dihydropyridine 20 192
(acetone)
2,4,6-Trimethyl-3,5-dicarbobenzy-
loxy-1,4-dihydropyridine 61 123
(methanol)
2,4,6-Trimethyl-3,5-dicarboallyloxy- ;
1,4-dihydropyridine 55 100
(benzene-hexane)
2,4,6-Trimethyl-3,5-di-(4'-carbochloro-
benzyloxy)-1,4-dihydropyridine28 161
(methanol)
2,4,6-Trimethyl-3,5-dicarbophenoxy-
1,4-dihydropyridine 5 186
(methanol)
2,6-Dimethyl-3,5-dicarbomethoxy-
4-phenyl-1,4-dihydropyridine 55 194
(acetone)
EXAMPLE 4
Pre~aration of 2,6-dimethvl-3.5-dicarbomethoxY-4-(1-propenYl)-
1, 4-dihvdropYridine
Into a reactor were introduced at room-temperature
23.2g (0.2 mol) of methyl acetoacetate and 7g (0 r 1 mol) of
crotonaldehyde. While stirring, a solution of 40g (0.42 mol)
of ammonium carbonate in 400g of water was added and stirring
- .

~19~76
was maintained ~or 20 hours at room-temperature.
The gummy precipitate was coled by ether and the
ethereal solution was washed with water, dried over sodium
sulphate and the ether was evaporated off.
The crude product was recrystallized from a mixture
of ethanol and hexane to give 2,6-di~ethyl-3,5-dicarbomethoxy-
4-(1-propenyl)-1,4-dihydropyridine.
Yield : 60%
Melting point : 176C.
- 36 -
'