~z5~7Si~
This invention relates to the synthesis of 2-
keto-1,4-diazacycloalkanes.
This application is a divisional application of
Canadian Patent Applicatlon S.N. 310,371, filed August 30,
1978.
Organic materials, whether natural or synthetic,
are conventionally protected against degradation by
ultraviolet ( W ) light by incorporating a UV light
stabilizer in the material. Many classes of compounds
are known to be useful UV light stabilizers, some being
more effective than others. Particularly effective com~
pounds, which provide compositions resistant to
degradation by UV light, include the decahydroquinolines
disclosed in U.S. Patents 4,069,195 and 3,073,770, the
1,5-diazacycloalkanes and 2-keto-1,5-diazacycloalkanes
disclosed in U.S. Patent 4,027,228 and, the 2-keto-1,4-
diazacycloalkanes disclosed in U.S. Patent 4,190,571.
Other cycloalkanes useful as W light stabilizers are
disclosed in German O~fenlegungsschrift 2,315,042,
Japanese Patent Numbers 7,453,571 and 7,453,572, and in
U.S. Patent Numbers 3,919,234, 3,920,659 and 3,928,330
which teach substituted piperazinediones.
The substituted piperazinediones are difficult
to prepare, particularly with dialkyl substituents on
each of two N4-adjacent symmetrical carbon atoms (here-
after "symmetrical c atoms"). Once prepared, however,
they may be reduced to the tetraalkyl substituted piper-
azine as disclosed in German Offenlegungsschrift
2,315,042. There is no suggestion as to how a mono-
keto structure, that is a 2-keto-1,4-diazacycloalkane
structure, may be prepared with a total of two or more
(hence "polysubstituted") substituents on symmetrical
C atoms.
It is known that 4,4,6,6-tetramethyl-',5-
diazacycloheptan-2-one may be prepared by a Schmidtls
rearrangement of a six-membered ring with sodium azide
(~ee German Patent Number 2,428,877) but there is no
known manner of similarl~ arriving at a six membered
1,4-diaza ring with an N -adjacent carbonyl
- 1 -
11~57S~
- la -
It is known 1,4-diaza(3,3,5,5)-dipentamethylene-
2-one may be prepared, starting with cyclohexanone by
cyclization of bis(l-cyanocyclohexyl)amine, reducing
with lithium aluminum hydride to form 1,4-diaza(2,2,5,5)-
dipentamethylene-2-imino, treating with acetic anhydride
and heating with hydrochloric acid. This is set out in
greater detail in an article by Helmut Egg in Monatshefto
fur Chemie 106, 1167-1173 (1975). However, starting
with acetone instead of cyclohexanone, the reactions do
not proceed in an analogous manner to give 3,3,5,5-
tetramethyl-piperazin-2-one. This Egg reference teaches
substituted piperazines wherein each symmetrical N4-
adjacent carbon is part of a six membered ring and the
cyclic substituent on each N -adjacent carbon is always the
~1~57S4
same. A single cyclic substituent on the N4-adjacent C atom of the fixed two-
carbon bridge cannot be prepared by following the techniques of Egg.
Cis-3,3-dimethyl-decahydroquinoxalin-2-one has been prepared by cis-
1,2-diaminocyclohexane, and it is disclosed that the cis-compounds are valuable
5 intermediates for the production of pharmaceuticals, textile auxiliary products and
synthetic materials. This reference states that the trans-1,2-diaminocyclohexaneis converted, with excess chloracetic acid, or with salts thereof, into 1,2-
diaminocyclohexane-N,N'-tetraacetic acid, which is quite unlike the behavior of the
cis starting material. The cis-2-keto-1,4-diazacycloalkane is prepared by reacting
10 an aqueous solution of cis-1,2-diaminocyclohexane with acetone cyanohydrin, and
heating the reaction solution to dryness. The reference does not teach formationof a trans-5,6-polyalkylene-2-keto-diazacycloalkane, and there is no suggestion as
to how it could be made. In fact, it is to be understood that the trans-2-keto-1,4-
diazacycloalkane cannot be made, since Bindler states that cis-1,2-diaminocyclo-
15 hexane behaves differently from trans-1,2-diaminocyclohexane; the positioning of
the two primary amine moieties imparts distinctly different properties to the
isomers. This dfference, and particularly the essential difference in cyclization
behavior of the primary amine moieties, is used to advantage in the separation of
the isomers. The cis isomer cyclizes and complexes with Ni and Cu; the trans
20 isomer does not. Nevertheless we have found that trans-2-keto-1,4-diazacyclohex-
ane can now be formed in a manner analogous to that in which the cis-2-keto-1,4-diazacyclohexane is formed.
Following the teachings of Bindler, ethylene diamine may be substituted
for cyclohexanediamine, and 3,3-dimethyl-2-keto-piperazine is obtained. However,25 when a substituted ethylene diamine is used, the substituents appear on the No. 6
carbon of the diaza ring. For example with 1,2-propane diamine, 3,3,6-trimethyl-2-
keto-piperazine is formed; and with 2-methyl-1,2-propane diamine the compound
obtained is 3,3,6,6--tetramethyl-2-keto-piperazine. No. 6-substituted and 3-
substituted carbons are not symmetrical carbon atoms about the same N-adjacent
30 atom in the diaza ring (hereinafter refer~ed to as "symmetrical N-adjacent C
atoms"). These compounds are quite unlike the novel compounds claimed.
Moreover, 3,3,6,6-tetraalkyl substituted diazacycloalkan-2-ones, in which the
substituents are not on symmetrical N-adjacent C atoms, are relatively ineffective
UV stabilizers, confirming my experience that the more substituents on symmetri-
35 cal N-adjacent C atoms, the better the stabilization effect.
It is known that 2,2,4-trimethyl-tetrahydroquirloline can be hydrogenat-
ed to form a mixture of cis and trans 2,2,4-trimethyldecahydroquinoline, and, ingeneral, the trans isomer is the major constituent. ~owever, 2,2-dimethyl-
tetrahydroquinoxaline is not hydrogenated in an analogous manner.
~ 3 ~ llZS~S'~
It is to the problem of synthesizing polysub-
stituted 2-keto-1,4-diazacycloalkanes, efficiently and
economically, so that they can be manufactured for com-
mercial use, that this invention is directed.
It has been discovered that polysubstituted 2-
keto-1,4-diazacycloalkanes may be prepared from readily
available starting materials, in simple, conventional
apparatus, without the high risks attendant upon using
hydrogen cyanide. This may be done by any of several
novel syntheses.
A. A novel synthesis has been discovered wherein
cis-3,3-dialkyl-3,4-dihydroquinoxalin-2-one is hydro-
genated in the presence of a suitable hydrogenation
catalyst, at elevated temperature and pressure, to yield
a cis-3,3-di-alkyl-decahydroquinoxalin-2-one.
B. A novel synthesis has been discovered wherein
trans-1,2-diaminocyclohexane is reacted with acetone cyano-
hydrin in the presence of water to yield trans-3,3-dimethyl-
decahydroquinoxalin-2-one.
- 20 C. A novel synthesis has been discovered (herein-
after referred to as "the cyanohydrin synthesis"), wherein
a cyclic or acyclic 1,2-diamine is reacted with cyclic or
acyclic cyanohydrins in the presence of a suitable organic
solvent in the presence of aqueous ~aOH at ambient
temperature and pressure, in the presence of an "onium salt"
(defined hereinafter) catalyst in conjunction with a halo-
form, to yield a polysubstituted 2-keto-1,4-diazacyc~oalkane.
D. A novel synthesis has been discovered (herein-
after referred to as "the ketoform synthesis") wherein a
preselected 1,2-diamine is reacted with a saturated acyclic
or cyclic monoketone, and, a haloform, in the presence of
(i) an onium salt catalyst (ii) an organic solvent, and
(iii) aqueous alkali.
The present invention is more particularly
concerned with synthesis A.
57S ~
- 3a -
The basic structure of the compounds prepared
by the syntheses described herein, is a polysubstituted
(hereafter also referred to as 'substituted for brevity)
~-keto-1,4-diazacycloalkane having (a) a fixed two-carbon
bridge between the two N atoms (the Nl and N atoms) of
the diaza ring, the remaining portion of the ring
having a variable length bridge o two or more carbon
atoms, (b) an Nl-adjacent carbonyl in the fixed two-
carbon bridge, and (c) at least the N - adjacent carbon
of the fixed two-carbon bridge has two substituents
(hence "polysubstituted"), which may be cyclizable,
that is, form a cyclic substituent. These compounds
which may be monocyclic, or with cyclizable substituents,
may be bicyclic or tricyclic, are particularly useful
as UV light stabilizers in substantially
1~25~54
colorless organic m~terials. The compounds may also form dimers and bis-
compounds. The diaza ring of the basic structure may have from 6 to 9 ring
members, more preferably from 6 to 8 ring members, and most preferably from 6
to 7 ring members.
These substituted 2-keto-1,4-diazacycloalkanes characteristically have
two substituents, which may be cyclizable, on the N4-adjacent C atom of the fixed
two~arbon bridge. They are particularly useful as UV light stabilizers in
compositions subjected to UV light degradation. As stabilizers they are used in the
range from about 0.01 to about 5 parts by weight, and preferably from about 0.1 to
10 about 1.0 part per one hundred parts (phr) of organic material subject to UV light.
These materials n~ay be low or high molecular weight materials, and particularlyinclude homopolymers, copolymers and mixtures thereof. Examples of materials
that can be stabilized against degradtion due to UV light are oils; monomers,
particularly ~ olefinically unsaturated monomers such as acrylates, dines, vinyl15 nitriles, and the like; and other relatively lower molecular weight materials than
synthetic resinous polymers, such as alcohols, aldehydes, and the like. Examples of
known materials which can be stabilized with polysubstituted 2-keto-1,4-diazacy-clofllkanes are natural rubber, synthetic rubbers such as cis-polystyrene, polyacryl-
onitrile, polymethacrylates, polycarbonates, varnish, phenol-formaldehyde resins,
20 polyepoxides, polyesters, and polyolefin homo and copolymers such as polyethylene,
polypropylene, ethylene-propylene polymers, ethylene-propylenediene polymers,
ethyl-vinyl acetate polymers, and the like. The substituted 2-keto-1,4-diazacyclo-
alkanes can also be used to stabilize mixtures and blends of polymeric materialssuch as ABS resin blends, PVC and polymethacrylate blends, and blends of
2S polyolefin homopolymers and copolymers such as blends of polypropylene in epdm
polymers.
The 2-keto-1,4~iazacycloalkanes prepared by the syntheses of this
invention have the structural formula: R1
2)m ~ R2 -- .. (I)
R4 3
30 wherein, m represents an integer in the range from 2 to 7, being the number of
methylene groups forming a bridge of variable length, and some of which groups (a)
together with the carbons to which they are bound, may form a cyclopentyl,
cyclohexyl or cycloheptyl endo ring, or (b) be substituted; when m is 2 then (I)represents a substituted 2-keto~iperazine, and when m is 6 and cyclized, then (I)
35 typically represents a substituted 2-keto-decahydroquinoxaline; Rl amd R4
independently represent hydrogen, alkyl having from 1 to about 24 carbon atoms,
:11257s4
hydroxyalkyl having from 1 to about 12 carbon atoms, haloalkyl having from 1 to
about 12 carbon atoms, cyanoalkyl having from 2 to about 12 carbon atoms,
aminoaLcyl or iminoalkyl having from 1 to about 12 carbon toms, ether groups
having from 3 to about 18 carbon atoms, hydroxyalkyl ether or cyanoalkyl ether
groups having from 4 to about 18 carbon atoms, alkenyl or aralkyl having from 7 to
about 14 carbon atoms, alkylene having from 2 to about 7 carbon atoms and
optionally containing a phosphite, ester or hindered phenol group; R4 may be
oxygen; and,
R2 and R3 on the N4-adjacent carbon of the fixed two-carbon bridge
independently each represent alkyl having from 1 to about 12 carbon atoms,
haloalkyl having from 1 to about 12 carbon atoms, cyanoalkyl having from 2 to
about 12 carbon atoms, aminoalkyl or iminoalkyl having from 2 to about 12 carbonatoms, cycloalkyl having from 5 to about 14 carbon atoms, hydroxy~ycloalkyl
having from 5 to about 14 carbon atoms, alkenyl and aralkyl having from 7 to about
14 carbon atoms, alkylene having from 2 to about 7 carbon atoms and optionally
containing a phosphite, ester or hindered phenol group, and which in combination,
one with another, represent cycloalkyl having from 5 to about 14 carbon atoms atleast four of which are cyclized and optionally containing a keto, ester, amide,ether, thio or hydroxy group.
When it is desired to prepare a compound having a substituted alkylene
group in the variable length bridge of the above-identified struc~ural formula (I),
the compound may be represented by a structural formula selected from
R1 R R
(CH2~1 0 ~
R~ ~R ~ ),and Rl~4 R3
wherein n represents an integer in the range from 0 to about 6; so when n is 0 then
(II) and (III) represent substituted 2-keto-piperazine, and when n is 4 with thevariable length bridge cyclized, then (II) and (III) represent 2-keto decahydroquin-
oxaline; and, R5, R6, R7, R8 in the variable length bridge have the same
connotation as R2 and R3 in (I) hereinabove, and additionally may be H, except that
R5 and R6 are different if either is H; R2, R3 may be cyclizable, as may be R5, R6,
R7, R8; and, if cyclized, the cyclic substituents may be the same or different.
~57S4
-- 6 --
Illustrative of the type of substituents that provide effective stabilizat-
ion in the above-identified 2-keto-diazacycloalkanes II and III are:
where Rl and/or R4 is alkyl, examples are methyl, ethyl, n-propyl, n-
butyl, t-butyl, n-hexyl, n-octyl, 2-ethylhexyl, n~ecyl, n-tetradecyl, n-octyldecyl,
5 and the like;
where R1 and/or R4 is hydroxyalkyl, examples are 2-hydroxyethyl, 2-
hydroxypropyl, 3-hydroxypropyl, 2-hydroxybutyl, 6-hydroxyhexyl, 8-hydroxyoctyl,
and the likei
where Rl and/or R4 is haloalkyl, examples are 2-chloroethyl, 2-
10 bromoethyl, 2-fluoroethyl, 2-chlorobutyl, 4-chlorobutyl, 2-chloroethylhexyl, and the
like;
where R1 and/or R4 is cyanoalkyl, examples are 2-cyanoethyl, 3-
cyanopropyl, 4-cyanobutyl, 8-cyanooctyl, and the like;
where Rl and R4 is aminoalkyl or iminoalkyl, examples are 2-
lS aminoethyl, 3-aminopropyl, 4-aminobutyl, 6-aminohexyl, 2-methyl-2-aminoethyl, and the like;
where R1 and R4 is ether, examples are methoxyethyl, ethoxyethyl,
ethoxypropyl, octyloxyethyl, phenoxyethyl, p-methylphenoxypropyl, and the like;
when R is hydroxyalkylether or cyanoalkyl ether, examples are 2-hydroxyethyloxa-
20 ethyl, p (2-hydroxypropyl)-phenyloxapropyl, 4-hydroxybutyloxahexyl, 2 cyanoethyl-
oxaethyl, 2-hydroxyethyl-di(oxaethyl), and the like;
for R2, R3, R5, R6, R7, and ~8, examples are methyl, ethyl, propyl, n-
butyl, isobutyl, n-hexyl, 2-ethylheptyl, n~ecyl, and where the substituents are
cyclizable, cyclopentyl, methylcyclopentyl, cyclohexyl, methylcyclonexyl, dimethyl
25 cycloheptyl, piperidyl, 2-2',6-6'-tetramethyl piperidyl, and the like.
Examples of specific substituted mono-keto-diazacycloaL`can-2-ones
derived from compounds prepared by the syntheses of this invention, wherein the
N4-adjacent C atom of the fixed two carbon bridge has two substituents which maybe cyclizable, are:
(a) diazamonocycloalkan-2-ones having a total of more than four
substituents on the diaza ring, for example, 3,3,5,5,6-pentaalkyl-1,4-piperazin-2-
one;
(b) trans-1,4-diazabicycloalkan-2-ones for example, trans-3,3-dialkyl-
decahydroquinoxalin-2-one; and
(c) mono ket~diazatricycloalkan-2-ones, for example, 3,3-( ~, ~ '-di-
tert-butylamine) decahydroquinoxalin-2-one.
1125754
-- 7
The more pre~erred substituted 2-keto-1,4-diazacycloalkane compounds
are those wherein: R1 and/or R4 is selected from the group consisting of alkyl
having from 4 to 18 carbon atoms, benzyl, cyclohexylmethyl, hydroxyalkyl having
from 1 to about 6 carbon atoms, hydroxyalkyl ether having from 4 to about 12
5 carbon atoms, cyanoalkyl having from 2 to about 6 carbon atoms, and sminoalkylhaving from 1 to about 6 carbon atoms, R2, R3, R5, R6, R7 and R8 are selected
from the group consisting of alkyl having from 1 to about 12 carbon atoms, and
polymethylene having from 5 to 6 carbon atoms which are cyclizable; only R2, R3
may be cyclized, or R2, R3 and R5, R6 may be cyclized; and if R2, R3, and R5, R610 are each cyclized, the cyclic substituents are different; and n is a numeral in the
range from 4 to about 6 when the methylene groups are cyclized.
Examples of the aforespecified more preferred substituted mono-keto-
diazaaL~<an-2-ones are:
N4-( ~-hydroxyethyl)-3,3,6-trimethyl-piperazin-2-one;
15 N4~ ~-hydroxyethyl) 3,3-pentamethylene-5,5-dimethylpiperazin-2-one;
N4~ B-hydroxyethyl)3~3,6-trimethyl-diazepin-2-one;
N4-( ~-hydroxyethyl) 3,3,6,6-tetramethyl-diazepin-2-one;
N4~ ~-hydroxyethyl) 3,3-pentamethylene-5,5-hexamethylene-diazepin-2-one;
N4-( 3-hydroxyethyl) 3,3-pentamethylene-diazepin-2-one;
20 N4-( ~-hydroxyethyl) 3,3,5,5,7,7-hexamethyl-diazepin-2-one;
N4-( ~-hydroxyethyl)3,3-pentamethylene-5,5,7,7-tetramethyl-diazepin-2-one;
N4~ ~-hydroxyethyl)3,3-dimethyl-5,5-pentamethylene-piperazin-2-one;
N4-( e-hydroxyethyl)3,3,6,6-tetraethyl-5,5-pentamethylene-diazepin-2-one;
N4-( ~-hydroxyethyl) 3,3-dimethyl-5,6-tetramethylene-diazeine-2-one;
25 N4~ ~-hydroxyethyl) 3,3,5,5-tetramethyl-6,7-tetramethylene-diazepin-2-one;
cis-3,3-dimethyl-decahydroquinoxalin-2-one;
cis-3,3-pentam ethylene-decahydroquinoxalin-2-one;
cis-Nl-(31,5'-di-t-butyl-4-hydroxybenzyl)3,3-dimethyl-decahydroquinoxalin-2-one);
trans-Nl-~3',5'-di-t-butyl-4-hydroxybenzyl)3,3,-dimethyl-decahydroquinoxalin-
30 2-one;
1,4-butane-bis [Nl-(3,3-dimethyl-decahydroquinoxalin-2-one~;
trans-1,6-hexanediol-bis [N -(3,3-dimethyl-decahydroquinoxaline-2-one)di-carboxylat~;
trans-1,6-hexan-bis ~N1-(3,3-pentamethylene-decahydroquinoxalin-2-one)di-carboxylate];
and, trans-N -carbobutoxy-3,3-dimethyl-decahydroquinoxalin-2-one.
.
112575~
8 --
Most preferred substituted mono-keto-1,4-diazaalkan-2-ones are:
Nl-dodecyl-3,3,5,5-tetramethyl-2-piperazinone;
Nl-t-octyl-3,3,5,5-tetramethyl-2-piperazinone;
1,2-ethane-bis-(N'-3,3,5,5-tetramethyl-2-piperazinone;
N4-t-octyl-3,3,6,6-tetramethyl-2-piperazinone;
Nl-phenyl-3,3,5,5-tetramethyl-2-piperazinone;
Nl-t-butyl-3,3-dimethyl-5,5-pentamethylene-2-piperazinone;
N -butyl-3,3,5,5,7-pentamethyl-1,4-diazepin-2-one;
trans-3,3-pentamethylenedecahydroquinoxalin-2-one;
10 trans-3,3-dimethyl-decahydroquinoxalin-2-one;
trans-3,3-dimethyl-N4- ~-hydroxyethyl-decahydroquinoxalin-2-one;
trans N1-dodecyl-3,3-dimethyl-decahydroquinoxalin-2-one;
trans-N1-benzyl-3,3-dimethyl decahydroquinoxalin-2-one;
trans-Nl-dodecyl-3,3-pentamethylene-decahydroquinoxalin-2-one;
15 trans N -3,3-pentamethylene-decahydroquinoxalin-2-one;
trans-3,3-dimethyl-N4- R-hydroxyethyl-decahydroquinoxalin-2-one.
It will now be evident that many of the substituents identified
hereinabove may not be made directly by the syntheses of this invention, but by
additional steps after having formed the substituted 2-keto-1~4-diazacycloalkane.
20 These additional steps are well known to those skilled in the art, and do not require
detailed description herein. In particular, dimers and bis compounds of substituted
2-keto-1,4-diazacycloalkanes can be prepared by known methods, once the desired
2-keto-1,4-diazacycloalkane is obtained by a chosen synthesis.
A. Hydrogenation of Unsaturated 2-keto Precursor (Synthesis "A"):
Hydrogenation of 3,4-dihydroquinoxalin-2-one with substituents, which
may be cyclizable, on the N4-adjacent C atom of the fixed two-carbon bridge,
yields the decahydroquinoxalin-2-one. For example, hydrogenation may be effectedwith Adams catalyst, ruthenium, rhodium, Raney nickel, or other suitable
hydrogenation catalyst, at a temperature in the range from about 100C to about
30 300C &nd a pressure in the range from about 1000 psi to about 3000 psi, to yield
3,3-dialkyl-decahydroquinoxalin-2-one. The product so obtained may thereafter befurther reacted with preselected reactants to provide desired substituents on the
N1 atom, the N4 atom or both in a known manner. Bis compounds and dimers may
be prepared.
In another particular embodiment, 3,3-pentamethylene-3,4-dihydroquin-
oxalin-2-one may be hydrogenated with a hydrogenation catalyst to yield 3,3-
pentamethylene-1,4-decahydroquinoxalin-2-one. Further substituents on the N1
9 1~5754
g
and N atoms may be made by conventional means, some of
which are more fully described in Canadian Patent 1,109,185
The following example serves to illustrate the
invention. Where not otherwise stated, parts are given as
parts by weight and the temperatures in degrees centigrade.
Example 1
Preparation of 3-hexyl-3-methyl-cis-decahydro-
quinoxalin-2-one by synthesis"A":
H
I
~ N ~ O
~N~C16H13
I C 3
H
1.5 g 3-hexy1-3-methyl-3,4-dihydroquinoxalin-2-one in 30 ml
ethanol is hydrogenated at about 180C and under about 2000
psi in the presence of 0.4 g. ruthenium (5%) on charcoal.
Hydrogenation is allowed to proceed for about 3 hours
after which the hydrogenated mixture is filtered. The
solvent is then remove~ and the residue distilled under
0.2 mm Hg at about 157-158C, to yield about 1.1 g of an
oily product which upon trituration with hexanes, gives
a white solid. The above structure is confirmed by I~,
~MR, GC and mass spectrometer data.
In a manner analogous with the foregoing;
3,3-dimethyl-3,4-dihydroquinoxalin-2-one is hydrogenated
at about 130C and 1500 psi in the presence of rhodium
(5%) on charcoal in 2 hours, to yield cis-3,3-dimethyl-
decahydroquinoxalin-2-one.
Other cis-2-keto-1,4-deazacycloalkane compounds
which are polysubstituted polycyclic compounds may be
formed by contacting a precursor polysubstituted poly-
cyclic unsaturated 2-keto-1,4-diaza compound with hydrogen
in the presence of a hydrogenation catalyst at a temperature
above about 100C but below a temperature which is
- lo 11~5'754
deleterious to the polycyclic cis-2-keto-1,4-diazacyclo-
alkane formed. Polysubstituted polycyclic trans-2-
keto-1,4~diaza unsaturated compounds are not similarly
obtained by hydrogenation.
~ ~,
,.~
.
