CA1109869A - Synthesis of 2-keto-1,4-diazacyclo-alkanes - Google Patents
Synthesis of 2-keto-1,4-diazacyclo-alkanesInfo
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Abstract
ABSTRACT OF THE DISCLOSURE
Polysubstituted 2-keto-1,4-diazacycloalkanes are produced by reaction of a 1,2-diamine with a mono-ketone or monoaldehyde and a haloform in the presence of an onium salt catalyst.
Polysubstituted 2-keto-1,4-diazacycloalkanes are produced by reaction of a 1,2-diamine with a mono-ketone or monoaldehyde and a haloform in the presence of an onium salt catalyst.
Description
.
This invention relates to the synthesis of 2-keto-1,4-diazacycloalkanes, This application is a divisional application of Canadian Patent Application 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 stabiliæers are disclosed in German Offenlegungsschrift 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 ~ubstituents on each of two N4-adjacent symmetrical carbon atoms (here-after "symmetrical c atGms"). Once prepared, however, they may be reduced to the tetraalkyl substituted piper-azine as disclosed in German Offenlegungsschrift
This invention relates to the synthesis of 2-keto-1,4-diazacycloalkanes, This application is a divisional application of Canadian Patent Application 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 stabiliæers are disclosed in German Offenlegungsschrift 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 ~ubstituents on each of two N4-adjacent symmetrical carbon atoms (here-after "symmetrical c atGms"). 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-1,5-diazacycloheptan-2-one may be prepared by a Schmidt's rearrangement of a six-membered ring with sodium azide (see German Patent Number 2,428,877) but there is no known manner of similarly arriving at a six membered 1,4-diaza ring with an Nl-adjacent carbonyl.
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 ~elmut 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 N -adjacent carbon is part of a six membered ring and the cyclic substituent on each ~ -adjacent carbon is always the same. A single cyclic substituent on the N4-adjacent C atom of the fixed two-carbon bridge cannot be prepared by following the techni~ues 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 intermediates for the production of pharmaceuticals, textile auxiliary products and synthetic materials. This reference states that the trans-1,2-diaminocyclohexane is converted, with excess chloracetic acid, or with salts thereof, into 1,2-diaminocyclohexane-~,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 an aqueous solution of cis-1,2-diaminocyclohexane with acetone cyanohydrin, and heating the reaction solution to dryness. The reference does not teach formation of 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-diazacyclo-alkane cannot be made, since Bindler states that cis-1,2-diaminocyclohexane behaves differently from trans-1,2-diaminocyclohexane; the positioning of the two primary amine moieties imparts distinctly different properties to the isomers. This difference, and particularly the 6~
essential diflerence in c~clization 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 isomer does not.
Nevertheless we have found that trans-2-keto-1,4-diaza-cyclohexane can now be formed in a manner analogous to that in which the cis-2-keto-1,4-diaæacyclohexane is ~ormed.
Following the teachings of Bindler, ethylene diamine may be substituted for cyclohexanediamine, and
It is known that 4,4,6,6-tetramethyl-1,5-diazacycloheptan-2-one may be prepared by a Schmidt's rearrangement of a six-membered ring with sodium azide (see German Patent Number 2,428,877) but there is no known manner of similarly arriving at a six membered 1,4-diaza ring with an Nl-adjacent carbonyl.
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 ~elmut 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 N -adjacent carbon is part of a six membered ring and the cyclic substituent on each ~ -adjacent carbon is always the same. A single cyclic substituent on the N4-adjacent C atom of the fixed two-carbon bridge cannot be prepared by following the techni~ues 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 intermediates for the production of pharmaceuticals, textile auxiliary products and synthetic materials. This reference states that the trans-1,2-diaminocyclohexane is converted, with excess chloracetic acid, or with salts thereof, into 1,2-diaminocyclohexane-~,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 an aqueous solution of cis-1,2-diaminocyclohexane with acetone cyanohydrin, and heating the reaction solution to dryness. The reference does not teach formation of 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-diazacyclo-alkane cannot be made, since Bindler states that cis-1,2-diaminocyclohexane behaves differently from trans-1,2-diaminocyclohexane; the positioning of the two primary amine moieties imparts distinctly different properties to the isomers. This difference, and particularly the 6~
essential diflerence in c~clization 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 isomer does not.
Nevertheless we have found that trans-2-keto-1,4-diaza-cyclohexane can now be formed in a manner analogous to that in which the cis-2-keto-1,4-diaæacyclohexane is ~ormed.
Following the teachings of Bindler, ethylene diamine may be substituted for cyclohexanediamine, and
3,3-dimethyl-2-keto-piperazine is obtained. However, when a substituted ethylene diamine is used, the sub-stituents 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,~-propane diamine the co~pound obtained is 3,3,6,6-tetramethyl-2-keto-piperazine. ~o. 6-substituted and 3-substituted carbons are not symmetrical carbon atoms about the same N-adjacent atom in the diaza ring (hereinafter referred to as "symmetrical N-adjacent C atoms"). These com-pounds are quite unlike the novel compounds claimed.
Moreover, 3,3,6,6-tetraalkyl substituted diazacyclo-alkan-2-ones, in which the substituents are not on symmetrical ~-adjacent C atoms, are relatively ineffective W stabili~ers, confirmin~ my experience that the more substituents on symmetrical ~-adjacent C atoms, the better the stabilization effect.
It is known that 2,2,4-trimethyl-tetrahydro-quinoline can be hydrogenated to form a mixture of cis and trans 2,2,4-trimethyldecahydroquinoline, and, in general, the trans isomer is the major constituent.
However, 2,2-dimethyltetrahydroquinoxaline is not hydro-genated in an analogous manner.
It is to the problem of synthesizing polysub-stituted 2-keto-1,4-diazacycloalkanes, efficiently and economically, 90 that they can be manufactured for com-mercial use, that this invention is directed.
~98~9
For example with 1,2-propane diamine, 3,3,6-trimethyl-2-keto-piperazine is formed, and with 2-methyl-1,~-propane diamine the co~pound obtained is 3,3,6,6-tetramethyl-2-keto-piperazine. ~o. 6-substituted and 3-substituted carbons are not symmetrical carbon atoms about the same N-adjacent atom in the diaza ring (hereinafter referred to as "symmetrical N-adjacent C atoms"). These com-pounds are quite unlike the novel compounds claimed.
Moreover, 3,3,6,6-tetraalkyl substituted diazacyclo-alkan-2-ones, in which the substituents are not on symmetrical ~-adjacent C atoms, are relatively ineffective W stabili~ers, confirmin~ my experience that the more substituents on symmetrical ~-adjacent C atoms, the better the stabilization effect.
It is known that 2,2,4-trimethyl-tetrahydro-quinoline can be hydrogenated to form a mixture of cis and trans 2,2,4-trimethyldecahydroquinoline, and, in general, the trans isomer is the major constituent.
However, 2,2-dimethyltetrahydroquinoxaline is not hydro-genated in an analogous manner.
It is to the problem of synthesizing polysub-stituted 2-keto-1,4-diazacycloalkanes, efficiently and economically, 90 that they can be manufactured for com-mercial use, that this invention is directed.
~98~9
4 --It has been discovered that polysubstituted 2-keto-1,4-diazacycloalkanes may be prepared from readily available starting materials, in simple, con-ventional apparatus, without the high risks attendant upon using hydrogen cyanide.
In accordance with the present invention novel synthesis have been discovered (hereinafter referred to as "the ketoform synthesis") wherein a pre-selected 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.
In particular there is provided, in accordance with the invention a method for preparing a polysub-stituted 2-keto-1,4-diazacycloalkane compound comprising reacting a diamine selected from the group consisting of an acyclic 1,2-diamine and a cyclic 1,2-diamine with a compound having a carbonyl bond selected from the group consisting of monoketones and monoaldehydes, in : 20 the presence of an aqueous alkali and an onium selected from the group consisting of the ternary salts of Group VIA elements and the quaternary salts of Group VA
elements, and a haloform, forming said polysubstituted 2-keto-1,4-diazacycloalkane compound and recovering said polysubstituted compound.
The basic structure o the compounds prepared by the syntheses described herein, is a polysubstituted (hereafter also referred to as "substituted" for brevity~
2-keto-1,4-diazacycloalkane having (a) a fixed two-carbon bridge between the two N atoms (the N and N atoms) of the diaza ring, the remaining portion of the ring having a variable length bridge of two or more carbon atoms, (b) an N -adjacent carbonyl in the fixed two-carbon bridg~, and (c) at least the ~4-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 -1~9~69 ~ 5 -which may be monocyclic, or with cyclizable substituents, may be bicyclic or tricyclic, are particularly useful as W light stabilizers in substantially colorless organic materials. The compounds may also form dimers and biscompounds. 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 ~ -adjacent C atom of the fixed two-carbon bridge. They are particularly useful as W
light stabilizers in compositions subject to W light degradation. As stabilizers they are used in the range from about 0.01 to about 5 parts by weight, and prefer-ably from about 0.1 to about 1.0 part per one hundred parts (phr) of organic material subject to W light.
These materials may be low or high molecular weight materials, and particularly include homopolymers, co-polymers and mixtures thereof. Examples of materialsthat can be stabilized against degradation due to W
light are oils; monomers, particularly ~,~-olefinically unsaturated monomers such as acrylates, dines, vinyl nitriles, and the like; and other relatively lower mole-cular weight materials than synthetic resinous polymers, such as alcohols, aldehydes, and the like. Examples of known materials which can be stabilized with polysub-stituted 2-keto-1,4-diazacycloalkanes are natural rubber, synthetic rubbers such as cis-polystyrene, polyacrylo-nitrile, polymethacrylates, polycarbonates, varnish,phenol-formaldehyde resins, 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 materials such as ABS resin blends, PVC
and polymethacrylate blends, and blends of polyolefin ~1 `..
,. .
~ .
6 - ;
homopolymers and copolymers such as blends of polypro- i pylene in epdm polymers.
The 2-keto-1,4-diazacycloalkanes prepared by the syntheses of this invention have the structural formula:
~1 ~4 (I) 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 cyclopenty~, cyclohexyl or cycloheptyl endo ring, or (b) be substituted, when m is 2 then (1) represents a substituted 2-keto-piperazine, and when m is 6 and cyclized, then (1) typically represents a substituted 2-keto-decahydroquinoxaline, Rl and R4 independently represent hydrogen, alkyl having from 1 to about 24 carbon atoms, 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, aminoalkyl or iminoalkyl having from 1 to about 12 carbon atoms, ether groups having from 3 to about 18 carbon atoms, hydroxyalkyl ether or cyanoalkyl ether groups having from 4 to ahout 18 carbon atoms, alkenyl or ar-alkyl 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 ~' , 3B6~
~ 7 --having from 2 to about 12 carbon atoms, cycloalkyl having from 5 to about 14 carbon atoms, hydroxy-cyclo-alkyl having from 5 to about 14 carbon atoms, alkenyl and aralkyl having from 7 to about 14 carbon atom~, 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 at least 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 structural formula (I), the compound may be represented by a structural formula selected from Rll Rll R6 ~ ~ ~ ... (II), and (III~ ~ ~ R2 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 the variable length bridge cyclized, then (II) and (III) represent 2-keto-decahydroquinoxaline; 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 andR6 are different if either 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.
Illustrative of the type of substituents that provide effective stabilization in the above-identified 2~keto-diazacycloalkanes II and III are:
~il , ;9 where Rl and/or R4 is alkyl, examples are methyl, ethyl, n-propyl, n-butyl, t~butyl, n-hexyl, n-octyl, 2-ethylhexyl, n-decyl, n-tetradecyl, n-octyldecyl, and the like, where Rl and/or R4 is hydroxyalkyl, examples are 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2-hydroxybutyl, 6-hydroxyhexyl, 8-hydroxyoctyl, and the like, where Rl and/or R4 is haloalkyl, examples are 2-chloroethyl, 2-bromoethyl, 2-fluoroethyl, 2-chlorobutyl, 4-chlorobutyl, 2-chloroethylhexyl, and the like, where Rl 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-aminoethyl, 3-aminopropyl, 4-aminobutyl, 6-aminohexyl, 2-methyl-2-aminoethyl, and the like:
where Rl and R4 is ether, examples are methoxy-ethyl, ethoxyethyl, ethoxypropyl, octyloxyethyl, phenoxy-ethyl, p-methylphenoxypropyl, and the like; when R is hydroxyalkylether or cyanoalkyl ether, examples are 2-hydroxyethyloxaethyl, p-(2-hydroxypropyl)-phenyloxa-propyl, 4-hydroxybutyloxahexyl, 2-cyanoethyloxaethyl, 2-hydroxyethyl-di(oxaethyl), andthe like;
for R2, R3, R5, R6, R7 and R8, examples are methyl, ethyl, propyl, n-butyl, isobutyl, n-hexyl, 2-ethylheptyl, n-decyl, and where the substituents are cyclizable, cyclopentyl, methylcyclopentyl, cyclohexyl, methylcyclonexyl, dimethyl cycloheptyl, piperidyl, 2-2',-6-6'-tetramethyl piperidyl, and the like.
Examples of specific substituted mono-keto-diazacycloalkan-2-ones derived from compounds prepared by the syntheses of this invention, wherein the N -adjacent C atom of the fixed two carbon bridge has two substituents which may be 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;
.
g (b) trans-1,4-diazabicycloalkan-2-ones for example, trans-3,3-dialkyldecahydroquinoxali~-2-one and (c) mono-keto-diazatricycloalkan-2-ones, for example, 3,3-(~,~'-di-tert-butylamine)decahydroquinoxalin-2-one.
The more preferred sub~tituted 2-keto-1,4-diaza-cycloalkane compounds are those wherein: Rl 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 carbon atoms, cyanoalkyl having from 2 to about 6 carbon atoms, and aminoalkyl having 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, R6 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 afore specified more preferred substituted mono-keto-diazaalkan-2-one~ are:
~4~ hydroxyethyl)-3,3,6-trimethyl-piperazin-2-one;
N4-(~-hydroxyethyl)-3,3-pentamethylene-5,5-dimethyl-piperazin-2-one, N4-(~-hydro~yethyl)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-di.azepin-2-one;
N4-(~-hydroxyethyl)3,3-pentamethylene-diazepin-2-one;
~4-(~-hydroxyethyl)3,3,5,5,7,7-hexamethyl-diazepin-2-one, N4-(~-hydro~yethyl)3,.3-pentamethylene-5,5,7,7-tetra-methyl-diazepin 2-one;
N4-(~-hydroxyethyl~3,3-dimethyl-5,5-pentamethylene-piperazin-2-one;
,, 1~986~ .
N4-(~-hydroxyethyl)3,3,6,6-tetraethyl-5,5~pentamethylene-diazepin--2-one, N4~ hydroxyethyl)3,3-dimethyl-5,6-tetramethylene-diazepin-2-one;
~4~ hydroxyethyl)3,3,5,5-tetramethyl-6,7-tetramethylene-diazepin-2-one, cis-3,3-dimethyl-decahydroquinoxalin-2-one;
cis-3,3-pentamethylene-decahydroquinoxalin-2-one, cis-~ -(3',5'-di-t-butyl-4-hydroxybenzyl)3,3-dimethyl-decahydroquinoxalin-2-one);
trans-~l-(3',5'-di-t-butyl-4-hydroxybenzyl)3,3-dimethyl-decahydroquinoxalin-2-one;
1,4-butane-bis[Nl-(3,3-dimethyl-decahydroquinoxalin-2-one)];
trans-1,6-hexanediol-bis-[Nl-(3,3-dimethyl-decahydro-quinoxaline-2-one)di-carboxylate], trans-1,6-hexan-bis-[Nl-(3,3-pentamethylene-decahydro-quinoxalin-2-one)di-carboxylate]; and trans-Nl-carbobutoxy-3,3-dimethyl-decahydroquinoxalin-2-one.
Most preferred substituted mono-keto-1,4-diaza-alkan-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-tetrarnethyl-2-piperazinone;
N -t-octyl-3,3,6,6-tetramethyl-2-piperazinone;
-phenyl-3,3,5,5~tetramethyl-2-piperazinone;
Nl-t-butyl-3,3-dimethyl-5,5-pentamethylene-2-piperazinone;
-butyl-3,3,5,5,7-pentamethyl-1,4-diazepin-2-one;
trans-3,3-pentamethylenedecahydroquinoxalin-2-one;
trans-3,3-dimethyl-decahydroquinoxalin-2-one;
trans-3,3-dimethyl-N4-~-hydroxyethyl-decahydroquinoxalin-2-one;
trans-Nl-dodecyl-3,3-dimethyl-decahydroquinoxalin-2-one;
trans-~ -benzyl-3,3-dimethyl-decahydroquinoxalin-2-one, trans-Nl-dodecyl-3,3-pentamethylene-decahydroquinoxalin-2-one;
trans-~ -3,3-pentamethylene-decahydroquinoxalin-2-one;
trans-3,3-dimethyl-N4-~-hydroxyethyl-decahydroguinoxlin-2-one.
~ '.
g8~9 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 fonmed the substituted 2-keto-1,4-diazacycloalkane.
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.
In the keto form synthesis of the invention 1~2-diamines are reacted with a saturated or unsaturated mono-ketone or monoaldehyde and a haloform reactant, in an organic solvent for the reactants, in the presence of aqueous alkali and an onium salt as a catalyst. By "onium Salts" is intended ternary or quaternary salts such as are generally used in the phase transfer catalysis of heterogeneous reactions in immiscible liquids. A wide variety of onium salts is effective in this ketoform synthesis~ m ese onium salts include the well-known salts ~ of Group VA of the Periodic Table, and some Group VIA
i elements such as are disclosed in a review in Angewandte Chemie, International Edition in English, 16 493-558 (August 1977). Discussed therein are various anion transfer reactions where the onium salt exchanges its original ion for other ions in the aqueous phase, making it possible to carry out chemistry there with the trans-ported anion includingOH ions.
m e onium salts suitably include one or more groups having the formula (RnY) X , wherein Y is either a pentavalent ion derived from an element of Group VA, or a tetravalent ion derived from an element of Group VIA, R is an organic moiety of the salt molecule bonded to Y by four covalent linkages when Y is pentavalent, and three co-valent linkages when Y is ~etravalent; X is an anion which will dissociate from the cation (RnY) in an aqueous environment. The group ~RnY)+X may be repeated as in the case .
: ' .
11`~98~9 of dibasic quaternary salts having two pentavalent Group VA ions substituted in the manner described.
The preferred onium salts for use in the invention have the formula ( RlR2R3R4Y+ ) X~
wherein Y is N or P, and Rl-R4 are monovalent hydro-carbon radicals preferably selected from the group con-sisting of alkyl, alkenyl, aryl, alkaryl, aralkyl and cycloalkyl moieties or radicals, optionally substituted with suitable heteroatom-containing functional groups.
The onium salts are generally selected to be less pre-ferentially less soluble in the less polar of the two distinct liquid phases. Any of the salts disclosed in U.S. Patent No. 3,992,~32 will be found effective, but most preferred are those in which the total number of carbon atoms in R , R , R3 and R4 cumulatively range from about 13 to about 57, and preferably range from about 16 to about 30. Most preferred onium salts have Y=N, and hydrocarbon radicals where Rl is CH3, and R2, R3 and ~ are each selected from the group consisting 4 ~ 5Hll; mixed C5Hll; n-C6~I13; mixed C H ; C6H5; C6H5CH2; n-C8H17, n C12 H25; 18 37 mixed C8-C10 alkyl; and the like. However, Rl may also be selected from C2H5~ n-C3H7 and n-C4Hg.
Various counterions may be used, including Cl , Br , I , N03 , S04 , HS04 and CH2C02 . Most preferred is Cl .
The reaction may be carried out at any temperature within a wide range frorn about the freezing point to the reaction mass to about the reflux temperature of the solvent, provided it is lower than a temperature -which is deleterious to the 2-keto-1,~-diazacycloalkane formed. The reaction is of particular interest because it generally proceeds at room temperature at satisfactory speed, substantially faster than the synthesis from tranq-1,2-diaminocycloalkane with cyanohydrin, parti-cularly acetone cyanohydrin in an aqueous medium to yield trans-3,3-dimethyl-decahydroquinoxalin-2-one, with better yields.
..
~-` llD~869 The reacti~n may also be carried ou~ at any desired pressure from subatmospheric to superatmospheric, but atmospheric pressure is preferably employed for con-venience, and because there appears to be no substantial advantage to be gained from operating at higher pressures.
The 1,2-diamines may include two primary amlne moieties, one primary amine moiety and one secondary amine moiety, or two secondary amine moieties. The amine i9 chosen to provide, upon cyclization, the desired number of C atoms in the variable length bridge, and also to provide the desired substituents on pre-selected C atoms of this bridge. It will thus be evident that a straight chain or acyclic diamine will will be appropriate where a monocyclo-1,4-diazacyclo-alkane is to be synthesized.
In particular the diamines may be acyclic 1,2-diamines, for example, alkyl amines; and cyclic 1,2-diamines, for example, o-phenyl diamine and cyclo-hexyldiamines, for example, 1,2-diaminocyclohexane.
The 1,2-diamines may be chosen to provide upon cyclization, the desired number of C atoms in the variable length bridge, and also to provide the desired substituents on preselected C atoms of this bridge. A cyclic diamine will be appropriate where a bicyclo-1,4-diazacycloalkane is to be synthesized.
The mono-ketone is preferably saturated and may be cyclic or acyclic. Useful ketones are those which cyclize forming a fixed two-carbon bridge between the and N4 atoms of the diaza ring. Preferred~mono-ketones are cycloalkanones, dialkylketones and aralkylketones.
The monoaldehyde is preferably saturated and may be cyclic or acyclic. Useful monoaldehydes are those which cyclize forming a fixed two-carbon bridge between the Nl and ~4 atoms of the diaza ring. Preferred monoaldehydes are cycloaldehydes, dialkylaldehydes and aralkylaldehydes.
~ .
. .
8~
I~ will presently be reco~nized from the examples herein, that polyketones and polyaldehydes, for example, diketones and dialdehydes, will yield bis compounds.
The presence of haloform in the reaction mass is essential, and it appears that the haloform is a reactant while the onium salt provides the catalytic action. Preferred haloforms are chloroform and bromo-form. It is essential that at least a stoichiometric amount of haloform be used if no amine is to be left unreacted. Though a small amount of unreacted amine is not deleterious, it is desirable to employ a slight excess over stoichiometric of the haloform. Though an excess up to about a 50% ex~ess over stoichiometric provides accept-able results, more than 50% over stoichiometric is to be avoided because of the formation of undesirable side pro-ducts.
The preferred aqueous alkali is an alkali metal hydroxide solution such as aq~eous sodium hydroxide, or potassium hydroxide, preferabl~ in the range from about 20 percent to about 70 percent. The amount used is not critical but at least a trace amount appears to be essential for the progress of the desired reaction.
It is preferred to use sufficient aqueous alkali solution to form a visually distinct aqueous phase in the presence of the organic solvent phase. In general, the amount of aqueous alkali used is preferably at least 5 percent by weight of the reaction mass. There is no advantage to using more aqueous alkali than about 75 percent by weight of the reaction mass.
Though the amount of onium salt catalyst used is not critical, its catalytic function appears to be unique in this ketoform synthesis. In general, it is sufficient to use less than 2 percent by weight of the reaction mass, and it is preferred to use in the range from about 0.1 to about 1 percent by weight.
8~9 In gerleral, this synthesis will provide a 2-keto-1,4-diazacycloalkane with substltuents both at the
In accordance with the present invention novel synthesis have been discovered (hereinafter referred to as "the ketoform synthesis") wherein a pre-selected 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.
In particular there is provided, in accordance with the invention a method for preparing a polysub-stituted 2-keto-1,4-diazacycloalkane compound comprising reacting a diamine selected from the group consisting of an acyclic 1,2-diamine and a cyclic 1,2-diamine with a compound having a carbonyl bond selected from the group consisting of monoketones and monoaldehydes, in : 20 the presence of an aqueous alkali and an onium selected from the group consisting of the ternary salts of Group VIA elements and the quaternary salts of Group VA
elements, and a haloform, forming said polysubstituted 2-keto-1,4-diazacycloalkane compound and recovering said polysubstituted compound.
The basic structure o the compounds prepared by the syntheses described herein, is a polysubstituted (hereafter also referred to as "substituted" for brevity~
2-keto-1,4-diazacycloalkane having (a) a fixed two-carbon bridge between the two N atoms (the N and N atoms) of the diaza ring, the remaining portion of the ring having a variable length bridge of two or more carbon atoms, (b) an N -adjacent carbonyl in the fixed two-carbon bridg~, and (c) at least the ~4-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 -1~9~69 ~ 5 -which may be monocyclic, or with cyclizable substituents, may be bicyclic or tricyclic, are particularly useful as W light stabilizers in substantially colorless organic materials. The compounds may also form dimers and biscompounds. 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 ~ -adjacent C atom of the fixed two-carbon bridge. They are particularly useful as W
light stabilizers in compositions subject to W light degradation. As stabilizers they are used in the range from about 0.01 to about 5 parts by weight, and prefer-ably from about 0.1 to about 1.0 part per one hundred parts (phr) of organic material subject to W light.
These materials may be low or high molecular weight materials, and particularly include homopolymers, co-polymers and mixtures thereof. Examples of materialsthat can be stabilized against degradation due to W
light are oils; monomers, particularly ~,~-olefinically unsaturated monomers such as acrylates, dines, vinyl nitriles, and the like; and other relatively lower mole-cular weight materials than synthetic resinous polymers, such as alcohols, aldehydes, and the like. Examples of known materials which can be stabilized with polysub-stituted 2-keto-1,4-diazacycloalkanes are natural rubber, synthetic rubbers such as cis-polystyrene, polyacrylo-nitrile, polymethacrylates, polycarbonates, varnish,phenol-formaldehyde resins, 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 materials such as ABS resin blends, PVC
and polymethacrylate blends, and blends of polyolefin ~1 `..
,. .
~ .
6 - ;
homopolymers and copolymers such as blends of polypro- i pylene in epdm polymers.
The 2-keto-1,4-diazacycloalkanes prepared by the syntheses of this invention have the structural formula:
~1 ~4 (I) 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 cyclopenty~, cyclohexyl or cycloheptyl endo ring, or (b) be substituted, when m is 2 then (1) represents a substituted 2-keto-piperazine, and when m is 6 and cyclized, then (1) typically represents a substituted 2-keto-decahydroquinoxaline, Rl and R4 independently represent hydrogen, alkyl having from 1 to about 24 carbon atoms, 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, aminoalkyl or iminoalkyl having from 1 to about 12 carbon atoms, ether groups having from 3 to about 18 carbon atoms, hydroxyalkyl ether or cyanoalkyl ether groups having from 4 to ahout 18 carbon atoms, alkenyl or ar-alkyl 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 ~' , 3B6~
~ 7 --having from 2 to about 12 carbon atoms, cycloalkyl having from 5 to about 14 carbon atoms, hydroxy-cyclo-alkyl having from 5 to about 14 carbon atoms, alkenyl and aralkyl having from 7 to about 14 carbon atom~, 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 at least 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 structural formula (I), the compound may be represented by a structural formula selected from Rll Rll R6 ~ ~ ~ ... (II), and (III~ ~ ~ R2 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 the variable length bridge cyclized, then (II) and (III) represent 2-keto-decahydroquinoxaline; 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 andR6 are different if either 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.
Illustrative of the type of substituents that provide effective stabilization in the above-identified 2~keto-diazacycloalkanes II and III are:
~il , ;9 where Rl and/or R4 is alkyl, examples are methyl, ethyl, n-propyl, n-butyl, t~butyl, n-hexyl, n-octyl, 2-ethylhexyl, n-decyl, n-tetradecyl, n-octyldecyl, and the like, where Rl and/or R4 is hydroxyalkyl, examples are 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2-hydroxybutyl, 6-hydroxyhexyl, 8-hydroxyoctyl, and the like, where Rl and/or R4 is haloalkyl, examples are 2-chloroethyl, 2-bromoethyl, 2-fluoroethyl, 2-chlorobutyl, 4-chlorobutyl, 2-chloroethylhexyl, and the like, where Rl 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-aminoethyl, 3-aminopropyl, 4-aminobutyl, 6-aminohexyl, 2-methyl-2-aminoethyl, and the like:
where Rl and R4 is ether, examples are methoxy-ethyl, ethoxyethyl, ethoxypropyl, octyloxyethyl, phenoxy-ethyl, p-methylphenoxypropyl, and the like; when R is hydroxyalkylether or cyanoalkyl ether, examples are 2-hydroxyethyloxaethyl, p-(2-hydroxypropyl)-phenyloxa-propyl, 4-hydroxybutyloxahexyl, 2-cyanoethyloxaethyl, 2-hydroxyethyl-di(oxaethyl), andthe like;
for R2, R3, R5, R6, R7 and R8, examples are methyl, ethyl, propyl, n-butyl, isobutyl, n-hexyl, 2-ethylheptyl, n-decyl, and where the substituents are cyclizable, cyclopentyl, methylcyclopentyl, cyclohexyl, methylcyclonexyl, dimethyl cycloheptyl, piperidyl, 2-2',-6-6'-tetramethyl piperidyl, and the like.
Examples of specific substituted mono-keto-diazacycloalkan-2-ones derived from compounds prepared by the syntheses of this invention, wherein the N -adjacent C atom of the fixed two carbon bridge has two substituents which may be 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;
.
g (b) trans-1,4-diazabicycloalkan-2-ones for example, trans-3,3-dialkyldecahydroquinoxali~-2-one and (c) mono-keto-diazatricycloalkan-2-ones, for example, 3,3-(~,~'-di-tert-butylamine)decahydroquinoxalin-2-one.
The more preferred sub~tituted 2-keto-1,4-diaza-cycloalkane compounds are those wherein: Rl 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 carbon atoms, cyanoalkyl having from 2 to about 6 carbon atoms, and aminoalkyl having 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, R6 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 afore specified more preferred substituted mono-keto-diazaalkan-2-one~ are:
~4~ hydroxyethyl)-3,3,6-trimethyl-piperazin-2-one;
N4-(~-hydroxyethyl)-3,3-pentamethylene-5,5-dimethyl-piperazin-2-one, N4-(~-hydro~yethyl)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-di.azepin-2-one;
N4-(~-hydroxyethyl)3,3-pentamethylene-diazepin-2-one;
~4-(~-hydroxyethyl)3,3,5,5,7,7-hexamethyl-diazepin-2-one, N4-(~-hydro~yethyl)3,.3-pentamethylene-5,5,7,7-tetra-methyl-diazepin 2-one;
N4-(~-hydroxyethyl~3,3-dimethyl-5,5-pentamethylene-piperazin-2-one;
,, 1~986~ .
N4-(~-hydroxyethyl)3,3,6,6-tetraethyl-5,5~pentamethylene-diazepin--2-one, N4~ hydroxyethyl)3,3-dimethyl-5,6-tetramethylene-diazepin-2-one;
~4~ hydroxyethyl)3,3,5,5-tetramethyl-6,7-tetramethylene-diazepin-2-one, cis-3,3-dimethyl-decahydroquinoxalin-2-one;
cis-3,3-pentamethylene-decahydroquinoxalin-2-one, cis-~ -(3',5'-di-t-butyl-4-hydroxybenzyl)3,3-dimethyl-decahydroquinoxalin-2-one);
trans-~l-(3',5'-di-t-butyl-4-hydroxybenzyl)3,3-dimethyl-decahydroquinoxalin-2-one;
1,4-butane-bis[Nl-(3,3-dimethyl-decahydroquinoxalin-2-one)];
trans-1,6-hexanediol-bis-[Nl-(3,3-dimethyl-decahydro-quinoxaline-2-one)di-carboxylate], trans-1,6-hexan-bis-[Nl-(3,3-pentamethylene-decahydro-quinoxalin-2-one)di-carboxylate]; and trans-Nl-carbobutoxy-3,3-dimethyl-decahydroquinoxalin-2-one.
Most preferred substituted mono-keto-1,4-diaza-alkan-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-tetrarnethyl-2-piperazinone;
N -t-octyl-3,3,6,6-tetramethyl-2-piperazinone;
-phenyl-3,3,5,5~tetramethyl-2-piperazinone;
Nl-t-butyl-3,3-dimethyl-5,5-pentamethylene-2-piperazinone;
-butyl-3,3,5,5,7-pentamethyl-1,4-diazepin-2-one;
trans-3,3-pentamethylenedecahydroquinoxalin-2-one;
trans-3,3-dimethyl-decahydroquinoxalin-2-one;
trans-3,3-dimethyl-N4-~-hydroxyethyl-decahydroquinoxalin-2-one;
trans-Nl-dodecyl-3,3-dimethyl-decahydroquinoxalin-2-one;
trans-~ -benzyl-3,3-dimethyl-decahydroquinoxalin-2-one, trans-Nl-dodecyl-3,3-pentamethylene-decahydroquinoxalin-2-one;
trans-~ -3,3-pentamethylene-decahydroquinoxalin-2-one;
trans-3,3-dimethyl-N4-~-hydroxyethyl-decahydroguinoxlin-2-one.
~ '.
g8~9 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 fonmed the substituted 2-keto-1,4-diazacycloalkane.
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.
In the keto form synthesis of the invention 1~2-diamines are reacted with a saturated or unsaturated mono-ketone or monoaldehyde and a haloform reactant, in an organic solvent for the reactants, in the presence of aqueous alkali and an onium salt as a catalyst. By "onium Salts" is intended ternary or quaternary salts such as are generally used in the phase transfer catalysis of heterogeneous reactions in immiscible liquids. A wide variety of onium salts is effective in this ketoform synthesis~ m ese onium salts include the well-known salts ~ of Group VA of the Periodic Table, and some Group VIA
i elements such as are disclosed in a review in Angewandte Chemie, International Edition in English, 16 493-558 (August 1977). Discussed therein are various anion transfer reactions where the onium salt exchanges its original ion for other ions in the aqueous phase, making it possible to carry out chemistry there with the trans-ported anion includingOH ions.
m e onium salts suitably include one or more groups having the formula (RnY) X , wherein Y is either a pentavalent ion derived from an element of Group VA, or a tetravalent ion derived from an element of Group VIA, R is an organic moiety of the salt molecule bonded to Y by four covalent linkages when Y is pentavalent, and three co-valent linkages when Y is ~etravalent; X is an anion which will dissociate from the cation (RnY) in an aqueous environment. The group ~RnY)+X may be repeated as in the case .
: ' .
11`~98~9 of dibasic quaternary salts having two pentavalent Group VA ions substituted in the manner described.
The preferred onium salts for use in the invention have the formula ( RlR2R3R4Y+ ) X~
wherein Y is N or P, and Rl-R4 are monovalent hydro-carbon radicals preferably selected from the group con-sisting of alkyl, alkenyl, aryl, alkaryl, aralkyl and cycloalkyl moieties or radicals, optionally substituted with suitable heteroatom-containing functional groups.
The onium salts are generally selected to be less pre-ferentially less soluble in the less polar of the two distinct liquid phases. Any of the salts disclosed in U.S. Patent No. 3,992,~32 will be found effective, but most preferred are those in which the total number of carbon atoms in R , R , R3 and R4 cumulatively range from about 13 to about 57, and preferably range from about 16 to about 30. Most preferred onium salts have Y=N, and hydrocarbon radicals where Rl is CH3, and R2, R3 and ~ are each selected from the group consisting 4 ~ 5Hll; mixed C5Hll; n-C6~I13; mixed C H ; C6H5; C6H5CH2; n-C8H17, n C12 H25; 18 37 mixed C8-C10 alkyl; and the like. However, Rl may also be selected from C2H5~ n-C3H7 and n-C4Hg.
Various counterions may be used, including Cl , Br , I , N03 , S04 , HS04 and CH2C02 . Most preferred is Cl .
The reaction may be carried out at any temperature within a wide range frorn about the freezing point to the reaction mass to about the reflux temperature of the solvent, provided it is lower than a temperature -which is deleterious to the 2-keto-1,~-diazacycloalkane formed. The reaction is of particular interest because it generally proceeds at room temperature at satisfactory speed, substantially faster than the synthesis from tranq-1,2-diaminocycloalkane with cyanohydrin, parti-cularly acetone cyanohydrin in an aqueous medium to yield trans-3,3-dimethyl-decahydroquinoxalin-2-one, with better yields.
..
~-` llD~869 The reacti~n may also be carried ou~ at any desired pressure from subatmospheric to superatmospheric, but atmospheric pressure is preferably employed for con-venience, and because there appears to be no substantial advantage to be gained from operating at higher pressures.
The 1,2-diamines may include two primary amlne moieties, one primary amine moiety and one secondary amine moiety, or two secondary amine moieties. The amine i9 chosen to provide, upon cyclization, the desired number of C atoms in the variable length bridge, and also to provide the desired substituents on pre-selected C atoms of this bridge. It will thus be evident that a straight chain or acyclic diamine will will be appropriate where a monocyclo-1,4-diazacyclo-alkane is to be synthesized.
In particular the diamines may be acyclic 1,2-diamines, for example, alkyl amines; and cyclic 1,2-diamines, for example, o-phenyl diamine and cyclo-hexyldiamines, for example, 1,2-diaminocyclohexane.
The 1,2-diamines may be chosen to provide upon cyclization, the desired number of C atoms in the variable length bridge, and also to provide the desired substituents on preselected C atoms of this bridge. A cyclic diamine will be appropriate where a bicyclo-1,4-diazacycloalkane is to be synthesized.
The mono-ketone is preferably saturated and may be cyclic or acyclic. Useful ketones are those which cyclize forming a fixed two-carbon bridge between the and N4 atoms of the diaza ring. Preferred~mono-ketones are cycloalkanones, dialkylketones and aralkylketones.
The monoaldehyde is preferably saturated and may be cyclic or acyclic. Useful monoaldehydes are those which cyclize forming a fixed two-carbon bridge between the Nl and ~4 atoms of the diaza ring. Preferred monoaldehydes are cycloaldehydes, dialkylaldehydes and aralkylaldehydes.
~ .
. .
8~
I~ will presently be reco~nized from the examples herein, that polyketones and polyaldehydes, for example, diketones and dialdehydes, will yield bis compounds.
The presence of haloform in the reaction mass is essential, and it appears that the haloform is a reactant while the onium salt provides the catalytic action. Preferred haloforms are chloroform and bromo-form. It is essential that at least a stoichiometric amount of haloform be used if no amine is to be left unreacted. Though a small amount of unreacted amine is not deleterious, it is desirable to employ a slight excess over stoichiometric of the haloform. Though an excess up to about a 50% ex~ess over stoichiometric provides accept-able results, more than 50% over stoichiometric is to be avoided because of the formation of undesirable side pro-ducts.
The preferred aqueous alkali is an alkali metal hydroxide solution such as aq~eous sodium hydroxide, or potassium hydroxide, preferabl~ in the range from about 20 percent to about 70 percent. The amount used is not critical but at least a trace amount appears to be essential for the progress of the desired reaction.
It is preferred to use sufficient aqueous alkali solution to form a visually distinct aqueous phase in the presence of the organic solvent phase. In general, the amount of aqueous alkali used is preferably at least 5 percent by weight of the reaction mass. There is no advantage to using more aqueous alkali than about 75 percent by weight of the reaction mass.
Though the amount of onium salt catalyst used is not critical, its catalytic function appears to be unique in this ketoform synthesis. In general, it is sufficient to use less than 2 percent by weight of the reaction mass, and it is preferred to use in the range from about 0.1 to about 1 percent by weight.
8~9 In gerleral, this synthesis will provide a 2-keto-1,4-diazacycloalkane with substltuents both at the
5~position (that is, the N4-adjacent C atom of the vari-able length bridge), and also the N -adjacent C atom of the variable length bridge. In addition, where an amine moiety has an alkyl (say) substituent either the Nl or N atom, or both, may be alkyl substituted. Thus, starting with N-propyl-2-methyl-1,2-propanediamine, the synthesis yields both Nl-propyl-3,3,5,5-tetramethyl-2-piperazinone and N -propyl-3,3,6,6-tetramethyl-2-piperazinone.
The following examples serve 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 Nl,N4-dimethyl-3,3-dimethyl-2-piperazinone by ketoform synthesis:
8.8 g Nj~'-dimethyl ethylene diamine, 12.0 g CHC13, and 6.0 g acetone are placed in a 250 ml flask in an ice-bath, and 1.1 g BTAC added. To provide a homo-geneous organic liquid phase, 100 ml dichloromethane is added. Then 40 ml conc NaOH (50% by wt) is dripped into the flask over about 30 minsO The reaction is allowed to proceed for about 5 hr and the reaction product is worked up. Upon distillation the product is obtained. The foregoing structure of the compound is supported by IR, NMR, GC and mass spectrometer data.
.~.~., ~1~9~
Example 2 In a manner analogous to that described in Example 1 hereinabove, N -propyl-3,3,5,5-tetramethyl-2-piperazinone is prepared according to Synthesis "D", utilizing acetone, chloroform, and a phosphonium salt.
The specific phosphonium salt used is (C4Hg)3P C16H33Br .
Upon working up in the usual manner, pure white crystalline needles of product are obtained.
Example 3 Preparation of N -propyl-3,3,5,5-tetramethyl-2-piperazinone (1) and N4-propyl-3,3,6,6-tetramethyl-2-piperazinone (II) by ketoform synthesis (one primary and one secondary amine moieties) Me ~ ~ Me ... ... (I),and Me ~ ~ Me ... ... (II) H H
The following examples serve 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 Nl,N4-dimethyl-3,3-dimethyl-2-piperazinone by ketoform synthesis:
8.8 g Nj~'-dimethyl ethylene diamine, 12.0 g CHC13, and 6.0 g acetone are placed in a 250 ml flask in an ice-bath, and 1.1 g BTAC added. To provide a homo-geneous organic liquid phase, 100 ml dichloromethane is added. Then 40 ml conc NaOH (50% by wt) is dripped into the flask over about 30 minsO The reaction is allowed to proceed for about 5 hr and the reaction product is worked up. Upon distillation the product is obtained. The foregoing structure of the compound is supported by IR, NMR, GC and mass spectrometer data.
.~.~., ~1~9~
Example 2 In a manner analogous to that described in Example 1 hereinabove, N -propyl-3,3,5,5-tetramethyl-2-piperazinone is prepared according to Synthesis "D", utilizing acetone, chloroform, and a phosphonium salt.
The specific phosphonium salt used is (C4Hg)3P C16H33Br .
Upon working up in the usual manner, pure white crystalline needles of product are obtained.
Example 3 Preparation of N -propyl-3,3,5,5-tetramethyl-2-piperazinone (1) and N4-propyl-3,3,6,6-tetramethyl-2-piperazinone (II) by ketoform synthesis (one primary and one secondary amine moieties) Me ~ ~ Me ... ... (I),and Me ~ ~ Me ... ... (II) H H
6.5 g ~-propyl-2-methyl-1,2-propanediamine and 50 ml methylene chloride are placed in a 250 ml flask.
32 g acetone and 6.9 g chloroform are added to the flask, followed by 0.5 g BTAC. While stirring in an ice-bath, 20 ml conc NaOH (50% by wt~ was added dropwise over about 0.5 hr. Water is added after 6.5 hr until all solids go into solution. Two distinct liquid phases are formed, and the layers are separated. The aqueous layer is extracted several times with 40 ml methyl chloride. The combined methylene chloride solutions are washed several times with H20, dried and concentrated. 8.6 g of a light yellow oil are obtained which is identified as (I) and (II) in a 7:3 ratio. The oil is distilled at 125-7C/8 mm and a colourless oil mixture of the compounds (I) and (II) is obtained. The foregoing structure of the compounds is supported by IR, ~MR, GC and mass spectrometer data.
., ~
ll~g86~
Example 4 Preparation of 3,3-pentamethyl~ne-2-quinoxalinone by ketoform synthesis: (two primary amine moieties) N ~0 N
H
In a 500 ml 3-neck flask place 10.8 g of o-phenylene diamine in 120 ml dichloromethane~ Add 14~7 g. of cyclohexanone and 18.06 g of chloroform, and stir.
While stirring, 1.14 g of BTEA are added to the flask.
Then add 40 ml conc NaQ~ t50% by wt) to the reaction mixture dropwise, so the'temperature does not exceed 30C. The reaction mixture is stirred overnight. Two distinct phases are formed which are separated, filtered, and worked up to yield 20 g off-white solid after washing with H20 (insoluble in both aqueous base and CH2C12).
The CH2C12 solu~ion is concentrated after drying. Cyclo-hexanone is distilled off under vacuum, and the residue triturated with benzene to obtain 1 g more of solid.
The total yield is 11 g (51% by wt). The solid is dis-solved in ethanol and conventionally hydrogenated.
Hydrogenation is conveniently effected with metal catalysts such as reduced nickel, Raney nickel, rhodium, ruthenium, platinum oxide or palladium, preferably deposited on a support such as charcoal.
The temperature of reaction is from about 20C to about 350C. Times of reaction are from about 0.5 to 8 hours or more~ High pressures, ranging up to 2000 psig are characteristic of the process. The hydrogenated compound is identified by carbon, hydrogen, nitrogen analysis, ~ mass spectrometry and ~MR spectroscopy, as cis-decahydro-3,3-pentamethylenequinoxalin-2-one. (A Perkin-Elmer Model 270 or duPont Model 21-490 mass spectrometer and a Varian A 60 NMR spectrometer are used).
l~g8~
~ 18 -Ex~nple 5 Preparation of trans-3,3-pentamethylene-deca-hydro-2-quinoxalinone by ketoform synthesis:
O
H H
In a SOO ml flask is placed 5.7 g of trans-1,2-diaminocyclohexane and 100 ml dichloromethane. 5.9 g cyclohexanone and 6.6 g chloroform are added, followed by 0.57 g BTAC. While stirring, 25 ml conc NaOH (50%
by wt) are added very slowly in about 3Q min. The reaction mixture is stirred overnight, then refluxed for 5 hr. As in the foregoing example, two layers of liquid are formed, and the reaction mixture is worked up and triturated with acetone. Akout O.5 g of white solid is obtained. The above structure of the compound is supported by IR, NMR, GC and mass spectrometer data.
In an analogous manner, a mixture of cis- and trans-isomers of 1,2 diamino-cyclohexane is reacted with cyclohexanone and chloroform to yield a mixture of cis-and trans- isomers of 3,3-pentamethylene-decahydro-2-quinoxalinone.
Example 6 Preparation of 3-hexyl-3-methyl-cis-decahydro-quinoxalin-2-one by the ketoform synthesis: (two primary amine moieties).
H
`~ 8~-~
5.4 g o-phenylenediamine and 70 ml CHC13 are placed in a 250 ml flask cooled in an ice-bath. 10.2 of 2-octanone are added followed by 0.5g BTAC. While stirring 25 ml conc NaOH (50% by wt) are added dropwise in 30 min.
The reaction mixture is kept in an ice-bath for 2.5 hrs, then at room temperature overnight. Gas chromatography (F & M Scientific Corp. Model 810 using a 6' x 0.25"
column packed with 10% OV-17 silicone rubber (methyl and phenyl) is used) indicated absence of starting material.
Water is added to dissolve the solid and the solution is separated into two layers. The aqueous layer is extracted with 40 ml CHC13 and the combined CHC13 solutions washed with water. ~ne organic phase is dried and concentrated.
An orange solid, identified as 3-hexyl-3-methyl-tetra-hydroquinoxalin-2-one, is recovered, 1.5 g of which is dissolved in 30 ml ethanol and hydrogenated with 0.4 g ruthenium (5%) on charcoal at 180C under 2000 psi for 3 hrs. The product is filtered and the solvent removed.
Upon distillation an oil is recovered which is triturated with hexanes to give a white solid. Upon recyrstallization - a white solid is recovered which melts at 115.7C and is identified as 3-hexyl-3-methyl-cis-decahydroquinoxalin-2-one.
0.5 parts of the novel hydrogenated compound is blended into polypropylene, and the composition is formed into film and tested in a manner analogous to that described in Example,l. The tests indicate that the composition is W stable for more than 6000 hrs.
32 g acetone and 6.9 g chloroform are added to the flask, followed by 0.5 g BTAC. While stirring in an ice-bath, 20 ml conc NaOH (50% by wt~ was added dropwise over about 0.5 hr. Water is added after 6.5 hr until all solids go into solution. Two distinct liquid phases are formed, and the layers are separated. The aqueous layer is extracted several times with 40 ml methyl chloride. The combined methylene chloride solutions are washed several times with H20, dried and concentrated. 8.6 g of a light yellow oil are obtained which is identified as (I) and (II) in a 7:3 ratio. The oil is distilled at 125-7C/8 mm and a colourless oil mixture of the compounds (I) and (II) is obtained. The foregoing structure of the compounds is supported by IR, ~MR, GC and mass spectrometer data.
., ~
ll~g86~
Example 4 Preparation of 3,3-pentamethyl~ne-2-quinoxalinone by ketoform synthesis: (two primary amine moieties) N ~0 N
H
In a 500 ml 3-neck flask place 10.8 g of o-phenylene diamine in 120 ml dichloromethane~ Add 14~7 g. of cyclohexanone and 18.06 g of chloroform, and stir.
While stirring, 1.14 g of BTEA are added to the flask.
Then add 40 ml conc NaQ~ t50% by wt) to the reaction mixture dropwise, so the'temperature does not exceed 30C. The reaction mixture is stirred overnight. Two distinct phases are formed which are separated, filtered, and worked up to yield 20 g off-white solid after washing with H20 (insoluble in both aqueous base and CH2C12).
The CH2C12 solu~ion is concentrated after drying. Cyclo-hexanone is distilled off under vacuum, and the residue triturated with benzene to obtain 1 g more of solid.
The total yield is 11 g (51% by wt). The solid is dis-solved in ethanol and conventionally hydrogenated.
Hydrogenation is conveniently effected with metal catalysts such as reduced nickel, Raney nickel, rhodium, ruthenium, platinum oxide or palladium, preferably deposited on a support such as charcoal.
The temperature of reaction is from about 20C to about 350C. Times of reaction are from about 0.5 to 8 hours or more~ High pressures, ranging up to 2000 psig are characteristic of the process. The hydrogenated compound is identified by carbon, hydrogen, nitrogen analysis, ~ mass spectrometry and ~MR spectroscopy, as cis-decahydro-3,3-pentamethylenequinoxalin-2-one. (A Perkin-Elmer Model 270 or duPont Model 21-490 mass spectrometer and a Varian A 60 NMR spectrometer are used).
l~g8~
~ 18 -Ex~nple 5 Preparation of trans-3,3-pentamethylene-deca-hydro-2-quinoxalinone by ketoform synthesis:
O
H H
In a SOO ml flask is placed 5.7 g of trans-1,2-diaminocyclohexane and 100 ml dichloromethane. 5.9 g cyclohexanone and 6.6 g chloroform are added, followed by 0.57 g BTAC. While stirring, 25 ml conc NaOH (50%
by wt) are added very slowly in about 3Q min. The reaction mixture is stirred overnight, then refluxed for 5 hr. As in the foregoing example, two layers of liquid are formed, and the reaction mixture is worked up and triturated with acetone. Akout O.5 g of white solid is obtained. The above structure of the compound is supported by IR, NMR, GC and mass spectrometer data.
In an analogous manner, a mixture of cis- and trans-isomers of 1,2 diamino-cyclohexane is reacted with cyclohexanone and chloroform to yield a mixture of cis-and trans- isomers of 3,3-pentamethylene-decahydro-2-quinoxalinone.
Example 6 Preparation of 3-hexyl-3-methyl-cis-decahydro-quinoxalin-2-one by the ketoform synthesis: (two primary amine moieties).
H
`~ 8~-~
5.4 g o-phenylenediamine and 70 ml CHC13 are placed in a 250 ml flask cooled in an ice-bath. 10.2 of 2-octanone are added followed by 0.5g BTAC. While stirring 25 ml conc NaOH (50% by wt) are added dropwise in 30 min.
The reaction mixture is kept in an ice-bath for 2.5 hrs, then at room temperature overnight. Gas chromatography (F & M Scientific Corp. Model 810 using a 6' x 0.25"
column packed with 10% OV-17 silicone rubber (methyl and phenyl) is used) indicated absence of starting material.
Water is added to dissolve the solid and the solution is separated into two layers. The aqueous layer is extracted with 40 ml CHC13 and the combined CHC13 solutions washed with water. ~ne organic phase is dried and concentrated.
An orange solid, identified as 3-hexyl-3-methyl-tetra-hydroquinoxalin-2-one, is recovered, 1.5 g of which is dissolved in 30 ml ethanol and hydrogenated with 0.4 g ruthenium (5%) on charcoal at 180C under 2000 psi for 3 hrs. The product is filtered and the solvent removed.
Upon distillation an oil is recovered which is triturated with hexanes to give a white solid. Upon recyrstallization - a white solid is recovered which melts at 115.7C and is identified as 3-hexyl-3-methyl-cis-decahydroquinoxalin-2-one.
0.5 parts of the novel hydrogenated compound is blended into polypropylene, and the composition is formed into film and tested in a manner analogous to that described in Example,l. The tests indicate that the composition is W stable for more than 6000 hrs.
Claims (11)
1. A method for preparing a polysubstituted 2-keto-1,4-diazacycloalkane compound comprising reacting a diamine selected from the group consisting of an acyclic 1,2-diamine and a cyclic 1,2-diamine with a compound having a carbonyl bond selected from the group consisting of monoketones and monoaldehydes, in the pre-sence of an aqueous alkali and an onium salt selected from the group consisting of the ternary salts of Group VIA
elements and the quaternary salts of Group VA elements, and a haloform, forming said polysubstituted 2-keto-1,4-diazacycloalkane compound and recovering said poly-substituted compound.
elements and the quaternary salts of Group VA elements, and a haloform, forming said polysubstituted 2-keto-1,4-diazacycloalkane compound and recovering said poly-substituted compound.
2. The method of claim 1, including, forming a polysubstituted unsaturated 2-keto-1,4-diaza cyclic com-pound, and hydrogenating said unsaturated cyclic compound to form said polysubstituted 2-keto-1,4-diazacycloalkane compound.
3. The method of claim 1, including adding a sufficient quantity of said aqueous alkali to form distinct organic and aqueous phases.
4. The method of claim 3, wherein said acyclic 1,2-diamine is an alkyl diamine and said cyclic 1,2-diamine is selected from the group consisting of o-phenylene diamine and cyclohexyldiamine; and said halo-form is selected from chloroform and bromoform.
5. The method of claim 1, wherein said onium salt is a salt of formula (R1R2R3R4Y+)X-wherein Y is N or P, and R1, R2, R3 and R4 are monovalent hydrocarbon radicals and X- is an anion which will dissociate from the cation in an aqueous environment.
6. The method of claim 5, whexein Y is N, R1 is CH3 and R2, R3 and R4 are each selected from the group consisting of n-C4H5; n-C5H11; mixed C5H11; n-C6H13;
mixed C6H13; C6H5; C6H5CH2; n-C8H17; n-C12H25; n-C18H37;
and mixed C8-C10 alkyl.
mixed C6H13; C6H5; C6H5CH2; n-C8H17; n-C12H25; n-C18H37;
and mixed C8-C10 alkyl.
7. The method of claim 1, 3 or 4, wherein said compound having a carbonyl bond is a monoketone selected from the group consisting of cycloalkanones, dialkyl-ketones and aralkylketones.
8. The method of claim 1, 3 or 4, wherein said compound having a carbonyl bond is a monoaldehyde selected from the group consisting of cycloalkanones, dialkyl-ketones and aralkylketones.
9. The method of claim 1, 3 or 4, wherein said halo-form is present in a stoichiometric excess up to a 50%
excess over the stoichiometric amount.
excess over the stoichiometric amount.
10. The method of claim 1, 3 or 4, wherein said alkali is sodium hydroxide or potassium hydroxide, and said aqueous alkali is present in an amount of about 20 to about 70 percent.
11. The method of claim 1, 3 or 4, wherein said onium salt is present in an amount of about 0.1 to about 1 percent by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA362,477A CA1109869A (en) | 1978-06-19 | 1980-10-15 | Synthesis of 2-keto-1,4-diazacyclo-alkanes |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/916,640 US4167512A (en) | 1977-09-21 | 1978-06-19 | Synthesis of 2-keto-1,4-diazacycloalkanes |
| US916,640 | 1978-06-19 | ||
| CA310,371A CA1109867A (en) | 1977-09-21 | 1978-08-30 | Synthesis of 2-keto-1,4-diazacycloalkanes |
| CA362,477A CA1109869A (en) | 1978-06-19 | 1980-10-15 | Synthesis of 2-keto-1,4-diazacyclo-alkanes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1109869A true CA1109869A (en) | 1981-09-29 |
Family
ID=27165836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA362,477A Expired CA1109869A (en) | 1978-06-19 | 1980-10-15 | Synthesis of 2-keto-1,4-diazacyclo-alkanes |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1109869A (en) |
-
1980
- 1980-10-15 CA CA362,477A patent/CA1109869A/en not_active Expired
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