IMPROVED PROCESS FOR THE SYNTHESIS OF 1,4-DIAZA-2-CYCLOALKANONE AND SUBSTITUTED DERIVATIVES THEREOF

Abstract: Improved process for the synthesis of 1,4-diaza-2-cycloalkanones and substituted derivatives thereof involving solid-liquid phase transfer phenomenon. More specifically, the subject compounds are prepared by combining a substituted diamine and suitable coreactant in the presence of a phase transfer catalyst and caustic.

Description: IMPROVED PROCESS FOR THE SYNTHESIS OF l,4-DIAZA-2-CYCLOALKANONE AND SUBSTITUTED DERIVATIVES THEREOF BACKGROUND OF THE INVENTION Field of the Invention - This invention relates to a process. More specifically, this invention is directed to the synthesis of l,4-diaza-2-cycloalkanonεs and substituted derivatives thereof by a technique involving solid-liquid phase transfer phenomena. Description of the Prior Art - The increasing use of polymers in place of the more traditional types of structural materials (e.g. wood, metals, etc.) has necessitated the compounding of such polymers,with a variety of stabilizers in order to enhance the ability of such polymers to withstand prolonged exposure to a variety of degradative forces. Degradation of such environmentally sensitive polymers can be caused by exposure to light, heat and/or air. Such degradation is usually manifest by either a partial or total loss cf structural integrity, changes in light transmission properties, changes in color, loss or reduction in flexibility and/or resiliency, or any combination of the above phenomenon. As will be appreciated, the stabil¬ izers which are used in conjunction with the above polymeric materials, in addition to providing protection against such degradative changes, must also be compatible with the aesthetic properties of the polymeric article and be effective at low concentrations. The economics of the marketplace dictate that these stabilizers be rela- tively inexpensive and capable of preparation from readily available starting materials by simple and straightforward synthesis techniques. The diazacycloalkancnes have been found to be highly effective in the stabilization of polymeric materials against the photodegradative forces of ultra¬ violet light. The efficacy of such materials in the UV stabilization of polymers is described in copending patent applications Serial No. 835,065 and 835,069, bot filed on September 21, 1977; the '065 application entitled "Substituted 2-keto-l,4-Diaza Cycloalkanes and UV Light Stabilized Compositions Containing Same" and the '069 application entitled "UV Light Stabilized Compositions Containing Substituted 1,5-diazacyclo- Alkanes and Novel Compounds". The aforementioned appli¬ cations disclose methods for the preparation of com- pounds useful in the stabilization of UV sensitive polymer compositions. A third copending application entitled "Synthesis of 2-keto-l,4-Diazacycloalkanes" (Ser. No. 835,066 also filed September 21, 1977) discloses a variety of techniques for the convenient synthesis of highly effective UV stabilizer compounds. The principal advantage of the synthesis described in the '066 application involves the utilization of readil available starting materials, conventional processing apparatus, the absence of hydrogen cyanide and the attendant hazards associated therewith. In copending application 835,066, in the section entitled "Background of the Invention", certain references are enumerated which disclose cycloalkanes as useful UV stabilizers - see for example OLS 2,315,042; JAP PATS. 74-53,571 and 74-53.572; and U.S. Patents 3,919,234; 3,920,659 and 3,928,330. Also discussed in this same Section are structurally similar compounds and the limitations on the synthesis of such compounds and the anologs thereof. To the extent that this discussio is relevant to subject matter of the invention described and c-laimed hereinafter, it is hereby incorporated by reference in its entirety. As noted in copending application Serial No. 835,066, prior art processes discussed therein do not described convenient techniques for the preparation of poly-substituted 1,4-diazacyclcalkanones. The li ita- ^h tions apparent in such processes are most pronounced where one attempts to synthesize symmetrically substi¬ tuted compounds. Other aspects of the prior art pro¬ cesses in need of improvement involve (a) reduction in size of reaction mass, (b) simplification of work-up procedure for separation of product from reaction mass, and (c) reduction in reaction time. To the extent that such deficiencies in the prior art can be remedied, synthesis of the desired product will be accomplished more efficiently and more economically. SUMMARY OF THE INVENTION Accordingly, it is the object of this invention to remedy the above as well as related deficiencies in the prior art. = More specifically, it is the principal object of this invention to provide a more efficient and economi¬ cal process for the synthesis of 1,4-diaza-cycloalka- nones. It is another object of this invention to provide a more efficient and economical process for the synthesis of symmetrically substituted 1,4-diaza-cyclo- alkanones. It is yet another object of this invention to provide a more efficient and economical process for the synthesis of symmetrically substituted 1,4-diaza-cyclo- alkanones from readily available starting materials. Additional objects of this invention include providing an improved process for the synthesis of symmetrically substituted 1,4-diaza-cycloalkanones without the risks attendant in the use of hydrogen cyanide. " The above and related objects are achieved by contacting an appropriately substituted diamine with- co-reactants in the presence of a phase transfer catalyst and solid caustic. In one of the preferred embodiments of this invention, the exother of the reaction is controlled by chilling of the reaction vessel. In another of the preferred embodiments of the invention, the reactants and catalysts are contacted with one another while dispersed in a nonpolar organic solvent, such as dichloromethane. DESCRIPTION OF THE INVENTION INCLUDING PREFERRED EMBODIMENTS In a typical embodiment of the process of this invention, an appropriately substituted diamine and a co reactant, such as an α-trichloroalkyl alcohol, a mixture of a haloform and an α-cyanoalkyl alcohol, or a mixture of a haloform and an aliphatic ketone, in the desired relative concentrations, are introduced into a reaction vessel followed thereafter by the addition to said vesse of a phase transformation catalyst dissolved in a non- polar organic solvent. ' To this reaction mass is there¬ after added solid caustic, such as solid sodium hydroxid The reaction vessel is preferably at least partially immersed in an ice bath to control the exotherm of the reaction. The presence of the solid caustic in the reaction medium also serves a similar function that is, it retards the rate of reaction and thus the heat genera ted during the combination of the reactants is reduced significantly. The ratio of reactants to one another in this process is not believed to be critical to the formation of its desired product. However, where one desires -co obtain high yields ana ease of separation of the reactio product from the various reactants and catalysts used in such preparation, it is preferable to adjust the relativ mole concentration of materials so that the ratio of diamine to co-reactant (e.g. -trihaloalkylalcohol) is i the range of from about 0.5:1 to about 1:1. As the result of the interaction of the above materials in the reaction vessel, a water-soluble solid is formed. This solid can be removed from the nonpolar reaction medium by filtration or by the addition of water to the reaction medium followed thereafter by separation of the aqueous from the organic fluid phase. The aqueous phase is thereafter further extracted with an organic solvent such as chloroform and the combined organic solutions washed with water, dried over sodium sulphate and concentrated. The desired product is crystallized or distilled from the combined organic solutions and recrvstallized in the conventional fashion to yield a relatively pure product. The substituted diamines suitable for use in this process have the following structural formula: - -R R, -C- NHR. (CH 2 ) n R^ —C— NHR ? I ■ 1 -^ R 3 wherein R, and R_ are independently selected from the group consisting of hydrogen, halogen, alkyl of 1 to 12 carbon atoms, hydroxyalkyl, haloalkyl, cyanoalkyl, a inoakyl, iminoalkyl, ether, nitro, hydroxyalkyl ethers, cyanoalkyl ethers, alkenyl, alkynyl and carboalkoxy; R_ through R fi are independently selected from the group consisting of alkyl of 1 to 12 carbon atoms, cycloalkyl, hydroxycycloalkyl, aminoalkyl, iminoalkyl, alkenyl, aralkyl and alkylene, provided further that any two of said substituents pendant from the same car¬ bon atom can collectively form a cyclic or alicyclic hydrocarbon: and n is 0 to 3. Compounds within the scope of the above structural for¬ mula which are especially suitable for use in the pro¬ cess of this invention are the '-alkvl-2-alkvl-l,2-alkane OMPI diamines, e.g. N*-isopropyl-2-methyl-l,2-propanediamine Additional 1,2-diamines which are highly effective for use in the process of this invention include N'-propyl- 2-methyl-l,2-propane-diamine, N'-isopropyl-2-methyl-l, 2-propanediamine, N'-t-butyl-2-methyl-l,2-propanediamin '-t-octyl-2-methyl-l,2-propanediamine, '-phenyl-2- methyl-1,2-propanediamine, ethylene-2, 2-bis-"N"- (2- methyl-l,2-propanediamine) , and 2,5-dimethylhexane-2,5- bis-'N'-(2-methyl-l,2-propanediamine) . The co-reactants which are suitable for use i the process of this invention can include Q .-trihaloalky alcohols, mixtures of a haloform and an α-cyanoalkyi alcohols, and/or mixtures of a haloform and an aliphati ketones. The trihaloalkylalcohol which is suitable for use in the process of this invention can be represented by the following formula: wherein R ? and R_ are selected from.the same group of substituents as Rj-. through R6 r above; X is halogen; and n is 0 to 5. In the preferred embodiments of the process of this invention, the ct-trihaloalkyl alcohol is symmetrically substituted at the 3 carbon. One such material which i especially preferred for use in the process of this invention is 1,I,l-trichloro-2-methyl-2-propanol hydrat The alcohols which are highly suitable for use in this process include a-trichloromethyl-2-propanol, cs-trichlo methyl-cyclohexanol, and -.-trichlorcmethyl-1-butanol. The co-reactant mixtures which are suitable fo use in the process of this invention contain a haloform, (e.g. chloroform or bro oform) in addition to an &- cyanoalkylalcohol or an aliphatic ketone. The concen¬ tration of the haloform relative to the other compon¬ ent of the mixture can vary and is preferably present in stoichiometric amounts (in relation to the α-cyanoalkyl- alcohol, at a mole ratio of about 1:2 and, in relation to the aliphatic ketone, at a mole ratio of about 1:1) although a stoichiometric excess is most preferred. The -cyanoalkylalcohols which are suitable for use in this process can be represented by the following formula: CN OH CH wherein R 7 and R„ are selected from the same group of substituents as R-, through R_ above; and n is defined the same as hereinabove. The aliphatic ketones which are suitable for use in the process of this invention can be represented by the following formula: 0 11 C / \ R ? Rg wherein R-, and R- are selected from the same group of substituents as R-. through R→ above. One or more of above co-reactants, as indicated previously, are contacted with the diamine in the presence of a "phase transfer catalysts". The phrase "-phase transfer catalysts" is intended to describe, in the context of this invention, any compound, which in the presence of the above reactants, causes a condensation of the co-reactants and the diamine in such a fashion so as to result in the formation of a cyclic ketone wherein the oxygen is doubly bonded to an -carbon of the co- reactant material. Materials which have been found to effectively catalyze condensation of the diamine and co-reactants in this fashion can be represented by the following formula Q + E- wherein Q + is NH R , PH 1^ provided that R is alkyl of 1 20 carbon atoms, aryl or aralkyl; n is 0 - 4, x, y and z are 0 - 4 provided further that the sum of n plus x, n plus y, and n plus z equals 4; B ~ is a monovalent anion, such as a halide, acetate, perchlorate, εulfate, or hydrosulfate. Catalyst compositions which are preferred for the proces of this invention include cetyl trimethylammonium bro¬ mide, methyl tricaprylylammonium chloride, cetyl tributy phosphonium bromide, tetrabutylammonium hydrogen sulfate and tetrabutylammonium chloride. In addition to the above reactants and cata¬ lysts, a controlled amount of solid caustic is also employed in the process of this invention. This caustic material is added in solid form to the reaction mass preferably subsequent to the addition to the reactor of all reactants and catalyst. The concentrations of caust relative to diamine used in this process can vary and will ordinarily be present in the reaction mass in excess of stoichiometric quantities; preferably at the relative mole ratio of about 3.3:1 to about 6:1. The addition of the solid caustic material in lieu of causti solution to the reaction mass (a) reduces the size of th re d action mass, (b) simplifies the separation of the desired product from the reaction mass, and (e) enhances the overall efficiency of the synthesis, thereby reducin the reaction time. The l,4-diaza-2-cycloalkanones produced in accord with the above procedures are highly effective at low concentrations in the stabilization of UV degradable polymeric materials. EXAMPLES The Examples which follow further define, describe and illustrate the process of this invention. Apparatus and techniques used in such process are standard or as ' hereinbefore described. Products and percentages appearing in such Examples are by weight unless otherwise stipulated. EXAMPLE I N'-isopropyl-2-methyl-l,2-propane diamine (13.Og, 0.1 mols) and 2-trichloromethyl-2-propanol hydrate (23.1 g, 0.13 mcl) were placed in a 3 neck flask which itself was immersed in an icebath. 50 milliliters di- chloro ethane and benzyltriethyl ammonium chloride (0.91 g, 0.004 mol) were then added to the flask, followed by the mεtεred addition of solid sodium hydroxide (a total of 48 g or 0.6 mols); the rate of addition being adjusted so as to maintain the reaction temperature below about 10°C. A few hours after the addition of caustic, the reaction was complete, as confirmed by gas chromatography. Water was added to the flask until all salts were dissolved. The two layers, which are formed in the flask, are sepa¬ rated and the aqueous phase extracted once with chloroform. The combined organic solutions were then washed three times with 50 milliliters water, dried over sodium sulfate and concentrated. The solid which is formed in the flask was recrystallized from pentane to obtain 9.5 grams- of needlelike crystals. The ir spectrum and elemen¬ tal analysis were consistent with the structure of the desired product. - EXAMPLE II The procedures of Example I are repeated except with the following combination of reactants. O H -- Example No, 1, 2-diamine Co-reactant II N'-propyl-2-methyl-l, 2-propane 2-trichloromethyl-2-propanol diamine hydrate III o-phenylene diamine 5 IV '-butyl-4-methyl-2,4-pentane diamine V N,N'-dimethyl-ethylene amine VI '-isopropyl-2-methyl-l,2-propane acetone cyanohydrin (0.12 moles) diamine chloroform (0.22 moles) 10 VII N '- (2-hydroxy-l,1-dimethyl) - acetone cyanohydrin 2-mcthyl-l, 2-propanediamine chloroform VIII '-isopropyl-2-methyl-l, 2- cyclohexanone cyanohydrin propane diamine chloroform IX 1,2-ethane-bi._-N '- (2-methy1-1,2- acetone cyanohydrin 15 propane diamine) chloroform X '-butyl-4-methyl-2,4- acetone chloroform The foregoing Examples have been provided to illustrate some of the preferred embodiments of the process of this invention and are not intended to de¬ lineate its scope, which is set forth in the following claims. O PI ,, IPO ^

Claims: CLAIMS 1. A process for the synthesis of 1,4-diaza- 2-cycloalkanones comprising contacting, in the presence of a phase transfer catalyst, a diamine of the formula: l . - R 3 wherein R, and R_ are independently selected from the group consisting of hydrogen, halogen, alkyl of 1 to 12 carbon atoms, hydroxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, iminoalkyl, ether, nitro, hydroxyalkyl ethers, cyano alkyl ethers, alkenyl, alkynyl and carboalkoxy; R_ through g being independently selective from the group consisting of alkyl of 1 to 12 carbo atoms, cycloalkyl, hydroxycycloalkyl, a ino- alkyl , iminoalkyl, alkenyl, aralkyl and alky- lene, provided further that any two of the above hydrocarbon substituents pendant from the same carbon atom can collectively form a cyclic or alicyclic hydrocarbon; and n is a number from 0 to 3; with a stoichiometric excess of both (i) solid caustic and (ii) an ct-trihaloalkylalcohol of the formula: CX-. OH / CH wherein R„ / , the same as R_ - defined hereinabove. O 2. The process of Claim 1 wherein the tempera¬ ture of the reactants is maintained at about 10°C or below. 3. The process of Claim 1, wherein the phase transfer catalyst is an ammonium salt. 4. The process of Claim 1 wherein the re¬ actants and catalyst are combined in a nonpolar organic reaction medium. • 5. The process of Claim 4, wherein the 1,4- diaza-2-cycloalkanonε is highly soluble in the nonpolar organic reaction medium. 6. The process of Claim 1 wherein the diamine is N'-isopropyl-2-methyl-l,-2-propanediamine. 7. The process of Claim 1 wherein the alcohol is an α-trichloroalkylalcohol. 8. The process of Claim 1 wherein the relative mole conc * entration of solid caustic to the diamine is in the range of from about 3.3:1 to about 6:1. 9. The process of Claim 1 wherein the solid caustic is sodium hydroxide. 10. A process for the synthesis of 1,4-diaza- 2-cycloalkanones comprising contacting, in the presence of a phase transfer catalyst, a diamine of the formula: " ?6 * R 0- -C-NHR- ι (CH- ) ι 2 n -C-NHR ι -^ « ' R 3 wherein R, and - are independently selected from the group consisting of hydrogen, . alogen, alkyl of 1 to 12 carbon atoms, hydroxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, iminoalkyl, ether, nitro, hydroxyalkyl ethers, cyano alkyl ethers, alkenyl, alkynyl and carboalkoxy; R OMPI through R fi being independently selective fro • the group consisting of alkyl of.1. to 12 car bon atoms, cycloalkyl, hydroxycyclfalkyl, aminoalkyl, iminoalkyl, alkenyl, aralkyl and alkylene, provided further that any two of t above hydrocarbon substituents pendant from the same carbon atom can collectively form a cyclic or alicyclic hydrocarbon; and n is a number from 0 to 3; with a stoichiometric excess of both (i) solid caustic and (ii) a mixture .of haldform and an α-cyanoalkylalco of the formula: CN OH -H wherein R_ and R_ are the same as R - R c defined herein above and n is defined the same as hereinabove. 11. A process for the synthesis of 1,4-diaz 2-cycloloalkanones comprising contacting, in the prese of a phase transfer catalyst, a diamine of the formul (CK 2 )n I wherein R and R„ are independently selected from the group consisting of hydrogen, halogen, alkyl of 1 to 12 carbon atoms, hydroxyalkyl, * haloalkyl, cyanoalkyl, aminoalkyl, iminoalky ether, nitro, hydroxyalkyl ethers, cyano alk ethers, alkenyl, alkynyl and carboalkoxy; R 3 through R fi being independently selective from the group consisting of alkyl of 1 to 12 carbon atoms, cycloalkyl, hydroxycycloalkyl, aminoalkyl, iminoalkyl, alkenyl, alalkyl and alkylene, provided further that any two of the above hydrocarbon substituents pendant from the same carbon atom can collectively form a cyclic or alicyclic hydrocarbon; and n is a number from 0 to 3; with a stoichiometric excess of both (i) solid caustic and (ii) a mixture of haloform and an aliphatic ketone of the formula: 0 II wherein R_ and R R are the same as R, - R, defined hereinabove.

Inventors: LAI J
Applicants: GOODRICH CO B F
Application year: 1979
Main classification: C07D243
IPC codes: B01J31, C07D241, C07D243