US3218246A - Electrolytic hydrodimerization of 2-or 4-alk-1-enyl pyridines, e. g., vinyl pyridines - Google Patents

Description

United States Patent 3 218,246 ELECTROLYTIC HiKDRODIMERIZATION 0F 2- 0R 4-ALK-1-ENYL PYRIDINES, e.g., VINYL PYRIDINES Manuel M. Baizer and Erhard J. Prill, St. Louis, Mo., assignors to Monsanto Company, a corporation of Delaware No Drawing. Filed June 18, 1963, Ser. No. 288,621 Claims. (Cl. 204-74) The present invention relates to the manufacture of poly-functional compounds and more particularly provides a process for electrolytically hydrodimerizing compounds having ethylenic bonds in conjugated relationship to the unsaturated system of a pyridine ring.

An object of the invention is the provision of a process for preparing butanes bearing 2- or 4-pyridine substituents in the 1 and 4 positions, e.g., l,4-bis(2-pyridyl) butane.

The process of tthe present invention is illustrated:

in which Z is a pyridine radical attached at the 2 or 4 position, i.e., an even numbered ring carbon atom, and R and R are hydrogen or hydrocarbyl radicals usually containing no non-benzenoid unsaturation, e.g., alkyl or aryl radicals. The pyridyl radicals can optionally be substituted by alkyl radicals, particularly lower alkyl radicals, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, isohexyl, etc., groups, e.g., such 2- and 4-pyridyl radicals as Z-pyridyl, 4pyridyl, 3-methyl- Z-pyridyl, 3,'6-dimethyl-'2-pyridyl, 2-methyl-4-pyridyl, 4- hexyl-Q-pyridyl, etc., are suitable, and the pyridyl radicals can also contain other nonreactive substituents which do not undergo undesired transformations during the electrolysis procedure. It is necessary to have the pyridyl group bonded to the ethylene at the 2 or 4 position in order to have the ethylenic bond properly activated for the electrolysis. The position on the pyridine ring in the product will correspond to that in the reactant. The R and R substituents are individually selected from hydrogen, alkyl or aryl groups, e.g., hydrogen, methyl, ethyl, propyl, isopropyl, butyl, hexyl, phenyl, alpha-naphthyl, beta-naphthyl, 2-ethylpheny1, benzyl, phenylethyl, etc. Some examples of suitable reactants are Z-Vinylpyridine, 4-vinylpyridine, 2-crotylpyridine, 4-but-1-enylpyridine, 2- hex-l-enyl-4-rnethylpyridine, 2(2-pyridyl)propene, 2- styrylpyridine, 1(2-pyridyl)-2-(2-tolyl-ethene and various other '2 or 4 pyridyl ethylenes. While in general the alpha,beta-olefinic substituents on the pyridine ring are hydrocarbyl, i.e., l-alkenyl groups, it is contemplated that the ethylenic carbon atoms can bear other functional groups which activate the olefinic bond, e.g., carbalkoxy, carboxamido or cyano groups. However, the present invention is concerned with the electrolytic reductive coupling of 2 or 4-olefinic pyridines, not with coupling such pyridines with other activated olefinic compounds as disclosed and claimed in the simultaneously filed copending application S.N. 288,629.

In .general, the electrolytic reductive coupling of the present invention is conducted in concentrated solution in an aqueous electrolyte. It is desirable to employ fairly concentrated solutions in order to minimize undesired reactions of intermediate ions with the Water of the electrolyte. The olefinic reactants will ordinarily comprise at least about 10% by weight of the electrolyte, and preferably at least by weight or more. It is generally desirable to employ fairly high concentrations of salts in the electrolyte, for example constituting 5% and usually 30% or more by weight of the total amount of 3,218,246 Patented Nov. 16, 1965 salt and water in the electrolyte, in order to obtain the desired solubility of the olefinic compounds.

Electrolysis, of course, has been practiced for many years and numerous materials suitable as electrolytes are known, making it within the skill of those in the art in the light of the present disclosure to select electrolytes for reductive coupling according to the present invention. Some olefinic compounds are subject to polymerization or other side reactions if the electrolyte is acidic, or excessively alkaline, and it will be necessary in such cases to conduct the reductive coupling in solutions which are not overly acidic and also in some cases below a pH at which undesirable side reactions occur, e.g., below about 12. In general, the 2- or 4-olefinic pyridine compounds employed in the present invention can be polymerized, and the pH is usually maintained within the range of about 3 to about 12 to obtain desired yields, preferably pHs of 6 to 9.5.

When the catholyte during electrolysis is acidic, it will generally be advisable to conduct the electrolysis under conditions which inhibit polymerization of the reactants involved or in the presence of a polymerization inhibitor for example, in an atmosphere containing suflicient oxygen to inhibit the polymerization in question, or in the presence of inhibitors effective for inhibiting free radical polymerization. Classes of inhibitors for inhibiting free radical polymerizations are well known, e.g., such inhibitors as hydroquinone, p-t-butyl catechol, quinone, p nitroso dimethylaniline, di-t-butyl hydroquinone, 2,5-dihydroxy-1,4-benzoquinone, 1,4-naphthoquinone, chloranil, 9,10-phenanthraquinone, 4-amino-1-naphthol, etc., are suitable.

In elfecting the reductive coupling of the present invention it is preferred to utilize a cathode having an overvoltage greater than that of copper and to subject to electrolysis in contact with such cathode a concentrated solution of the defined olefinic compounds in an aqueous electrolyte under mildly alkaline conditions. It is understood that both the cathode and the anode will be in actual direct physical contact with electrolyte. In effecting the reductive couplings of the present invention, it is essential to obtain cathode potentials required for such couplings and therefore the salt employed should not contain cations which are discharged at numerically substantially lower, i.e., less negative, cathode potentials. It is desirable that the salt employed have a high degree of water solubility to permit us of very concentrated solutions, for concentrated salt solutions dissolve greater amounts of the organic olefinic compounds.

In addition to the foregoing considerations, a number of other factors are important in selecting salts suitable for good results. For example, it is undesirable that the salt cation form an insoluble hydroxide at the operating pH, or that it discharge on the cathode forming an alloy which substantially changes the hydrogen overvoltage and leads to poorer current efficiencies. The salt anion should not be lost by discharge at the anode with possible formation of by-products. If a cell containing a separating membrane is used, it is desirable to avoid types of anions which, in contact with hydrogen ions present in the anolyte chamber, would form insoluble acids and clog the pores of the membrane. Alternatively, the use of an ion exchange membrane eifectively separates catholyte and anolyte and the use of different anions in the two chambers may minimize any difficulties a particular anion would cause in one of the chambers.

In general amine and quaternary ammonium salts are suitable for use in the present process. Certain salts of alkali and alkaline earth metals can also be employed to some extent, although they are more subject to interfering discharge at the cathode and the alkaline earth metal salts in general tend to have poor water solubility, making their use inadvisable.

Example 1 A catholyte was prepared by mixing 43 grams of 85% by weight methyl triethylammonium p-toluenesulfonate in water and 43 grams 4-vinylpyridine to form a solution and diluting with 43 grams dimethylformamide to a convenient volume. A small amount of hydroquinone was added as stabilizer. The cathode was 110 ml. mercury. As anolyte, 15 ml. of the 85 salt solution was diluted with 5 ml. water and placed in an Alundum cup in which a platinum anode was immersed. Electrolysis was conducted for about two hours at cell voltage of about 30, cathode voltage of l.4 to 1.5 (vs. saturated calomel electrode) and a current of about 2 amperes for a total of 3.8 ampere hours. During the electroylsis about 3.7 ml. acetic acid was added to the catholyte to control the alkalinity. The solid l,4-bis(4-pyridyl)butane product, 6 grams, was separated by filtration, using dimethylformamide for washing, and dried to a white solid, M.P. 120 C. By diluting the filtrate with water, extracting with methylene dichloride, absorbing on and eluting from an alumina column, an additional 6.4 grams of product, M.P. 119-121, was isolated, for a yield of 82%.

Example 2 employing a solution of 50 grams 85% by weight methyl triethylammonium methylsulfate in water, 50 grams dimethylformamide and 50 grams 2-vinylpyridine as catholyte. The anolyte was a 47% aqueous solution of methyl tributylammonium p-toluenesulfonate. The electrolysis was conducted at 1.4 to 1.5 cathode volts (vs. saturated calomel electrode) for a total of 5.4 ampere hours. The catholyte was diluted with water and extracted with methylene dichloride, dried over calcium sulfate, and distilled under vacuum, using hydroquinone as stabilizer. About 30 grams of vinyl pyridine was recovered, and grams product was obtained. The product was redistilled through micro apparatus, fractions being collected at 124-6" at 0.2 mm. and 128 at 0.2 mm. The samples analyzed as 1, 4-bis(2-pyridyl)butane. Calcd: C, 79.2; H, 7.6; N, 13.2; Mol. wt. 212. Found: C, 77.22 .and 78.47; H,7.85 and 7.86; N, 12.35 and 12.47; Mol. wt. 215 and 213. The infra red spectra of the sample were identical and confirmed the 1,4-bis(2-pyridyl) butane structure.

The above examples are illustrative of the present process and the reductive couplings of the various olefinic pyridines set forth herein can be conducted under the same conditions or numerous variations thereof. In addition, the procedures of copending application S.N. 228,740, filed October 5, 1962, and now abandoned, and of the application referred-to therein are applicable to the hydrodimerization of the olefinic pyridine reactants employed herein.

While high concentrations of the reactants are readily obtained with some salts, concentrations can be increased by using a polar solvent along with the water, e.g., acetonitrile, dioxane, ethylene glycol, dimethylformamide, dimethylacetamide, ethanol or isopropanol, in addition to the salts.

The electrolytic reductive couplings of the present invention are conducted in solution in electrolyte, generally in fairly concentrated solution in an aqueous electrolyte. It will be recognized that as used herein an electrolyte is considered aqueous even if the amount of water is small. Many electrolytes can be employed in the present invention but some are less suitable than others. The salts employed, either to provide conductivity or to increase solubility of the reactants have an important hearing on the electrolysis and will be discussed at length below. The acidity or basicity is also significant, neutral or mildy alkaline solutions generally being preferred.

Many of the olefinic compounds employed in the present invention tend to polymerize when electrolyzed in strongly acidic solution, such as solutions of mineral acids, and it is desirable or necessary in such cases to avoid excesive acidity, making it desirable to operate at pHs above about 5 or 6, such as provided by solutions of salts of strong bases. Moreover, the hydrogen ion has a cathode discharge potential of about 1.5 volts, making it desirable to avoid high concentrations of hydrogen ion in the catholyte if the reductive coupling occurs at similar or more negative cathode potentials. The reductive couplings can suitably be conducted at pHs higher than those at which substantial polymerization of olefinic compound occurs, or higher than those at which there is undue generation of hydrogen, for example pHs at which more than half the current is expended in discharging hydrogen ions. The pHs referred to are those obtaining in the buk of the catholyte solution, such as determinable by a pH meter on a sample of the catholyte removed from the cell. The electrolysis in effect generates acid at the anode and base at the cathode; it will be recognized that in an undivided cell the pH in the immediate vicinity of the cathode may diifer considerably from that near the anode, particularly if good stirring is not employed. To some extent the effects of acidity can be counteracted by high current density to cause more rapid generation of hydroxyl ions. However, high current densities also require good stirring or turbulence to move the reactants to the cathode.

During the electrolysis in a divided cell, alkalinity increases in the catholyte. However, the anolyte becomes acidic. When a porous diaphragm is used to separate the catholyte from the anolyte, the alkalinity of the catholyte will depend upon the rate of difiusion of acid from the anolyte through the porous barrier. Control of alkalinity in the cathoylte when employing a diaghragm, may thus be realized by purposely leaking acid from the anolyte into the catholyte. It can also be achieved, of course, by extraneous addition to the catholyte of an acid material, e.g., glacial acetic acid, phosphoric acid or p-toluenesulfonic acid. Alkalinity may also be controlled, whether or not a diaphragm is used inthe cell, by employing buffer systems of cations which will maintain the pH range while not reacting at the reaction conditions.

It is known that strongly alkaline solution can cause pyridethylation reactions of vinyl pyridines and it will be desirable to maintain the pH low enough to avoid or substantially minimize such reactions, for example below 9.5. However, good agitation or turbulence may counteract excess alkalinity to some extent by minimizing local concentrations of hydroxyl ions at the cathode. The use of high current densities and other provisions to minimize the electrolysis reaction time will also be useful in this regard.

When a divided cell is employed, it will often be desirable to use an acid as the anolyte, any acid being suitable, particularly dilute mineral acids such as sulfuric or phosphoric aid. Hydrochloric acid can be employed but would have the disadvantage of generating chlorine at the anode, and of being more corrosive with respect to some anode materials. When an acid is employed as anolyte, it is advantageous to use an ion exchange membrane to separate the anolyte from the catholyte. If desired, a salt solution can be used as anolyte, those useful as catholyte also being suitable as anolyte, although there are many other salt solutions suitable for such use.

Material-s suitable for constructing the electrolysis cell employed in the present process are well known to those skilled .in the art. The electrodes can be of any suitable cathode and anode material. The anode may be of virtually any conductor, although it will usually be advantageous to employ those that are relatively inert or attacked or corroded only slowly by the electrolytes; suitable anodes are, for example, platinum, carbon, gold, nickel, nickel silicide, Duriron, lead, and lead-antimony and leadcopper alloys, and alloys of various of the foregoing and other metals.

Any suitable material can be employed as cathode, various metals and alloys being known to the art. It is generally advantageous to employ metals of fairly high hydrogen overvoltage in order to promote current efficiency and minimize generation of hydrogen during the electrolysis. In general it will be desirable to employ cathodes having overvoltages at least about as great as that of copper, as determined in a 2N sulfuric acid solution at current density of 1 miliarnp/square centimeter (Carman, Chemical Constitution and Properties of Engineering Materials, Edward Arnold and Co., London, 1949, page 290). Suitable electrode materials include, for example, mercury, cadmium, tin, zinc, bismuth, lead, graphite, aluminum, nickel, etc., in general those of higher overvoltage being preferred. It will be realized that overvoltage can vary with the type of surface and prior history of the metal as well as with other factors; therefore the term overvoltage as used herein with respect to copper as a gauge has reference to the overvoltage under the conditions of use in electrolysis.

Among the salts which can be employed according to the present invention for obtaining the desired concentration of dissolved olefinic compound, the amine and quaternary ammonium salts are gene-rally suitable, especially those of sulfonic and alkyl sulfuric acids.

Such salts can be the saturated aliphatic amine salts or heterocyclic amine salts, e.g., the mono-, dior tri-alkylamine salts, or the mono-, dior trialkanolamine salts, or the piperidine, pyrrolidine or morpholine salts, e.g., the ethylamine, dimethylamine or triisopropylamine salts of various acids, especially various sulfonic acids. Especially preferred are aliphatic and heterocyclic quaternary ammonium salts, i.e., the tetraalkylammonium or the tetraalkanolammonium salts or mixed alkyl alkanol ammonium salts such as the alkyltrialkanolammonium, the dialkyldialkanolammonium, the alkanoltrialkylammonium or the N-heterocyclic N-alkyl ammonium salts of sulfonic or other suitable acids. The saturated aliphatic or heterocyclic quaternary ammonium cations in general have suitably high cathode discharge potentials for use in the present invention and readily form salts having suitably high water solubility with anions suitable for use in the electrolytes employed in the present invention. The saturated, aliphatic or heterocyclic quaternary ammonium salts are therefore in general well adapted to dissolving high amounts of olefinic compounds in their aqueous solutions and to effecting reductive couplings of such olefinic compounds. It is understood, of course, that it is undesirable that the ammonium groups contain any reactive groups which might interfere to some extent with the reductive coupling reaction. In this connection it should be noted that aromatic unsaturation as such does not interfere as benzyl substituted ammonium cations can be employed; (as also can aryl sulfonate anions).

Among the anions useful in the electrolytes, the aryl and alkaryl sulfinic acids are especially suitable, for example, salts of the following acids; benzenesulfonic acid, 0-, mor p-toluenesulfonic acid, 0-, mor p-ethylbenzenesulfonic acid, o-, mor p-cumenesulfonic acid, o-, mor -p-tert-a myl-benzenesulfonic acid, 0-, mor p-hexylbenzensulfonic acid, o-xylene-4-sulfonic acid, p-xylene-2- sulfonic acid, m-xylene-4 or S-sulfonic acid, mesitylene- 2-sulfonic acid, durene-3-sulfonic acid, pentamethylbenenesulfonic acid, o-dipropylbenzene-4-sulfonic acid, alphaor beta-naphthalenesulfonic acid, o-, mor p-biphenylsulfonic acid, and alpha-methylbet-a-naphthalenesulfonic acid. Alkali metal salts are useful in the present invention with certain limitations, and the alkali metal salts of such sulfonic acids can be employed, i.e., the sodium, potassium, lithium, cesium or rubidium salts such as sodium benzenesulfon-ate, potassium, p-toluenesulfonate, lithium o-biphenylsulfonate, rubidium betanaphthalenesulfonate, cesium p-ethylbenzenesulfonate,

sodium o-xylene-Seulfonate, or potassium pentamethylbenzenesulfonate. also be the saturated, aliphatic amine or heterocyclic amine salts, e.g., the mono-, dior trialkylamine salts, or the mono-, dior trialkanolamiue salts, or the piperidine, pyrrolidine or morpholine salts, e.g., the ethylamine, dimethylamine or triisopropylamine salt of benzenesulfonic acid or of o-, por m-toluenesulfonic acid; the isopropanolamine, dibutanolamine or triethanolarnine salt of o-, por m-toluenesulfonic acid or of o-, por m-biphenylsulfonic acid; the piperidine salt of alphaor betanaphthalenesulfonic acid or of the cumenesulfonic acids; the pyrrolidine salt of o-, m-, p-amylbenzenesulfonate; the morpholine salt of henezesulfonic acid, of o-, mor p-toluenesulfonic acid, or of .alphaor beta-naphthalenesulfonic acid, etc. In general, the sulfonates of any of the ammonium cations disclosed generically or specifically herein can be employed in the present invention. The aliphatic sulfonates are prepared by reaction of the correspondingly substituted ammonium hydroxide with the sulfonic acid or with an acyl halide thereof. For example, by reaction of a sulfonic acid such as p-toluenesulfonic acid with a tetraalkylammonium hydroxide such as tetraethyla'mmonium hydroxide there is obtained tetraethylammonium p-toluenesulfonate, use of which in the presently provided process has been found to give very good results. Other presently useful quaternary ammonium sulfonates are, e.g., tetraethylammonium oor mtoluenesulfonate or benzenesulfonate; tetraethylammonium o-, mor p-cumenesulfonate or o-, mor p-ethylbenzenesulfonate, tetramethylammonium benzenesulfonate, or 0-, mor p-toluenesulfonate; N,N-di-methylpiperidiniu-m o-, mor p-toluenesulfonate or o-, mor p-biphenylsulfonate; tetrabutylammonium alphaor betanaphthalenesulfonate or o-, mor p-toluenesulfonate; tetrapropylammonium o-, mor p-arnylbenezenesulfonate or alpha-ethyl-beta-naphthalenesulfonate; tetraethanolammonium o-, mor p-cumene sulfonate or o-, mor p-toluenesulfonate; tetra-butanola-mmonium benzenesulfonate or p-xylene-3-sulfonate; tetrapentylammonium o-, mor p-toluenesulfonate or o-, mor p-hexylbenzenesulfonate, tetrapentanolammonium p-cumene-3- sulfonate or benzenesulfonate; methyltriethylammonium o-, mor p-toluenesulfonate or mesitylene-Z-sulfonate; trimethylethylarnmonium o-xylene-4-sulfonate or o-, rnor p-toluenesulfonate; triethylpentylammonium alphaor beta-naphthalene sulfonate or o-, mor p-butylbenzenesulfonate, trimethylethanolammonium benzenesulfonate or o-, mor p-toluenesulfonate; N,N-di-ethylpiperidinium or N-methyl-pyrrolidinium o-, mor p-hexyl-benzenesulfonate or o-, m, or p-toluenesulfonate, N,N-di-isopropyl or N,N-di-butylmorpholinium o-, mor p-toluenesulfonate or o-, mor p-biphenylsulfonate, etc.

The tetraalkylammonium salts of the aryl or alkarylsulfonic acids are generally preferred for use as the salt constituents of the electrolysis solution because the electrolyses in the tetraalkylammonium sulfonates are exclusively electrochemical processes.

Among the ammonium and amine sulfonates useful as electrolytes in the present invention are the alkyl, aralkyl, and heterocyclic amine and ammonium sulfonates, in which ordinarily the individual substituents on the nitrogen atom contain no more than 10 atoms, and usually the amine or ammonium radical contains from 3 to 20 carbon atoms. It will be understood, of course, that diand poly-amines and diand poly-ammonium radicals are operable and included by the terms amine and ammonium. The sulfonate radical can be from aryl, alkyl, alkaryl or aralkyl sulfonic acids of various molecular Weights up to for example 20 carbon atoms, preferably about 6 to 20 carbon atoms, and can include one, two or more sulfonate groups. Any of the quaternary ammonium sulfates disclosed and claimed in copending application SN. 75,- 123 filed December 12, 1960 can suitably be employed.

Another especially suitable class of salts for use in the The salts of such sulfonic acids may present invention are the alkylsulfate salts such as methosulfate salts, particularly the amine and quaternary ammonium methosulfate salts. Methosulfate salts such as the methyltriethylammonium, tri-n-propylmethylammoniurn, triamylmethylammonium, tri-n-butylmethylammonium, etc., are very hygroscopic, and the tri-n-butylmethylammonium in particular forms very concentrated aqueous solutions which dissolve large amounts of organic materials. In general the amine and ammonium cations suitable for use in the alkylsulfate salts are the same as those for the sulfonates.

The 1,4-bis(pyridyl)butanes produced by the present invention are a known class of compounds and the diquaternary salts formed therefrom by reaction with alkyl halides are known to have germicidal activity and to also have curare-like activity and neuromuscular blocking activity when hydrogenated to the corresponding alkylpiperidinium salts.

What is claimed is:

1. The method of reductively coupling pyridyl ethylenes which comprises subjecting a solution of such compound to electrolysis in contact with a cathode, the said pyridyl ethylenes having the pyridyl ring bonded to the ethylene by one of the even-numbered ring carbon atoms with respect to the nitrogen atom.

2. The method of claim 1 in which a 2-vinyl pyridine is hydrodimerized to a 1,4-bis(2-pyridyl)butane.

3. The method of claim 1 in which a 4-vinyl pyridine is hydrodimerized to a l,4-bis(4-pyridyl)butane.

4. The method of hydrodimerization which comprises subjecting an aqueous solution of olefinic compound represented by the formula:

in which Z represents a pyridyl radical with its valence bond on an even-numbered carbon atom, and R and R are selected from the group consisting of hydrogen and hydrocarbyl radicals containing no non-benzenoid unsaturation to electrolysis in contact with a cathode having a hydrogen overvoltage greater than that of copper, causing development of the cathode potential required for bydrodimerization, the solution containing at least about 10% by weight of olefinic compound and having a pH above about 6, and recovering the resulting bis pyridyl butane.

I 5. The method of claim 4 in which the olefinic compound is a 2-vinyl pyridine.

6. The method of claim 4 in which the olefinic compound is 4-vinyl pyridine.

7. The method of claim 4 in which the pH is about 7 to 9.5.

8. The method of claim 1 in which a polymerization inhibitor is present.

9. The method of claim 4 in which an aqueous electrolysis solution is employed and a quaternary ammonium salt constitutes at least 30% by weight of the water and salt, the said salt being soluble in such amounts.

10. The method of claim 1 in which the electrolysis is conducted in a quaternary ammonium aromatic sulfonate solution.

References Cited by the Examiner UNITED STATES PATENTS 2,632,729 3/1953 Woodman 20472 2,726,204 12/ 1955 Park et a1. 20472 OTHER REFERENCES Technique of Organic Chemistry, vol. II, Catalytic, Photochemical, Electrolytic Reactions, 2nd edition, 1956, Interscience Publishers, Inc., New York, pages 435 and 451- 457.

JOHN H. MACK, Primary Examiner.

Claims (1)

1. THE METHOD OF REDUCTIVELY COUPLING PYRIDYL ETHYLENES WHICH COMPRISES SUBJECTING A SOLUTION OF SUCH COMPOUND TO ELECTROLYSIS IN CONTACT WITH A CATHODE, THE SAID PYRIDYL EHTYLENES HAVING THE PYRIDYL RING BONDED TO THE ETHYLENE BY ONE OF THE EVEN-NUMBERED RNG CARBON ATOMS WITH RESPECT TO THE NITROGEN ATOM.