Modified Nickel Catalyst Systems and Their Use in Reductive Alkylation Reactions

This invention relates to new and highly effective catalytic systems and to processes in which they may be used. More particularly the invention relates to improved catalytic systems that are useful in reductive alkylation reactions.

Reductive alkylation reactions such as take place between an amine, a nitro or a nitroso compound when reacted with an aldehyde or ketone in the presence of hydrogen are commonly employed to produce N-alkyl substituted amines. Such reductive alkylation reactions are known to be catalyzed by certain metallic catalysts. However, many of the previously known metallic catalysts that are reasonably effective in promoting reductive alkylation reactions also have a tendency to promote one or more undesirable side reactions. For example, reductive alkylation reactions employing an amine, hydrogen and an aldehyde or ketone frequently result in the reduction of a substantial portion of the aldehyde or ketone to the corresponding alcohol. Another undesirable competing reaction when the nitro, nitroso or amine employed is an aryl compound is the reduction of the aromatic ring.

Co-pending U.S. patent application Ser. No. 426,408 discloses improved and highly effective catalytic systems for reductive alkylation reactions. This catalytic system comprises a nickel catalyst in combination with free sulfur or sulfur-containing compounds. The use of sulfur or sulfur-containing compounds along with the nickel alkylation catalyst is shown to increase the yields obtained in reductive alkylation reactions without promoting undesirable side reactions.

It is an object of this invention to provide other improved and highly effective catalytic systems for reductive alkylation reactions. It is a broad object of this invention to provide reductive alkylation catalytic systems which will produce high yields of the desired N-alkyl substituted amine. It is a specific object of this invention to provide a reductive alkylation catalyst that will produce a high yield of the desired N-alkyl substituted amine without promoting undesirable side reactions and in particular the reduction of the aldehyde or ketone alkylating agent to the corresponding alcohol. It is a still further object of this invention to provide an improved process for producing a high yield of N-alkyl substituted amines.

In accordance with the present invention some of the above objects are accomplished by using a two-component catalytic system while other objects are accomplished by using a three-component catalytic system to effectively reductively alkylate nitro, nitroso or amine compounds. The two-component system comprises concentrated metallic nickel or nickel dispersed on an inert carrier material and an acid containing no sulfur (i.e., sulfur-free acids) and sulfur-containing acids in which the sulfur is in the form of a ##STR1## radical. The three-component system comprises the two-component system and a modifier comprising free sulfur or sulfur-containing compounds which contain at least a portion of said sulfur in the form of a -- S -- and/or a ##STR2## radical.

Nickel catalysts broadly may be used in accordance with the present invention to produce improved catalytic compositions. The term "nickel catalyst" as employed throughout this specification and in the accompanying claims includes the following materials:

1. relatively pure metallic nickel that may be in finely subdivided form;

2. metallic nickel further modified with small amounts of other metals such as cobalt, chromium and zirconium; and

3. metallic nickel in pure form or modified with small amounts of other metals supported on an inert carrier such as kieselguhr, charcoal, clays, alumina, etc.

Examples of suitable sulfur-free acids and sulfur-containing acids in which the sulfur is in the form of a ##STR3## radical are sulfonic acids and organic acids and inorganic acids containing no sulfur. In the two-component system the preferred acids are sulfuric acid, toluene sulfonic acid and oxalic acid. The most preferred acid in the two-component system is sulfuric acid. The preferred acids in the three-component system are aromatic sulfonic acids, the most preferred acid being toluene sulfonic acid.

Examples of suitable sulfur-containing compounds that may be employed as catalyst modifiers in the three-component system include sulfur and:

1. mercaptans

2. sulfenyl thiocyanates

3. sulfenamides

4. sulfenic esters

5. sulfenic anhydrides

6. thiophosphites

7. thiophosphates

8 thio ortho esters

9. alkyl thio sulfates

10. thio sulfonic esters

11. thio sulfinic esters

12. thio sulfite esters

13. hydroxy mercaptans

14. alkoxy mercaptans

15. cyano mercaptans

16. aldehyde mercaptans

17. keto mercaptans

18. sulfide mercaptans

19. amino mercaptans

20. mercapto acids

21. organic sulfides

22. inorganic sulfides

23. hydroxy disulfides

24. amino disulfides

25. aldehyde sulfides

26. keto sulfides

27. thio amines

28. cyano sulfides

29. heterocyclic compounds containing ring sulfur

30. thiones

31. sulfide acids

32. disulfide acids

33. mercaptals

34. mercaptoles

35. disulfides

36. polysulfides

37. thio acids

38. thiol esters

39. thion esters

40. thio anhydrides

41. dithio acids

42. thio amides

43. thiol carbonic esters

44. thion carbonic esters

45. dithio carbonic esters

46. dithiol carbonic esters

47. dithiol carbonic salts

48. trithio carbonic esters

49. trithio carbonic salts

50. thiol carbamic esters

51. thion carbamic esters

52. dithio carbamic acid esters

53. thiol carbazates

54. thiuram monosulfides

55. thiuram disulfides

56. thiuram polysulfides

57. thioureas

58. isothiuronium salts

59. thiols

60. thio semi carbazide

61. thio carbazone

62. sulfur halides

63. sulfoxides

64. sulfide acid esters

In addition to the above classes of compounds that may be effectively employed as sulfur-containing modifiers in the practice of this invention, any compounds containing a multiplicity of any of the above characteristic groupings may also be employed.

The preferred sulfur-containing modifiers include sulfur and the following classes of sulfur-containing compounds selected from the classes enumerated above.

thioureas

sulfide acids

mercapto acids

thio amides

disulfide acids

thiuram disulfides

mercaptans of heterocyclics containing ring sulfur

disulfides of heterocyclics containing ring sulfur

heterocyclics containing ring sulfur

disulfides

cyano sulfides

sulfoxides

thio acids

organic sulfides

mercaptans

dithio acids

sulfides of heterocyclics containing ring sulfur

sulfide acid esters

The most preferred modifiers that may be employed in accordance with the present invention are those compounds which when employed with a nickel catalyst and an acid according to this invention produce a catalytic system that is effective in catalyzing a reductive alkylation reaction to provide at least a 95 percent yield of the desired N-alkyl substituted amine compounds. These most preferred modifiers include sulfur and the following classes of sulfur-containing compounds.

sulfide acids

thiuram disulfides

cyano sulfides

sulfoxides

organic sulfides

mercaptans of heterocyclics containing ring sulfur

sulfides of heterocyclics containing ring sulfur

heterocyclics containing ring sulfur

The most highly preferred three-component catalytic system is comprised of a nickel catalyst, thiodipropionic acid and toluene sulfonic acid. The three-component system is preferred in general over the two-component system.

Any of the aldehydes and ketones that are normally employed in a conventional reductive alkylation type reaction may be employed in the practice of this invention. Typical examples of suitable aldehydes and ketones include methyl ethyl ketone, methyl isobutyl ketone, methyl isoamyl ketone, methyl hexyl ketone, butyl aldehyde and benzaldehyde.

The amine or amine precursors that are useful in carrying out reactions of the type contemplated by the present invention are any of the primary amines or amine precursors that will produce primary amines of the type normally employed in a conventional reductive alkylation reaction. Typical examples of suitable amines or amine precursors include aniline, para-nitrodiphenylamine, para-aminodiphenylamine, ortho-phenylenediamine and para-nitroso-diphenylamine.

The amount of acid to be used in the two-component and three-component systems will vary somewhat, depending upon the particular reductive alkylation reaction in which the catalyst is to be employed, the sulfur-containing modifier used to modify the catalyst (if a three-component system is used) and the acids. However, it will in general be found that from 0.005 to 0.100 gram molecular weight of the acid should be employed per 100 grams of nickel in the metallic catalyst.

The amount of sulfur-containing material that should be used to modify the nickel catalyst will also vary somewhat, depending upon the particular reductive alkylation reaction in which the catalyst is to be employed, the sulfur-containing modifier used to modify the catalyst and the acid. However, in general it has been found from about 0.05 to about 8.0 grams of contained sulfur should be employed per 100 grams of nickel in the metallic catalyst.

The nickel catalyst sulfur-containing modifier (if a three-component system is used) and acid may be added to the reaction mixture separately, all together or in any combination and in any order. One way, but by no means the only way, in which such a physical mixture may be conveniently prepared, is by slurrying the nickel catalyst in a solvent and adding the acid (or acid and sulfur-containing modifier) dissolved in the same solvent, mixing and then removing the solvent. The reductive alkylation reaction is normally conducted at temperatures between 50.degree. and 240.degree. C. Since a reductive alkylation reaction employs hydrogen it is necessary to conduct the reaction under substantial pressure. Normal pressures employed generally range from 250 to 2000 pounds per square inch, but in some cases may be substantially higher in the range of 4000 to 5000 pounds per square inch.

In order to most effectively catalyze a reductive alkylation reaction the catalytic systems of this invention are employed in an amount from 0.10 to 8 grams, based on the weight of contained nickel, per mol of primary amine in the reaction mixture.

In carrying out a reductive alkylation reaction wherein the catalytic systems of this invention are conveniently employed, the amine, nitro or nitroso compound is charged into a suitable reactor with an aldehyde or ketone that is to be employed as the alkylating agent and a catalytic system as has been described above. The aldehyde or ketone alkylating agent is normally employed in excess and acts as a solvent for the reactants and thus alleviates the necessity of other solvent diluents being employed in the reaction. Other solvent diluents such as ethyl alcohol, isopropyl alcohol, benzene and toluene may be used if the aldehyde or ketone alkylating agent is not employed in an excess amount sufficient to act as a solvent for the reactants. The mixture is heated to a reaction temperature in the range of between 50.degree. and 240.degree. C. and hydrogen under pressure of from 250 to 2000 pounds per square inch is then introduced to the reaction vessel. The reaction is permitted to proceed for a period of time sufficient to obtain conversion of the reactants to the N-alkyl substituted amine. The pressure on the reaction vessel is then released and the product is recovered by distilling off the volatile materials. The employment of the catalytic systems of this invention results in high yields of the reductively alkylated product. The employment of the three-component catalytic system of this invention enables the reaction to be conducted at comparatively high temperatures where it proceeds readily without any significant conversion of the aldehyde or ketone alkylating agent to its corresponding alcohol. Reductive alkylation reactions of the type described may be carried out on either a batch or continuous basis.

The preparation of the catalytic systems of this invention and their use in reductive alkylation reactions are illustrated by the following examples, which should be considered representative rather than restrictive of the scope of the invention.

Example 1 is a control reaction using only a nickel catalyst. Examples 2 through 13 illustrate reactions using the two-component system.

Into a one liter autoclave equipped with a stirrer were charged 138 grams of distilled para-aminodiphenylamine, 300 grams of methyl isobutyl ketone and two grams of a 63 percent nickel-on-Kieselguhr catalyst.* The mixture was reacted for 4 hours at 165.degree. C. under hydrogen at 750 to 1000 pounds per square inch pressure. The resulting product was then removed from the autoclave and filtered. It was then distilled to 200.degree. C. pot temperature at 15 to 25 millimeters of mercury. Analysis of volatiles and product was conducted by gas chromatography. The volatiles showed 10.0 percent of the original ketones charged had been reduced to the corresponding alcohol. Analysis of the product showed a 75.5 percent yield of N-4-methyl-2-pentyl-N'-phenyl-para-phenylenediamine.

Examples 2 to 13 were run in the same manner as Example 1 with the exception that various acids were used in combination with the nickel catalyst.

The above data indicate that the presence of an acid improved the percent yield in each case. The oxalic acid, toluene sulfonic acid and sulfuric acid in addition reduced the amount of ketone that was reduced to the alcohol. This was particularly true where sulfuric acid was used.

Example 14 is a control reaction using only a nickel catalyst. Examples 15 through 66 were run in the same manner as Example 14 with the exception that the odd numbered Examples were run using various sulfur-containing compounds in combination with the nickel catalyst while the even numbered Examples were run using both sulfur-containing compounds and acids in combination with the nickel catalyst. The odd numbered Examples 15 through 65 illustrate reactions using two-component systems disclosed in co-pending U.S. patent application Ser. No. 426,408. The even numbered Examples 16 through 66 illustrate reactions using three-component catalyst systems within the practice of the present invention.

Into a one liter autoclave equipped with stirrer were charged 138 grams of distilled para-amine diphenylamine, 300 grams of methyl isobutyl ketone and two grams of a 63 percent nickel-on-Kieselguhr catalyst. This reaction was run for four hours at 165.degree. C. under hydrogen at 750 to 1000 pounds per square inch pressure. The resulting product was then removed from the autoclave and filtered. It was then distilled to 205.degree. C. pot temperature at 20 millimeters of mercury. Analysis of volatiles and product was conducted by gas chromatography. The volatiles showed 26.6 percent of the original ketones charged had been reduced to the corresponding alcohol. Analysis of the product showed a 57.8 percent yield of N-4-methyl-2-pentyl-N'-phenyl-para-phenylenediamine.

Combinations of 63 percent nickel-on-Kieselguhr catalyst and various sulfur-containing modifiers were evaulated in the production of N-4-methyl-2-pentyl-N'-phenyl-para-phenylenediamine both in the absence and in the presence of an acid, toluene sulfonic acid, using the same concentration of reactants and nickel catalyst and the same reaction conditions as described in Example 14. The sulfur-containing modifiers were added to the reaction mixture either as a solution or as a solid as indicated in column 2 of the following table wherein the effectiveness of various catalyst systems is summarized. The toluene sulfonic acid was added in absolute ethanol.

The yield data from the above table demonstrate that the addition of an acid to nickel catalyst/sulfur-containing modifier catalytic systems increases the percent yield in reductive alkylation reactions. The data also reveal that the melting point ranges were narrowed by using an acid, thereby indicating that the alkylation products possessed a high degree of purity.

The three-component catalytic system of this invention was compared with the nickel catalyst/sulfur-containing modifier catalytic system in various reductive alkylation systems other than the para-amino diphenylamine/methyl isobutyl ketone system. The same experimental conditions as described in Example 14 were used. The effectiveness of the various catalyst systems is summarized in the following table. Thiodipropionic acid dissolved in absolute ethanol was used as the sulfur-containing modifier in each case in a concentration of 0.0258 gram of sulfur-containing modifier per gram of catalyst. This resulted in a sulfur concentration of 0.0047 gram of sulfur per gram of catalyst. The toluene sulfonic acid was added in absolute ethanol, in a concentration of 0.0229 gram per gram of catalyst.

The percent yield data in the above table reveal that the catalytic system of the present invention enhances the yield in various types of alkylation systems. Naturally in the cases where the percent yield is near theoretical it is impossible for the addition of an acid to substantially increase the percent yield. One of the advantages in using an acid in such systems is that it will allow the use of lower alkylation temperatures to obtain close to theoretical yields. Another advantage is that faster reaction rates for a given reaction temperature may be obtained. An indication of such an effect is demonstrated by the percent yield data in Examples 69, 70, 71 and 72. In the latter two examples the alkylation reaction was run at reduced temperature of 140.degree. C. instead of 165.degree. C. and yet close to theoretical yields were obtained.

Various acids were evaluated in the production of N-4-methyl-2-pentyl-N'-phenyl-para-phenylenediamine using a three-component catalytic system and the same experimental reactants and conditions as described in Example 14. Thiodipropionic acid dissolved in absolute ethanol was used as the modifier in each case in a concentration of 0.0258 gram of modifier per gram of catalyst. The acids were added in solution, the solvents being identified in column 3 of the following table. The effectiveness of the various acids is summarized in the following table.

The above data demonstrate that acids other than organic sulfonic acids may be used in the practice of this invention.

Premodified catalytic systems were prepared by slurrying the nickel catalyst in absolute ethanol and adding the sulfur-containing modifier and acid also dissolved in absolute ethanol. The slurry was mixed well and dried in a vacuum oven. The free flowing solid premodified catalytic systems were then used in place of the normal catalytic systems using the same charge and conditions as described in Example 14 to produce N-4-methyl-2-pentyl-N'-phenyl-para-phenylenediamine. Both premodified nickel catalyst/sulfur-containing modifier and nickel catalyst/sulfur-containing modifier/acid catalytic systems were used. The effectiveness of these premodified systems is compared in the following table.

The data in the above table demonstrate that the catalytic systems of this invention are also effective when prepared as premodified catalytic systems and that the addition of an acid increases the percent yield.

In summary, the co-pending U.S. application Ser. No. 426,408 has shown that the use of sulfur-containing materials with a nickel catalyst enhances the yields in reductive alkylation reactions without promoting undesirable side reactions. The present application demonstrates that the use of various acids in combination with nickel catalysts results in an improved yield in reductive alkylation reactions and in some cases reduces undesirable side reactions. In addition, the present application has shown that the use of various sulfur-containing materials in combination with the nickel catalyst/acid system results in even greater yields than are obtained with either the nickel catalyst/sulfur-containing material or nickel catalyst/acid systems without promoting undesirable side reactions.

While certain representative embodiments and details have been shown for the purpose of illustrating the invention it will be apparent to those skilled in this art that various changes and modifications may be made therein without departing from the spirit or scope of the invention.