Processes for the preparation of high molecular weight saturated ketones Number:7,071,361 from the United States Patent and Trademark Office (PTO) owispatent Continuous single-step processes for producing higher molecular weight ketones are disclosed that involve a liquid-phase crossed condensation of an aldehyde with a ketone in the presence of a hydrogenation catalyst and a small amount of a catalyst comprising a concentrated hydroxide or alkoxide of an alkali-metal (from Group 1 or Group IA of the Periodic Table of the Elements) or alkali-earth metal (from Group 2, or Group IIA of the Periodic Table of the Elements), wherein the amount of water provided to the reaction mixture, or reaction zone, is relatively low, with respect to the total initial weight of the reaction mixture. The reaction may be carried out in the absence of solubilizing agents or phase transfer agents. The product mixture is largely free of by-products resulting from further condensation reactions of the desired ketone product or intermediates, and free of the self-condensation products of the reactant aldehyde, that are afterward difficult to remove from the reaction mixture.<H preparation, saturated, Processes, for, t, 7071361.html, Patent, pto, 7071361

Title: Processes for the preparation of high molecular weight saturated ketones

Abstract: Continuous single-step processes for producing higher molecular weight ketones are disclosed that involve a liquid-phase crossed condensation of an aldehyde with a ketone in the presence of a hydrogenation catalyst and a small amount of a catalyst comprising a concentrated hydroxide or alkoxide of an alkali-metal (from Group 1 or Group IA of the Periodic Table of the Elements) or alkali-earth metal (from Group 2, or Group IIA of the Periodic Table of the Elements), wherein the amount of water provided to the reaction mixture, or reaction zone, is relatively low, with respect to the total initial weight of the reaction mixture. The reaction may be carried out in the absence of solubilizing agents or phase transfer agents. The product mixture is largely free of by-products resulting from further condensation reactions of the desired ketone product or intermediates, and free of the self-condensation products of the reactant aldehyde, that are afterward difficult to remove from the reaction mixture.

Patent Number: 7,071,361 Issued on 07/04/2006 to Barnicki, et al.

Inventors: Barnicki; Scott Donald (Kingsport, TN); McCusker-Orth; Jennifer Ellen (Kingsport, TN); Knight; Joseph Franklin (Kingsport, TN); Miller; Jerry Lynn (Kingsport, TN)
Assignee: Fastman Chemical Company (Kingsport, TN)

Appl. No.: 877339

Filed: June 25, 2004

Current U.S. Class: 568/390 ; 568/392; 568/396

Current International Class: C07C 45/73 (20060101)

Field of Search: 568/390,392,396

References Cited [Referenced By]

U.S. Patent Documents


2088015	July 1937	Wickert
2088016	July 1937	Wickert
2088017	July 1937	Wickert et al.
2088018	July 1937	Wickert et al.
2200216	May 1940	Loewenberg et al.
2499172	February 1950	Smith
2852563	September 1958	Hagemeyer, Jr. et al.
3248428	April 1966	Porter, Jr. et al.
3670026	June 1972	Lamparsky et al.
4049571	September 1977	Nissen et al.
4101586	July 1978	Deem et al.
4102930	July 1978	Deem
4146581	March 1979	Nissen et al.
4270006	May 1981	Heilen et al.
4701562	October 1987	Olson
4739122	April 1988	Letts
4956505	September 1990	Mais et al.
5055621	October 1991	Payne
5243081	September 1993	Ishino et al.
5300654	April 1994	Nakajima et al.
5434313	July 1995	Harrison et al.
5583263	December 1996	Muthusamy et al.
5663452	September 1997	Kulmala et al.
5840992	November 1998	Kido et al.
5936131	August 1999	Teissier et al.
6232506	May 2001	Kido et al.
6271171	August 2001	Teissier et al.
6288288	September 2001	Springer
6433230	August 2002	Bueschken et al.
6583323	June 2003	Krill
6603047	August 2003	Wiese et al.
2002/0058846	May 2002	Krill et al.
2002/0128517	September 2002	Krill
2002/0161264	October 2002	Wiese et al.
2002/0169347	November 2002	Kalzik et al.

Foreign Patent Documents


0 141 569	May., 1985	EP
446026	Apr., 1936	GB
549066	Nov., 1942	GB
1010695	Nov., 1965	GB
WO 02/24621	Mar., 2002	WO

Other References

Weizmann and Garrard, "Some Condensations of N-butyl Alcohol and N-butaldehyde", J. Chem. Soc. Trans., vol. 117, 1920, pp. 324-338. cited by other .
M. Lakshmi Kantam et al, "Aldol and Knoevenagel condensations catalysed by modified Mg-Al hydrotalcite:a solid base as catalyst useful in synthetic organic chemistry" Chem. Comm., 1998, pp. 1033-1034. cited by other .
PCT International Search Report and Written Opinion for PCT/US2004/020489. cited by other .
U.S. Appl. No. 10/611,394, filed Jul. 1, 2003. cited by other .
U.S. Appl. No. 10/713,727, filed Nov. 14, 2003. cited by other .
Weizmann and Garrard, J. Chem, Soc., Pt. 1, vol. 117, 1920 pp. 324-338. cited by other .
Eccott and Linstead, J. Chem. Soc., Pt. 1, vol. 133, pp. 905-911. cited by other .
Kyrides, Journal of the Amer. Chem. Soc., vol. 55, Aug. 1933, pp. 3431-3435. cited by other .
Powell, Journal of the Amer. Chem. Soc., vol. 46, 1924, pp. 2514-2517. cit- ed by other .
Streitwiser and Heathcock, "Introduction to Organic Chemistry", 2d Ed., 1981, pp. 392-396. cited by other .
H. O. House, Modern Synthetic Reactions, 2d Ed., 1972, pp. 595-599, 629-640. cited by other .
Period Table of the Elements, as published in "Chemical and Engineering News", 63(5), 27, 1985. cited by other .
Roger Adams et al., Organic Reactions, vol. 2, 1944, pp. 94-113. cited by other .
Grignard and Dubien, Action of Organomagnesium Compounds on Butylidence-Acetone and its Ketol, Ann. De Chim., 10.sup.th serier, 2:282-290, Nov.-Dec. 1924. cited by other .
Office Action mailed Jun. 15, 2004 in U.S. Appl. No. 10/611,394. cited by other.

Primary Examiner: Richter; Johann
Assistant Examiner: Witherspoon; Sikarl A.
Attorney, Agent or Firm: Owen; Polly C. Graves, Jr.; Bernard J.

Claims

We claim:

1. A process for producing a higher molecular weight saturated ketone, the process comprising reacting an aldehyde reactant with a ketone reactant having at least one hydrogen atom alpha to the carbonyl, in a reaction mixture comprising the aldehyde reactant, the ketone reactant, and an aldol catalyst comprised of a hydroxide or alkoxide of an alkali metal or an alkaline earth metal provided as a solution or as a solid, wherein no more than about 16 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture, the molar ratio of ketone reactant to aldehyde reactant is from 1:1 to 20:1, and the molar ratio of the hydroxide or alkoxide of the alkali metal or alkaline earth metal aldol catalyst to the aldehyde reactant is from 0.001:1 to 0.45:1, and wherein the reacting is carried out at a reaction time of no more than 120 minutes in a reactor provided with a solid hydrogenation catalyst and hydrogen gas.

2. The process according to claim 1, wherein no more than 12 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture.

3. The process according to claim 1, wherein no more than 5 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture.

4. The process according to claim 1, wherein no more than 3 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture.

5. The process according to claim 1, wherein no more than 1 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture.

6. The process according to claim 1, wherein the aldol catalyst is provided as a solution of a hydroxide or alkoxide of an alkali metal or an alkaline earth metal, wherein the hydroxide or alkoxide is provided in the solution at a concentration of at least 15 wt. %.

7. The process according to claim 1, wherein the aldol catalyst is provided as a solution of a hydroxide or alkoxide of an alkali metal or an alkaline earth metal, wherein the hydroxide or alkoxide is provided in the solution at a concentration of at least 25 wt. %.

8. The process according to claim 1, wherein the aldol catalyst is provided as a solution of a hydroxide or alkoxide of an alkali metal or an alkaline earth metal, wherein the hydroxide or alkoxide is provided in the solution at a concentration of at least 50 wt. %.

9. The process according to claim 1, wherein the reacting is carried out in the substantial absence of a solubilizing agent.

10. The process according to claim 1, wherein the molar ratio of ketone reactant to aldehyde reactant is from 1:1 to 14:1.

11. The process according to claim 1, wherein the molar ratio of ketone reactant to aldehyde reactant is from 1.05 to 10.

12. The process according to claim 1, wherein the molar ratio of the hydroxide or alkoxide of an alkali metal or alkaline earth metal aldol catalyst to the aldehyde reactant is from 0.005:1 to 0.45:1.

13. The process according to claim 1, wherein the molar ratio of the hydroxide or alkoxide of the alkali metal or alkaline earth metal aldol catalyst to the aldehyde reactant is from 0.001:1 to 0.25:1.

14. The process according to claim 1, wherein the molar ratio of the hydroxide or alkoxide of the alkali metal or alkaline earth metal aldol catalyst to the aldehyde reactant is from 0.005:1 to 0.15:1.

15. The process according to claim 1, wherein the molar ratio of the hydroxide or alkoxide of the alkali metal or alkaline earth metal aldol catalyst to the aldehyde reactant is from 0.005:1 to 0.10:1.

16. The process according to claim 1, wherein the hydroxide or alkoxide of the alkali metal or alkaline earth metal comprises one or more of: sodium hydroxide, potassium hydroxide, cesium hydroxide, lithium hydroxide, magnesium hydroxide, calcium hydroxide, barium hydroxide, sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, potassium methoxide, potassium ethoxide, potassium propoxide, potassium butoxide, cesium methoxide, cesium ethoxide, cesium propoxide, cesium butoxide, lithium methoxide, lithium ethoxide, lithium propoxide, lithium butoxide, magnesium methoxide, magnesium ethoxide, magnesium propoxide, magnesium butoxide, calcium methoxide, calcium ethoxide, calcium propoxide, calcium butoxide, barium methoxide, barium ethoxide, barium propoxide, or barium butoxide.

17. The process according to claim 1, wherein the hydroxide or alkoxide of the alkali metal or alkaline earth metal comprises one or more of: sodium hydroxide or potassium hydroxide.

18. The process according to claim 1, wherein the reacting is carried out at a temperature from 25.degree. C. to 200.degree. C.

19. The process according to claim 1, wherein the reacting is carried out at a temperature from 40.degree. C. to 175.degree. C.

20. The process according to claim 1, wherein the aldol catalyst is provided as an oxide of an alkali metal or an alkaline earth metal which forms in the reaction mixture a hydroxide.

21. The process according to claim 1, wherein the reacting is carried out in a series of two or more continuous stirred tank reactors.

22. The process according to claim 1, wherein the aldehyde reactant comprises one or more of: acetaldehyde; propionaldehyde; n-butyraldehyde; 2-methyl-propanal; n-pentanal; 2-methyl-butanal; 3-methyl-butanal; 2,2-dimethyl-propanal; n-hexanal; 2-ethyl-butanal; 2,2-dimethylbutanal; 2,3-dimethylbutanal; 2-methyl-pentanal; 3-methylpentanal; 4-methyl-pentanal; n-heptanal; 2-methylhexanal; 2-ethylpentanal; 2,2-dimethylpentanal; 2,3-dimethylpentanal; 2,4-dimethylpentanal; 2-ethyl-3-methylbutanal; 2-ethyl-2-methylbutanal; n-octanal; 2-ethylhexanal; n-nonanal; n-decanal; n-undecanal; n-dodecanal; benzaldehyde; 4-chlorobenzaldehyde; 3-chlorobenzaldehyde; 2-chlorobenzaldehyde; phenyl acetaldehyde; o-tolualdehyde; m-tolualdehyde; p-tolualdehyde; p-methoxybenzaldehyde; o-ethoxybenzaldehyde; m-methoxybenzaldehyde; cyclopropane carboxaldehyde; cyclobutane carboxaldehyde; cyclopentane carboxaldehyde; cyclohexane carboxaldehyde; 2-methylcyclohexane carboxaldehyde; 3-methylhexane carboxaldehyde; or 4-methylhexane carboxaldehyde.

23. The process according to claim 1, wherein the ketone reactant comprises one or more of: acetone, 2-butanone, 2-pentanone, 3-methyl-2-butanone, 2-hexanone, 4-methyl-2-pentanone, pinacolone, 2-heptanone, 5-methyl-2-hexanone, 2-octanone, 2-nonanone, 2-decanone, 2-undecanone, 2-dodecanone, cyclobutanone, cyclopentanone, cyclohexanone, cyclooctanone, 3,3-5-trimethylcyclohexanone, tricyclo[5.2.1.02,6]decan-8-one, or acetophenone.

24. The process according to claim 1, wherein the hydrogen gas is provided at a pressure from about 3 to about 150 bar.

25. The process according to claim 1, wherein the hydrogen gas is provided at a pressure from about 15 to about 50 bar.

26. The process according to claim 1, wherein the residence time of the reaction mixture in the reactor is from about 2 to about 200 minutes.

27. The process according to claim 1, wherein the residence time of the reaction mixture in the reactor is from about 5 to about 60 minutes.

28. The process according to claim 1, where the hydrogenation catalyst is a shaped or extruded transition metal catalyst supported on a stable support.

29. The process according to claim 1, wherein the hydrogenation catalyst comprises one or more of: Ni, Co, Cu, Cr, Pt, Pd, Rh, Ru, Re, or Ir.

30. The process according to claim 1, wherein the hydrogenation catalyst is supported on a support comprising one or more of: alumina, silica, silica-alumina, or carbon.

31. The process according to claim 1, wherein the hydrogenation catalyst comprises palladium on carbon.

32. The process according to claim 1, wherein the hydrogenation catalyst has a metal loading of from about 0.1 to about 90 wt. %.

33. The process according to claim 1, wherein the hydrogenation catalyst has a metal loading of from about 0.1 to about 5 wt. %.

34. A process for producing 2-heptanone, the process comprising reacting n-butyraldehyde with acetone, in a reaction mixture comprising the n-butyraldehyde, the acetone, and an aldol catalyst comprised of a hydroxide or alkoxide of an alkali metal or an alkaline earth metal provided as a solution or as a solid, wherein no more than about 16 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture, the molar ratio of acetone reactant to n-butyraldehyde reactant is from 1:1 to 20:1, and the molar ratio of the hydroxide or alkoxide of the alkali metal or alkaline earth metal aldol catalyst to the butyraldehyde reactant is from 0.001:1 to 0.45:1, and wherein the reacting is carried out at a reaction time of no more than 120 minutes in a reactor provided with a solid hydrogenation catalyst and hydrogen gas.

Description

FIELD OF THE INVENTION

This invention relates to processes for producing ketones, and more specifically, to processes for producing higher molecular weight saturated ketones that result in higher yields, higher space-time yields, and greater selectivity for the target product, while minimizing the formation of by-products.

BACKGROUND OF THE INVENTION

Aldol condensation reactions are important in the production of intermediates needed to synthesize many commercially important products. The condensation of ketones to obtain aldols (.beta.-hydroxy ketones) is a well-known reaction. Dehydration of the resulting aldol to obtain an unsaturated ketone is also known. Subsequent catalytic hydrogenation of the unsaturated ketone may be carried out to obtain the corresponding saturated higher ketone.

In an aldol condensation reaction, an aldehyde or ketone, with a hydrogen atom alpha to the carbonyl, react together to form a .beta.-hydroxy-aldehyde or a .beta.-hydroxy-ketone. The .beta.-hydroxy-aldehyde or .beta.-hydroxy-ketone can dehydrate in the presence of either an acid or a base to give a conjugated .alpha.,.beta.-unsaturated aldehyde or ketone. The conditions needed for the aldol dehydration are often only slightly more vigorous than the conditions needed for the aldol condensation itself. As a result, the product of such aldol reactions often comprises both the .beta.-hydroxy aldehyde or ketone and the .alpha.,.beta.-unsaturated aldehyde or ketone.

Many methods have been disclosed in the art to perform aldol condensation reactions. These include two-phase liquid reactions using dilute aqueous base as the catalyst, see, for example, U.S. Pat. No. 6,232,506, U.S. Pat. Appln. No. 2002/0161264, U.S. Pat. No. 6,433,230, U.S. Pat. No. 2,200,216, U.S. Pat. No. 6,288,288; base-catalyzed, liquid phase aldol condensation reactions that include the use of a solubilizing or phase transfer agent, see, for example, U.S. Pat. Nos. 2,088,015, 2,088,016, 2,088,017, and 2,088,018; and the use of polymeric or oligomeric ethylene glycols or polyhydric alcohols as phase transfer catalysts or solvents in combination with dilute alkali metal hydroxide catalysts, see, for example, U.S. Pat. Nos. 5,055,621, and 5,663,452, and U.S. Pat. Publ. No. 2002/0058846.

Several authors have disclosed processes for crossed aldol condensations catalyzed by relatively high levels of caustic. Weizmann and Garrard, J. Chem. Soc, Pt. 1, Vol. 117, 1920, pp. 324 338, prepared 3-hepten-2-one by the batch-wise crossed condensation of n-butyraldehyde and acetone catalyzed with solid sodium hydroxide. Eccott and Linstead, J. Chem. Soc, Pt. 1, Vol. 133, 1930, pp. 904 911, prepared a mixture of 4-hydroxy-2-heptanone and 3-hepten-2-one by the low-temperature, (5 10.degree. C.) batch-wise crossed condensation of n-butyraldehyde and acetone catalyzed by 50 weight percent sodium hydroxide. As another example, U.S. patent application Ser. No. 10/611,394, filed Jul. 1, 2003 and having common assignee herewith, describes a process for the preparation of .beta.-hydroxy-ketones and/or .alpha.,.beta.-unsaturated ketones in unexpectedly high yields by the liquid-phase crossed condensation of an aldehyde with a ketone, in the presence of a small amount of a catalyst comprising a concentrated hydroxide or alkoxide of an alkali-metal or alkali-earth metal, wherein the amount of water present in the reaction mixture is kept relatively low, with respect to the total weight of reactants.

The .beta.-hydroxy-aldehyde or .beta.-hydroxy-ketone product of such aldol condensations can dehydrate to give a conjugated .alpha.,.beta.-unsaturated aldehyde or ketone. Many methods are known in the art for dehydrating .beta.-hydroxy-aldehydes or .beta.-hydroxy-ketones to .alpha.,.beta.-unsaturated aldehydes or ketones, in fair to excellent yields. These include simple heating; acid-catalyzed dehydration using mineral acids or solid acid catalysts, with or without azeotropic removal of the water of reaction, as exemplified in U.S. Pat. No. 5,583,263, U.S. Pat. No. 5,840,992, U.S. Pat. No. 5,300,654, and Kyrides, JACS, Vol 55, August, 1933, pp. 3431 3435; heating with iodine crystals, as in Powell, JACS, Vol. 46, 1924, pp. 2514 17; and base-catalyzed dehydration, as taught in Streitwieser and Heathcock, "Introduction to Organic Chemistry", 2.sup.nd Ed., 1981, pp. 392 396.

Aldehydes are more reactive, in general, than are ketones in base-catalyzed aldol condensations, because of the greater ease of enolate ion formation of an aldehyde. As such, in a crossed condensation of a ketone with an aldehyde to produce a desired .beta.-hydroxyketone, the self-condensation of the aldehyde typically occurs in substantial quantities to produce an undesired .beta.-hydroxyaldehyde by-product. Further, unhindered aldehydes, i.e., straight-chain aldehydes such as acetaldehyde, propionaldehyde, n-butyraldehyde, and n-pentanal, are more reactive toward self-condensation than are hindered aldehydes, i.e., branched aldehydes such as 2-methyl-propanal and 3-methyl-butanal.

It is understood that the rate-limiting step in these reactions is often the enolate ion formation, and that condensation and the subsequent dehydration reaction occur in rapid succession. These .alpha.-.beta. unsaturated ketones and aldehydes are known to those skilled in the art to be quite reactive and susceptible to further consecutive, non-selective condensation, cyclization, and Michael-type addition reactions with the starting ketones and aldehydes, as well as themselves and other ketonic and aldehydic by-products. See, for example, H. O. House, Modern Synthetic Reactions, 2.sup.nd. Ed., 1972 pp. 595 599, 629 640.

Thus, without being bound by any theory, in the base-catalyzed condensation of an aldehyde of Formula 1, possessing at least one hydrogen atom alpha to the carbonyl, with a ketone of Formula II, to form a desired .beta.-hydroxy-ketone or .alpha.-.beta. unsaturated ketone of Formulae III or IV, three parallel reaction pathways are known to compete:

##STR00001## ##STR00002##

In general, R2 represents a C1 to C10 organic radical and R1, R3, and R4 represent hydrogen or a C1 to C10 organic radical.

R1 may represent a hydrogen, or else R1 and R2 may form members of a common cycloalkyl or aromatic ring, either of which may be substituted with one or more functional groups, or else R2 represents an alkyl group, which may be straight or branched, and which may be substituted with one or more functional groups;

R3 and R4 each independently represent hydrogen, or else R3 and R4 form members of a common cycloalkyl or aromatic ring, either of which may be substituted with one or more functional groups, or else one or both may represent a branched or unbranched, saturated or unsaturated aliphatic or alkyl-substituted cycloalkyl hydrocarbon radical; or else each represents an aryl hydrocarbon radical, or an alkylaryl hydrocarbon radical, either of which may be substituted with one or more functional groups.

One skilled in the art would expect a broad range of products from these reactions, and difficulty in stopping the reactions at the .beta.-hydroxy-ketone stage. The further condensation of the .alpha.-.beta. unsaturated ketones with the ketone of Formula II, or with the aldehyde of Formula I, or with other ketonic and aldehydic species, leads to a plethora of by-products and can represent significant yield losses as well as necessitating complicated and expensive purification schemes for the commercial production of high purity .beta.-hydroxy-ketones and/or .alpha.,.beta.-unsaturated ketones. For example, in the preparation of 2-heptanone via the condensation of n-butyraldehyde with acetone, the self-condensation of n-butyraldehyde to form 2-ethyl-2-hexenal is a particularly troublesome by-product. Its hydrogenated form, 2-ethylhexanal, boils less than 10.degree. C. apart from 2-heptanone, and is therefore difficult to separate economically from 2-heptanone by distillation.

One method of preventing unwanted further condensation side products in aldol condensation reactions is to quickly hydrogenate the .alpha.,.beta.-unsaturated ketones. This can be accomplished in situ or in a separate hydrogenation step.

In some cases, it is desirable to selectively hydrogenate the carbon--carbon double bond of the resulting .alpha.,.beta.-unsaturated ketone to give a saturated ketone. Catalysts and methods are known for such hydrogenation reactions, as exemplified in U.S. Pat. Nos. 5,583,263 and 5,840,992, and U.S. Pat. Appl. Nos., 2002/0128517, 2002/058846, and 2002/0169347. Alkenes react with hydrogen gas in the presence of a suitable metal catalyst, typically palladium or platinum, to yield the corresponding saturated alkane addition products. The metal catalysts are normally employed on a support or inert material, such as carbon or alumina. Commercially important products of this type include methyl amyl ketone, methyl isoamyl ketone, and methyl propyl ketone, made by the crossed condensation of acetone with n-butryaldehyde, isobutyraldehyde, or acetaldehyde, respectively.

The production of higher molecular weight ketones using aldol condensations and catalytic hydrogenations can be carried out either by a multi-step process or a single-step process. A multi-step process uses sequentially discrete steps in two or three separate reactors. In a single-step process the reactions are carried out simultaneously in one reactor.

When ketones are synthesized by a multi-step process, using sequentially discrete steps, the aldol reaction occurs first, which is then followed by dehydration, and by subsequent hydrogenation. Each step is independent of the others, and the process often requires difficult separation techniques between steps. For example, U.S. Pat. No. 5,583,263 describes a multi-step process for the coproduction of methyl amyl ketone and methyl isobutyl ketone. In this process, dimethyl ketone is reacted with n-butyraldehyde using a fixed-bed basic ion exchange cross-aldol condensation catalyst to form a .beta.-hydroxy ketone mixture. The product is then dehydrated to form an olefinic ketone using a catalytic quantity of an acidic substance, such as H.sub.2SO.sub.4, NaHSO.sub.4, or a sulfonic acid resin. The resulting .alpha.,.beta.-unsaturated ketone is then hydrogenated using a solid phase hydrogenation catalyst to produce the desired amyl ketone. Three discrete steps are required, with costly separations between the steps. There is no acknowledgment that by-products other than methyl isobutyl ketone are produced, nor is there any suggestion how one might avoid impurities such as 2-ethylhexaldehyde and high boiling by-products that result from unwanted side reactions. On the basis of a comparative example, the authors conclude that commercial coproduction of methyl isobutyl ketone and methyl amyl ketone is impractical in one-step processes employing ordinary catalyst systems.

Another example of a multi-step process is found in U.S. Pat. No. 5,840,992 ('992), which teaches a process for producing 6-methylheptan-2-one by the crossed condensation of acetone with 3-methyl-butanal, in the presence of an aqueous alkali or alkali earth metal hydroxide as catalyst, at a catalyst-aldehyde molar ratio of 0.001 to 0.20. In a separate step, the resulting .beta.-hydroxy ketone condensation product is further subjected to reduction under dehydrating conditions to produce 6-methylheptan-2-one. The process according to the '992 patent may be carried out continuously in plug flow or batch-wise mode. Typical molar selectivities on 3-methyl-butanal are about 75 to 80 percent, with the best results being achieved in the batch mode of operation. Although the '992 patent suggests that the basic catalyst substance may be used as an aqueous solution at a concentration between 1 and 50 percent, the process is reduced to practice only with a catalyst concentration of 5 weight percent aqueous sodium or potassium hydroxide. The authors of the '992 patent clearly fail to contemplate the advantages of using concentrated hydroxides or alkoxides of alkali earth- or alkali-metals as catalysts, for example at greater than 15 or 20 weight percent, while controlling the absolute amount of water present in the reaction mixture. Thus, the process disclosed in the '992 patent achieves only modest yields.

U.S. Pat. No. 6,232,506 discloses a multi-step process for producing 6-methyl-3-heptan-2-one, and its analogues, by the crossed aldol condensation of acetone with 3-methyl-butanal (isovaleraldehyde), in the presence of an aqueous alkali containing an alkaline substance. The 6-methyl-3-hepten-2-one is then separately hydrogenated to 6-methyl-3-heptan-2-one in the presence of a hydrogenation catalyst. The aldol catalyst is provided as a 0.5 to 30 weight percent, preferably 1 to 10 weight percent, aqueous solution, at a caustic-aldehyde molar ratio of 0.001 to 0.2. The process is carried out in semi-batch mode, with separate continuous feeds of aldehyde and dilute caustic to a stirred reaction zone initially comprising acetone. In Example 3 of the patent, using the preferred 2 wt. % aqueous caustic catalyst solution, the reaction mixture forms distinct aqueous and organic phases, with water being present in an amount of about 39 wt. %, based on the total weight of the reactant mixture. 6-methyl-3-hepten-2-one is hydrogenated in the presence a 5% palladium on carbon catalyst for 7 hours. Cited yields are typically about 66% to 6-methyl-3-hepten-2-one and 3.3% 6-methyl-4-hydroxy-heptan-2-one.

U.S. Pat. No. 6,603,047 discloses a step-wise process for the preparation of ketones by the crossed condensation of an aldehyde with a ketone, followed by the hydrogenation of the unsaturated ketone. The condensation reaction described can be carried out in a tubular reactor as a multiphase liquid reaction in which a dilute aqueous caustic catalyst (0.1 to 15 weight percent caustic, preferably 0.1 to 5 weight percent) is the continuous phase and the aldehyde/ketone reactants are the dispersed phase. This patent explains that the reaction must be conducted with separate catalyst and reactant phases, and that the mass ratio of the aqueous caustic phase to the organic reactant phase can be from 2:1 to 10:1, preferably even greater. The reference clearly fails to contemplate the advantages of a high caustic catalyst phase reaction in which the amount of water present is kept relatively low. The patent claims the unsaturated ketone is hydrogenated in a separate step, but this concept is not reduced to practice in the examples.

When ketones are produced in a single-step process, the aldol reaction, dehydration, and hydrogenation occur simultaneously in one reactor. Such single-step processes can be either batch or continous processes.

In a single-step batch process, the reactions are carried out simultaneously in one reactor, and there is neither inflow nor outflow of reactants or products while the reaction is being carried out. In a one-step continuous process, the reactions are carried out simultaneously in one reactor, and reactants flow in and the products flow out while the reaction is being carried out. While the hydrogenation reaction is typically heterogeneously catalyzed, the aldol condenstion can be either heterogeneously or homogeneously catalyzed in a one-step process.

For example, U.S. Pat. No. 2,499,172 (the '172 patent) describes a single-step batch process for the conversion of low-boiling ketones to high boiling ketones. Higher boiling ketones, such as methyl isobutyl ketone, are produced when lower boiling ketones, such as acetone and ethyl methyl ketone, are treated with hydrogen in the presence of a liquid alkaline condensation catalyst and a solid hydrogenation catalyst. The liquid alkaline condensation catalyst can be ammonia; amines, such as isopropylamine, diisopropylamine, trimethylamine, furfurylamine, difurfurylamine, and aniline; alkali-metal hydroxides; alkaline-earth-metal oxides and hydroxides; and alkali-metal salts of weak acids, such as sodium borate, carbonate, acetate and phosphates. The solid hydrogenation catalyst can contain palladium, for example 5% Pd/C.

The examples of the '172 patent describe a single-step batch process for the self-condensation of ketones. In general, self-aldol condensations of ketones lead to only one product. For example, the self-aldol condensation and hydrogenation product of dimethylketone is methyl isobutyl ketone. However, crossed aldol condensations--between ketones and aldehydes--lead to mixtures of products. For example, the crossed aldol condensation and hydrogenaton products of dimethylketone and n-butyraldehyde are methyl amyl ketone, methyl isobutyl ketone, and 2-ethylhexaldehyde. We have found that when the one-step batch process described in the '172 patent is applied to the crossed aldol condensation of acetone and n-butyraldehdye, as seen in Example 1 (Comparative) of the present application, a large amount of high-boiling material is produced. As a result, the selectivity of n-butyraldehyde to methyl amyl ketone is poor. A further disadvantage of batch processes in general is that they often require large reaction vessels and storage tanks, because their productive capacity relative to the reaction volume is very small. Other drawbacks include high energy consumption and high labor requirements.

U.S. Pat. No. 6,583,323 describes a single-step process for the preparation of 6-methylheptan-2-one and corresponding homologous .beta.-branched methylketones, in particular phytone and tetrathydrogeranyl acetone, by the two-liquid phase crossed condensation of acetone with 3-methyl-butanal, prenal or the like, in the presence of both a dilute aqueous alkali or alkali earth metal hydroxide catalyst for the aldol step and a noble metal catalyst for hydrogenation. A base concentration of 0.01 to 20 weight percent in the aqueous catalyst phase is said to be useful, from 0.5 to 5 wt. % being preferred, though the concentration is said not to be critical. The processes exemplified in this document use relatively low concentrations of caustic with a relatively high amount of water, with respect to the total weight of the reactants. The reactivity toward self-condensation of the hindered, branched aldehyde, 3-methyl-butanal, is low, resulting in molar selectivities based on the aldehyde of around 93 95 mole percent.

U.S. Pat. Publ. No. 2002/0058846 teaches a single-step process for the preparation of 6-methylheptan-2-one and corresponding homologous .beta.-branched methylketones, in particular phytone and tetrathydrogeranyl acetone, by the two-liquid phase crossed condensation of acetone with 3-methyl-butanal, prenal or the like, in the presence of a dilute aqueous alkali or alkali earth metal hydroxide catalyst dissolved in a polyhydric alcohol for the aldol step, and a noble metal catalyst for hydrogenation. The polyhydric alcohol is preferably glycerol. This process suffers from low reaction rates and complicated separation schemes for recovery and recycling of the phase transfer catalyst.

U.S. patent application Ser. No. 10/713,727, filed Nov. 14, 2003 and having common assignee herewith, describes a single-step process for producing higher molecular weight ketones, which occurs in a fixed-bed reactor system. Aliphatic ketones or aldehydes are condensed together using a dilute liquid base as an aldol catalyst. The resulting intermediate is dehydrated by the liquid base to yield an unsaturated intermediate. This olefinic species is then hydrogenated over a solid metal catalyst on an inert support. While high conversions and good selectivity are achieved with this process, high recycle rates are suggested for low by-product formation. There remains a need for an improved process for producing higher molecular weight ketones having a higher yield and greater selectivity for the target product, which minimizes the amounts of unwanted by-products that are afterward difficult to remove from the reaction mixture.

BRIEF SUMMARY OF THE INVENTION

We have discovered that higher molecular weight ketones may be produced with high yields, and high space-time yields, in a continuous single-step process by the liquid-phase crossed condensation of an aldehyde with a ketone in the presence of a hydrogenation catalyst and a small amount of a catalyst comprising a concentrated hydroxide or alkoxide of an alkali-metal (from Group 1 or Group IA of the Periodic Table of the Elements) or alkali-earth metal (from Group 2, or Group IIA of the Periodic Table of the Elements), wherein the amount of water provided to the reaction mixture, or reaction zone, is relatively low, with respect to the total weight of the reaction mixture. The reaction may be carried out in the absence of solubilizing agents or phase transfer agents. The product mixture is largely free of by-products resulting from further condensation reactions of the desired ketone product or intermediates, and free of the self-condensation products of the reactant aldehyde that are afterward difficult to remove from the reaction mixture.

DETAILED DESCRIPTION OF THE INVENTION

The present invention may be understood more readily by reference to the following detailed description of the invention, and to the Examples included therein.

Before the present compositions of matter and methods are disclosed and described, it is to be understood that this invention is not limited to specific synthetic methods or to particular formulations, unless otherwise indicated, and, as such, may vary from the disclosure. It is also to be understood that the terminology used is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the invention.

The singular forms "a," "an," and "the" include plural referents, unless the context clearly dictates otherwise.

Optional or optionally means that the subsequently described event or circumstances may or may not occur. The description includes instances where the event or circumstance occurs, and instances where it does not occur.

Ranges may be expressed herein as from about one particular value, and/or to about another particular value. When such a range is expressed, it is to be understood that another embodiment is from the one particular value and/or to the other particular value.

Throughout this application, where patents or publications are referenced, the disclosures of these references in their entireties are intended to be incorporated by reference into this application, in order to more fully describe the state of the art to which the invention pertains.

By the term "higher" molecular weight ketones, as used herein, we mean that the molecular weights of the ketone products are higher than are the molecular weights of the reactants. Conversely, by the terms "lower" molecular weight ketones and "lower" molecular weight aldehydes, as used herein, we mean that the molecular weights of these reactants are lower than the molecular weights of the resulting ketone products.

All mention herein to elements of Groups of the Periodic Table, unless the context indicates otherwise, are made in reference to the Periodic Table of the Elements, as published in "Chemical and Engineering News", 63(5), 27, 1985. In this reference, the groups are numbered 1 to 18.

New processes have been found for producing higher molecular weight ketones, having a combination of product selectivity and space-time yield heretofore unrecognized in the art.

According to one embodiment of the invention, a higher molecular weight saturated ketone of Formula V is produced by the liquid-phase crossed condensation of an aldehyde reactant of Formula I with a ketone reactant of Formula II.

##STR00003##

The aforementioned crossed condensation is carried out in the presence of a heterogeneous (solid) hydrogenation catalyst, typically a metal catalyst, wherein the transition metal is typically supported on an inert stable support. Further, the condensation is carried out in the presence of a small amount of an aldol catalyst comprising one or more bases, and especially a concentrated hydroxide or alkoxide of an alkali- or alkali-earth metal, wherein the amount of water provided to the reaction mixture, or the reaction zone, is relatively low, in certain embodiments being no more than about 16 wt. %, with respect to the total weight of the reactant mixture. In other embodiments, the amount of water provided to the reaction mixture, or the reaction zone, may be no more than about 12 wt. %, with respect to the total weight of the reactant mixture, or no more than 5 wt. %, or no more than 3 wt. %, or even 1 wt. % or less, with respect to the total initial weight of the reaction mixture.

In one embodiment, R1 represents hydrogen, or else R1 and R2 form members of a common alicyclic ring of 4 to 12 carbon atoms, preferably 4 to 8 carbon atoms, and especially 5 to 6 carbon atoms, which alicyclic ring may be substituted with one or more branched or unbranched, saturated or unsaturated aliphatic or alkyl-substituted cycloaliphatic, or aromatic hydrocarbon radicals of 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, or with halogens, ethers, thio ethers, or amine functionalities; or else R2 represents a branched or unbranched, saturated or unsaturated aliphatic or alkyl-substituted cycloaliphatic hydrocarbon radical of 1 to 20 carbon atoms, preferably from 1 to 12 carbon atoms, or from 1 to 4 carbon atoms, and especially a methyl, ethyl, n-butyl, t-butyl, or i-butyl radical, which aliphatic or alkyl-substituted cycloaliphatic hydrocarbon radical may be substituted with halogens or ether functionalities; or else R2 represents a saturated or unsaturated alkyl-substituted cycloaliphatic hydrocarbon radical of 3 to 12 carbon atoms, preferably 3 to 8 carbon atoms, and especially 5 to 6 carbon atoms, which cycloaliphatic hydrocarbon radical may contain alkyl groups as substituents, and which may be substituted with halogens or ether functionalities; or else R2 represents an aryl hydrocarbon radical of 6 to 15 carbon atoms, preferably 6 to 9 carbon atoms, and especially a phenyl radical, which aryl hydrocarbon radical may be substituted with halogens or ether functionalities; or else R2 represents an alkylaryl hydrocarbon radical of 7 to 15 carbon atoms, preferably 7 to 10 carbon atoms, and especially a benzyl radical, which alkylaryl hydrocarbon radical may be substituted with halogens or ether functionalities;

R3, and R4 may each independently represent hydrogen, or else R3 and R4 form members of a common alicyclic ring of 4 to 12 carbon atoms, preferably from 4 to 8 carbon atoms, and especially 5 to 6 carbon atoms, such as a cyclohexyl radical, which alicyclic ring may be substituted with one or more branched or unbranched, saturated or unsaturated aliphatic or alkyl-substituted cycloaliphatic, or aromatic hydrocarbon radicals of 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, or with halogens or ether functionalities; or else R3 or R4 may represent a branched or unbranched, saturated or unsaturated aliphatic or alkyl-substituted cycloaliphatic hydrocarbon radical of 1 to 20 carbon atoms, preferably from 1 to 12 carbon atoms, and especially from 1 to 6 carbon atoms, such as a methyl, ethyl, n-propyl, or n-butyl radical, which aliphatic or cycloaliphatic hydrocarbon radical may be substituted with halogens or ether functionalities; or R3 or R4 may represent a saturated or unsaturated alkyl-substituted cycloaliphatic hydrocarbon radical of 3 to 12 carbon atoms, preferably from 3 to 8 carbon atoms, and especially from 5 to 6 carbon atoms, which cycloaliphatic hydrocarbon radical may contain alkyl groups as substituents, or which may be substituted with halogens or ether functionalities; or else R3 or R4 may represent an aryl hydrocarbon radical of 6 to 15 carbon atoms, preferably from 6 to 9 carbon atoms, and especially a phenyl radical, which aryl hydrocarbon radical may be substituted with halogens or ether functionalities; or else R3 or R4 may represent an alkylaryl hydrocarbon radical of 7 to 15 carbon atoms, preferably from 7 to 10 carbon atoms, and especially a benzyl radical, which alkylaryl hydrocarbon radical may be substituted with halogens or ether functionalities.

In a similar embodiment, R1, R3, and R4 each represent hydrogen, or R1, R2, R3, and R4 each represent a substituted or unsubstituted, straight or branched chain aliphatic radical containing 1 to 10 carbon atoms; a substituted or unsubstituted, straight or branched chain alkenyl radical containing 2 to 10 carbon atoms; a substituted or unsubstituted cycloalkyl or cycloalkenyl radical containing 4 to 10 carbon atoms; a substituted or unsubstituted aryl radical containing 6 to 10 carbon atoms, e.g., phenyl or napthyl; or a substituted or unsubstituted 4- to 10-membered heterocylic radical containing from 1 to 3 heteroatoms selected from oxygen and sulfur. The term "heterocyclic radical" denotes optionally substituted four to ten-membered rings that have 1 to 3 heteroatoms, selected independently from oxygen and sulfur. These four- to ten-membered rings may be saturated, partially unsaturated, or fully unsaturated.

The term "substituted" as used herein in conjunction with each of the above alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, and heterocyclic radicals which may be represented by R1, R2, R3, and R4 denotes the above radicals substituted with one or more halogen, C.sub.1 C.sub.6-alkyl, C.sub.1 C.sub.6-alkoxy, substituted C.sub.1 C.sub.6-alkyl, C.sub.1 C.sub.6-alkylthio, aryl, arylthio, aryloxy, C.sub.2 C.sub.6-alkoxycarbonyl, C.sub.2 C.sub.6-alkanoylamino, hydroxy, carboxyl, cycloalkoxy, nitro, keto, thioether, aldehydo, carboalkoxy, imido, sulfinato, sulfanato, sulfonamide, sulfoxy, phosphato, cycloalkyl, amino, mono-substituted amino, di-substituted amino, acyloxy, alkylcarboxamide, substituted alkylcarboxamide, dialkylcarboxamide, substituted dialkylcarboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, thiohaloalkyl, alkoxy, substituted alkoxy, haloalkoxy, acyloxy, acyl, alkyl, alkoxy, aminoacyl, acylamino, azido, carboxylalkyl, cyano, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy, trihalomethyl, aminosulfonyl optionally N-mono- or N,N-di-substituted with alkyl, aryl or heteroaryl groups, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, alkylcarbonylamino, or arylcarbonylamino groups.

Examples of substituted and unsubstituted alkyl and alkenyl radicals include, but are not limited to, methyl, ethyl, cyanomethyl, nitromethyl, hydroxymethyl, trityloxymethyl, propionyloxymethyl, aminomethyl, carboxymethyl, allyloxycarbonylmethyl, allyloxycarbonylaminomethyl, carbamoyloxymethyl, methoxymethyl, ethoxymethyl, t-butoxymethyl, acetoxymethyl, chloromethyl, bromomethyl, iodomethyl, 6-hydroxyhexyl, 2,4-dichloro(n-butyl), 2-amino(iso-propyl), 2-carbamoyloxyethyl, n-propyl, isopropyl, isobutyl, n-butyl, tertiary butyl, pentyl, hexyl, 2-ethylhexyl, octyl, decyl, vinyl, 1-propenyl, 1-butenyl, 1-pentenyl, 2-octenyl, and various isomers thereof.

Examples of substituted and unsubstituted cycloalkyl and cycloalkenyl radicals include, but are not limited to, cyclopropyl, cyclobutyl, hydroxymethylcyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexylcarbonyloxy, cyclohexenyl, cycloheptyl, 2-methylcyclopropyl, cycloheptenyl, 4-methylcyclohexyl, 3-methylcyclopentenyl, 4-(isopropyl)-cyclohexylethyl or 2-methylcyclopropylpentyl, and the like. Examples of heterocyclic radicals are tetrahydrofuranyl, tetrahydrothiofuranyl, thienyl, dioxanyl, pyranyl, furyl, chromenyl, xanthenyl, phenoxathiinyl, oxepane, oxathiolanyl, benzothienyl, and the like.

Examples of substituted and unsubstituted aryl radicals are 4-chlorophenyl, 2,6-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 3-chlorophenyl, 3-bromophenyl, 4-bromoindenyl, 3,4-dibromophenyl, 3,4-dibromonaphthyl, 3-chloro-4-fluorophenyl, 2-fluorophenyl and the like; a mono- or di(hydroxy)aryl radical such as 4-hydroxyphenyl, 3-hydroxyphenyl, 2,4-dihydroxyphenyl, and the like; a nitroaryl group such as 3- or 4-nitrophenyl; a cyanoaryl group, for example, 4-cyanophenyl; a mono- or di(lower alkyl)aryl radical such as 4-methylphenyl, 2,4-dimethylphenyl, 2-methylnaphthyl, 4-(iso-propyl)phenyl, 4-ethylnaphthyl, 3-(n-propyl)phenyl and the like; a mono- or di(alkoxy)aryl radical, for example, 2,6-dimethoxyphenyl, 4-methoxyphenyl, 3-ethoxyindenyl, 4-(iso-propoxy)phenyl, 4-(t-butoxy)phenyl, 3-ethoxy-4-methoxyphenyl and the like; 3- or 4-trifluoromethylphenyl, a mono- or dicarboxyaryl radical such as 4-carboxyphenyl, 4-carboxynaphthyl; a mono- or di(hydroxymethyl)aryl radical such as 3,4-di(hydroxymethyl)phenyl, a mono- or di(aminomethyl)aryl radical such as 2-(aminomethyl)phenyl, or a mono- or di(methylsulfonylamino)aryl radical such as 3-(methylsulfonylamino)naphthyl. For the present process, it is preferred that R1 is methyl, phenyl, or vinyl; however, it is especially preferred that R1 is hydrogen.

In another, more general, embodiment, the invention relates to a process for producing higher molecular weight saturated ketones, the process comprising reacting an aldehyde reactant with a ketone reactant, the ketone reactant having at least one hydrogen atom alpha to the carbonyl, in a reaction mixture comprising the aldehyde reactant, the ketone reactant, and a basic catalyst that may comprise a hydroxide or alkoxide of an alkali- or alkali-earth metal, wherein no more than about 16 wt. % water is provided to the reaction mixture, with respect to the total initial weight of the reaction mixture. The process may be carried out in the presence of a hydrogenation catalyst, which is typically a metal catalyst, wherein the transition metal is typically supported on an inert stable support. The basic aldol catalyst (the hydroxide or alkoxide) may be provided in a solution having a concentration of at least 15 wt. %, or at least 25 wt. %, or at least 50 wt. %, or as a solid. The amount of water in the reaction mixture will, of course, increase during the course of the reaction, because of the water generated by the reaction, and some of this water may optionally be removed during the course of the reaction.

Alternatively, in various embodiments, the amount of water provided to the reaction mixture may be no more than about 12 wt. % water, or no more than about 5 wt. % water, or no more than about 3 wt. % water, or even 1 wt. % water or less, in each case with respect to the total initial weight of the reaction mixture.

In yet a further embodiment, the invention relates to a process for preparing a higher molecular weight saturated ketone compound of the formula:

##STR00004## wherein each R is independently a hydrocarbyl group, which process comprises contacting in a reaction mixture an aldehyde compound of the formula

##STR00005## with a ketone compound of the formula

##STR00006## wherein each R is independently a hydrocarbyl group, and R' is a hydrocarbyl group having at least one hydrogen atom on the carbon atom which serves as the point of attachment, in the presence of (i) an aldol catalyst, comprised of a hydroxide or C.sub.1 C.sub.8 alkoxide of an alkali metal or alkaline earth metal, wherein the hydroxide or C.sub.1 C.sub.8 alkoxide of an alkali metal or alkaline earth metal is provided as at least one of: (a) a solution or (b) a solid, wherein no more than about 16 weight percent water is provided to the reaction mixture, with respect to the total weight of the reaction mixture; and (ii) a heterogeneous hydrogenation catalyst, such as a metal catalyst, wherein the transition metal is typically supported on an inert stable support.

As already noted, in alternative embodiments, the amount of water provided to the reaction mixture may be no more than about 12 weight percent water, or no more than about 5 wt. % water, or no more than about 3 wt. % water, or even 1 wt. % or less, in each case with respect to the total initial weight of the reaction mixture.

Again as noted, when the aldol catalyst is provided as a solution, the solution may have a concentration of at least 15 wt. %, or at least 25 wt. %, or at least 50 wt. %. The aldol catalyst may alternatively be provided as a solid.

As used herein, a "hydrocarbyl" group means a monovalent or divalent, linear, branched, or cyclic group which contains only carbon and hydrogen atoms. Examples of monovalent hydrocarbyls include the following: C.sub.1 C.sub.20 alkyl; C.sub.1 C.sub.20 alkyl substituted with one or more groups selected from C.sub.1 C.sub.20 alkyl, C.sub.3 C.sub.8 cycloalkyl or aryl; C.sub.3 C.sub.8 cycloalkyl; C.sub.3 C.sub.8 cycloalkyl substituted with one or more groups selected from C.sub.1 C.sub.20 alkyl, C.sub.3 C.sub.8 cycloalkyl or aryl; C.sub.6 C.sub.14 aryl; and C.sub.6 C.sub.14 aryl substituted with one or more groups selected from C.sub.1 C.sub.20 alkyl, C.sub.3 C.sub.8 cycloalkyl or aryl. As used herein, the term "aryl" preferably denotes a phenyl, napthyl, or anthracenyl group. When the above groups are substituted, they are preferably substituted from one to four times with the listed groups. Examples of divalent (bridging hydrocarbyls) include: --CH.sub.2--, --CH.sub.2CH.sub.2--, --C.sub.6H.sub.4--, and --CH.sub.2CH.sub.2CH.sub.2--.

Exemplary aldehydes suitable for use as reactants in the process of the invention include, but are not limited to, acetaldehyde; propionaldehyde; n-butyraldehyde; 2-methyl-propanal; n-pentanal and structural isomers such as 2-methyl-butanal, 3-methyl-butanal, and 2,2-dimethyl-propanal; n-hexanal and structural isomers such as 2-ethyl-butanal, 2,2-dimethylbutanal, 2,3-dimethylbutanal, 2-methyl-pentanal, 3-methylpentanal, and 4-methyl-pentanal; n-heptanal and structural isomers such as 2-methylhexanal, 2-ethylpentanal, 2,2-dimethylpentanal, 2,3-dimethylpentanal, 2,4-dimethylpentanal, 2-ethyl-3-methylbutanal, and 2-ethyl-2-methylbutanal; n-octanal and structural isomers such as 2-ethylhexanal, n-nonanal and structural isomers; n-decanal and structural isomers; n-undecanal and structural isomers; n-dodecanal and structural isomers; benzaldehyde; 4-chlorobenzaldehyde; 3-chlorobenzaldehyde; 2-chlorobenzaldehyde; phenyl acetaldehyde; o-tolualdehyde; m-tolualdehyde; p-tolualdehyde; p-methoxybenzaldehyde; o-methoxybenzaldehyde; m-methoxybenzaldehyde; cyclopropane carboxaldehyde; cyclobutane carboxaldehyde; cyclopentane carboxaldehyde; cyclohexane carboxaldehyde; 2-methylcyclohexane carboxaldehyde; 3-methylhexane carboxaldehyde; 4-methylhexane carboxaldehyde.

Exemplary ketones suitable for use as reactants in the process of the invention include, but are not limited to, acetone, 2-butanone, 2-pentanone, 3-methyl-2-butanone, 2-hexanone, 4-methyl-2-pentanone, 3-methyl-2-pentanone, pinacolone, 2-heptanone, 5-methyl-2-hexanone, 2-octanone, 2-nonanone, 2-decanone, 2-undeca