(12) Patent Application Publication (10) Pub. No.: US 2011/0251399 A1 Dingerdissen Et Al

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US 2011 O251399A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0251399 A1 Dingerdissen et al. (43) Pub. Date: Oct. 13, 2011

(54) METHOD FOR PRODUCING ALDEHYDES (86). PCT No.: PCT/EP10/50772 AND KETONES FROM PRIMARY AND SECONDARY ALCOHOLS S371 (c)(1), (2), (4) Date: Jun. 20, 2011 (75) Inventors: Uwe Dingerdissen, Seeheim (DE); (30) Foreign Application Priority Data Jan Pfeffer, Essen (DE); Thomas Tacke, Alzenau (DE); Thomas Feb. 6, 2009 (DE) ...... 10 2009 OOO662.1 Haas, Muenster (DE); Harald Publication Classification Schmidt, Muelheim an der Ruhr (51) Int. Cl. (DE); Florian Klasovsky, Haltern C07D 40/04 (2006.01) am See (DE); Roger Sheldon, C07C 45/78 (2006.01) Hoog-Kappel (NL); Michiel C07D 307/68 (2006.01) Janssen, Den Haag (NL); Michael CD7C 45/82 (2006.01) Volland, Duelmen (DE); Michael CD7C 45/38 (2006.01) Rimbach, Herne (DE); Stefanie CD7C 45/6 (2006.01) Rinker, Huenxe (DE) CD7C 45/8 (2006.01) (52) U.S. Cl...... 546/276.4:568/354:568/397; (73) Assignee: EVONIK DEGUSSA GMBH, 568/471; 549/498 ESSEN (DE) (57) ABSTRACT The invention relates to a method for producing aldehydes (21) Appl. No.: and ketones from easily accessible primary and secondary 13/140,921 alcohols by oxidation with atmospheric oxygen or pure oxy gen using a catalyst system which consists of a derivative of (22) PCT Filed: Jan. 25, 2010 a free nitroxyl radical.

Patent Application Publication Oct. 13, 2011 Sheet 2 of 10 US 2011/0251399 A1

Fig. 2: Oxidation of isomannitol with with AA-Tempo/nitrite/nitrate Oxygen

eeJW Xee

000,000|- 000’00!.-- 000'00/— | 000'009-- 000006, 000'009–------+---- |---- 000'008+/ 000'009–—————————Á----- 000'007-7 —~~~~~~~---- O------~~~~4%…• 00?.080907

C. O O If u Oeulueouoso Patent Application Publication Oct. 13, 2011 Sheet 3 of 10 US 2011/0251399 A1

Fig. 3

--e-Diketa-e-looketo--sosorbide ------Cyfy. - -- keto -g-konsketc. --S&Soft).ds -- (oft,

C 4. 9. 8 gtra 3003) - - - s 5G 2000 t

2 O 2 OQ

... O

10 9. 8 arx 70 60 50 it 208 30an 38 || 58 {{ 2 13 O 30 SO SO 2 EC 80 2G Time (min) Patent Application Publication Oct. 13, 2011 Sheet 4 of 10 US 2011/0251399 A1

Figure 4: Oxidation of 2-propanol with AA-TEMPO/nitric acid/oxygen -e-2-Propanol -a-Acetone.--Isopropyl acetate 100 80 60 40 20 O

Timeh) Patent Application Publication Oct. 13, 2011 Sheet 5 of 10 US 2011/0251399 A1

Figure 5: Oxidation of 1-propanol with AA-TEMPO/nitric acid/oxygen

-o-1-Propanol -- Propanal -- Propy acetate 100

Timeh Patent Application Publication Oct. 13, 2011 Sheet 6 of 10 US 2011/0251399 A1

Figure 6. Oxidation of cyclohexanol with AA-TEMPO/nitric acid/oxygen

|-o- Cyclohexanol -A - Cyclohexanone -- Cyclohexyl acetate

80 60 40 20 O

Time (h) Patent Application Publication Oct. 13, 2011 Sheet 7 of 10 US 2011/0251399 A1

Figure 7. Oxidation of furfuryl alcohol with AA-TEMPO/nitric acid/oxygen

-o- Furfury alcohol -- Furtural --Furfural acetate 100 80 SS: 60 40 20 O Patent Application Publication Oct. 13, 2011 Sheet 8 of 10 US 2011/0251399 A1

Figure 8. Oxidation of 1,3-dihydroxycyclohexane with AA-TEMPO/nitric acid/oxygen

-o- 1 3-Dihydroxycyclohexane -A-3-hydroxycyclohexanone -- 2-Cyclohexenone 100 SS 80 : 60 40 20 O O 1 2 3 Patent Application Publication Oct. 13, 2011 Sheet 9 of 10 US 2011/0251399 A1

Figure 9. Oxidation of nicotinyl alcohol with AA-TEMPO/nitric acid/oxygen -e-Nicotinyl alcohol -- Nicotinaldehyde |-- Nicotinyl acetate 1 OU 80 60 40 20 O

Timeh) Patent Application Publication Oct. 13, 2011 Sheet 10 of 10 US 2011/0251399 A1

Figure 10: Oxidation of borneol with AA-TEMPO/nitric acid/oxygen

-e-Borneol -d- Menthol -- Bornyl acetate 100 :O O

Time (h) US 2011/025 1399 A1 Oct. 13, 2011

METHOD FOR PRODUCING ALDEHYDES wherein nitric acid is used as a further reagent. However, the AND KETONES FROM PRIMARY AND ketone yields reported are below 90% and conversions were SECONDARY ALCOHOLS only between 24 and 72% in the case of the aldehydes. This method is more useful for synthesizing carboxylic acids (U.S. Pat. No. 5,239,116). It is only when nitric acid is used as a 0001. The present invention describes a process for pro Stoichiometric reagent, i.e., when oxygen is omitted as an ducing aldehydes and ketones from inexpensively available inexpensive oxidant (U.S. Pat. No. 5,155,279), conversions primary and secondary alcohols by oxidation with atmo of 42-84% are reported at selectivities of 69-81%. spheric oxygen or pure oxygen using a catalyst system con 0009. The prior art processes have the disadvantage that sisting of a free nitroxyl radical derivative. they are frequently unsuitable for large scale industrial pro 0002 Stable nitroxyl radical derivatives were first duction of aldehydes and ketones owing to the low yields and described by Hoffmann (A. K. Hoffmann, A.T. Henderson, J. many process steps or the Stoichiometric use of costly, cor Am. Chem. Soc. 83 (1961) 4671) and Lebeder (O. L. Leb rosive and poisonous reagents. Particularly the addition of eder, S.N. Kazarnovski, Zh. Obshch. Khim. 30 (1960) 1631; halogen Sources which is needed in the nitroxyl radical-cata O. L. Lebeder, S. N. Kazarnovski, C A 55 (1961) 1473a.). lyzed reaction of alcohols, in conjunction with carboxylic They were first used as radical Scavengers. Their usefulness acids, but also in organic solvents, is an extremely corrosive as catalysts for the oxidation of alcohols was only discovered system which makes implementation on an industrial scale recently (e.g., J. M. Bobbitt, C. L. Flores, Heterocycles 27 difficult. Alternatively, poisonous and difficult-to-remove (1988) 509 or A. E. J. de Nooy, A. C. Besemer, H. van transition metals are frequently used as catalyst constituent. Bekkum, Synthesis (1996) 1153). 0010. It is an object of the present invention to provide a 0003. One disadvantage with this type of catalysis is that process for producing aldehydes and ketones which allows the oxygen required for oxidation frequently is generated the use of primary or secondary alcohols as a starting material from expensive sources of oxygen. The use of hypochlorite, and which is such that the addition of halogen sources, more chloroperbenzoic acid, peroxomonosulfuric acid, periodic particularly bromine sources and the use of transition metals acid or trichloroisocyanuric acid for example has been can be dispensed with. reported (e.g. L. Anelli, C. Biffi, F. Montanari, S. Quici, J. 0011 We have found that this object is achieved, surpris Org. Chem. 52 (1987) 2559; J. A. Cella, J. A. Kelley, E. F. ingly, by a process for producing aldehydes and ketones Kenehan, J. Org. Chem. 40 (1975) 1850; S. D. Rychovsky, R. which allows the use of primary and secondary alcohols as a Vaidyanathan, J. Org. Chem. 64 (1999) 310: Bolm, Carsten; starting material and which overcomes precisely the above Magnus, Angelika S.; Hildebrand, Jens P. Organic Letters mentioned disadvantages of the prior art. (2000), 208), 1173-1175: S. S. Kim, K. Nehru, Synletter 0012. The present invention accordingly provides a pro (2002) 616; De Luca, Lidia; Giacomelli, Giampaolo; cess for producing aldehydes and ketones comprising the Porcheddu, Andrea. Organic Letters (2001), 3(19), 3041 oxidation of primary or secondary alcohols with an oxygen 3043). In addition, many of the reagents mentioned contain containing gas in the presence of a catalyst composition com halogens (chlorine, bromine and iodine in particular) which, prising at least one nitroxyl radical, one or more NO sources under the reaction conditions, can have a corrosive effect and and at least one or more carboxylic acids oranhydrides and/or often lead to undesired secondary reactions. mineral acids or anhydrides, optionally in the presence of one 0004. The oxidation of alcohols with oxygen by using or more solvents, characterized in that the primary and sec nitroxyl radical derivatives is accomplished through addition ondary alcohols used have a value of less than 2 for the of transition metals, for example cobalt, copper, tungsten, decadic logarithm of the n-octanol-water partition coefficient ruthenium, manganese and iron (e.g., Sheldon Roger A.; (log P), and in that the aldehydes and ketones are preferably Arends, Isabel W. C. E. Journal of Molecular Catalysis A: obtained in a yield of more than 92%, based on the alcohol Chemical (2006), 251(1-2), 200-214; Minisci, Francesco; used. Punta, Carlo: Recupero, Francesco. Journal of Molecular 0013 The process of the present invention has the advan Catalysis A: Chemical (2006), 251(1-2), 129-149). One dis tage that the alcohol is oxidized using a mild method in the advantage with this method is the frequently difficult removal presence of nitroxyl radicals in a single process step. This of the transition metal salts and their toxic properties. mild method Surprisingly makes it possible to oxidize even 0005 Augustine (U.S. Pat. No. 7,030,279) describes in sterically hindered alcohols which are not available using general the oxidation of primary or secondary alcohols with other methods. This oxidation frequently provides almost oxygen as oxidant to the corresponding aldehydes and quantitative conversions and selectivities, i.e., the high yields ketones using a catalyst system consisting of a free nitroxyl testify to the high efficiency of the process according to the radical derivative, a nitrate Source, a bromine source and a present invention. This high efficiency is completely Surpris carboxylic acid, which is acetic acid in all cases. ing on the basis of the prior art. 0006 Xinquan Hu et al. describe in J. AM. CHEM. SOC. 0014 More particularly, corrosive sources of halogen are 2004, 126, 4112-41 13 the alcohol oxidation using nitroxyl avoided as is the use of transition metals, and the Substrate radical derivative and oxygen, wherein the nitrate source was which constitutes the NO source is adjusted to the particular replaced by a nitrite source. It is explicitly stated that the use process requirements so as to avoid the formation of salt of a bromine source is indispensable. The solvent mentioned contents which are difficult and hence energy-intensive to is dichloromethane in the examples described. work up. A particular advantage, however, is that the process 0007. The use of halogen sources is indispensable in the proceeds without addition of external sources of halogen, i.e., method of Augustine and Xinquan Hu. in a halogen-free manner. Halogen Sources for the purposes of 0008. The halogen-free and transition metal-free catalysis the present invention means any halogen-containing com using nitroxyl radical derivatives and oxygen is described in pound capable of releasing halogens in elemental form or Fried (U.S. Pat. No. 5,136,103 and U.S. Pat. No. 5,155.280), halogen-containing ions in any oxidation state. An addition of US 2011/025 1399 A1 Oct. 13, 2011

halogen-containing compounds, such as chlorites or bro 0021. In the context of the present invention, log P is mine-containing compound Such as N-bromosuccinimide, determined according to the method of Advanced Chemistry N-bromo-phthalimide, tetrabutylammonium bromide or Development Inc., Toronto using the ACD/Log PDB pro inorganic salts, for example NHBr, alkali or alkaline earth gram module. metal bromides to carry out the oxidation can accordingly be 0022. Examples of appropriate alcohols include lower ali omitted, contrary to the prior art. phatic alcohols such as ethanol, ethylene glycol and glycerol for example, but also higher molecular weight systems such 0015. It follows that the process product obtained is also as Sugar alcohols, for example isosorbitol, isomannitol and very substantially halogen free in that halogen free for the derivatives thereof, or polyols, for example polyethylene gly purposes of the present invention means that no halogen cols. comes from an external source of halogen. 0023 The oxidation of the process according to the inven 0016. The process step of the process of the present inven tion is performed using a catalyst composition in the absence tion utilizes primary and secondary alcohols, for which the of transition metals. use of polyfunctional alcohols and poly(alcohol)S is also pos 0024. Nitroxyl radicals are an essential constituent part of sible. It is a particular advantage that the process of the the catalyst composition used in the process of the present present invention achieves the conversion of sterically invention. For the purposes of this invention, nitroxyl radicals demanding alcohols into alcohols/ketones. The fundamental are compounds which contain the moiety condition for an alcohol to be usable is that it have a value of less than 2.4 and preferably of less than 2 for the decadic logarithm of the n-octanol-water partition coefficient (log P). V+ V The n-octanol-water partition coefficient K, or P is a dimen N- O so- N-Oo sionless partition coefficient which indicates the ratio of the A A concentrations of a chemical in a binary system composed of 1-octanol and water (see J. Sangster, Octanol-Water Partition Coefficients. Fundamentals and Physical Chemistry, Vol. 2 of and which at room temperature are stable in the presence of Wiley Series in Solution Chemistry, John Wiley & Sons, oxygen for at least one week. These nitroxyl radicals have no Chichester, 1997). hydrogen atoms on the C-C-atom next to the nitrogen atom. 0025. The nitroxyl radicals used in the catalyst composi 0017. The K/P value only ever relates to one species of tion of the process according to the present invention prefer a chemical, and is represented by the following equation: ably comprise compounds having the structure (I) and/or saltlike compounds having the structure (II):

KowOW = fP = C;C (I) Rs R6 where DNuk I0018 C-concentration of species iof a chemical in the R4 R octanol-rich phase, Oo (II) 0019 C°-concentration of species i of a chemical in the Rs R6 water-rich phase R3 R P is generally reported in the form of the decadic logarithm as log P (or else log P or more rarely log pCW): R4>Ne-k R 0020. The K value is a model measure of the ratio O Y G between the lipophilicity (fat solubility) and hydrophilicity (water solubility) of a substance. The expectation is that the partition coefficient of a Substance in the octanol-water sys where tem will make it possible to estimate the partition coefficients R. R. R. R. Rand R=(C-C)-alkyl, (C-C)-alkenyl, of this substance in other systems involving an aqueous (C-Co)-alkoxy, (C-Cls)-aryl, (C7-C8)-aralkyl, (C-Cls)- phase. K is greater than one when a Substance is more aryl-(C-C)-alkyl or (C-C-heteroaryl, wherein the Sub soluble in fatlike solvents such as n-octanol and less than one stituents of the type R', R. R. R. RandR are the same or when it is more soluble in water. Accordingly, Log P is posi different and the substituents of the type R and R can also tive for lipophilic substances and negative for hydrophilic combine to form a (C-C)-alkylene bridge, which can be substances. Since the KOW cannot be measured for all saturated or unsaturated, unsubstituted or Substituted, par chemicals, there are various predictive models, for example ticularly with one or more substituents selected from R', via quantitative structure-activity relationships (QSARs) or C-Cs-amido, halogen, oxy, hydroxyl, amino, alkylamino, via linear free energy relationships (LFERs), described for dialkylamino, arylamino, diarylamino, alkylcarbonyloxy, example in Eugene Kellogg G, Abraham DJ: Hydrophobic arylcarbonyloxy, alkylcarbonylamino and arylcarbonyl ity: is Log P(ofw) more than the sum of its parts? Eur J Med. amino. In structure (II)Y is any desired halogen-free anion. Chem. 2000 July-August;35(7-8):651-61 or Gudrun Wienke, 0026. The process of the present invention can utilize not Measurement and Predictive Computation of n-Octanol/Wa only one nitroxyl radical but also a mixture of various nitroxyl ter Partition Coefficients Messung and Vorausberechnung radicals. von n-Octanol/Wasser-Verteilungskoeffizienten, PhD the 0027. The nitroxyl radicals used in the process of the sis, Oldenburg University, 1-172, 1993. present invention preferably include 2.2.6,6-tetra-methylpip US 2011/025 1399 A1 Oct. 13, 2011

eridine-1-oxyl (TEMPO) and/or the 2.2.6,6-tetramethylpip and even more preferably in the range from 0.1 to 2 mol %, eridine-1-oxyl derivatives substituted at position 4 of the het based on the amount of alcohol used. erocycle, wherein the derivatives display one or more 0032. The catalyst composition used in the process of the Substituents selected from R', C.-Cs-amido, halogen, oxy, present invention further comprises at least one NO source. In hydroxyl, amino, alkylamino, dialkylamino, arylamino, dia the process of the present invention, the NO source used may rylamino, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbony comprise ammonium nitrate or nitrite, alkali or alkaline earth lamino and arylcarbonyl-amino groups, where R' is a (C- metal nitrates or nitrites, for example magnesium nitrate, or Co-alkyl, (C-Co)-alkenyl, (C-Co)-alkoxy, (Co-Co)-aryl, sodium nitrite. In addition to the nitrates or nitrites or as (C7-C8)-aralkyl, (C-C)-aryl-(C-C)-alkyl or (C-C)- replacement for the nitrates or nitrites it is possible to use heteroaryl group. Examples of appropriate compounds nitrous gases such as NO, NO, N.O., NO, NO, and NOs. include 4-methoxy-2.2.6.6-tetramethylpiperidine-1-oxyl Useful NO sources further include mixtures of various of the (4-MeO-TEMPO), 4-oxo-2.2,6,6-tetramethylpiperidine-1- NO sources mentioned above. The proportion of NO source oxyl (4-oxo-TEMPO), 4-hydroxy-2.2.6,6-tetramethylpiperi (s) used in the process of the present invention is in the range dine-1-oxyl (4-hydroxy-TEMPO), 4-benzoyloxy-2.2.6,6-tet from 0.001 to 10 mol %, preferably in the range from 0.01 to ramethyl-piperidine-1-oxyl (BnO-TEMPO), 4-acetamido-2, 5 mol% and more preferably in the range from 0.1 to 2 mol%. 2.6,6-tetramethylpiperidine-1-oxyl, 4-acetamino-2,2.6.6- based on the amount of alcohol used. tetramethylpiperidine-1-oxyl (AA-TEMPO), 4-amino-2,2.6, 0033. The catalyst composition used in the process of the 6-tetramethylpiperidine-1-oxyl N,N-dimethyl-amino-2,2.6, present invention further comprises at least one or more car 6-tetramethylpiperidine-1-oxyl (NNDMA-TEMPO), 3.6- boxylic acids and/or anhydrides and/or mineral acids oranhy dihydro-2.2.6,6-tetramethyl-1 (2H)-pyridinyloxyl (DH drides. The process of the present invention preferably uti TEMPO) or bis(2.2.6,6-tetramethyl-piperidine-1-oxyl-4-yl) lizes acetic acid or acetic anhydride, propionic acid or some sebacate, and may include one or more Substituents selected other carboxylic acid or anhydride that dissolves in the reac from R', C.-Cs-amido, halogen, oxy, hydroxyl, amino, alky tion mixture as carboxylic acid or carboxylic anhydride. The lamino, dialkylamino, arylamino, diarylamino, alkylcarbo process of the present invention preferably utilizes acetic nyloxy, arylcarbonyloxy, alkylcarbonylamino and arylcarbo acid. Mixtures of various suitable carboxylic acids or solu nyl-amino. tions of carboxylic acids in a Suitable solvent can also be used. 0028. The tetramethylpiperidine-N-oxyl structural frag The amount of carboxylic acid used is preferably in the range ment conforming to structures (I) or (II) can also be a con from 0.1 to 200 mol % and more preferably in the range from stituent part of a larger macromolecule, of an oligomer or else 10 to 50 mol %, based on the amount of alcohol used. of a polymeric structure. An example of such a nitroxyl radi 0034) For the purposes of the present invention, the term cal is shown by structure (III): “mineral acids is used as a collective name for all inorganic acids. Suitable mineral acids include for example HCO HPO, HNO, HNO, HSO, HSO, HBO, their anhy (III) drides or mixtures thereof. Oo 0035. The oxidizing agent used in the process of the Oo present invention is an oxygen-containing gas. Pure oxygen N can be used as oxygen-containing gas, but it is also possible to N use mixtures of oxygen with an inert gas or air or with a gas involved in the reaction. Suitable inert gases include for example nitrogen, carbon dioxide, helium or argon. Examples of gases involved in the reaction include nitrogen N N oxides as mentioned above in the description of the NO N Sources. The oxygen partial pressure is preferably in the range from 0.1 to 100 bar and more preferably in the range from 0.2 to 50 bar. N 0036. The process of the present invention can be carried NHR out in a solvent or without use of a solvent: 0037. In one particular embodiment of the process accord 0029. The “heterogenized” form of the nitroxyl radicals ing to the present invention, the process step is carried out in can also be used in the process of the present invention. This the presence of a solvent. Preference is here given to using means that the nitroxyl radicals are Supported on, for polar solvents, more particularly polar organic solvents. Pref example, aluminum oxide, silicon dioxide, titanium dioxide erence for use as solvents is given to acetonitrile, tetrahydro or Zirconium dioxide. Polymers, composites or carbon mate furan, ethyl acetate, acetone, diethyl ether, methyl tert-butyl rials can also be used as a Support material for the nitroxyl ether, tertiary alcohols such as tert-amyl alcohol, tert-butyl radical. alcohol, esters of carbonic acid such as dimethyl carbonate, 0030 The process of the present invention preferably uti diethyl carbonate, hydrocarbons, or a mixture thereof. The lizes the abovementioned compounds AA-TEMPO, 4-hy amount of solvent used is preferably in the range from 0.1% droxy-TEMPO. TEMPO and 4-oxo-TEMPO as nitroxyl radi to 70% by volume, more preferably in the range from 0.5% to cals. Particular preference is given to using AA-TEMPO, 60% by volume and most preferably in the range from 1% to 4-hydroxy-TEMPO and TEMPO, more particularly 50% by volume, based on the amount of alcohol used. AA-TEMPO. 0038. In a further preferred embodiment of the process 0031. The proportion of nitroxyl radical in the process of according to the present invention, no additional solvent is the present invention is preferably in the range from 0.001 to used in the process step. In this case, the carboxylic acidor the 10 mol %, more preferably in the range from 0.01 to 5 mol % mineral acid serves not just as a component of the catalyst US 2011/025 1399 A1 Oct. 13, 2011

composition but also as a solvent to keep the reaction mixture 0049 b) extracting and optionally recycling the nitroxyl homogeneous. This has the advantage that the use of solvents radicals, that are flammable and possibly hazardous to health can be 0050 c) removing any salts from the NO sources via ion dispensed with, and/or special removal of the solvent can be exchangers, electrodialysis or ultrafiltration, omitted. 0051 d) and/or purifying the product by crystallization, 0039. In what follows, the practice of the process accord distillation, extraction and/or chromatographic separa ing to the present invention is elucidated. The oxidation of the tion. process according to the present invention is preferably car 0.052 The process steps mentioned can be carried out ried out at a temperature of 0 to 100° C. or at the boiling point alone or in any desired combination with one another. of the solvent. 0053. The aldehydes and ketones obtained via the process 0040 Total pressure in the oxidation in the process of the according to the present invention are very useful as interme present invention is preferably in the range from 1 to 300 bar diates for further reaction. For instance, they can be con and more preferably in the range from 1 to 50 bar. Verted, by reductive amination with ammonia, hydroxy 0041. The process can be run as a batch process, as a lamine or hydrazine, into the corresponding amines which are semi-batch process or as a continuous process. Furthermore, very useful as raw materials for the production of plastics. the process of the present invention is not limited to a certain 0054 Even without further exposition it is believed that a reactor type; on the contrary, the process step can be carried person skilled in the art will be able to make the widest use of out in a stirred tank, a tube reactor, a tank cascade, a micro the above description. Therefore, the preferred embodiments reactor or a combination thereof. and examples are merely to be understood as a descriptive 0042. In one embodiment of the process according to the disclosure which is not in any way intended to be limiting. present invention, initially the alcohol is dissolved or Sus 0055. The present invention will now be more particularly pended in a Suitable solvent and then the catalyst composition described with reference to examples. Alternative embodi is added individually or as a mixture to this solution or Sus ments of the present invention are obtainable analogously. pension. Pressure and temperature are then adjusted. How ever, it is also possible to charge the catalyst composition EXAMPLES initially and to add the solution or suspension of the alcohol to the catalyst composition. When the process of the present invention is run as a continuous process, it is preferable to a) Sterically Demanding Alcohols in Glacial Acetic Acid: feed the alcohol together with the reaction gases in the 0056 1. Oxidation of Isosorbitol with AA-Tempo/O/Ni embodiment of a trickle bed. trate-/Nitrite, Bromine Free 0043. It is particularly advantageous in the process of the present invention for the level of water in the reaction com Material: position to be very low, since high proportions of water can reduce the yields. In addition, the reaction can be speeded by 0.057 removing the water of reaction from the reaction environ ment. 0044) There are several options to minimize the water isosorbitol (1,4:3,6-dianhydro- 100 mmol -> 73.07 g/L content. Water-absorbing agents, preferably sodium Sulfate, D-sorbitol) AA-TEMPO 5 mol% -> 5.35 g/L calcium oxide and molecular sieves, for example Zeolites, can NaNO, 2 mol% -> 2.55 g/L be added to the reaction mixture. Concentrated Strongly Mg(NO) x 6H2O 2 mol% -> 0.70 g/L hydrating acids or salts can also be used. For example, the acetic acid (100%) 200 mL. abovementioned mineral acids and/or anhydrides can be used decane (internal standard for 7 g -> 35 g/L as water-binding acids. It is further possible to use very analysis) strongly water-complexing solvents, for example glacial ace logP isosorbitol -1.67 tic acid. 0045. It is additionally also possible to use solvents capable of binding water chemically. Preferably, the anhy Reaction Conditions: drides of the carboxylic acids used in the process of the 0058 reaction temperature: T=50° C. present invention are concerned here. Thus the carboxylic anhydrides act not only as solvents for the reaction but at the reaction time: t—4h same time also as a water-binding agent. This makes for an oxygen: 10 bar efficient reaction management which at the same time leads to reactor volume: 450 mL high yields, an effect not known in that form from the prior art. Procedure: 0046 Alternatively, the water of reaction can also be with 0059. The reactant, the catalyst, the salts and the internal drawn from the reaction mixture by distillative removal or by standard are initially charged, dissolved in the acetic acid extractive removal from the reaction environment. (addition of acetic acid until the volume of 200 ml is reached) 0047. The reaction mixture is generally worked up in a and transferred into the high pressure reactor. The reactor is way which depends on the polarity of the target molecules sealed and twice inertized with nitrogen. The solution is then and the solubility of the nitroxyl radicals. A procedure for heated to a temperature of 50° C. under agitation. The reac readily water-soluble aldehydes and ketones comprises: tion is started by injecting 10 bar of oxygen into the autoclave. 0048 a) removing the solvents and the carboxylic acid The pressure in the reactor is kept at a constant 10 bar by by distillation or extraction, replenishing consumed oxygen via an opened oxygen Supply US 2011/025 1399 A1 Oct. 13, 2011

up to a pressure of 10 bar. After four hours, the reaction is 3. Oxidation of Isosorbitol with Various N-Oxy Radicals/O/ discontinued by inertization with nitrogen and cooling down Nitrite/Nitrate Bromine Free of the system. Material: Result: 0067 0060 A conversion of above 97% is observed at a 100% selectivity of the diketone (2,6-dioxabicyclo-(3.3.0)-octane isosorbitol (1,4:3,6-dianhydro- 10 mmol -> 73.07 g/L 4,8-dione). D-sorbitol) N-oxy radical 5 mol% 0061 FIG. 1 shows the development of the isosorbitol, NaNO- 2 mol% -> 2.55 g/L diketone and monoketone concentrations as a function of Mg(NO) x 6H2O 2 mol% -> 0.70 g/L time during the performance of the process of the present acetic acid (100%) 20 mL. hexadecane (internal standard 0.05 g -> 2.5 g/L invention. The isosorbitol and diketone concentrations were for analysis) evaluated via calibration curves and the internal standard. The logP isosorbitol -1.67 monoketone concentrations are evaluated via the peak areas. 2. Oxidation of Isomannitol with AA-Tempo/O/Nitrite-/Ni trate, Bromine Free: Reaction Conditions:

Material: 0068 reaction temperature: T=50° C. reaction time: t—1.5 h-4.5 h 0062 oxygen: 10 mL/min Procedure: isomannitol (14:3,6-dianhydro- 25 mmol -> 73.07 g/L 0069. The reactant, the catalyst and the salts are initially D-mannitol) charged to a three neck flask equipped with a reflux condenser AA-TEMPO 5 mol% -> 5.35 g/L NaNO- 2 mol% -> 2.55 g/L and a gas inlet frit, admixed with 20 ml of acetic acid and Mg(NO) x 6H2O 2 mol% -> 0.70 g/L dissolved under agitation. The Solution is then heated to a acetic acid (100%) 50 mL. temperature of 50° C. under agitation. The reaction is started decane (internal standard for 1.75 g -> 35 g/L by introducing oxygen into the reaction Solution via the gas analysis) inlet fritat a flow rate of 20 ml/min. The reactions are run for logP isomannitol -1.67 a period of 1.5h-4.5 h during which a sample is takenevery 30 minto record the kinetics.

Reaction Conditions: Result: reaction temperature: T=50° C. 0070 Various N-oxy radicals are used for the reaction in 0063 accordance with the protocol described above. The reaction is reaction time: t—1.5 h run for a period of 1.5 h-4.5 h depending on the N-oxy radical oxygen: 10 mL/min used. The N-oxy radical AA-Tempo gives a conversion of 100% and a 100% selectivity to the diketone. Procedure: 0071 FIG. 3 shows the results of comparative tests in respect of the reactions. Plots are shown of the oxidation of 0064. The reactant, the catalyst, the salts and the internal isosorbitol with AA-Tempo (at top left), PIPO (at top right), standard are initially charged, dissolved in the acetic acid Tempo (at bottom left) and also a comparison of the conver (addition of acetic acid until the volume of 50 ml is reached) sions of all three N-oxy radicals as a function of time. The and transferred into a four neck flask equipped with reflux graphs show the normalized areas from GC analysis and the condenser, thermometer, gas inlet frit and septum for sample conversion of the isosorbitol in % evaluated using hexade taking. The solution is then heated to a temperature of 50° C. cane as internal standard. under agitation. The reaction is started by introducing oxygen 4. Oxidation of Isosorbitol with AA-Tempo/O/Nitrite, Bro into the reaction solution via the gas inlet frit at a flow rate of mine Free 10 ml/min. The reaction is run for a period of 1.5 h during which a sample is taken every 15 minto record the kinetics. Material: Result: 0072 0065. A conversion of 100% is observed at a 100% selec tivity of the diketone (2,6-dioxabicyclo-(3.3.0)-octane-4,8- isosorbitol (1,4:3,6-dianhydro- 100 mmol -> 73.07 g/L D-sorbitol) dione). AA-TEMPO 5 mol% -> 5.35 g/L 0066 FIG. 2 shows the development of the isomannitol, NaNO- 2.5 mol% -> 3.19 g/L diketone and monoketone concentrations as a function of acetic acid (100%) 200 mL. decane (internal standard for 7 g -> 35 g/L time during the performance of the process of the present analysis) invention. The isomannitol and diketone concentrations were logP isosorbitol -1.67 evaluated via calibration curves and the internal standard. The monoketone concentrations are evaluated via the peak areas. US 2011/025 1399 A1 Oct. 13, 2011

Reaction Conditions: 6. Oxidation of Isosorbitol with AA-TEMPO/O/Nitrite-/ HNO (Comparative Experiment) 0073 reaction temperature: T=50° C. reaction time: t—4h Material: oxygen: 10 bar 0080 reactor volume: 450 mL

Procedure: isosorbitol (14:3,6-dianhydro-D- 10 mmol 0074 The reactant, the catalyst, the salts and the internal sorbitol) standard are initially charged, dissolved in the acetic acid AA-TEMPO 5 mol% NaNO- 2 mol% (addition of acetic acid until the volume of 200 ml is reached) HNO 10 mol% and transferred into the high pressure reactor. The reactor is Water 20 mL. sealed and twice inertized with nitrogen. The solution is then hexadecane (internal standard for 0.05 g heated to a temperature of 50° C. under agitation. The reac analysis) tion is started by injecting 10 bar of oxygen into the autoclave. The pressure in the reactor is kept at a constant 10 bar by replenishing consumed oxygen via an opened oxygen Supply Reaction Conditions: up to a pressure of 10 bar. After four hours, the reaction is discontinued by inertization with nitrogen and cooling down I0081 reaction temperature: T=50° C. of the system. reaction time: t—4h oxygen: 20 mL/min Result: Procedure: 0075. A conversion of above 97% is observed coupled I0082. The reactant, the catalyst, the salts and the nitric acid with 100% selectivity for the diketone (2,6-dioxabicyclo-(3. are initially charged to a three neck flask equipped with a 3.0)-octane-4,8-dione). reflux condenser and a gas inlet frit and filled with 10 ml of 5. Oxidation of Isosorbitol with Tempo/NaOC1/Bromide water, are made up to 20 ml with water and are dissolved (Comparative Experiment by Chlorate Method) under agitation. The Solution is then heated to a temperature of 50° C. under agitation. The reaction is started by introduc Material: ing oxygen into the reaction solution via the gas inlet frit at a flow rate of 20 mL/min. The reactions are run for a period of 0076 4h. Result: isosorbitol (14:3,6-dianhydro-D- -> 20 g/L sorbitol) I0083. The oxidizing system used did not give any observ Tempo -> 1.71 g/L able conversion into either monoketone or diketone. NaBr -> 11.30 g/L NaOCl -> 81.5 g/L b) Sterically Undemanding Alcohols in Glacial Acetic Acid Water -> 100 ml logP isosorbitol -1.67 I0084) 1. Oxidation of 2-Propanol with AA-Tempo/O/Ni tric Acid, Bromine Free Material: Reaction Conditions: 0077 reaction temperature: T=2-5°C. 0085 reaction time: t2h

Procedure: 2-propanol 200 mmol -> 119.34 g/L AA-TEMPO 3.5 mol% -> 14.94 g/L nitric acid (>99.8%) 3.5 mol% -> 4.53 g/L 0078 2 g of isosorbitol, 1127 mg of sodium bromide and acetic acid (100%) 100 mL. 171 mg of TEMPO are suspended in 100 ml of water and logP 2-propanol O.38 cooled to 0°C. in an ice-water bath. The continuously mea sured pH of this mixture is adjusted to exactly pH 10 by adding 0.5N aqueous sodium hydroxide solution. The run is carried out at a constant pH of 10. It is achieved through Reaction Conditions: continuous titration of the resulting acids with 0.5N in aque I0086 reaction temperature: T=50° C. ous sodium hydroxide solution, the pH being kept constant reaction time: t—3 h using an automatic titration system TITRINO, from oxygen: 1 bar Metrohm, Herisau (CH). reactor volume: 250 mL

Result: Procedure: 0079. The reaction leads to small amounts of monoketone I0087. The reactant is initially charged, dissolved in the and diketone cannot be detected. acetic acid (acetic acid being added until the volume of 100 US 2011/025 1399 A1 Oct. 13, 2011

ml is reached) and transferred into the reactor. The solution is 3. Oxidation of Cyclohexanol with AA-Tempo/O/Nitric then heated to a temperature of 50° C. under agitation and Acid, Bromine Free oxygen injection. The reaction is started by adding the acid and the catalyst to the reaction mixture. The pressure in the Material: reactor is maintained at a constant 1 bar by replenishing 0.095 consumed oxygen via an opened oxygen Supply up to a pres sure of 1 bar. After three hours the reaction is discontinued by interrupting the oxygen feed and cooling down of the system. cyclohexanol 200 mmol -> 200.32 g/L AA-TEMPO 3.5 mol% -> 14.94 g/L Result: nitric acid (>99.8%) 3.5 mol% -> 4.53 g/L acetic acid (100%) 100 mL. 0088 A conversion of above 15% is observed coupled logP cyclohexanol 1.27 with a 70% selectivity for the ketone (acetone). By-produced isopropyl acetate can be detected in a small amount. 0089 FIG. 4 shows the development of the 2-propanol, Reaction Conditions: acetone and isopropyl acetate concentrations as a function of time in the performance of the process according to the (0096) reaction temperature: T=50° C. present invention. The concentrations are evaluated via the reaction time: t—3 h peak areas. oxygen: 1 bar 2. Oxidation of 1-Propanol with AA-Tempo/O/Nitric Acid, reactor volume: 250 mL Bromine Free Procedure: Material: 0097. The reactant is initially charged, dissolved in the acetic acid (acetic acid being added until the volume of 100 0090 ml is reached) and transferred into the reactor. The solution is then heated to a temperature of 50° C. under agitation and oxygen injection. The reaction is started by adding the acid 1-propanol 200 mmol -> 119.34 g/L and the catalyst to the reaction mixture. The pressure in the AA-TEMPO 3.5 mol% -> 14.94 g/L reactor is maintained at a constant 1 bar by replenishing nitric acid (>99.8%) 3.5 mol% -> 4.53 g/L consumed oxygen via an opened oxygen Supply up to a pres acetic acid (100%) 100 mL. sure of 1 bar. After three hours the reaction is discontinued by logP1-propanol 0.55 interrupting the oxygen feed and cooling down of the system. Result: Reaction Conditions: 0098. A conversion of above 14% is observed coupled 0091 reaction temperature: T=50° C. with a 81% selectivity for the ketone (cyclohexanone). By reaction time: t—3 h produced cyclohexyl acetate can be detected in a small oxygen: 1 bar amount. (0099 FIG. 6 shows the development of the cyclohexanol, reactor volume: 250 mL cyclohexanone and cyclohexyl acetate concentrations as a function of time in the performance of the process according Procedure: to the present invention. The concentrations are evaluated via 0092. The reactant is initially charged, dissolved in the the peak areas. acetic acid (acetic acid being added until the volume of 100 4. Oxidation of Furfuryl Alcohol with AA-Tempo/O/Nitric ml is reached) and transferred into the reactor. The solution is Acid, Bromine Free then heated to a temperature of 50° C. under agitation and oxygen injection. The reaction is started by adding the acid Material: and the catalyst to the reaction mixture. The pressure in the 01.00 reactor is maintained at a constant 1 bar by replenishing consumed oxygen via an opened oxygen Supply up to a pres sure of 1 bar. After three hours the reaction is discontinued by interrupting the oxygen feed and cooling down of the system. furfuryl alcohol 200 mmol -> 197.8 g/L AA-TEMPO 3.5 mol% -> 14.94 g/L nitric acid (>99.8%) 3.5 mol% -> 4.53 g/L Result: acetic acid (100%) 100 mL. logP furfuryl alcohol O.08 0093. A conversion of above 27% is observed coupled with a 20% selectivity for the aldehydes (propanal). By produced propyl acetate can be detected in a small amount. Reaction Conditions: 0094 FIG. 5 shows the development of the 1-propanol, acetone and isopropyl acetate concentrations as a function of 0101 reaction temperature: T=50° C. time in the performance of the process according to the reaction time: t—3 h present invention. The concentrations are evaluated via the oxygen: 1 bar peak areas. reactor volume: 250 mL US 2011/025 1399 A1 Oct. 13, 2011

Procedure: of the process according to the present invention. The con centrations are evaluated via the peak areas. 0102 The reactant is initially charged, dissolved in the 6. Oxidation of Nicotinyl Alcohol with AA-Tempo/O/Nitric acetic acid (acetic acid being added until the volume of 100 ml is reached) and transferred into the reactor. The solution is Acid, Bromine Free then heated to a temperature of 50° C. under agitation and Material: oxygen injection. The reaction is started by adding the acid and the catalyst to the reaction mixture. The pressure in the 0110 reactor is maintained at a constant 1 bar by replenishing consumed oxygen via an opened oxygen Supply up to a pres nicotinyl alcohol 200 mmol -> 218.26g/L sure of 1 bar. After three hours the reaction is discontinued by AA-TEMPO 3.5 mol% -> 14.94 g/L interrupting the oxygen feed and cooling down of the system. nitric acid (>99.8%) 3.5 mol% -> 4.53 g/L acetic acid (100%) 100 mL. Result: logP nicotinyl alcohol O.12 0103) A conversion of above 96% is observed coupled with a 93% selectivity for the aldehydes (furfural). By-pro duced furfuryl acetate can be detected in a small amount. Reaction Conditions: 0104 FIG. 7 shows the development of the furfuryl alco 0111 reaction temperature: T=50° C. hol, furfural and furfuryl acetate concentrations as a function reaction time: t—3 h of time in the performance of the process according to the oxygen: 1 bar present invention. The concentrations are evaluated via the reactor volume: 250 mL peak areas. 5. Oxidation of 1,3-Dihydroxycyclohexane with AA-Tempo/ Procedure: O/Nitric Acid, Bromine Free 0112 The reactant is initially charged, dissolved in the Material: acetic acid (acetic acid being added until the volume of 100 ml is reached) and transferred into the reactor. The solution is 01.05 then heated to a temperature of 50° C. under agitation and oxygen injection. The reaction is started by adding the acid and the catalyst to the reaction mixture. The pressure in the 1,3-dihydroxycyclohexane 86 mmol -> 100 g/L reactor is maintained at a constant 1 bar by replenishing AA-TEMPO 3.5 mol% -> 6.49 g/L consumed oxygen via an opened oxygen Supply up to a pres nitric acid (>99.8%) 3.5 mol% -> 1.51 g/L sure of 1 bar. After three hours the reaction is discontinued by acetic acid (100%) 100 mL. interrupting the oxygen feed and cooling down of the system. logP 1,3-dihydroxycyclohexane O.O1 Result: 0113. A conversion of above 17% is observed coupled Reaction Conditions: with a 79% selectivity for the aldehydes (nicotinaldehyde). 0106 reaction temperature: T=50° C. By-produced nicotinyl acetate can be detected in a small reaction time: t—3 h amount. oxygen: 1 bar 0114 FIG.9 shows the development of the nicotinyl alco reactor volume: 250 mL hol, nicotinyl aldehyde and nicotinyl acetate concentrations as a function of time in the performance of the process accord Procedure: ing to the present invention. The concentrations are evaluated via the peak areas. 0107 The reactant is initially charged, dissolved in the 7. Oxidation of Borneol with AA-Tempo/O/Nitric Acid, acetic acid (acetic acid being added until the volume of 100 Bromine Free ml is reached) and transferred into the reactor. The solution is then heated to a temperature of 50° C. under agitation and Material: oxygen injection. The reaction is started by adding the acid and the catalyst to the reaction mixture. The pressure in the 0115 reactor is maintained at a constant 1 bar by replenishing consumed oxygen via an opened oxygen Supply up to a pres borneol 200 mmol -> 308.50 g/L sure of 1 bar. After three hours the reaction is discontinued by AA-TEMPO 3.5 mol% -> 14.94 g/L interrupting the oxygen feed and cooling down of the system. nitric acid (>99.8%) 3.5 mol% -> 4.53 g/L acetic acid (100%) 100 mL. Result: logP borneol 1.63 0108. A conversion of above 11% is observed coupled with a 72% selectivity for the monooxygenated ketone (3-hy droxycyclohexanol). By-produced 2-cyclohexenone can be Reaction Conditions: detected in a small amount. 0116 reaction temperature: T=50° C. 0109 FIG.8 shows the development of the 1,3-dihydroxy reaction time: t—3 h cyclohexane, 3-hydroxycyclohexanone and 2-cyclohex oxygen: 1 bar enone concentrations as a function of time in the performance reactor volume: 250 mL US 2011/025 1399 A1 Oct. 13, 2011

Procedure: bonyloxy, alkylcarbonylamino and arylcarbonylamino groups, where R' is a (C-Clio)-alkyl, (C-Co)-alkenyl, (C- 0117 The reactant is initially charged, dissolved in the Co)-alkoxy, (C-Cls)-aryl, (C7-C8)-aralkyl, (C-Cls)-aryl acetic acid (acetic acid being added until the volume of 100 (C-Cs)-alkyl and (C-C)-heteroaryl group. ml is reached) and transferred into the reactor. The solution is 4. The process according to claim 1, wherein the proportion then heated to a temperature of 50° C. under agitation and of nitroxyl radical is in the range from 0.001 to 20 mol %, oxygen injection. The reaction is started by adding the acid based on the amount of alcohol. and the catalyst to the reaction mixture. The pressure in the 5. The process according to claim 1, wherein at least one reactor is maintained at a constant 1 bar by replenishing carboxylic acid is present as acetic acid or at least one anhy consumed oxygen via an opened oxygen Supply up to a pres dride is present as acetic anhydride. sure of 1 bar. After three hours the reaction is discontinued by 6. The process according to claim 1, wherein the proportion interrupting the oxygen feed and cooling down of the system. of carboxylic acid and/or anhydride is in the range from 0.1 to 200 mol %, based on the amount of alcohol. Result: 7. The process according to claim 1, wherein at least one 0118. A conversion of above 22% is observed coupled mineral acid is present and is H2CO, HPO, HSO, HSOs, with a 82.9% selectivity for the ketone (menthol). By-pro HBO or their anhydrides or mixtures thereof. duced bornyl acetate can be detected in a small amount. 8. The process according to claim 1, wherein one or more 0119 FIG.10 shows the development of the borneol, men NO sources is present and comprises ammonium nitrate or thol and bornyl acetate concentrations as a function of time in nitrite, alkali or alkaline earth metal nitrates or nitrites, the performance of the process according to the present nitrous gases or mixtures thereof. 9. The process according to claim 1, wherein one or more invention. The concentrations are evaluated via the peak NO sources is present and the proportion of NO source(s) is in aaS. the range from 0.001 to 10 mol %, based on the amount of 1. A process for producing aldehydes and ketones compris alcohol. ing the oxidation of primary or secondary alcohols with an 10. The process according to claim 1, wherein no addi oxygen-containing gas in the presence of a catalyst compo tional Solvent is present. sition comprising at least one nitroxyl radical, one or more 11. The process according to claim 1, wherein the water of NO sources and at least one or more carboxylic acids or reaction is removed from the reaction mixture. anhydrides and/or mineral acids or anhydrides, optionally in 12. The process according to claim 11, wherein the water of the presence of one or more solvents, wherein the primary and reaction is removed by addition of water-absorbing agents to secondary alcohols have a value of less than 2 for the decadic the reaction mixture and/or by distillative or extractive logarithm of the n-octanol-water partition coefficient (log P). removal from the reaction mixture during the reaction. 2. The process according to claim 1, wherein the aldehydes 13. The process according to claim 11, wherein the solvent and ketones are obtained in a yield of more than 92%, based is a water-complexing solvent or a solvent that chemically on the alcohol. binds water. 3. The process according to claim 1, wherein the one or 14. The process according to claim 1, further comprising more nitroxyl radicals comprise 2.2.6.6-tetramethylpiperi removing the carboxylic acid and, if present, the solvent by dine-1-oxyl (TEMPO) and/or the 2.2.6,6-tetramethylpiperi distillation or extraction, extracting and optionally recycling dine-1-oxyl derivatives substituted at position 4 of the hetero the nitroxyl radicals removing the salts from the NO sources cycle, wherein the derivatives display one or more and/or purifying the aldehyde/ketone by crystallization, dis substituents selected from the group consisting of R', C.-Cs tillation, extraction and/or chromatographic separation. amido, halogen, oxy, hydroxyl, amino, alkylamino, dialky lamino, arylamino, diarylamino, alkylcarbonyloxy, arylcar c c c c c