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WO 2017/129796 Al 3 August 2017 (03.08.2017) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/129796 Al 3 August 2017 (03.08.2017) P O P C T (51) International Patent Classification: Deutschland GmbH & Co. KG, Knollstr. 50, 67061 Lud C07D 215/227 (2006.01) C07D 239/26 (2006.01) wigshafen (DE). LINDNER, Tanja; c/o Abbvie Deutsch C07B 37/04 (2006.01) C07D 409/04 (2006.01) land GmbH & Co. KG, Knollstr. 50, 67061 Ludwigshafen C07B 43/04 (2006.01) C07F 5/02 (2006.01) (DE). C07B 43/06 (2006.01) C07D 307/36 (2006.01) (74) Agent: REITSTOTTER - KINZEBACH; Im Zollhof 1, C07D 405/04 (2006.01) 67061 Ludwigshafen (DE). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP2017/05 1858 kind of national protection available): AE, AG, AL, AM, (22) International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 27 January 2017 (27.01 .2017) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (26) Publication Language: English KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (30) Priority Data: NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 62/288,890 29 January 2016 (29.01.2016) US RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, PCT/EP2016/053238 TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, 16 February 2016 (16.02.2016) EP ZA, ZM, ZW. (71) Applicants: ABBVIE DEUTSCHLAND GMBH & CO. (84) Designated States (unless otherwise indicated, for every KG [DE/DE]; Mainzer Str. 81, 65189 Wiesbaden (DE). kind of regional protection available): ARIPO (BW, GH, ABBVIE INC. [US/US]; 1, North Waukegan Road, North GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, Chicago, Illinois 60064 (US). TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (72) Inventors: BRAJE, Wilfried; c/o AbbVie Deutschland TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, GmbH & Co. KG, Knollstr. 50, 67061 Ludwigshafen (DE). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, BRITZE, Katarina; c/o Abbvie Deutschland GmbH & LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Co. KG, Knollstr. 50, 67061 Ludwigshafen (DE). DIET¬ SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). RICH, Justin, D.; c/o Abbvie Inc., 1, North Waukegan Road, North Chicago, Illinois 60064 (US). JOLIT, Anais; Published: c/o Abbvie Deutschland GmbH & Co. KG, Knollstr. 50, — with international search report (Art. 21(3)) 6706 1 Ludwigshafen (DE). KASCHEL, Johannes; c/o Abbvie Deutschland GmbH & Co. KG, Knollstr. 50, 6706 1 Ludwigshafen (DE). KLEE, Johanna; c/o Abbvie (54) Title: ORGANIC REACTIONS CARRIED OUT IN AQUEOUS SOLUTION IN THE PRESENCE OF A HYDROXYAL - KYL(ALKYL)CELLULOSE OR AN ALKYLCELLULOSE (57) Abstract: The present invention relates to a method of carrying out an organic reaction in aqueous solution in the presence of a hydroxyalkyl(alkyl)cellulose or an alkylcellulose. ORGANIC REACTIONS CARRIED OUT IN AQUEOUS SOLUTION IN THE PRESENCE OF A HYDROXYALKYL(ALKYL)CELLULOSE OR AN ALKYLCELLULOSE FIELD OF THE INVENTION The present invention relates to a method of carrying out an organic reaction in aqueous solution in the presence of a hydroxyalkyl(alkyl)cellulose or an alkylcellulose. BACKGROUND OF THE INVENTION With the growing concern for environmental protection, chemical synthesis and process chemistry are increasingly scrutinized with respect to sustainability. The term "green chemistry" illustrates the goal to provide a more resource-efficient and inherently safer design of molecules, materials, products, and processes. One goal is to provide chemical processes which minimize the use of substances which do not origin from renewable sources and/or cause disposal problems. Especially reducing or avoiding the use of organic solvents is the primary objective, as these account for the major part of the feedstock used in many chemical processes. Most organic solvents are of mineral origin and thus not from a renewable source. They are rather expensive, not only because of their production costs, but also because of the costs related with their disposal. They often pose significant risks to the environment and humans handling them, being mostly flammable or even explosive, and need to be handled and stored with precaution. Many efforts have therefore been made to replace at least a part of the organic solvents with water. Water is readily available, cheap, neither flammable nor explosive, and non toxic. Unfortunately however, it has only poor solubility for most organic compounds, so that reaction times and yields are generally inefficient. Many reactants agglomerate in aqueous medium, which hampers their efficient reaction and makes their processing, especially stirring, difficult. To enhance conversion rates and reduce reaction times in aqueous medium, surfactants and emulsifiers are often used. Lipshutz and coworkers developed surfactants based on polyoxyethanyl-a-tocopheryl succinate (TPGS-750-M and TPGS-1000) or sebacate (PTS-600) which in aqueous solution forms micelles in which organic reactions can take place. TPGS-750-M, which is the most promising, is a polyoxyethanyl-a-tocopheryl succinate derivative of following formula: The use of these micelle-forming surfactants is described, for example, in J. Org. Chem., 201 1, 76 ( 11), 4379-4391 or Green Chem. 2014, 16, 3660-3679, where the authors report the performance of various reactions, including Heck, Suzuki-Miyaura, Sonogashira, and Negishi-like couplings, as well as aminations, C-H activations, and olefin metathesis reactions in water in the presence of TPGS-750-M. While the results obtained with this surfactant are impressive, TPGS-750-M as well as the other polyoxyethanyl-a-tocopheryl derivatives are a rather expensive and sophisticated material. Moreover, they tend to agglomerate in the aqueous reaction medium , which hampers the efficient reaction of the reactants and makes their processing, especially stirring, difficult. Cellulose and its derivatives are inexpensive and biodegradable. Organic reactions in water catalyzed by a transition metal and carried out in the presence of cellulosic material have been reported. Cellulose as such is not water-soluble or swellable and thus cannot act as a surfactant. It is used as carrier for transition metal catalysts; see for example - Baruah et al, Catalysis Commun. 2015, 69, 68-71, where cellulose-supported copper nanoparticles are used as a catalyst for the protodecarboxylation and oxidative decarboxylation of aromatic acids; water or acetonitrile being used as solvents; - Baruah et al, Tetrahedron Lett. 2015, 56, 2543-2547, where cellulose-supported copper nanoparticles are used as a catalyst for the selective oxidation of alcohols to aldehydes; water or acetonitrile being used as solvents; - Baruah et al, RSC Adv. 2014, 4, 59338-59343, where cellulose-supported copper nanoparticles are used as a catalyst for the deprotection of oximes, imines and azines to carbonyl; water being used as solvent; - Chavan et al, RSC Adv. 2014, 4, 42137-42146, where cellulose-supported Cul nanoparticles are used as a catalyst for the one-pot synthesis of 1,4-disubstituted 1,2,3- triazoles in water; and - Jamwal et al, Internat. J. Biol. Macromolecules 201 1, 49, 930-935, where cellulose- supported Pd(0) is used as a catalyst for Suzuki coupling and aerobic oxidation of benzyl alcohols in water. Modified celluloses are also used as carriers for transition metal catalysts; see for example - Bhardwaj et al., where Pd(0) nanoparticles supported on ethylene diamine functionalized silica cellulose is used as a catalyst for C-C and C-S coupling reactions in water; - Faria et al, RSC Adv. 2014, 4, 13446-13452, where celluloseacetate-supported Pd(0) nanoparticles are used as a catalyst for Suzuki reactions in water; - Xiao et al, Appl. Organometal Chem. 2015, 29, 646-652, where carboxymethyl cellulose-supported Pd nanoparticles are used as a catalyst for Suzuki and Heck couplings in water; - Huang et al, Beilstein J. Org. Chem. 2013, 9, 1388-1396, where Au nanoparticles covalently bonded to thiol-functionalized nanocrystalline cellulose films are used as a catalyst for A3 coupling in water; - Keshipour et al, Cellulose 2013, 20, 973-980, where Pd(0) nanoparticles supported on ethylene diamine functionalized cellulose is used as a catalyst for Heck and Sonogashira couplings in water; - Harrad et al, Catalysis Commun. 2013, 32, 92-100, where colloidal Ni(0) carboxymethyl cellulose particles are used as a catalyst for hydrogenation of nitro aromatic compounds and carbonyl compounds in aqueous medium ; - Zhang et al., Catal. Sci. Technol. 2012, 2, 1319-1323, where sodium carboxymethyl cellulose-stabilized Pd is used as a catalyst for the selective hydrogenation of acetylene in water; - Azetsu et al, Catalysis 201 1, 1, 83-96, where Au/Pd bimetallic nanoparticles supported on TEMPO-oxidized cellulose nano fibers are used as a catalyst in the aqueous reduction of 4-nitrophenol; and - Lam et al, Nanoscale 2012, 4, 997, where Au nanoparticles supported on poly(diallyldimethylamoniumchloride)-coated nanocrystalline cellulose are used as a catalyst in the aqueous reduction of 4-nitrophenol. These documents do however not use the modified celluloses as surfactants. It was the object of the present invention to provide a surfactant which allows the performance of organic reactions in water with good yields and short reaction times, but which is less expensive than TPGS-750-M and the other polyoxyethanyl-a-tocopheryl derivatives described above, and which is readily available.
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