(19)
(11)EP 3 257 831 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
27.11.2019 Bulletin 2019/48

(21)Application number: 17176464.0

(22)Date of filing:  16.06.2017
(51)Int. Cl.: 
C07C 5/333  (2006.01)
C07C 13/465  (2006.01)
C07C 5/48  (2006.01)
C07C 5/367  (2006.01)
C07B 35/04  (2006.01)
C07C 5/10  (2006.01)

(54)

CIRCULAR ECONOMY METHODS OF PREPARING UNSATURATED COMPOUNDS

KREISLAUFWIRTSCHAFTSVERFAHREN ZUR HERSTELLUNG VON UNGESÄTTIGTEN VERBINDUNGEN

PROCÉDÉS D'ÉCONOMIE CIRCULAIRE DE PRÉPARATION DE COMPOSÉS INSATURÉS


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 16.06.2016 US 201662351062 P

(43)Date of publication of application:
20.12.2017 Bulletin 2017/51

(73)Proprietor: International Flavors & Fragrances Inc.
New York, NY 10019 (US)

(72)Inventors:
  • TADEPALLI, Sunitha Rao
    Morganville, NJ New Jersey 07751 (US)
  • TAMPY, Geatesh Karunakaran
    Colts Neck, NJ New Jersey 07722 (US)
  • NARULA, Anubhav P.S.
    Hazlet, NJ New Jersey 07730 (US)

(74)Representative: Barker Brettell LLP 
100 Hagley Road Edgbaston
Birmingham B16 8QQ
Birmingham B16 8QQ (GB)


(56)References cited: : 
WO-A2-2005/073157
US-A- 3 751 500
CN-A- 1 117 037
US-A- 3 847 993
  
  • TAKAHIRO FUJII ET AL: "Thermal Dehydrogenation of Cyclooctane by Supported Noble Metal Catalysts", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 64, no. 3, 1 March 1991 (1991-03-01), pages 938-941, XP55449183, JP ISSN: 0009-2673, DOI: 10.1246/bcsj.64.938
  • MUKTA GUPTA ET AL: "Catalytic Dehydrogenation of Cycloalkanes to Arenes by a Dihydrido Iridium P-C-P Pincer Complex", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 119, no. 4, 1 January 1997 (1997-01-01), pages 840-841, XP55449525, US ISSN: 0002-7863, DOI: 10.1021/ja962560x
  • SHVO Y ET AL: "REGIOSELECTIVE CATALYTIC DEHYDROGENATION OF ALDEHYDES AND KETONES", THE JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 63, no. 16, 7 August 1998 (1998-08-07), pages 5640-5642, XP000768928, ISSN: 0022-3263, DOI: 10.1021/JO980112X
  • WATARU NINOMIYA ET AL: "Dehydrogenation of cycloalkanes over noble metal catalysts supported on active carbon", RESEARCH ON CHEMICAL INTERMEDIATES : AN INTERNAT. JOURNAL, vol. 34, no. 8-9, 1 August 2008 (2008-08-01), pages 663-668, XP55449531, NL ISSN: 0922-6168, DOI: 10.1007/BF03036923
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description

CROSS-REFERENCE TO A RELATED APPLICATION



[0001] This application claims priority to US Application, Serial No. 62/351,062, filed on June 16,2016.

FIELD OF THE INVENTION



[0002] This application relates to methods of preparing unsaturated compounds, especially unsaturated carbocyclic compounds useful in the fragrance industry, through hydrogenation of aromatic compounds or dehydrogenation of saturated compounds using sustainable, green engineering and circular economy methods.

BACKGROUND OF THE INVENTION



[0003] Olefins (alkenes) are versatile raw materials in organic synthesis, polymerization, and chemical processes, but they are not as widely available naturally as alkanes. Given the abundance of saturated hydrocarbon or alkanes in nature, dehydrogenation of alkanes provides a sustainable production of alkenes. This approach eliminates significant amount of waste generated from alternate multi-step chemical methods that are used to produce these olefins.

[0004] Different dehydrogenation methods have been developed. CN1117037 relates to a method for preparing polymethyl substituted tetrahydroindane by selective hydrogenation of polymethyl substituted indane. WO 2005/073157 relates to a method for dehydrating hydrocarbons by means of a catalytically active composition containing Pd and Bi and an element selected from Rh, Au, Sb, V, Cr, W, Mn, Fe, Co, Ni, Na, Cs and Ba.

[0005] Traditional methods involve use of stoichiometric amounts of halogenated reagents and/or precious metals thus generating a lot of waste. Alternate one-step catalytic methods have been developed, but productivity and selectivity remains to be an issue especially when multiple regio-isomers can be formed in the dehydrogenation process. Especially in the case of higher alkanes, low selectivity and conversion often severely limit the utility of dehydrogenation.

[0006] Accordingly, there remains a need for green dehydrogenation methods that can produce high yield and great selectivity via engineering and catalytic methods. In one aspect, the present disclosure provides inventions aiming to meet such needs.

SUMMARY OF THE INVENTION



[0007] Many fragrance intermediates and ingredients contain unsaturated backbones - linear or branched chain, mono- or multi-cyclic carbon backbones with or without functional groups. Dehydrogenation from the corresponding saturated compounds to yield these unsaturated compounds often encounters low-selectivity issues, giving rise to different regio-isomers of olefins or the aromatic counterparts. To access some of the unsaturated carbocyclic compounds, an alternative approach is through hydrogenation of the corresponding aromatic carbocycles, but control of hydrogenation at the olefin stage to avoid complete hydrogenation to fully saturated carbocyclic compounds remains a challenge. It has been unexpectedly discovered that various new catalytic systems and engineering methods are efficient to tackle this challenge.

[0008] In one aspect, the present invention provides a method of preparing an unsaturated compound, comprising dehydrogenation of a corresponding saturated compound in the presence of a catalyst system under conditions that effect loss of one or more molecules of hydrogen (H2) per molecule of the saturated compound, wherein the unsaturated compound is a compound of formula I(a) or I(b), and the saturated compound is a compound of formula II:

wherein R is H or =O; and Q is CH2, CH2CH2, CH(CH3), or C(CH3)2.

[0009] In another aspect, the present invention provides a method of preparing an unsaturated compound, comprising dehydrogenation of a corresponding saturated compound in the presence of a catalyst system under conditions that effect loss of one or more molecules of hydrogen (H2) per molecule of the saturated compound, wherein the unsaturated compound is 1,1,2,3,3-pentamethylindane (PMI), the saturated compound is 1,1,2,3,3-pentamethyloctahydro-1H-indene (HHPMI), and the dehydrogenation is performed in a flow reactor in the presence of a fixed-bed catalyst:



[0010] Also within the scope of this invention is a process of preparing 1,1,2,3,3-Pentamethyl-4,5,6,7-tetrahydro-1H-indene (THPMI) comprising the steps of:
  1. (a) feeding 1,1,2,3,3-pentamethylindane (PMI) into a first reactor having a first catalyst;
  2. (b) hydrogenating PMI in the first reactor to obtain a hydrogenation mixture containing THPMI as the desired product, 1,1,2,3,3-pentamethyloctahydro-1H-indene (HHPMI) as a by-product, and optionally unreacted PMI;
  3. (c) separating HHPMI from the hydrogenation mixture in a first separation column to obtain a first side stream containing HHPMI and a main stream containing THPMI and PMI;
  4. (d) passing the first side stream into a second flow reactor having a second catalyst;
  5. (e) dehydrogenating HHPMI to PMI in the second flow reactor to obtain a dehydrogenation stream;
  6. (f) feeding the dehydrogenation stream into the first flow reactor;
  7. (g) separating THPMI in the main stream from PMI in a second separation column to obtain a second side stream containing PMI and a product stream containing THPMI;
  8. (h) feeding the second side stream into the first flow reactor; and
  9. (i) collecting the product stream containing THPMI.
Each of the first and second reactors, independently, is either a batch reactor or a flow reactor. In one embodiment, each of the first and second reactors is a flow reactor, and each of the first and second catalysts, having a particle size of 300 microns or greater, is a fixed-bed catalyst.

[0011] The term "unsaturated compound" refers to an aromatic compound or an aliphatic hydrocarbon having one or more carbon-carbon double bonds (C=C). The aliphatic hydrocarbon can be a cyclic (carbocyclic) compound or straight or branched open chain without a ring. The term "corresponding saturated compound" refers to a compound having a hydrocarbon backbone the same as the unsaturated compound but having no carbon-carbon double bond.

[0012] The term "fixed-bed catalyst" refers a catalyst, typically in pellet or granule form, packed in a static bed that allows a gas or liquid to pass through.

[0013] The term "flow reactor" refers to a reactor wherein reactants are continuously fed into the reactor and emerge as continuous stream of product.

[0014] The term "batch reactor" refers to a vessel in which reactants

[0015] Other aspects or benefits of the present invention will be reflected in the following drawings, detailed description, and claims.

BRIEF DESCRIPTION OF THE FIGURES



[0016] FIG. 1 illustrates a process scheme for pentamethyl indane (PMI) to form tetrahydro pentamethyl indane (THPMI) using combination of selective hydrogenation, dehydrogenation and separation in a continuous mode.

DETAILED DESCRIPTION OF THE INVENTION



[0017] The text below when referring to disclosure or subject-matter disclosed does not form part of the claimed invention. In one aspect, the present disclosure provides a method of preparing an unsaturated compound, comprising dehydrogenation of a corresponding saturated compound in the presence of a catalyst system under conditions that effect loss of one or more molecules of hydrogen (H2) per molecule of the saturated compound.

[0018] In one aspect of the disclosure, the conditions include one or more solvents (e.g., acetic acid, toluene, ethyl acetate, DMSO, and DMF), an elevated temperature (e.g., at least 50 °C, at least 100 °C, 50-800 °C, 100-800 °C, 100-400 °C, and 150-350 °C), and/or a stream of nitrogen to purge liberated hydrogen. In one embodiment, the conditions include one or more hydrogen acceptor (e.g., tertiary butyl ethylene, cyclohexene and other alkenes) to consume the liberated hydrogen.

[0019] In one aspect of the disclosure, the catalyst system is selected from the group consisting of heterogeneous catalyst systems, homogeneous catalyst systems, bi-metallic catalyst systems, and combinations thereof.

[0020] In another aspect of the disclosure, the heterogeneous catalyst system is selected from Pd/C, Pd/Alumina, Pd/CG, Pt/C, Pt/Alumina, Molybdenum Oxide, Vanadium Pentoxide, Rh/Alumina, Ru/Al2O3, Bismuth Molybdate, and combinations thereof.

[0021] In another aspect of the disclosure, the heterogeneous catalyst system is a bi-metallic catalyst system comprising a metal pair including but not limited to Pt-Sn, Pt-Tl, Pt-Co, and Pd-Ag.

[0022] In another aspect of the disclosure, the homogeneous catalyst system is selected from soluble transition metal salts (e.g., Pd(TFA)2, Pd(OAc)2) with or without ligands, pincer-based catalysts (see J. Am. Chem. Soc. 1997, 119, 840-841, Chem. Commun., 1999, 2443-2449; Alkane Dehydrogenation. In Alkane C-H Activation by Single-Site Metal Catalysis, Perez, P. J., Ed. Springer: New York, 2012; Vol. 38., Chapter 4; Chem. Rev. 2014, 114, 12024-12087; US20150251171A1), and combinations thereof.

[0023] A pincer-based catalyst is a catalyst having a metal (typically a transitional metal such as ruthenium, rhodium, palladium, osmium, iridium, and platinum) and a pincer ligand that binds tightly to three adjacent coplanar sites, usually on a transition metal in a meridional configuration.

[0024] Exemplary pincer-based catalysts include iridium complex having the structures described in US 2015/0251171 such as (iPr4PCP)Ir(C2H4) and (p-OK-iPr4PCP)Ir(C3H6), in which iPr refers to isopropyl groups, PCP is C6H3(CH2PBut2)2-2,6), Ir refers to iridium, C2H4 is ethylene, and C3H6 is propylene. The iridium complex is either unsupported or immobilized on a solid support including silica, γ-alumina, florisil, neutral alumina.

[0025] In another aspect of the disclosure, the saturated compound comprises of straight chain or branched alkanes with or without functional groups such as aldehyde, ketone, ester, ethers or in combination thereof, each optionally substituted.

[0026] In another aspect of the disclosure, the saturated compound comprises a formula selected from the group consisting of:



and

wherein:

n is 0 or an integer selected from 1 to 20; X is a lactone or ether

R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and R18 are each independently H, methyl, ethyl, C3-C10 branched, cyclic or straight chain alkyl, ketone, ester, ether, aldehyde, alcohol or vinyl group, or a combination thereof, each optionally substituted; or alternatively, two R groups on the same carbon atom together form an oxo (=O) group.



[0027] In another aspect of the disclosure, the saturated carbocyclic compound comprises a backbone structure selected from the group consisting of:

wherein m is an integer from 1 to 20; each of R19, R20, and R21, independently, is hydrogen or oxo (=O), and each open position of said backbone structures is optionally substituted.

[0028] In another aspect of the disclosure, the saturated carbocyclic compound is selected from the group consisting of:

and



[0029] In another aspect of the disclosure, the present disclosure provides method of preparing a compound of formula I(a) or I(b), comprising flow dehydrogenation of a compound of formula II (starting material) in the presence of a fixed-bed catalyst:

wherein each of R22, R23, and R24, independently, is H or =O; and

Q is CH2, CH2CH2, CH(CH3), or C(CH3)2, preferably, Q is CH2CH2 or CH(CH3).



[0030] In another aspect of the disclosure, the present disclosure provides a method of preparing a compound of formula I(a) or I(b). The method comprises selective hydrogenation of a compound of formula III in the presence of a catalyst:

wherein Q is CH2, CH2CH2, CH(CH3), or C(CH3)2.

[0031] In another aspect of the disclosure, the catalyst is a fixed-bed catalyst, and the hydrogenation is conducted in a flow reactor.

[0032] In another aspect of the disclosure, the hydrogenation reaction is combined with dehydrogenation reaction and continuous separation process to separate product from the starting material and by-product.

[0033] In another aspect of the disclosure, the compound of formula (III) is 1,1,2,3,3-pentamethylindane (PMI), and said formula I(a) is 1,1,2,3,3-Pentamethyl-4,5,6,7-tetrahydro-1H-indene (THPMI):



[0034] In another aspect of the disclosure, the present disclosure provides a method of preparing 1,1,2,3,3-pentamethylindane (PMI), comprising flow dehydrogenation of 1,1,2,3,3-pentamethyloctahydro-1H-indene (HHPMI) in the presence of a fixed-bed catalyst:



[0035] In another aspect of the disclosure, the fixed-bed catalyst comprises 5%Pd/C, and the dehydrogenation is conducted in a flow reactor, and a nitrogen stream is passed through the reactor to remove hydrogen molecules formed.

[0036] In another aspect of the disclosure, the dehydrogenation reaction is combined with selective hydrogenation of PMI to form THPMI.

[0037] In other aspect of the disclosure, the present disclosure provides selective dehydrogenation of a saturated carbocyclic compound to form an unsaturated carbocyclic compound as substantially described and shown.

[0038] In other aspect of the disclosure, the present disclosure provides selective hydrogenation of an aromatic compound to form an unsaturated carbocyclic compound as substantially described and shown.

[0039] While not intended to be limiting, the generic structures of the fragrance backbones are used to illustrate application of the technologies disclosed herein in synthesis of compounds useful as fragrances, and the general technology of dehydrogenation is applicable to synthesis of these backbones to introduce double bond(s) into the molecule using various precious and non-precious metal catalyst systems.

[0040] The method for dehydrogenation for these substrates can be Standard dehydrogenation using catalysts including but not limited to heterogeneous dehydrogenation catalysts: platinum group metals, combination of metals, supported and non-supported metal catalysts and homogenous catalysts including but not limited to pincer based catalyst systems with or without hydrogen acceptor. The method for dehydrogenation can also be oxidative dehydrogenation using oxygen, air, peroxides and catalysts including but not limited to heterogeneous catalysts such as boric acid, vanadium oxide, molybdenum oxide supported or unsupported and homogeneous catalysts including but not limited to metal complexes with or without solvents and ligand systems. The operating temperatures for dehydrogenations can be from 50 to 800°C (with a lower limit of 50, 80, 100, 120, 150, or 200 °C and an upper limit of 800, 700, 600, 500, 400, 300, 200, or 150 °C), more preferably in the range of 100-400°C.

[0041] The following general synthetic schemes illustrate utility of the dehydrogenation processes to the synthesis of fragrance-related compounds:





























[0042] In the above schemes, --- is a single or double bond and at least one --- is a double bond.

[0043] The values and dimensions disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such value is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a value disclosed as "50%" is intended to mean "about 50%."

[0044] The invention is described in greater detail by the following non-limiting examples. Without further elaboration, it is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent.

[0045] Examples 1 - 6 are reference examples.

EXAMPLE 1: Dehydrogenation using Commercial Heterogeneous catalysts



[0046] Two commercially available heterogeneous catalysts 5%Pd/C and 10%Pd/C were used to prepare fragrance ingredients such as galaxolide analogs (e.g., Galaxolide HC, which is 2,3-Dihydro-1,1,2,3,3-Pentamethyl-1H-Indene, hereinafter "PMI") from 1,1,2,3,3-pentamethyloctahydro-1H-indene (HHPMI) at 70% and 100% yields respectively, as demonstrated in the following formula:


EXAMPLE 2: Selective Dehydrogenation using Bi-metallic Catalyst Formulations



[0047] Different compositions of bimetallic catalyst systems were prepared and tested for preparation of THPMI from HHPMI. (Cf. the limited literature precedents: Pt-Sn, Pt-Tl, Pt-Co, Pd-Ag with a selectivity of 25-60% and a very low conversion (<5%). See Applied Catalysis A: General Volume 469 (2014), 300-305; International Journal of hydrogen energy 37(2012), 6756-63.)

[0048] Use of the 5%Pd-1%Ag catalyst on silica support led to 26% selectivity of THPMI at about 10% conversion from HHPMI.



[0049] Various combinations and compositions of bi-metallic systems could be prepared and usable in preparing an unsaturated compound including THPMI.

EXAMPLE 3: Selective Dehydrogenation using Homogeneous Pincer-Based Catalyst Systems



[0050] Suitable homogenous iridium-based pincer catalyst systems include those reported in the publications such as J. Am. Chem. Soc. 1997, 119, 840-41; Chem. Commun. 1999, 2443-49; Alkane Dehydrogenation, In Alkane C-H Activation by Single-Site Metal Catalysis, Perez, P. J., Ed. Springer: New York, 2012, Vol. 38, Chapter 4; Chem. Rev. 2014, 114, 12024-87; and US20150251171A1.



[0051] Dehydrogenation using homogeneous pincer based catalyst systems gives high conversions, e.g., 50% or higher, with high selectivity (e.g., 80% or high and 90% or higher) for unsaturated backbones described above and those shown below:




EXAMPLE 4: Oxidative Dehydrogenation



[0052] Oxidative dehydrogenation of cycloalkane to cycloalkene using boric acid involves a 2-step process, oxidation to alcohol and dehydration to cycloalkene.



[0053] Suitable catalysts include molybdenum oxide, vanadium oxide, magnesium-doped vanadium and molybdenum oxide, and cobalt-doped vanadium phosphorous oxide with or without various oxidants using one step process. Other useful catalysts are described in J. Cat. 12, 287-91 (1991); J. Cat. 164, 28-35 (1996); Journal of the Taiwan Institute of Chemical Engineers (2015) 1-10). As an illustration, oxidative dehydrogenation of cyclohexane to cyclohexene was achieved in 70% selectivity at 40% conversion .



[0054] Results from Cyclopentadecane dehydrogenation are shown in Table 1 below:

Table 1.
ConditionsCatalyst
In a batch reactor at Molybdenum Oxide
180 °C
800 rpm
With Air
In a flow reactor at Vanadium Oxide Pd/CG
450 °C
No Air

EXAMPLE 5



[0055] Results on Isolongifolene dehydrogenation using various catalyst systems are shown below:


EXAMPLE 6



[0056] Dehydrogenation of ketones or aldehydes can yield the corresponding α,β-unsaturated ketones or aldehydes using the catalysts described above including palladium catalysts, e.g., palladium (II) acetate Pd(OAc)2 and dimethyl sulfoxide (DMSO) coordinated palladium trifluoroacetate Pd(DMSO)2(TFA)2 with oxygen and solvent. See, e.g., S. Stahl et al, Chem. Sci., 2012, 3, 887-891; J. Zhu et al., Adv. Synth. Catal., 2009, 351, 1229; J. Liu et al., Chem.-Asian J., 2009, 4, 1712; and Zhao et al, Chem. Sci., 2012, 3, 883-886.



[0057] In the scheme above, the reaction is carried out using DMSO coordinated palladium (II) trifluoroacetate Pd(TFA)2 with oxygen (O2) at a pressure of 1 atmosphere in ethyl acetate (EtOAc) at a temperature of 60 to 80 °C.

[0058] Specific applications to fragrance backbones are shown below.










EXAMPLE 7: Engineering solution to enhance yield of mono-unsaturated alkene via combination of hydrogenation, dehydrogenation and separation- THPMI



[0059] The selective hydrogenation of 1,1,2,3,3-pentamethylindane (PMI) to 1,1,2,3,3-pentamethyl-4,5,6,7-tetrahydro-1H-indene (THPMI) is an intermediate step in the synthesis of Cashmeran family of products. A significant amount of over-hydrogenated by-product is formed in known processes.

[0060] A process of this invention is a breakthrough to this long standing problem in the known processes. This process utilizes a combination of hydrogenation and dehydrogenation steps in converting the waste stream to the starting material (PMI) and then converting PMI to THPMI in a continuous fashion, e.g., in a flow reactor. The combination of selective hydrogenation and dehydrogenation in flow reactors turn the waste stream to the useful intermediates or products in a continuous reactor, e.g., a flow reactor, thus improving the overall yield.



[0061] THPMI is prepared following these steps: (a) feeding PMI into a first flow reactor having a fixed bed catalyst; (b) hydrogenating PMI in the first flow reactor to produce a product mixture; (c) separating HHPMI from the product mixture in a first separation column to obtain a first side stream containing the by-product HHPMI and a main stream containing THPMI; (d) passing the first side stream into a second flow reactor having a second fixed bed catalyst; (e) dehydrogenating HHPMI to PMI in the second flow reactor to obtain a dehydrogenation stream; (f) feeding the dehydrogenation stream into the first flow reactor; (f) separating the main stream in a second separation column to obtain a second side stream containing PMI and a product stream containing THPMI with a purity of 85% or greater; (g) feeding the second side stream into the first flow reactor; and (h) collecting the product stream containing THPMI.

[0062] The first fixed bed catalyst provides a high selectivity for preparing THPMI. Any catalysts described above can be used as the first fixed bed catalyst.

[0063] This process of the invention can have a continuous 2-column separation of THPMI from the reaction mixture with a high efficiency and a high purity, e.g., at 85% or greater, and at the same time, recovering the by-product HHPMI and the unreacted starting material PMI in a separate side stream. PMI is then fed into the first flow reactor, i.e., the hydrogenation flow reactor, to be converted to THPMI. HHPMI is fed into the second flow reactor, i.e., the dehydrogenation reactor, to be converted to PMI, which is in turn fed into the first flow reactor for conversion to THPMI.

[0064] This process scheme is depicted in FIG. 1 and described in greater detail below.

Flow Hydrogenation of PMI



[0065] 



[0066] PMI is allowed to pass through the first flow reactor containing the first fixed bed catalyst. In the first flow reactor, PMI is selectively hydrogenated to the desired product THPMI. The reaction is highly exothermic and preferred carried out at a high pressure (e.g., >500 psi and 600 to 1200 psi) in the flow reactor and a temperature of 165-185°C for good selectivity of THPMI. Major by-product obtained from the reaction is HHPMI from over hydrogenation of THPMI as shown in the side reaction below. Some unreacted PMI is also present for typical process conditions.

Side reaction



[0067] 


Catalysts for hydrogenation



[0068] Several fixed bed catalysts were used in the hydrogenation of PMI to THPMI. The results are shown in the Table 2 below. Combining this process with continuous separation and dehydrogenation of waste streams (described in following sections) has proved to prepare THPMI in a high overall yield. The overall yield is calculated as: the actual yield of THPMI by weight/the theoretical yield of THPMI based on the initial PMI fed into the flow reactor x 100%.
Table 2. Hydrogenation results using different types of of fixed bed 5% PD/C catalysts
CatalystAvg. Pressure (psi)Gas flowrate (sccm)Liquid flowrate (ml/min)T (°C)THPMI Conc. (%)Conversion PMI (%)Selectivity (%)
Catalyst A 700 60 0.2 180 44.6 66.7 67
Catalyst B 700 30 0.15 175 18.8 50.7 37
Catalyst C 700 60 0.12 170 47.4 60.6 78
Catalyst D 700 25 0.17 165 43.2 59 74


[0069] Avg. Pressure is calculated as (the pressure in the inlet of the flow reactor + the pressure in the outlet of the flow reactor)/2.

[0070] The gas flow rate refers to the flow rate of hydrogen gas fed into the flow reactor measured at 1 atmosphere and 0 °C. It is measured in sccm units, i.e., Standard Cubic Centimeters per Minute, indicating cm3/min at a standard temperature and pressure (i.e., 1 atmosphere and 0 °C). The standard temperature and pressure vary according to different regulatory bodies.

[0071] The liquid flow rate is the flow rate of PMI fed into the flow reactor.

[0072] THPMI is the concentration of THMPI in the stream coming out of the flow reactor.

[0073] Conversion PMI is the moles of PMI consumed / the moles of PMI fed into the flow reactor.

[0074] The selectivity is calculated as the moles of THPMI / the total moles of PMI consumed.

Continuous Separation of Product Stream Containing THPMI



[0075] The product stream from the hydrogenation contains the desired product THPMI, the by-product HHPMI, and the unreacted PMI. THPMI is separated from the product stream using two separate columns, together having a high efficiency of 40-50 stage separation. After the separation, THPMI is obtained at a purity of 85%. HHPMI is easily separated from THPMI and PMI using a separation column, leaving a mixture of THPMI and PMI, which requires a separation column with a very high efficiency.

Flow Dehydrogenation of HHPMI to PMI



[0076] The separated HHPMI constitutes about 20 to 25% of the product stream. It is then dehydrogenated to PMI in a second flow reactor. The newly generated PMI is allowed to pass through the first flow reactor again to be converted to THPMI.



[0077] The reaction is an equilibrium limited process and in order to drive the process to the desired product, hydrogen must be removed from the process. Nitrogen is typically used to purge the liberated hydrogen from the system. The reaction is highly endothermic and requires high operating temperatures and high catalyst loading.

Catalysts for dehydrogenation



[0078] Catalysts suitable for dehydrogenation of HHPMI include Pd/C and Pt/C. The dehydrogenation results are shown in Table 2 below. The results show ∼70% conversion of HHPMI to PMI with these two catalysts.
Table 3. Dehydrogenation results in the second flow reactor using different types of 5% Pd/C
Catalyst Entry#Nitrogen flowrate (sccm)Liquid flowrate (ml/min)T (°C)Conv. of HHPMI to PMI (%)
Catalyst C 10 0.03 340 69.12
Catalyst D 10 0.05 300 70.06

Process Scheme



[0079] Based on the results from continuous hydrogenation, distillation and dehydrogenation, a new process scheme proposed to obtain 85% THPMI yield at low cost is illustrated in FIG. 1.

Experimental Setup for Hydrogenation of PMI



[0080] The liquid reactant was pumped using the HPLC pump which can deliver liquid in the flowrate range from 0 to 10 ml/min. The hydrogen gas flows through the Mass Flow Controller (MFC) at the desired flowrate and mixed with the liquid stream using a micromixer. The combined gas-liquid mixture then entered the fixed bed reactor which was immersed in a constant temperature oil bath (or heated using electric furnace). Frits made of SS316L, with 2 microns opening were connected to the ends of the reactor to prevent the catalyst from moving out of the reactor. From the reactor, the reaction mixture was passed through the back pressure regulator. From the back pressure regulator, the mixture was passed to a product receiver where the liquid was collected in a glass vessel and the gas phase is vented to the atmosphere.

Experimental Setup for Dehydrogenation of PMI



[0081] The liquid reactant is pumped using the HPLC pump which can deliver liquid in the flowrate range from 0 to 10 mL/min. Compressed nitrogen flows through the Mass Flow Controller (MFC) at the desired flow and mixed with the liquid stream using a micromixer. The combined gas-liquid mixture then enters the fixed bed reactor containing the catalyst which is heated using an electric furnace. From the reactor, the reaction mixture is cooled using a cooling bath and then the product mixture is collected in a receiver.


Claims

1. A method of preparing an unsaturated compound, comprising dehydrogenation of a corresponding saturated compound in the presence of a catalyst system under conditions that effect loss of one or more molecules of hydrogen (H2) per molecule of the saturated compound, wherein the unsaturated compound is a compound of formula I(a) or I(b), and the saturated compound is a compound of formula II:

wherein R is H or =O; and Q is CH2, CH2CH2, CH(CH3), or C(CH3)2.
 
2. The method of claim 1, wherein said conditions comprise one or more solvents, an elevated temperature, a stream of nitrogen to purge liberated hydrogen, and/or one or more hydrogen acceptors to the dehydrogenation reaction to consume hydrogen.
 
3. The method of claim 1 or 2, wherein said catalyst system is selected from the group consisting of heterogeneous catalyst systems, homogeneous catalyst systems, and combinations thereof.
 
4. The method of claim 3, wherein said heterogeneous catalyst system is selected from the group consisting of Pd/C, Pd/Alumina, Pd/CG, Pt/C, Pt/Alumina, Molybdenum Oxide, Vanadium Pentoxide, Rh/Alumina, Ru/Al2O3, Bismuth Molybdate, bi-metallic catalyst systems comprising of metal pairs, and combinations thereof; and said homogeneous catalyst system is selected from soluble transition metal salts, Pincer-based catalysts, and combinations thereof.
 
5. A method of preparing an unsaturated compound, comprising dehydrogenation of a corresponding saturated compound in the presence of a catalyst system under conditions that effect loss of one or more molecules of hydrogen (H2) per molecule of the saturated compound, wherein the unsaturated compound is 1,1,2,3,3-pentamethylindane (PMI), the saturated compound is 1,1,2,3,3-pentamethyloctahydro-1H-indene (HHPMI), and the dehydrogenation is performed in a flow reactor in the presence of a fixed-bed catalyst:


 
6. The method of claim 5, wherein said conditions comprise one or more solvents, an elevated temperature, a stream of nitrogen to purge liberated hydrogen, and/or one or more hydrogen acceptors to the dehydrogenation reaction to consume hydrogen.
 
7. The method of claim 5 or 6, wherein said catalyst system is selected from the group consisting of heterogeneous catalyst systems, homogeneous catalyst systems, and combinations thereof.
 
8. The method of claim 7, wherein said heterogeneous catalyst system is selected from the group consisting of Pd/C, Pd/Alumina, Pd/CG, Pt/C, Pt/Alumina, Molybdenum Oxide, Vanadium Pentoxide, Rh/Alumina, Ru/Al2O3, Bismuth Molybdate, bi-metallic catalyst systems comprising of metal pairs, and combinations thereof; and said homogeneous catalyst system is selected from soluble transition metal salts, Pincer-based catalysts, and combinations thereof.
 
9. The method of claim 5, wherein said fixed-bed catalyst comprises 5%Pd/C, a nitrogen stream is passed through the flow reactor to remove hydrogen molecules formed, and/or the dehydrogenation reaction is combined with selective hydrogenation of PMI to form THPMI.
 
10. A process of preparing 1,1,2,3,3-Pentamethyl-4,5,6,7-tetrahydro-1H-indene (THPMI) comprising the steps of:

(a) feeding 1,1,2,3,3-pentamethylindane (PMI) into a first reactor having a first catalyst;

(b) hydrogenating PMI in the first reactor to obtain a hydrogenation mixture containing THPMI as the desired product, 1,1,2,3,3-pentamethyloctahydro-1H-indene (HHPMI) as a by-product, and optionally unreacted PMI;

(c) separating HHPMI from the hydrogenation mixture in a first separation column to obtain a first side stream containing HHPMI and a main stream containing THPMI and PMI;

(d) passing the first side stream into a second flow reactor having a second catalyst;

(e) dehydrogenating HHPMI to PMI in the second flow reactor to obtain a dehydrogenation stream;

(f) feeding the dehydrogenation stream into the first flow reactor;

(g) separating THPMI in the main stream from PMI in a second separation column to obtain a second side stream containing PMI and a product stream containing THPMI;

(h) feeding the second side stream into the first flow reactor; and

(i) collecting the product stream containing THPMI.


 
11. The process of claim 10, wherein each of the first and second reactors, independently, is a batch reactor or a flow reactor, and/or each of the first and second catalysts, having a particle size of 300 microns or greater, is independently a fixed-bed catalyst.
 
12. The process of claim 10 or 11, wherein the hydrogenating step (b) is performed using a method of preparing a compound of formula I(a) or I(b), and/or the dehydrogenating step (e) is performed using the method of claim 5 or 9,
wherein the method of preparing the compound of formula I(a) or I(b), comprises selective hydrogenation of a compound of formula III in the presence of a catalyst:

wherein Q is CH2, CH2CH2, CH(CH3), or C(CH3)2,
wherein said compound of formula (III) is 1,1,2,3,3-pentamethylindane (PMI), and said formula I(a) is 1,1,2,3,3-Pentamethyl-4,5,6,7-tetrahydro-1H-indene (THPMI):


 
13. The method of claim 12, wherein said catalyst is a fixed-bed catalyst, and the hydrogenation is conducted in a flow reactor.
 
14. The method of claim 12 or 13, wherein the hydrogenation reaction is combined with dehydrogenation reaction and a continuous separation process to separate product from the starting material.
 


Ansprüche

1. Verfahren zur Herstellung einer ungesättigten Verbindung, umfassend die Dehydrierung einer entsprechenden gesättigten Verbindung in Gegenwart eines Katalysatorsystems unter Bedingungen, die den Verlust von einem oder mehreren Molekülen Wasserstoff (H2) pro Molekül der gesättigten Verbindung bewirken, wobei es sich bei der ungesättigten Verbindung um eine Verbindung der Formel I(a) oder I(b) handelt und es sich bei der gesättigten Verbindung um eine Verbindung der Formel II handelt:

wobei R für H oder =O steht und Q für CH2, CH2CH2, CH(CH3) oder C(CH3)2 steht.
 
2. Verfahren nach Anspruch 1, bei dem die Bedingungen ein oder mehrere Lösungsmittel, eine erhöhte Temperatur, einen Stickstoffstrom zum Abführen von freigesetztem Wasserstoff und/oder einen oder mehrere Wasserstoffakzeptoren zur Dehydrierungsreaktion zum Verbrauch von Wasserstoff umfassen.
 
3. Verfahren nach Anspruch 1 oder 2, bei dem das Katalysatorsystem aus der Gruppe bestehend aus heterogenen Katalysatorsystemen, homogenen Katalysatorsystemen und Kombinationen davon ausgewählt wird.
 
4. Verfahren nach Anspruch 3, bei dem das heterogene Katalysatorsystem aus der Gruppe bestehend aus Pd/C, Pd/Aluminiumoxid, Pd/CG, Pt/C, Pt/Aluminiumoxid, Molybdänoxid, Vanadiumpentoxid, Rh/Aluminiumoxid, Ru/Al2O3, Bismutmolybdat, bimetallischen Katalysatorsystemen, die aus Metallpaaren bestehen, und Kombinationen davon ausgewählt wird und das homogene Katalysatorsystem aus löslichen Übergangsmetallsalzen, Pincer-Katalysatoren und Kombinationen davon ausgewählt wird.
 
5. Verfahren zur Herstellung einer ungesättigten Verbindung, umfassend die Dehydrierung einer entsprechenden gesättigten Verbindung in Gegenwart eines Katalysatorsystems unter Bedingungen, die den Verlust von einem oder mehreren Molekülen Wasserstoff (H2) pro Molekül der gesättigten Verbindung bewirken, wobei es sich bei der ungesättigten Verbindung um 1,1,2,3,3-Pentamethylindan (PMI) handelt, es sich bei der gesättigten Verbindung um 1,1,2,3,3-Pentamethyloctahydro-1H-inden (HHPMI) handelt und die Dehydrierung in einem Durchflussreaktor in Gegenwart eines Festbettkatalysators durchgeführt wird:


 
6. Verfahren nach Anspruch 5, bei dem die Bedingungen ein oder mehrere Lösungsmittel, eine erhöhte Temperatur, einen Stickstoffstrom zum Abführen von freigesetztem Wasserstoff und/oder einen oder mehrere Wasserstoffakzeptoren zur Dehydrierungsreaktion zum Verbrauch von Wasserstoff umfassen.
 
7. Verfahren nach Anspruch 5 oder 6, bei dem das Katalysatorsystem aus der Gruppe bestehend aus heterogenen Katalysatorsystemen, homogenen Katalysatorsystemen und Kombinationen davon ausgewählt wird.
 
8. Verfahren nach Anspruch 7, bei dem das heterogene Katalysatorsystem aus der Gruppe bestehend aus Pd/C, Pd/Aluminiumoxid, Pd/CG, Pt/C, Pt/Aluminiumoxid, Molybdänoxid, Vanadiumpentoxid, Rh/Aluminiumoxid, Ru/Al2O3, Bismutmolybdat, bimetallischen Katalysatorsystemen, die aus Metallpaaren bestehen, und Kombinationen davon ausgewählt wird und das homogene Katalysatorsystem aus löslichen Übergangsmetallsalzen, Pincer-Katalysatoren und Kombinationen davon ausgewählt wird.
 
9. Verfahren nach Anspruch 5, bei dem der Festbettkatalysator 5 % Pd/C umfasst, ein Stickstoffstrom durch den Durchflussreaktor geleitet wird, um gebildete Wasserstoffmoleküle zu entfernen, und/oder die Dehydrierungsreaktion mit der selektiven Hydrierung von PMI zu THPMI kombiniert wird.
 
10. Prozess zur Herstellung von 1,1,2,3,3-Pentamethyl-4,5,6,7-tetrahydro-1H-inden (THPMI), das folgende Schritte umfasst:

(a) Einspeisen von 1,1,2,3,3-Pentamethylindan (PMI) in einen ersten Reaktor mit einem ersten Katalysator;

(b) Hydrieren von PMI in den ersten Reaktor zum Erhalt eines Hydrierungsgemischs, das THPMI als das gewünschte Produkt, 1,1,2,3,3-Pentamethyloctahydro-1H-inden (HHPMI) als ein Nebenprodukt und gegebenenfalls nicht umgesetztes PMI enthält;

(c) Abtrennen von HHPMI aus dem Hydrierungsgemisch in einer ersten Trennsäule zum Erhalt eines ersten Nebenstroms, der HHPMI enthält, und eines Hauptstroms, der THPMI und PMI enthält;

(d) Einleiten des ersten Nebenstroms in einen zweiten Durchflussreaktor mit einem zweiten Katalysator;

(e) Dehydrieren von HHPMI zu PMI in dem zweiten Durchflussreaktor zum Erhalt eines Dehydrierungsstroms;

(f) Einspeisen des Dehydrierungsstroms in den ersten Durchflussreaktor;

(g) Trennen von THPMI in dem Hauptstrom von PMI in einer zweiten Trennsäule zum Erhalt eines zweiten Nebenstroms, der PMI enthält, und eines Produktstroms, der THPMI enthält;

(h) Einspeisen des zweiten Nebenstroms in den ersten Durchflussreaktor; und

(i) Sammeln des Produktstroms, der THPMI enthält.


 
11. Prozess nach Anspruch 10, bei dem es sich bei dem ersten und zweiten Reaktor jeweils unabhängig um einen diskontinuierlichen Reaktor oder einen Durchflussreaktor handelt und/oder es sich bei dem ersten und zweiten Katalysator mit einer Teilchengröße von 300 Mikron oder mehr jeweils unabhängig um einen Festbettkatalysator handelt.
 
12. Verfahren nach Anspruch 10 oder 11, bei dem der Hydrierungsschritt (b) unter Verwendung eines Verfahrens zur Herstellung einer Verbindung der Formel I(a) oder I(b) durchgeführt wird und/oder der Dehydrierungsschritt (e) unter Verwendung des Verfahrens nach Anspruch 5 oder 9 durchgeführt wird,
wobei das Verfahren zur Herstellung der Verbindung der Formel I(a) oder I(b) die selektive Hydrierung einer Verbindung der Formel III in Gegenwart eines Katalysators umfasst:

wobei Q für CH2, CH2CH2, CH(CH3) oder C(CH3)2 steht, wobei es sich bei der Verbindung der Formel (III) um 1,1,2,3,3-Pentamethylindan (PMI) handelt und es sich bei der Verbindung der Formel I(a) um 1,1,2,3,3-Pentamethyl-4,5,6,7-tetrahydro-1H-inden (THPMI) handelt:


 
13. Verfahren nach Anspruch 12, bei dem es sich bei dem Katalysator um einen Festbettkatalysator handelt und die Hydrierung in einem Durchflussreaktor durchgeführt wird.
 
14. Verfahren nach Anspruch 12 oder 13, bei dem die Hydrierungsreaktion mit einer Dehydrierungsreaktion und einem kontinuierlichen Trennprozess zur Trennung von Produkt von dem Ausgangsstoff kombiniert wird.
 


Revendications

1. Procédé de préparation d'un composé insaturé, comprenant la déshydrogénation d'un composé saturé correspondant en présence d'un système de catalyseur dans des conditions qui permettent la perte d'une ou plusieurs molécules d'hydrogène (H2) par molécule du composé saturé, dans lequel le composé insaturé est un composé de formule 1(a) ou 1(b), et le composé saturé est un composé de formule II :

dans lequel R est H ou =O ; et Q est CH2, CH2CH2, CH(CH3) ou C(CH3)2.
 
2. Procédé selon la revendication 1, dans lequel lesdites conditions comprennent un ou plusieurs solvants, une température élevée, un flux d'azote pour purger l'hydrogène libéré et/ou un ou plusieurs accepteurs d'hydrogène pour la réaction de déshydrogénation afin de consommer l'hydrogène.
 
3. Procédé selon la revendication 1 ou 2, dans lequel ledit système de catalyseur est choisi dans le groupe constitué de systèmes de catalyseur hétérogènes, de systèmes de catalyseur homogènes, et des combinaisons de ceux-ci.
 
4. Procédé selon la revendication 3, dans lequel ledit système de catalyseur hétérogène est choisi dans le groupe constitué de Pd/C, Pd/alumine, Pd/CG, Pt/C, Pt/alumine, oxyde de molybdène, pentoxyde de vanadium, Rh/alumine, Ru/Al2O3, molybdate de bismuth, des systèmes de catalyseurs bimétalliques constitués de paires de métaux, et des combinaisons de ceux-ci ; et ledit système de catalyseur homogène est choisi parmi des sels de métal de transition solubles, des catalyseurs à base de pince, et des combinaisons de ceux-ci.
 
5. Procédé de préparation d'un composé insaturé, comprenant la déshydrogénation d'un composé saturé correspondant en présence d'un système de catalyseur dans des conditions qui permettent la perte d'une ou plusieurs molécules d'hydrogène (H2) par molécule du composé saturé, dans lequel le composé insaturé est le 1,1,2,3,3-pentaméthylindane (PMI), le composé saturé est le 1,1,2,3,3-pentaméthyloctahydro-1H-indène (HHPMI), et la déshydrogénation est conduite dans un réacteur à circulation en présence d'un catalyseur à lit fixe :


 
6. Procédé selon la revendication 5, dans lequel lesdites conditions comprennent un ou plusieurs solvants, une température élevée, un flux d'azote pour purger l'hydrogène libéré et/ou un ou plusieurs accepteurs d'hydrogène pour la réaction de déshydrogénation afin de consommer l'hydrogène.
 
7. Procédé selon la revendication 5 ou 6, dans lequel ledit système de catalyseur est choisi dans le groupe constitué de systèmes de catalyseur hétérogènes, de systèmes de catalyseur homogènes, et des combinaisons de ceux-ci.
 
8. Procédé selon la revendication 7, dans lequel ledit système de catalyseur hétérogène est choisi dans le groupe constitué de Pd/C, Pd/alumine, Pd/CG, Pt/C, Pt/alumine, oxyde de molybdène, pentoxyde de vanadium, Rh/alumine, Ru/Al2O3, molybdate de bismuth, des systèmes de catalyseurs bimétalliques constitués de paires de métaux, et des combinaisons de ceux-ci ; et ledit système de catalyseur homogène est choisi parmi des sels de métal de transition solubles, des catalyseurs à base de pince, et des combinaisons de ceux-ci.
 
9. Procédé selon la revendication 5, dans lequel ledit catalyseur à lit fixe comprend Pd/C 5 %, on fait passer un flux d'azote à travers le réacteur à circulation pour éliminer les molécules d'hydrogène formées, et/ou la réaction de déshydrogénation est combinée avec l'hydrogénation sélective de PMI pour former THPMI.
 
10. Procédé de préparation de 1,1,2,3,3-pentaméthyl-4,5,6,7-tétrahydro-1H-indène (THPMI) comprenant les étapes de :

(a) introduction de 1,1,2,3,3-pentaméthylindane (PMI) dans un premier réacteur contenant un premier catalyseur ;

(b) hydrogénation de PMI dans le premier réacteur pour obtenir un mélange d'hydrogénation contenant THPMI en tant que produit souhaité, 1,1,2,3,3-pentaméthyloctahydro-1H-indène (HHPMI) en tant que sous-produit, et facultativement PMI n'ayant pas réagi ;

(c) séparation de HHPMI à partir du mélange d'hydrogénation dans une première colonne de séparation pour obtenir un premier flux secondaire contenant HHPMI et un flux principal contenant THPMI et PMI ;

(d) passage du premier flux secondaire dans un deuxième réacteur à circulation comportant un deuxième catalyseur ;

(e) déshydrogénation de HHPMI en PMI dans le deuxième réacteur à circulation pour obtenir un flux de déshydrogénation ;

(f) alimentation du flux de déshydrogénation dans le premier réacteur à circulation ;

(g) séparation de THPMI dans le flux principal provenant de PMI dans une deuxième colonne de séparation pour obtenir un deuxième flux secondaire contenant PMI et un flux de produit contenant THPMI ;

(h) alimentation du deuxième flux secondaire dans le premier réacteur à circulation ; et

(i) collecte du flux de produit contenant THPMI.


 
11. Procédé selon la revendication 10, dans lequel chacun des premier et deuxième réacteurs, est indépendamment un réacteur discontinu ou un réacteur à circulation, et/ou chacun des premier et deuxième catalyseurs, ayant une taille de particule de 300 microns ou plus, est indépendamment un catalyseur à lit fixe.
 
12. Procédé selon la revendication 10 ou 11, dans lequel l'étape d'hydrogénation (b) est conduite en utilisant un procédé de préparation d'un composé de formule 1(a) ou 1(b), et/ou l'étape de déshydrogénation (e) est conduite en utilisant le procédé selon la revendication 5 ou 9,
dans lequel le procédé de préparation du composé de formule 1(a) ou 1(b), comprend l'hydrogénation sélective d'un composé de formule III en présence d'un catalyseur :

dans lequel Q est CH2, CH2CH2, CH(CH3), ou C(CH3)2,
dans lequel ledit composé de formule (III) est le 1,1,2,3,3-pentaméthylindane (PMI), et ladite formule 1(a) est le 1,1,2,3,3-pentaméthyl-4,5,6,7-tétrahydro-1H-indène (THPMI) :


 
13. Procédé selon la revendication 12, dans lequel ledit catalyseur est un catalyseur à lit fixe, et l'hydrogénation est conduite dans un réacteur à circulation.
 
14. Procédé selon la revendication 12 ou 13, dans lequel la réaction d'hydrogénation est combinée avec une réaction de déshydrogénation et un processus de séparation continue pour séparer le produit du matériau de départ.
 




Drawing






REFERENCES CITED IN THE DESCRIPTION



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Patent documents cited in the description




Non-patent literature cited in the description