WO2022208553A1 - Palladium nano catalyzed fluorination of aromatic halides with support of bacterial cellulose nano-crystals (bnc) - Google Patents
Palladium nano catalyzed fluorination of aromatic halides with support of bacterial cellulose nano-crystals (bnc) Download PDFInfo
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- WO2022208553A1 WO2022208553A1 PCT/IN2022/050326 IN2022050326W WO2022208553A1 WO 2022208553 A1 WO2022208553 A1 WO 2022208553A1 IN 2022050326 W IN2022050326 W IN 2022050326W WO 2022208553 A1 WO2022208553 A1 WO 2022208553A1
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- palladium
- nano
- catalyst
- bacterial cellulose
- crystals
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 title claims abstract description 140
- 229910052763 palladium Inorganic materials 0.000 title claims abstract description 61
- 229920002749 Bacterial cellulose Polymers 0.000 title claims abstract description 56
- 239000005016 bacterial cellulose Substances 0.000 title claims abstract description 56
- 239000002159 nanocrystal Substances 0.000 title claims abstract description 49
- 238000003682 fluorination reaction Methods 0.000 title claims abstract description 33
- -1 aromatic halides Chemical class 0.000 title claims description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 34
- 239000011943 nanocatalyst Substances 0.000 claims abstract description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 239000011541 reaction mixture Substances 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000002105 nanoparticle Substances 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000012025 fluorinating agent Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 3
- AHLATJUETSFVIM-UHFFFAOYSA-M rubidium fluoride Chemical compound [F-].[Rb+] AHLATJUETSFVIM-UHFFFAOYSA-M 0.000 claims description 3
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 3
- 238000000527 sonication Methods 0.000 claims description 2
- 150000001491 aromatic compounds Chemical class 0.000 abstract description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000004293 19F NMR spectroscopy Methods 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 229920002678 cellulose Polymers 0.000 description 8
- 239000001913 cellulose Substances 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000002121 nanofiber Substances 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 238000001878 scanning electron micrograph Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000219991 Lythraceae Species 0.000 description 3
- 235000014360 Punica granatum Nutrition 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000013399 edible fruits Nutrition 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- DYOWGCNNYMLFQV-UHFFFAOYSA-N 2-acetyloxybenzoic acid;2-hydroxybenzamide;1,3,7-trimethylpurine-2,6-dione Chemical compound NC(=O)C1=CC=CC=C1O.CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C DYOWGCNNYMLFQV-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 238000007341 Heck reaction Methods 0.000 description 2
- 241001596500 Komagataeibacter rhaeticus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000005693 aromatic fluorination reaction Methods 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 2
- 239000002114 nanocomposite Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- OGTSHGYHILFRHD-UHFFFAOYSA-N (4-fluorophenyl)-phenylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=CC=C1 OGTSHGYHILFRHD-UHFFFAOYSA-N 0.000 description 1
- QUGUFLJIAFISSW-UHFFFAOYSA-N 1,4-difluorobenzene Chemical compound FC1=CC=C(F)C=C1 QUGUFLJIAFISSW-UHFFFAOYSA-N 0.000 description 1
- QMATYTFXDIWACW-UHFFFAOYSA-N 1-(2-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1F QMATYTFXDIWACW-UHFFFAOYSA-N 0.000 description 1
- HCEKGPAHZCYRBZ-UHFFFAOYSA-N 1-(3-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1 HCEKGPAHZCYRBZ-UHFFFAOYSA-N 0.000 description 1
- KBTYCHYYHABWFS-UHFFFAOYSA-N 1-[3-(4-fluorophenyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C=2C=CC(F)=CC=2)=C1 KBTYCHYYHABWFS-UHFFFAOYSA-N 0.000 description 1
- MRCAAFFMZODJBP-UHFFFAOYSA-N 1-fluoro-3-phenylbenzene Chemical group FC1=CC=CC(C=2C=CC=CC=2)=C1 MRCAAFFMZODJBP-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- UWDCUCCPBLHLTI-UHFFFAOYSA-N 1-fluoropyridin-1-ium Chemical class F[N+]1=CC=CC=C1 UWDCUCCPBLHLTI-UHFFFAOYSA-N 0.000 description 1
- JFJNVIPVOCESGZ-UHFFFAOYSA-N 2,3-dipyridin-2-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CN=C1C1=CC=CC=N1 JFJNVIPVOCESGZ-UHFFFAOYSA-N 0.000 description 1
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
- BAGQBTMEEISJLK-UHFFFAOYSA-N 2-fluoronaphthalene Chemical compound C1=CC=CC2=CC(F)=CC=C21 BAGQBTMEEISJLK-UHFFFAOYSA-N 0.000 description 1
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 1
- 241001120493 Arene Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920001046 Nanocellulose Polymers 0.000 description 1
- HJAXHGKQQWJCLH-LSBLOZSASA-N [(3s,6r,8s,9s,13r,14s,17r)-3-hydroxy-13-methyl-17-[(2r)-6-methylheptan-2-yl]-1,2,3,4,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-6-yl]methylastatine-211 Chemical compound C1([C@H](C[211At])C[C@H]2[C@@H]3CC[C@@H]([C@]3(CC[C@@H]22)C)[C@H](C)CCCC(C)C)=C2CC[C@H](O)C1 HJAXHGKQQWJCLH-LSBLOZSASA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 150000001501 aryl fluorides Chemical class 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- RUWPGPOBTHOLHF-UHFFFAOYSA-N ethyl 2-fluorobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1F RUWPGPOBTHOLHF-UHFFFAOYSA-N 0.000 description 1
- UMPRJGKLMUDRHL-UHFFFAOYSA-N ethyl 4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C=C1 UMPRJGKLMUDRHL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012070 reactive reagent Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/12—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
Definitions
- the present invention relates to insoluble, moisture resistant, and reusable palladium catalysts that fluorinate diverse aromatic halides.
- the present invention relates to palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) for fluorinating diverse aromatic halides.
- the present invention relates to the preparation of insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystal (BNC).
- the present invention relates to the fluorination of aromatic compounds using the palladium nano-catalyst supported by bacterial cellulose nano crystals (BNC).
- the invention finds immense application in chemical synthesis, especially in the field of drugs and pharmaceuticals, insecticides, pesticides and also in imaging.
- Fluorine is the most oxidizing and most electronegative element (Pauling electronegativity 4.0).
- the fluoride anion due to its electronegativity and small ionic radius (1.33 A), can form strong hydrogen bonds with a variety of hydrogen bond donors such as water, alcohols, amines, and amides.
- the high solvation energy of the fluoride ion in aqueous media results in a tightly bound hydration shell of water molecules around the ion. Therefore, fluoride is typically only weakly nucleophilic in the presence of hydrogen bond donors, and this attenuated nucleophilicity of fluoride limits access to C-F bonds via nucleophilic substitution reactions.
- WO2017156265 discloses palladium complexes comprising either ligands of terpyridine or derivatives or phenanthroline or derivatives that can be used in methods of fluorinating aryl and heteroaryl substrates.
- Fluorine is the key element present in the most of the pharmaceutical, agrochemical, and material industries.
- drug discovery development an increasing number of drugs in the market 30% of drugs contained at list one fluorine atom.
- Most of the previous literature reports indicate that palladium is the best catalyst for fluorination.
- depletion of palladium sources and its excessive use have led to the increase in cost of the palladium. Due to this high cost and less availability, there is a need to look for newer way to synthesize the reusable palladium catalyst.
- the inventors of the present invention realized that there exists a dire need to develop Bacterial cellulose/Cellulose nano-crystal supported Palladium nano catalysts; wherein the catalyst is insoluble, moisture resistant, and fully reusable, and can be used to fluorinate diverse aromatic substrates, further reducing the overall cost and synthesis time.
- the main objective of the present invention is to provide insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) that can fluorinate diverse aromatic halides.
- the present invention discloses insoluble, moisture resistant, and reusable palladium catalysts that can fluorinate diverse aromatic halides. More particularly, the present invention provides insoluble, moisture resistant, and reusable palladium catalyst comprising palladium nano catalyst supported on bacterial cellulose nano-crystals (BNC) obtained by Komagateibacter rhaeticus MCC 0157 at 1:1 ratio, that can fluorinate aromatic compounds of formula II to synthesize fluorinated compounds of formula I.
- BNC bacterial cellulose nano-crystals
- the present invention also provides a process for the preparation of the palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) comprises the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose (BC) or bacterial cellulose nano-crystal (BNC) in the reaction mixture obtained at step a); c) sonicating the reaction mixture obtained at steep b) for 5 - 10 minutes at a temperature in the range of 25-30 °C; d) adding the sodium borohydride into the reaction mixture obtained at step c) and again sonicating for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction mixture obtained at step d) and drying at 100°C to afford palladium nano-catalyst supported on bacterial cellulose nano-crystals.
- the present invention also provides a process of fluorinating aromatic halides using the insoluble, moisture resistant, and reusable palladium catalyst supported on bacterial cellulose nanocrystals (BNC) comprises the steps of reacting a compound of formula II with a fluorinating agent in the presence of bacterial cellulose supported palladium nano-catalyst in a suitable solvent to afford a fluorinated compound of formula I.
- the reaction is carried out at a temperature in the range of 60-120 °C for a period in the range of 10-12 hours.
- the process for the fluorination of aromatic halide include
- X C, N, O or S
- GL Cl, Br, I or OTf
- R same or different and selected form the group comprising of C1-C5 alkyl, C1-C1 0 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C1 0 alkyl or aryl or any two or more adjacent carbon atoms of ring ⁇ ’ may form 5-6 membered aromatic ring.
- the fluorination process of aromatic halides using the palladium nano-catalyst supported on bacterial cellulose nanocrystals produce a yield in the range of 70- 95%.
- the palladium nano-catalyst supported on cellulose nano-crystals can be reused more than five times in the fluorination process without any loss in its activity.
- the present invention provides Palladium nano-catalyst supported on bacterial cellulose nano crystals (BNC) comprising palladium nanoparticles as the active component and bacterial cellulose nano-crystals as support, wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90: 10 to 60:40, and wherein the said catalyst is insoluble, moisture resistant, and reusable.
- BNC bacterial cellulose nano crystals
- the present invention provides a palladium catalyst, wherein the size of palladium nanoparticles ranges from 20 to 50 nm.
- the present invention provides a palladium catalyst, wherein it is reusable for five cycles with no loss in activity.
- the present invention provides a fluorination process of aromatic halides catalyzed by the palladium nano-catalyst as discussed above, wherein the process comprises the steps of reacting a compound of formula II with a fluorinating agent in the presence of 1.0 mol wt/wt to 10.0 mol wt/wt of the palladium catalyst in a suitable solvent to synthesize a fluorinated compound of formula I,
- X C, N, O or S
- GL Cl, Br, I or OTf
- R same or different and selected form the group comprising of C1-C5 alkyl, C1-C10 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C10 alkyl or aryl or any two or more adjacent carbon atoms of ring ⁇ ’ may form 5-6 membered aromatic ring.
- the present invention provides a fluorination process, wherein the solvent is selected from a group consisting of Dimethyl formamide (DMF), Dimethylsulfoxide (DMSO), Toluene (PhCH3), Tetrahydrofuran (THF), and Flurobenzene (PhF).
- the solvent is selected from a group consisting of Dimethyl formamide (DMF), Dimethylsulfoxide (DMSO), Toluene (PhCH3), Tetrahydrofuran (THF), and Flurobenzene (PhF).
- the present invention provides a fluorination process, wherein the fluorinating agent is selected from a group consisting of Cesium fluoride (CsF), Potassium fluoride (KF), Sodium fluoride (NaF), and Rubidium fluoride (RbF).
- the fluorinating agent is selected from a group consisting of Cesium fluoride (CsF), Potassium fluoride (KF), Sodium fluoride (NaF), and Rubidium fluoride (RbF).
- the present invention provides a fluorination process, wherein the reaction step is carried out at a temperature of between 60°C and 120°C for 10-12 hours.
- the present invention provides a fluorination process, wherein the yield of the fluorination process is in the range of 70% to 95%.
- the present invention provides a process for the preparation of a palladium catalyst comprising the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose nano-crystals (BNC) in the reaction mixture obtained in step (a) wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90: 10 to 60:40; c) sonicating the reaction mixture obtained in step (b) for 5-10 minutes at a temperature in the range of 25-30 °C; d) adding sodium borohydride in the reaction mixture obtained in step (c) followed by sonication for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction mixture obtained in step (d) and drying at 100°C to obtain palladium nano-catalyst supported on bacterial cellulose .
- Figure 1 depicts the SEM image Bacterial cellulose (Pd).
- Figure 2 depicts the SEM image Bacterial cellulose Nano crystals (Pd). SEM images demonstrated Pd-C12 nanoparticles having size in the range of 20-50nm attached to the BNC.
- Figure 3 depicts the hygroscopicity data of Pd: BNC catalyst at (A) Ohrs and (B) 24hrs.
- Figure 4 depicts the insolubility of Pd: BNC catalyst.
- Figure 5 TEM of BNC showing the particle size to be in the range 10-17 nm.
- the Bacterial Cellulose [BC] producing novel bacterial strain of Komagataeibacter rhaeticus MCC 0157 was isolated from a rotten pomegranate fruit sample and used for bacterial cellulose production. Pomegranate fruit was procured from local fruit vendor at NCL Shopping Center, Pashan, Vietnamese, India. The said isolated bacterial strain was deposited with the International Depositary Authority NCCS, Pune India on 3 rd of January 2019. DETAILED DESCRIPTION OF THE INVENTION
- the inventors propose insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystal (BNC) for fluorinating diverse aromatic halides.
- the present invention provides insoluble, moisture resistant, and reusable palladium catalyst used for fluorinating aromatic halides comprise palladium nanoparticles as the catalyst active component and bacterial cellulose nano-crystals (BNC) as the catalyst support.
- palladium nanoparticles as the catalyst active component
- bacterial cellulose nano-crystals BNC
- the insoluble, moisture resistant, and reusable palladium catalyst can fluorinate aromatic compounds of formula II to synthesize fluorinated compounds of formula I.
- the process for the preparation of palladium nano-catalyst supported on cellulose nano-crystals comprises the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose (BC) or bacterial cellulose nano-crystals (BNC) separately in the reaction mixture obtained in step a) wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90: 10 to 60:40; c) sonicating the reaction mixture obtained in step b) for 5-10 minutes at a temperature in the range of 25-30 °C; d) adding sodium borohydride in the reaction mixture obtained in step c) and again sonicating for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction
- the process of fluorinating aromatic halides using the insoluble, moisture resistant, and reusable palladium catalyst supported on bacterial cellulose nanocrystals comprises the steps of reacting a compound of formula II with 1.0 mol wt/wt to 10.0 mol wt/wt of a fluorinating agent in the presence of bacterial cellulose supported palladium nano-catalyst in a suitable solvent at a temperature in the range of 60-120 °C for a period in the range of 10-12 hours to afford a fluorinated compound of formula I.
- the process for the fluorination of aromatic halide include
- X C, N, O or S
- GL Cl, Br, I or OTf
- R same or different and selected form the group comprising of C1-C5 alkyl, C1-C1 0 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C1 0 alkyl or aryl or any two or more adjacent carbon atoms of ring ⁇ ’ may form 5-6 membered aromatic ring.
- the solvent is selected from the group comprising of Dimethyl formamide (DMF), Dimethylsulfoxide (DMSO), Toulene (PI1CH3), Tetrahydrofuran (THF), and Flurobenzene (PhF).
- DMF Dimethyl formamide
- DMSO Dimethylsulfoxide
- PI1CH3 Toulene
- THF Tetrahydrofuran
- PhF Flurobenzene
- toluene is used as a solvent.
- the fluorinating agent is selected from the group comprising of Cesium fluoride (CsF), Potassium fluoride (KF), Sodium fluoride (NaF), and Rubidium fluoride (RbF).
- Nano crystals have more space and so hold more Pd.
- Bacterial nano cellulose is a sheet and is used as such.
- BNC nanocrystals are synthesized by hydrolysis of dried BC powder (1% w/v) using 50% w/v H2SO4. The cellulose suspension is stirred at 45° C for 3 hours using magnetic stirrer. The reaction is then stopped by diluting the resultant cellulose suspension 10 times using deionized water. The CNC suspension is centrifuged and the pellet is washed with deionized water 3-4 times. The pellet is then resuspended in deionized water. The obtained BNC suspension is dialyzed against deionized water for 3-4 days with exchange of water in each day. The BNC suspension is then dried by lyophilization to obtain dry BNC powder.
- bacterial cellulose nanocrystals provide better loading of palladium as shown in Table 1. Pd nano particles could not be loaded beyond 0.4 % w/w on BNC. The optimum ratio of BNC: Pd is 60:40.
- the fluorination yield depends on the Pd: BNC catalyst (from 0.4 maximum load) and is in the range of 5-95%, further shown in Table 2.
- the palladium supported on the bacterial cellulose nano-crystals provide better yield of the fluorinated compounds as compared with palladium supported on only bacterial cellulose fibers as shown in Table 3.
- Nano fibers are different from nanocrystals, fibers ranges from 50-100nm whereas BNC is in the range 10- 17nm, refer figure 5, which provides better surface area for the loading property.
- the fluorination yield is enhanced in the catalyst of the current invention.
- the palladium nano-catalyst supported on bacterial cellulose nano-crystals can be reused more than five times in the fluorination process without any loss in its activity.
- Table 4 shows the results obtained after reusing the catalyst for more than five times.
- BC Bacterial cellulose
- HS Hestrin-Schramm
- BNC Bacterial cellulose nanocrystals
- BNC catalyst After synthesis of Pd: BNC catalyst both hygroscopicity and solubility were tested.
- BNC catalyst was recorded at 30°C with 80% humidity at Ohrs and 24hrs further depicted in Figure 3A and 3B.
- solubility Pd BNC was suspended in 100% DMF and no solubility was observed after rigorous mixing of the samples after several hours further depicted in Figure 4.
- New bacterial cellulose nano-crystals supported stable Pd catalyst is developed for the fluorination of aromatic compounds.
- the catalyst is reusable several times and gives high yield of aromatic fluorination product.
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Abstract
The present invention relates to novel catalyst and process for fluorination of aromatic compounds using a novel insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC). Fluorination of aromatic compounds using this novel catalyst produces a yield in the range of 70-95%, and further this catalyst can also be reused more than five times without losing its effectiveness.
Description
PALLADIUM NANO CATALYZED FLUORINATION OF AROMATIC HALIDES WITH SUPPORT OF BACTERIAL CELLULOSE NANO-CRYSTALS (BNC)
FIELD OF THE INVENTION
The present invention relates to insoluble, moisture resistant, and reusable palladium catalysts that fluorinate diverse aromatic halides. In particular, the present invention relates to palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) for fluorinating diverse aromatic halides. More particularly, the present invention relates to the preparation of insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystal (BNC). Further, the present invention relates to the fluorination of aromatic compounds using the palladium nano-catalyst supported by bacterial cellulose nano crystals (BNC). The invention finds immense application in chemical synthesis, especially in the field of drugs and pharmaceuticals, insecticides, pesticides and also in imaging.
BACKGROUND AND PRIOR ART OF THE INVENTION
In recent years, there has been a dramatic increase in available methods for the installation of fluorine and fluorine-containing functional groups in organic molecules, and the importance of fluorinated organic molecules to a variety of applications in modem society has become well- appreciated. Although recent advances in fluorination methods have led to an increase in fluorination methods, an unwanted effect has been to obscure the fact that C-F bonds remain challenging to form, especially when synthesizing aryl fluorides.
A fundamental challenge of any C-F bond-forming reaction, regardless of the approach, is the nature of fluorine itself. Fluorine is the most oxidizing and most electronegative element (Pauling electronegativity 4.0). The fluoride anion, due to its electronegativity and small ionic radius (1.33 A), can form strong hydrogen bonds with a variety of hydrogen bond donors such as water, alcohols, amines, and amides. The high solvation energy of the fluoride ion in aqueous media results in a tightly bound hydration shell of water molecules around the ion. Therefore, fluoride is typically only weakly nucleophilic in the presence of hydrogen bond donors, and this attenuated nucleophilicity of fluoride limits access to C-F bonds via nucleophilic substitution reactions.
Conventional methods for aromatic fluorination require elemental fluorine or similarly reactive reagents, or combine high temperature and/or directing groups with milder electrophilic
fluorinating reagents which are unselective and require specialized equipment to handle safely. Bench-stable electrophilic fluorinating reagents — such as N-fluoropyridinium salts, N- fluorobenzenesulfonimide (NFSI) and Selectfluor — are easier to handle but less reactive, and require either very electron-rich arenes or multiple equivalents of the arene to accomplish direct C-H fluorination. Catalysis of aromatic C-H fluorination reactions has been reported using coordination-assistance to promote fluorination proximal to Lewis-basic functional groups, but such approaches are limited in scope to those substrates containing the required directing groups.
Madhukar S. Saidet al. in a research study published in Asian Journal of Organic Chemistry (Asian JOC) 2020, titled “A new TBAF complex, highly stable, facile and selective source for nucleophilic fluorination: applications in batch and flow chemistry” disclose a highly stable, non-hygroscopic, efficient, cost-effective and renewable cellulose-supported TBAF complex that can be used in SN2 fluorination of diverse substrates possessing mesylate, tosylate, triflate, nosylate, and halide leaving groups.
Anthony R. Mazzotti et al. in a research study published in Journal of the American Chemical Society 2013, titled “Palladium (Ill)-Catalyzed Fluorination of Arylboronic Acid Derivatives” discloses palladium-catalyzed fluorination of aryl boronic acid derivatives, using terpyridyl Pd (II) complex 1 as a precatalyst, whereas the complex 1 in the fluorination process is prepared in one step from Pd(OAc)2, terpyridine (terpy), and HBF4.
Hong Geun Lee et al. in a research study published in Journal of the American Chemical Society 2014, titled “Pd-Catalyzed Nucleophilic Fluorination of Aryl Bromides” discloses a Pd-catalyzed method for converting unactivated (hetero) aryl bromides to the corresponding fluorides, whereas the reaction proceeds by the nucleophilic fluorination of aryl (pseudo)halides with a metal fluoride salt without significant formation of reduction byproducts, which are difficult to separate from the desired product.
WO2017156265 discloses palladium complexes comprising either ligands of terpyridine or derivatives or phenanthroline or derivatives that can be used in methods of fluorinating aryl and heteroaryl substrates.
Reference may be made to the article, “Bacteria Cellulose Nanofibers Supported Palladium(O) nanocomposite and Its Catalysis Evaluation in Heck Reaction”. April 2012 Industrial & Engineering Chemistry Research 51( 16):5743— 5748 D01: 10.1021/ie300395q which reports that Bacteria cellulose (BC) nanofibers supported palladium(O) nanocomposites were prepared and fully characterized in terms of morphology, crystallinity, composition, and thermal stability. However, nanofibers are different from nanocrystals, fibers ranges from 50-100nm whereas BNC is in the range 10-17nm, which provides better surface are for the loading property. Heck reaction demonstrated is completely different from fluorination.
In short, it may be summarized that Fluorine is the key element present in the most of the pharmaceutical, agrochemical, and material industries. In the drug discovery development, an increasing number of drugs in the market 30% of drugs contained at list one fluorine atom. Most of the previous literature reports indicate that palladium is the best catalyst for fluorination. However, depletion of palladium sources and its excessive use have led to the increase in cost of the palladium. Due to this high cost and less availability, there is a need to look for newer way to synthesize the reusable palladium catalyst.
Thus, keeping in view the drawbacks of the hitherto reported prior art, the inventors of the present invention realized that there exists a dire need to develop Bacterial cellulose/Cellulose nano-crystal supported Palladium nano catalysts; wherein the catalyst is insoluble, moisture resistant, and fully reusable, and can be used to fluorinate diverse aromatic substrates, further reducing the overall cost and synthesis time.
OBJECTIVES OF THE INVENTION
The main objective of the present invention is to provide insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) that can fluorinate diverse aromatic halides.
Another object of the present invention is to provide a process for the preparation of the insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystal (BNC).
Still another object of the present invention is to provide a process of fluorinating aromatic halides using the palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC).
SUMMARY OF THE INVENTION
The present invention discloses insoluble, moisture resistant, and reusable palladium catalysts that can fluorinate diverse aromatic halides. More particularly, the present invention provides insoluble, moisture resistant, and reusable palladium catalyst comprising palladium nano catalyst supported on bacterial cellulose nano-crystals (BNC) obtained by Komagateibacter rhaeticus MCC 0157 at 1:1 ratio, that can fluorinate aromatic compounds of formula II to synthesize fluorinated compounds of formula I.
The present invention also provides a process for the preparation of the palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) comprises the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose (BC) or bacterial cellulose nano-crystal (BNC) in the reaction mixture obtained at step a); c) sonicating the reaction mixture obtained at steep b) for 5 - 10 minutes at a temperature in the range of 25-30 °C; d) adding the sodium borohydride into the reaction mixture obtained at step c) and again sonicating for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction mixture obtained at step d) and drying at 100°C to afford palladium nano-catalyst supported on bacterial cellulose nano-crystals.
The present invention also provides a process of fluorinating aromatic halides using the insoluble, moisture resistant, and reusable palladium catalyst supported on bacterial cellulose nanocrystals (BNC) comprises the steps of reacting a compound of formula II with a fluorinating agent in the presence of bacterial cellulose supported palladium nano-catalyst in a suitable solvent to afford a fluorinated compound of formula I. In one of the embodiments of the present invention, the reaction is carried out at a temperature in the range of 60-120 °C for a period in the range of 10-12 hours.
In still another embodiment of the present invention, the process for the fluorination of aromatic halide include
Formula II Formula I wherein, ring Ύ’ is aromatic, 5-membered or 6-membered;
X= C, N, O or S;
GL= Cl, Br, I or OTf;
R= same or different and selected form the group comprising of C1-C5 alkyl, C1-C10 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C10 alkyl or aryl or any two or more adjacent carbon atoms of ring Ύ’ may form 5-6 membered aromatic ring.
In yet another embodiment of the present invention, the fluorination process of aromatic halides using the palladium nano-catalyst supported on bacterial cellulose nanocrystals produce a yield in the range of 70- 95%.
In a preferred embodiment of the present invention, the palladium nano-catalyst supported on cellulose nano-crystals can be reused more than five times in the fluorination process without any loss in its activity.
The present invention provides Palladium nano-catalyst supported on bacterial cellulose nano crystals (BNC) comprising palladium nanoparticles as the active component and bacterial cellulose nano-crystals as support, wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90: 10 to 60:40, and wherein the said catalyst is insoluble, moisture resistant, and reusable.
In one of the embodiments, the present invention provides a palladium catalyst, wherein the size of palladium nanoparticles ranges from 20 to 50 nm.
In another embodiment, the present invention provides a palladium catalyst, wherein it is reusable for five cycles with no loss in activity.
The present invention provides a fluorination process of aromatic halides catalyzed by the palladium nano-catalyst as discussed above, wherein the process comprises the steps of reacting a compound of formula II with a fluorinating agent in the presence of 1.0 mol wt/wt to 10.0 mol wt/wt of the palladium catalyst in a suitable solvent to synthesize a fluorinated compound of formula I,
Formula II Formula I wherein, ring Ύ’ is aromatic, 5-membered or 6-membered;
X= C, N, O or S;
GL= Cl, Br, I or OTf;
R= same or different and selected form the group comprising of C1-C5 alkyl, C1-C10 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C10 alkyl or aryl or any two or more adjacent carbon atoms of ring Ύ’ may form 5-6 membered aromatic ring.
In one embodiment, the present invention provides a fluorination process, wherein the solvent is selected from a group consisting of Dimethyl formamide (DMF), Dimethylsulfoxide (DMSO), Toluene (PhCH3), Tetrahydrofuran (THF), and Flurobenzene (PhF).
In another embodiment, the present invention provides a fluorination process, wherein the fluorinating agent is selected from a group consisting of Cesium fluoride (CsF), Potassium fluoride (KF), Sodium fluoride (NaF), and Rubidium fluoride (RbF).
In yet another embodiment, the present invention provides a fluorination process, wherein the reaction step is carried out at a temperature of between 60°C and 120°C for 10-12 hours.
In still another embodiment, the present invention provides a fluorination process, wherein the yield of the fluorination process is in the range of 70% to 95%.
The present invention provides a process for the preparation of a palladium catalyst comprising the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose nano-crystals (BNC) in the reaction mixture obtained in step (a) wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90: 10 to 60:40; c) sonicating the reaction mixture obtained in step (b) for 5-10 minutes at a temperature in the range of 25-30 °C; d) adding sodium borohydride in the reaction mixture obtained in step (c) followed by sonication for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction mixture obtained in step (d) and drying at 100°C to obtain palladium nano-catalyst supported on bacterial cellulose nano-crystals.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
The invention has other advantages and features which will be more readily apparent from the following detailed description of the invention and the appended claims, when taken in conjunction with the accompanying drawings, in which:
Figure 1: depicts the SEM image Bacterial cellulose (Pd).
Figure 2: depicts the SEM image Bacterial cellulose Nano crystals (Pd). SEM images demonstrated Pd-C12 nanoparticles having size in the range of 20-50nm attached to the BNC.
Figure 3: depicts the hygroscopicity data of Pd: BNC catalyst at (A) Ohrs and (B) 24hrs.
Figure 4: depicts the insolubility of Pd: BNC catalyst.
Figure 5: TEM of BNC showing the particle size to be in the range 10-17 nm.
SOURCE OF BIOLOGICAL MATERIAL
The Bacterial Cellulose [BC] producing novel bacterial strain of Komagataeibacter rhaeticus MCC 0157 was isolated from a rotten pomegranate fruit sample and used for bacterial cellulose production. Pomegranate fruit was procured from local fruit vendor at NCL Shopping Center, Pashan, Pune, India. The said isolated bacterial strain was deposited with the International Depositary Authority NCCS, Pune India on 3rd of January 2019.
DETAILED DESCRIPTION OF THE INVENTION
While the invention has been disclosed with reference to certain embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the scope of the invention. In addition, many modifications may be made to adapt to a particular situation or material to the teachings of the invention without departing from its scope.
Throughout the specification and claims, the following terms take the meanings explicitly associated herein unless the context clearly dictates otherwise. The meaning of "a", "an", and "the" include plural references. The meaning of "in" includes "in" and "on." Referring to the drawings, like numbers indicate like parts throughout the views. Additionally, a reference to the singular includes a reference to the plural unless otherwise stated or inconsistent with the disclosure herein.
The tables, figures and protocols have been represented where appropriate by conventional representations in the drawings, showing only those specific details that are pertinent to understanding the embodiments of the present invention so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having benefit of the description herein.
Accordingly, to accomplish the objectives of the present invention, the inventors propose insoluble, moisture resistant, and reusable palladium nano-catalyst supported on bacterial cellulose nano-crystal (BNC) for fluorinating diverse aromatic halides.
More particularly, the present invention provides insoluble, moisture resistant, and reusable palladium catalyst used for fluorinating aromatic halides comprise palladium nanoparticles as the catalyst active component and bacterial cellulose nano-crystals (BNC) as the catalyst support.
In an embodiment of the present invention, the insoluble, moisture resistant, and reusable palladium catalyst can fluorinate aromatic compounds of formula II to synthesize fluorinated compounds of formula I.
In another embodiment of the present invention, the process for the preparation of palladium nano-catalyst supported on cellulose nano-crystals comprises the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose (BC) or bacterial cellulose nano-crystals (BNC) separately in the reaction mixture obtained in step a) wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90: 10 to 60:40; c) sonicating the reaction mixture obtained in step b) for 5-10 minutes at a temperature in the range of 25-30 °C; d) adding sodium borohydride in the reaction mixture obtained in step c) and again sonicating for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction mixture obtained in step d) and drying at 100°C to obtain palladium nano-catalyst supported on bacterial cellulose nano-crystals.
In an embodiment of the present invention, the process of fluorinating aromatic halides using the insoluble, moisture resistant, and reusable palladium catalyst supported on bacterial cellulose nanocrystals (BNC) comprises the steps of reacting a compound of formula II with 1.0 mol wt/wt to 10.0 mol wt/wt of a fluorinating agent in the presence of bacterial cellulose supported palladium nano-catalyst in a suitable solvent at a temperature in the range of 60-120 °C for a period in the range of 10-12 hours to afford a fluorinated compound of formula I.
In another embodiment of the present invention, the process for the fluorination of aromatic halide include
Formula II Formula I wherein, the ring Ύ’ is aromatic, 5-membered or 6-membered;
X= C, N, O or S;
GL= Cl, Br, I or OTf;
R= same or different and selected form the group comprising of C1-C5 alkyl, C1-C10 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C10 alkyl or aryl or any two or more adjacent carbon atoms of ring Ύ’ may form 5-6 membered aromatic ring.
In still another embodiment of the present invention, the solvent is selected from the group comprising of Dimethyl formamide (DMF), Dimethylsulfoxide (DMSO), Toulene (PI1CH3), Tetrahydrofuran (THF), and Flurobenzene (PhF). In particularly, useful embodiment toluene is used as a solvent.
In yet another embodiment of the present invention, the fluorinating agent is selected from the group comprising of Cesium fluoride (CsF), Potassium fluoride (KF), Sodium fluoride (NaF), and Rubidium fluoride (RbF).
Nano crystals have more space and so hold more Pd. Bacterial nano cellulose is a sheet and is used as such. BNC nanocrystals are synthesized by hydrolysis of dried BC powder (1% w/v) using 50% w/v H2SO4. The cellulose suspension is stirred at 45° C for 3 hours using magnetic stirrer. The reaction is then stopped by diluting the resultant cellulose suspension 10 times using deionized water. The CNC suspension is centrifuged and the pellet is washed with deionized water 3-4 times. The pellet is then resuspended in deionized water. The obtained BNC suspension is dialyzed against deionized water for 3-4 days with exchange of water in each day. The BNC suspension is then dried by lyophilization to obtain dry BNC powder.
In an embodiment of the present invention, bacterial cellulose nanocrystals (BNC) provide better loading of palladium as shown in Table 1. Pd nano particles could not be loaded beyond 0.4 % w/w on BNC. The optimum ratio of BNC: Pd is 60:40.
Table-1
In another embodiment of the present invention, the fluorination yield depends on the Pd: BNC catalyst (from 0.4 maximum load) and is in the range of 5-95%, further shown in Table 2.
Table-2
In still another embodiment of the present invention, the palladium supported on the bacterial cellulose nano-crystals (BNC) provide better yield of the fluorinated compounds as compared with palladium supported on only bacterial cellulose fibers as shown in Table 3. Nano fibers are different from nanocrystals, fibers ranges from 50-100nm whereas BNC is in the range 10- 17nm, refer figure 5, which provides better surface area for the loading property. Thus in view of an improved loading of Pd nano particles, the fluorination yield is enhanced in the catalyst of the current invention.
Table-3
In yet another embodiment of the present invention, there usability of the catalyst is improved when bacterial cellulose nano-crystals are used instead of only bacterial cellulose. The SEM image of Bacterial cellulose (Pd) and Bacterial cellulose Nano crystals (Pd) are further depicted in Figures 1 and 2 respectively.
In a preferred embodiment of the present invention, the palladium nano-catalyst supported on bacterial cellulose nano-crystals can be reused more than five times in the fluorination process without any loss in its activity. Table 4 shows the results obtained after reusing the catalyst for more than five times.
Table-4
EXAMPLES
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.
Example 1:
Bacterial cellulose (BC) was produced using Komagataeibacter rhaeticus PG2 strain isolated from rotten pomegranate in a modified Hestrin-Schramm (HS) media) containing glycerol as a carbon source for culture medium. The detailed procedure is given in M. N. Thorat, S. G. Dastager, RSC advances 2018, 8, 29797. The purified BC pellicle was stored under 4 °C to avoid any contamination.
Bacterial cellulose nanocrystals (BNC) were synthesized by hydrolysis of dried BC powder (1% w/v) using 50% w/v H2SO4. The cellulose suspension was stirred at 45° C for 3h using magnetic stirrer. The reaction was then stopped by diluting the resultant cellulose suspension
10 times using deionised water. The BNC suspension was centrifuged and the pellet was washed with deionized water 3-4 times. The pellet was then re-suspended in deionised water. The obtained BNC suspension was dialysed against deionised water for 3-4 days with exchange of water in each day. The BNC suspension was then dried by lyophilization to obtain dry BNC powder.
Example 2: Synthesis of Pd nano-catalyst.
Palladium chloride dissolved in water (lmg in 10ml). Bacterial cellulose (BC) and bacterial cellulose nano crystal (BNC) were added separately and sonicated the reaction mixture for five mins at 25-30 °C; wherein the bacterial cellulose nano-crystals and palladium nanoparticles were mixed in a ratio ranging from 90: 10 to 60:40. Sodium borohydride (NaBHi) was added into BC and BNC solution and again sonicated for another 20 min at 25-30°C. The reaction mixture was filtered and dried at 100 °C to afford Pd/BC and PD/BNC nano-catalyst.
Example 3:
After synthesis of Pd: BNC catalyst both hygroscopicity and solubility were tested. For hygroscopicity Pd: BNC catalyst was recorded at 30°C with 80% humidity at Ohrs and 24hrs further depicted in Figure 3A and 3B. For solubility Pd: BNC was suspended in 100% DMF and no solubility was observed after rigorous mixing of the samples after several hours further depicted in Figure 4.
Example 4: General procedure for the fluorination of aromatic compounds of formula (II) to afford compound of formula (I):
In round bottom flask 1.0 mmol of a compound of formula (II) and 3.0 mmol of fluorine source was added in 20 ml of toluene. Then 1-10.0 mmol % (w/w) Pd-nano particles were added to the reaction. The reaction mixture was heated to the temperature of 60-120 degrees. The reaction mixture was maintained at a temperature of 60-120 degrees for 12 hours. After completion of the reaction, the product was purified using Colum chromatography to afford the fluorinated product.
Characteristic Data: i. 1 -fluoro-4-nitrobenzene : ¾ NMR (400 MHz, CDCb) d 8.38 - 8.20 (m, 2 H), 7.36 - 7.07
(m, 3 H), 13C NMR (100 MHz, CDCb) d 168.2, 164.6, 144.0, 126.0, 125.9, 116.1, 115.9, 103 19F NMR (376 MHz, CDCb) d 108
ii. ethyl 2-fluorobenzoate: ¾NMR (400 MHz, CDCb) d 7.95 (dt, / = 1.8, 7.6 Hz, 1 H), 7.55 - 7.48 (m, 1 H), 7.24 - 7.09 (m, 2 H), 4.41 (q, / = 7.1 Hz, 2 H), 1.44 - 1.36 (m, 3 H), 13C NMR (100 MHz, CDCb) d 164.4, 162.2, 160.6, 134.3, 134.2, 132.0, 123.9, 119.1, 119.0, 117.0, 117.8, 61.2, 14.2, 19F NMR (376 MHz, CDCb) d 109. iii. 1 -(2-fluorophenyl)ethan- 1 -one : ¾ NMR (400 MHz, CDCb) d 7.93 - 7.75 (m, 1 H), 7.63 - 7.44 (m, 1 H), 7.31 - 7.02 (m, 2 H), 2.64 (d, J = 4.9 Hz, 3 H) 13C NMR (100 MHz, CDCb) d 195.9, 163.5, 160.9, 134.7, 134.6, 130.5, 130.5, 125.7, 125.8, 124.3, 124.3, 116.7, 116.5,31.4, 31.4, 19F NMR (376 MHz, CDCb) d 109. iv. 2-fluorobenzonitrile : ¾ NMR (400 MHz, CDCb) d 7.71 - 7.58 (m, 2 H), 7.34 - 7.20 (m, 3 H) 13C NMR (100 MHz, CDCb) d 164.3, 161.7, 136.1, 135.0, 133.4, 124.8, 124.8, 116.5, 116.3, 113.7, 101.4, 101.3, 19F NMR (376 MHz, CDCb) d 106. v. 1 -(3 -fluorophenyl)ethan- 1 -one : ¾ NMR (400 MHz, CDCb) d 7.78 - 7.69 (m, 1 H), 7.65 - 7.58 (m, 1 H), 7.44 (dt, /= 5.5, 8.0 Hz, 1 H), 7.33 - 7.19 (m, 1 H), 2.58 (s, 3 H), 13C NMR (100 MHz, CDCb) d 196.7, 164.0, 161.6, 139.1, 139.2, 131.3, 130.3, 124.1, 124.1, 120.2, 120.0, 115.0, 115.8,26.6, 19F NMR (376 MHz, CDCb) d 110. vi. 3 -fluoro- 1 , 1 '-biphenyl: ¾ NMR (400 MHz, CDCb) d 7.66 - 7.58 (m, 2 H), 7.52 - 7.46 (m, 2 H), 7.47 - 7.37 (m, 3 H), 7.36 - 7.30 (m, 1 H), 7.15 - 7.03 (m, 1 H) 13C NMR (100 MHz, CDCb) d 164.4, 162.0, 143.5, 143.5, 139.9, 131.2, 130.1, 128.9, 128.7, 127.8, 127.8, 127.2, 127.2, 127.1, 123.8, 122.7, 114.1, 113.9, 114.9, 19F NMR (376 MHz, CDCb) d 112. vii. ethyl 4-fluorobenzoate: ¾ NMR (400 MHz, CDCb) d8.10 - 8.01 (m, 2 H), 7.11 (t, /= 8.8 Hz, 2 H), 4.37 (q, /= 7.1 Hz, 2 H), 1.41 (t, /= 7.1 Hz, 4 H), 13C NMR (100 MHz, CDCb) d 166.9, 165.6, 164.4, 132.1, 133.0, 126.7, 126.7, 115.5, 115.3, 62.1, 14.3 19F NMR (376 MHz, CDCb) d 106 viii. 1 ,4-difluorobenzene : ¾ NMR (400 MHz, CDCb) d 7.03 (t, / = 6.1 Hz, 4 H) 13C NMR (100 MHz, CDCb) d 161.0, 160.0, 157.6, 156.6, 116.5, 116.5, 116.5, 116.3, 116.2, 116.1, 19F NMR (376 MHz, CDCb) d 118
ix. (4-fluorophenyl)(phenyl)methanone: 'H NMR (400 MHz, CDCb) d 7.86 - 7.83 (m, 2 H), 7.78 (dd, / = 1.4, 8.2 Hz, 2 H), 7.59 (d, / = 7.8 Hz, 1 H), 7.53 - 7.46 (m, 2 H), 7.16 (t, / = 8.7 Hz, 2 H), 13C NMR (100 MHz, CDCb) d 195.6, 166.9, 164.4, 137.8, 134.1, 134.0, 133.1, 132.9, 132.7, 130.1, 127.7, 128.6, 115.8, 116.6, 19F NMR (376 MHz, CDCb) d 105. x. 2-fluoronaphthalene: ¾NMR (400 MHz, CDCb) d 8.18 - 8.13 (m, 1 H), 7.93 - 7.86 (m, 1 H), 7.67 (d, J= 8.2 Hz, 1 H), 7.62 - 7.54 (m, 2 H), 7.42 (dt, /= 5.5, 7.8 Hz, 1 H), 7.18 (dd, / = 7.8, 10.5 Hz, 1 H) 13C NMR (100 MHz, CDCb) d 161.0, 158.5, 134.9, 134.8, 127.5, 127.5, 126.8, 126.1, 126.6, 125.5, 123.8, 123.6, 122.6, 120.5, 120.5, 109.5, 108.3, 19F NMR (376 MHz, CDCb) d124. xi. 2-fluoropyridine : ¾ NMR (400 MHz, CDCb) d 8.25 (d, J = 4.0 Hz, 1 H), 7.85 - 7.68 (m, 1 H), 7.23 - 7.16 (m, 1 H), 6.95 (dd, / = 2.7, 8.3 Hz, 1 H) 13C NMR (100 MHz, CDCb) d 164.7, 162.4, 147.7, 147.5, 141.0, 140.9, 121.1, 122.0, 109.7, 109.3, 19F NMR (376 MHz, CDCb) d 68. xii. 1 -(4'-fluoro-[ 1 , 1 '-biphenyl] -3 -yl)ethan- 1 -one : ¾ NMR (400 MHz, CDCb) d 7.38 - 7.25 (m, 2 H), 7.01 - 6.74 (m, 4 H), 6.56 - 6.37 (m, 2 H), 1.97 - 1.85 (m, 3 H) 13C NMR (100 MHz, CDCb) d 197.6, 164.2, 161.7, 144.7, 136.0, 136.01, 135.8, 128.9, 128.9, 126.0, 116.0, 115.8, 19F NMR (376 MHz, CDCb) d 26.7
ADVANTAGES OF THE INVENTION
• New bacterial cellulose nano-crystals supported stable Pd catalyst is developed for the fluorination of aromatic compounds. · Insoluble, moisture resistant, and reusable Pd catalyst.
• The catalyst is reusable several times and gives high yield of aromatic fluorination product.
• Developed Pd-catalyst is cost effective in comparison with previously used catalysts.
Claims
1. Palladium nano-catalyst supported on bacterial cellulose nano-crystals (BNC) comprising palladium nanoparticles as the active component and bacterial cellulose nano-crystals as support, wherein the bacterial cellulose nano-crystals and palladium nanoparticles are mixed in a ratio ranging from 90:10 to 60:40, and wherein the said catalyst is insoluble, moisture resistant, and reusable.
2. The palladium nano-catalyst as claimed in claim 1, wherein the size of palladium nanopartciles ranges from 20 to 50 nm.
3. The palladium nano-catalyst as claimed in claim 1 , wherein it is reusable for five cycles with no loss in activity.
4. A fluorination process of aromatic halides catalyzed by the palladium nano-catalyst as claimed in claim 1, wherein the process comprises the steps of reacting a compound of formula II with a fluorinating agent in the presence of 1.0 mol wt/wt to 10.0 mol wt/wt of the palladium catalyst in a suitable solvent to synthesize a fluorinated compound of formula I,
Formula II Formula I wherein, ring Ύ’ is aromatic, 5-membered or 6-membered;
X= C, N, O or S;
GL= Cl, Br, I or OTf;
R= same or different and selected form the group comprising of C1-C5 alkyl, C1-C10 cycloalkyl, aryl, alkoxy, cyano, -COORa, ketone, aldehyde, and NO2; wherein, Ra is C1-C10 alkyl or aryl or any two or more adjacent carbon atoms of ring Ύ’ may form 5-6 membered aromatic ring.
5. The fluorination process as claimed in claim 4, wherein the solvent is selected from a group consisting of Dimethyl formamide (DMF), Dimethylsulfoxide (DMSO), Toluene (PhCH3), Tetrahydrofuran (THF), and Flurobenzene (PhF).
6. The fluorination process as claimed in claim 4, wherein the fluorinating agent is selected from a group consisting of Cesium fluoride (CsF), Potassium fluoride (KF), Sodium fluoride (NaF), and Rubidium fluoride (RbF).
7. The fluorination process as claimed in claim 4, wherein the reaction step is carried out at a temperature of between 60°C and 120°C for 10-12 hours.
8. The fluorination process as claimed in claim 4, wherein the yield of the fluorination process is in the range of 70% to 95%.
9. A process for the preparation of the palladium nano-catalyst as claimed in claim 1 comprising the steps of: a) dissolving palladium chloride in water; b) adding bacterial cellulose nano-crystals (BNC) in the reaction mixture obtained in step (a) in a ratio ranging from 90: 10 to 60:40; c) sonicating the reaction mixture obtained in step (b) for 5-10 minutes at a temperature in the range of 25-30 °C; d) adding sodium borohydride in the reaction mixture obtained in step (c) followed by sonication for 15-20 minutes at a temperature in the range of 25-30 °C; e) filtering the reaction mixture obtained in step (d) and drying at 100°C to obtain palladium nano-catalyst supported on bacterial cellulose nano-crystals.
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Non-Patent Citations (5)
| Title |
|---|
| JEREMIC SANJA, DJOKIC LIDIJA, AJDAČIĆ VLADIMIR, BOŽINOVIĆ NINA, PAVLOVIC VLADIMIR, MANOJLOVIĆ DRAGAN D., BABU RAMESH, SENTHAMARAIK: "PRODUCTION OF BACTERIAL NANOCELLULOSE (BNC) AND ITS APPLICATION AS A SOLID SUPPORT IN TRANSITION METAL CATALYSED CROSS-COUPLING REACTIONS", INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, vol. 129, 15 May 2019 (2019-05-15), pages 351 - 360, XP055977587 * |
| LEE HONG GEUN, MILNER PHILLIP J., BUCHWALD STEPHEN L.: "PD-CATALYZED NUCLEOPHILIC FLUORINATION OF ARYL BROMIDES", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 136, no. 10, 21 February 2014 (2014-02-21), pages 3792 - 3795, XP055977592 * |
| MAIUOLO LOREDANA, ALGIERI VINCENZO, OLIVITO FABRIZIO, TALLARIDA MATTEO ANTONIO, COSTANZO PAOLA, JIRITANO ANTONIO, DE NINO ANTONIO: "CHRONICLE OF NANOCELLULOSES (NCS) FOR CATALYTIC APPLICATIONS: KEY ADVANCES", CATALYSTS, vol. 11, no. 96, 12 January 2021 (2021-01-12), pages 1 - 35, XP055977589 * |
| SATHER AARON C., BUCHWALD STEPHEN L.: "THE EVOLUTION OF PDO/PDII-CATALYZED AROMATIC FLUORINATION", ACCOUNTS OF CHEMICAL RESEARCH, vol. 49, no. 10, 22 October 2016 (2016-10-22), pages 2146 - 2157, XP055977602 * |
| ZHOU PEIPEI, WANG HUANHUAN, YANG JIAZHI, TANG JIAN, SUN DONGPING, TANG WEIHUA: "BACTERIA CELLULOSE NANOFIBERS SUPPORTED PALLADIUM(0) NANOCOMPOSITE AND ITS CATALYSIS EVALUATION IN HECK REACTION", INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, vol. 51, no. 16, 4 August 2012 (2012-08-04), pages 5743 - 5748, XP055977579 * |
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