WO1996004229A1 - The preparation of organic compounds - Google Patents
The preparation of organic compounds Download PDFInfo
- Publication number
- WO1996004229A1 WO1996004229A1 PCT/GB1995/001764 GB9501764W WO9604229A1 WO 1996004229 A1 WO1996004229 A1 WO 1996004229A1 GB 9501764 W GB9501764 W GB 9501764W WO 9604229 A1 WO9604229 A1 WO 9604229A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- organic compound
- fluorine
- oxidation
- aryl
- solvent
- Prior art date
Links
- 150000002894 organic compounds Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 31
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 30
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 29
- 239000011737 fluorine Substances 0.000 claims abstract description 29
- 230000003647 oxidation Effects 0.000 claims abstract description 29
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 10
- 150000002009 diols Chemical class 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 229920005862 polyol Polymers 0.000 claims abstract description 6
- 150000003077 polyols Chemical class 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims abstract description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims abstract description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007789 gas Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 2
- 238000006243 chemical reaction Methods 0.000 description 30
- 125000003118 aryl group Chemical group 0.000 description 24
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 description 8
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 8
- 239000007800 oxidant agent Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 150000000180 1,2-diols Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 4
- MHXSJBXDLWNIAN-UHFFFAOYSA-N acetonitrile;hypofluorous acid Chemical compound FO.CC#N MHXSJBXDLWNIAN-UHFFFAOYSA-N 0.000 description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- -1 polycarbonyl Polymers 0.000 description 3
- ODZTXUXIYGJLMC-UHFFFAOYSA-N 2-hydroxycyclohexan-1-one Chemical compound OC1CCCCC1=O ODZTXUXIYGJLMC-UHFFFAOYSA-N 0.000 description 2
- ISTJMQSHILQAEC-UHFFFAOYSA-N 2-methyl-3-pentanol Chemical compound CCC(O)C(C)C ISTJMQSHILQAEC-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HYTRYEXINDDXJK-UHFFFAOYSA-N Ethyl isopropyl ketone Chemical compound CCC(=O)C(C)C HYTRYEXINDDXJK-UHFFFAOYSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- QNVRIHYSUZMSGM-UHFFFAOYSA-N hexan-2-ol Chemical compound CCCCC(C)O QNVRIHYSUZMSGM-UHFFFAOYSA-N 0.000 description 2
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- YCQANBSROMMIQP-UHFFFAOYSA-N 1-chloropyrrolidine-2,5-dione;methylsulfanylmethane Chemical compound CSC.ClN1C(=O)CCC1=O YCQANBSROMMIQP-UHFFFAOYSA-N 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N 9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- JMAYFSUXBFDECX-UHFFFAOYSA-N [Cl].CS(C)=O Chemical compound [Cl].CS(C)=O JMAYFSUXBFDECX-UHFFFAOYSA-N 0.000 description 1
- ZJQALQKVUGRLFF-UHFFFAOYSA-N [Cl].CSC Chemical compound [Cl].CSC ZJQALQKVUGRLFF-UHFFFAOYSA-N 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- BDGDWWGTAFXEEW-UHFFFAOYSA-N methylsulfinylmethane;oxalyl dichloride Chemical compound CS(C)=O.ClC(=O)C(Cl)=O BDGDWWGTAFXEEW-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LMYJGUNNJIDROI-UHFFFAOYSA-N oxan-4-ol Chemical compound OC1CCOCC1 LMYJGUNNJIDROI-UHFFFAOYSA-N 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HUAUNKAZQWMVFY-UHFFFAOYSA-M sodium;oxocalcium;hydroxide Chemical compound [OH-].[Na+].[Ca]=O HUAUNKAZQWMVFY-UHFFFAOYSA-M 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
Definitions
- the present invention relates to the preparation of organic compounds.
- it relates to the synthesis of compounds containing one or more carbonyl groups by oxidation of alcohols, diols and polyols.
- Oxidants derived from chromium, manganese, ruthenium, silver, aluminium and cerium have all been the subject of intense study. However, the toxicity and, therefore, disposal problems associated with using such materials makes these methods environmentally less acceptable.
- Non-metallic oxidants in general use include DMSO (dimethyl sulfoxide) with various oxidants, but the formation of significant quantities of by-products in such oxidations again causes disposal problems.
- Halogens and related halogen containing compounds have also been studied as potentially useful oxidation systems. Yields of oxidations using these reagents are generally low and both chlorine and bromine may be used only if the structural features of the product do not allow chlorination or bromination at the ⁇ -position to the carbonyl.
- 1,2-diols to 1,2-hydroxycarbonyl compounds are a special case and is not easily achieved by reaction of the free diols as, generally, oxidation of 1,2-diols results in carbon-carbon bond cleavage.
- the formation of 1,2-hydroxycarbonyl compounds from 1,2-diols requires the use of oxidants such as silver carbonate, dimethyl sulfoxide-phosphorous pentoxide, dimethyl sulfoxide-chlorine, dimethyl sulfide-N-chlorosuccinimide or dimethyl sulfide-chlorine to effect such transformations.
- Oxidation of 1,2-diols to 1,2-diones may be achieved with DMSO-oxalyl chloride.
- a method for the oxidation of one or more hydroxyl groups in an organic compound to one or more carbonyl groups which comprises reacting the organic compound with elemental fluorine.
- the said organic compound may be an aliphatic or aromatic alcohol, diol or polyol.
- the organic compound is contained in a liquid through which fluorine is passed as a gas.
- the rate of delivery of fluorine gas may vary between wide limits depending upon the scale of the reaction and may be adjusted to control the rate of the oxidation reaction.
- the said liquid may comprise the appropriate organic compound to be oxidised together with a substantially inert solvent, eg a neutral substance such as water optionally together with an inert neutral organic solvent such as acetonitrile.
- a substantially inert solvent eg a neutral substance such as water optionally together with an inert neutral organic solvent such as acetonitrile.
- the liquid may optionally include also a solvent for fluorine, eg a fluorinated or perfluorinated organic compound such as a fluoro- or perfluoro-alkane.
- the method according to the present invention may be carried out in a vessel in which the solution is present or alternatively a flowing stream of the solution may be contacted with a gaseous flow of fluorine in countercurrent fashion.
- the method according to the present invention may be carried out at a temperature in the range -60°C to +90°C although a temperature of from -20°C to +50°C is preferred. Ambient temperatures eg 15°C to 25°C may conveniently be employed.
- the ratio of fluorine to the organic compound to be oxidised may be varied within wide limits although it is preferred that the molar ratio is in the range 0.5 to 2.0:1, especially 1.1 to 1.25:1 (fluorine: organic compound) .
- Fluorine is preferably passes slowly through a solution of the alcohol, diol or polyol in a solvent containing water at room temperature, thus oxidising the alcohol, diol or polyol in a reaction that can be easily controlled simply by adjusting the flow rate of the introduction of fluorine gas into the reaction vessel.
- the desired product can be selected by adjustment of the amount of fluorine taking part in the reaction.
- the rate may for example be less than lOml/min eg less than 5ml/min, for small scale apparatus and at higher rates for larger scale apparatus.
- the ability to control the level of oxidation in the method according to the present invention allows for example 1,2-diols to be converted to either 1,2-hydroxycarbonyl compounds when one equivalent of fluorine is used in the oxidation, or to 1,2-diones when two equivalents of fluorine are passed through the reaction medium. Such control of the level of oxidation is not possible if the oxidant is the preformed HOF.MeCN reagent as employed in the prior art.
- the present invention also allows, for example, the selective oxidation of any number of hydroxyl groups in either a cyclic or acyclic polyalcohol to the corresponding polycarbonyl derivative. .
- R, R lf R 2 , R3 , R4, R5 and R 6 are each independently selected from hydrogen or the following groups which may be optionally substituted or contain optional hetero atoms: alkyl, alkoxy, cycloalky] , aryl, acyl, acyloxy nitro, cyano halogen.
- R, R lf R 2 , R3 , R4, R5 and R 6 are each independently selected from hydrogen or the following groups which may be optionally substituted or contain optional hetero atoms: alkyl, alkoxy, cycloalky] , aryl, acyl, acyloxy nitro, cyano halogen.
- any of the groups is or contains an alkyl group the group is preferably C- -n alkyl.
- n is an integer in the range 1 to 8 inclusive.
- the fluorinated product in the process according to "the present invention may be isolated by purging the reaction mixture with inert gas to remove any residual fluorine gas followed by neutralisation with sodium bicarbonate solution and extraction into a suitable solvent followed by purification by distillation or column chromatography.
- the present process according to the present invention provides an inexpensive and convenient synthetic route for the oxidation of alcohols to the corresponding carbonyl derivatives.
- trans-cyclohexane-l,2-diol (2.0g, 17mmol) and fluorine (17mmol) gave a crude yellow oil of 2-hydroxy- cyclohexanone; GC/MS (87% conversion; 100% yield) .
- Reaction with 2, 4-dinitrophenylhydrazine gave the 2,4- dinitrophenylhydrazone of 2-hydroxy-cyclohexanone as an orange solid (3.7g, 85% yield based on 87% conversion); .p. 153°C (lit. 150°C) ; (Found: C, 49.4; H, 4.6; N, 18.9.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A method for the oxidation of one or more hydroxyl groups in an organic compound to one or more carbonyl groups which comprises reacting the organic compound with elemental fluorine. The said organic compound may be an aliphatic or aromatic alcohol, diol or polyol and is contained in a liquid through which fluorine is passed as a gas.
Description
The preparation of organic compounds
The present invention relates to the preparation of organic compounds. In particular, it relates to the synthesis of compounds containing one or more carbonyl groups by oxidation of alcohols, diols and polyols.
The oxidation of an alcohol to a carbonyl compound is one of central importance in organic synthesis and, accordingly, many reagents have been devised to perform such transformations. The development of oxidising systems that are capable of achieving high alcohol to carbonyl conversions with good selectivity in a variety of substrates continues to interest both industry and academia.
The majority of oxidation methods for preparing carbonyl compounds from alcohols utilise metal compounds as oxidising agents. Oxidants derived from chromium, manganese, ruthenium, silver, aluminium and cerium have all been the subject of intense study. However, the toxicity and, therefore, disposal problems associated with using such materials makes these methods environmentally less acceptable. Non-metallic oxidants in general use include DMSO (dimethyl sulfoxide) with various oxidants, but the formation of significant quantities of by-products in such oxidations again causes disposal problems.
Halogens and related halogen containing compounds have also been studied as potentially useful oxidation systems. Yields of oxidations using these reagents are generally low and both chlorine and bromine may be used only if the structural features of the product do not allow chlorination or bromination at the α-position to the carbonyl.
An alternative to these oxidants is the use of the HOF.MeCN system which has previously been studied by others. In this process .the HOF.MeCN reagent is pre¬ formed at low temperature (-10°C) by passing dilute fluorine through a solution of water and acetonitrile
followed by the addition of the substrate alcohol at. low temperature. However, this process suffers from a number of drawbacks. As the HOF.MeCN complex is unstable at room temperature and has a half life of around 4 hours, the storage of such a reagent is very difficult, and, due to the highly oxidising nature of the reagent, potentially hazardous. This factor alone precludes the use of such an oxidising system on a large scale. Furthermore, the degree of oxidation cannot be controlled since the alcohol is added to a large excess of the oxidising reagent, resulting in concomitant Baeyer-Villager oxidation of the product ketone.
The oxidation of 1,2-diols to 1,2-hydroxycarbonyl compounds is a special case and is not easily achieved by reaction of the free diols as, generally, oxidation of 1,2-diols results in carbon-carbon bond cleavage. The formation of 1,2-hydroxycarbonyl compounds from 1,2-diols requires the use of oxidants such as silver carbonate, dimethyl sulfoxide-phosphorous pentoxide, dimethyl sulfoxide-chlorine, dimethyl sulfide-N-chlorosuccinimide or dimethyl sulfide-chlorine to effect such transformations. Oxidation of 1,2-diols to 1,2-diones may be achieved with DMSO-oxalyl chloride.
According to the present invention there is provided a method for the oxidation of one or more hydroxyl groups in an organic compound to one or more carbonyl groups which comprises reacting the organic compound with elemental fluorine. The said organic compound may be an aliphatic or aromatic alcohol, diol or polyol.
Desirably, the organic compound is contained in a liquid through which fluorine is passed as a gas. The rate of delivery of fluorine gas may vary between wide limits depending upon the scale of the reaction and may be adjusted to control the rate of the oxidation reaction.
The said liquid may comprise the appropriate organic compound to be oxidised together with a substantially
inert solvent, eg a neutral substance such as water optionally together with an inert neutral organic solvent such as acetonitrile. The liquid may optionally include also a solvent for fluorine, eg a fluorinated or perfluorinated organic compound such as a fluoro- or perfluoro-alkane.
The amount of water in the solvent or solvent system to which the organic compound is added to form the said liquid may vary between 0% and 100% although a water volume content of from 5% and 25% of the solvent system is preferred.
The method according to the present invention may be carried out in a vessel in which the solution is present or alternatively a flowing stream of the solution may be contacted with a gaseous flow of fluorine in countercurrent fashion.
The method according to the present invention may be carried out at a temperature in the range -60°C to +90°C although a temperature of from -20°C to +50°C is preferred. Ambient temperatures eg 15°C to 25°C may conveniently be employed.
The ratio of fluorine to the organic compound to be oxidised may be varied within wide limits although it is preferred that the molar ratio is in the range 0.5 to 2.0:1, especially 1.1 to 1.25:1 (fluorine: organic compound) .
Thus we now provide an improved method for the oxidation of hydroxyl groups to carbonyl groups using elemental fluorine as the oxidant. Fluorine is preferably passes slowly through a solution of the alcohol, diol or polyol in a solvent containing water at room temperature, thus oxidising the alcohol, diol or polyol in a reaction that can be easily controlled simply by adjusting the flow rate of the introduction of fluorine gas into the reaction vessel. In other words, the desired product can be selected by adjustment of the amount of fluorine taking
part in the reaction. Also, by controlling the rate of reaction potentially dangerous reactions are prevented from going out of control. the rate may for example be less than lOml/min eg less than 5ml/min, for small scale apparatus and at higher rates for larger scale apparatus.
The ability to control the level of oxidation in the method according to the present invention allows for example 1,2-diols to be converted to either 1,2-hydroxycarbonyl compounds when one equivalent of fluorine is used in the oxidation, or to 1,2-diones when two equivalents of fluorine are passed through the reaction medium. Such control of the level of oxidation is not possible if the oxidant is the preformed HOF.MeCN reagent as employed in the prior art. The present invention also allows, for example, the selective oxidation of any number of hydroxyl groups in either a cyclic or acyclic polyalcohol to the corresponding polycarbonyl derivative. .
As further examples of the method according to the present invention there is provided a method for the production of carbonyl containing molecules of formula (1), (2), (3) , (4), (5) and (6) as follows:
(1) (2) (3) (4)
(5) (6)
which comprises converting the corresponding compound of formula (7), (8) , (9) or (10) as follows:
(7) (8) (9) (10)
into compounds of formula (1) , (2) , (3) , (4) , (5) or (6) by reaction with elemental fluorine, wherein R, Rlf R2 , R3 , R4, R5 and R6 are each independently selected from hydrogen or the following groups which may be optionally substituted or contain optional hetero atoms: alkyl, alkoxy, cycloalky] , aryl, acyl, acyloxy nitro, cyano halogen. Where any of the groups is or contains an alkyl group the group is preferably C- -n alkyl.
In the above formulae, n is an integer in the range 1 to 8 inclusive.
When oxidation is complete the fluorinated product in the process according to "the present invention may be isolated by purging the reaction mixture with inert gas to remove any residual fluorine gas followed by neutralisation with sodium bicarbonate solution and extraction into a suitable solvent followed by purification by distillation or column chromatography.
Thus the present process according to the present invention provides an inexpensive and convenient synthetic route for the oxidation of alcohols to the corresponding carbonyl derivatives.
Embodiments of the present invention will now be described by way of example only with reference to the following Examples:
Example 1: Oxidation of cvclohexanol
Cyclohexanol (2.0g, 20mmol) dissolved in acetonitrile (30ml) was placed in a PTFE fluorination apparatus fitted with a drying tube filled with soda lime. Elemental fluorine (20mmol) as a 10% mixture in nitrogen was passed through the stirred mixture at room temperature at ca. lOml/min for 6 hours. The mixture was poured into water (30 ml) , neutralised with saturated sodium bicarbonate solution and extracted with dichloromethane (3 x 30 ml) . The crude carbonyl product was dried (MgS0 ) and concentrated by removal of solvent under reduced pressure to give a yellow oil containing cyclohexanone; GC/MS (60% conversion; 100% yield) which was identified as the 2,4- dinitrophenylhydrazone derivative, as follows:
A solution of acidified 2,4-dinitrophenylhydrazine (2.4g, 12 mmol) in hot methanol (50ml) was added to methanolic solution of crude cyclohexanone (12 mmol, as estimated from GC/MS) . The mixture was cooled (ice) until an orange precipitate formed. The precipitate was filtered off and recrystalised (MeOH) to give the 2,4- dinitrophenylhydrazone of cyclohexanone (3.0g, 90% yield based on 60% conversion of cyclohexanol); .p. 160°C (lit. 162°C); (Found: C, 51.8; H, 5.4; N, 20.2. C12H14N4θ4 requires C, 51.8; H, 5.0; N, 20.1%); δH (200MHz, CDC13, Me4Si) 11.21ppm (br s, 1 H, NH) , 9.12 (d, J 2.40, 1 H, aryl) , 8.29 (d d, J 2.40, J 9.87, 1 H, aryl) , 7.97 (d,m J 9.87, 1 H, aryl) and 2.49-1.58 (m, 10 H) ; δc (100MHz, CDCI3, Me Si) 161.42ppm (C=N) , 155.20, 145.33, 137.45, 129.95, 123.63, 116.24, 35.61, 27.22, 27.05, 26.01 and 25.50; m/z (Cl+, NH3) 279 (M++l, 76%), 239 (100%) and 58 (37%) . Example 2: Oxidation of trans-cvclohexane-1.2-diol
By a similar process to that described in Example 1, trans-cyclohexane-l,2-diol (2.0g, 17mmol) and fluorine (17mmol) gave a crude yellow oil of 2-hydroxy- cyclohexanone; GC/MS (87% conversion; 100% yield) .
Reaction with 2, 4-dinitrophenylhydrazine gave the 2,4- dinitrophenylhydrazone of 2-hydroxy-cyclohexanone as an orange solid (3.7g, 85% yield based on 87% conversion); .p. 153°C (lit. 150°C) ; (Found: C, 49.4; H, 4.6; N, 18.9. C12H13N405 requires C, 49.1; H, 4.4; N, 19.1%); δH (200MHz, CDC13, Me4Si) 11.45ppm (br s, 1 H, NH) , 9.21 (d, J=2.58 Hz, 1 H, aryl), 8.32 (dd, J=2.58 Hz, 9.65 Hz, l H, aryl), 7.97 (d, J=9.65 Hz, 1 H, -aryl), 3.40-3.30 (m, 1 H, CHOH) , 2.62-1.51 (m, 8H) and 1.1 (br s, OH); δc (100MHz, CDC13, Me4Si) 160.31ppm (C=N) , 147.94, 140.55, 139.67, 128.99, 123.59, 117.21, 43.42 (C-OH) , 32.67, 27.43, 23.87 and 23.26; m / z (Cl+, NH3) 295 (M++l, 32%), 277 (100%) , 230 (34%) and 112 (46%) . Example 3: Oxidation of cyclopentanol
By a similar process to that described in Example 1, cyclopentanol (1.7g, 20mmol) and fluorine (20mmol) gave a crude yellow oil containing cyclopentanone; GC/MS (78% conversion; 71% yield). Reaction with 2,4- dinitrophenylhydrazine (2.2g, llmmol) gave the 2,4- dinitrophenyl-hydrazone of cyclopentanone as an orange solid (2.5g, 61% yield based on 78% conversion) ; m.p. 142°C (lit. 146°C) ; (Found: C, 47.5; H, 4.4; N, 19.9. C11H12N 0 requires C, 47.-1; H, 4.3; N, 20.0%); δH (200MHz, CDCI3, Me4Si) 10.90ppm (br s, 1 H, NH) , 9.12 (d, J=2.58 Hz, 1 H, aryl), 8.28 (dd, J=2.58 Hz, 9.66 Hz, 1 H, aryl), 7.92 (d, J=9.66 Hz, 1H, aryl) and 2.30-1.90 (m, 8 H) ; δc (100MHz, CDCI3, Me4Si) 171.05ppm (C=N) , 151.01, 144.01, 140.99, 129.95, 123.58, 116.20, 33.61, 28.15, 24.89 and 24.81; / z (Cl+, NH3) 265 (M++l, 68%) and 84 (30%). Example 4: Oxidation of 2-methyl-pentan-3-ol
By a similar process to that described in Example 1, 2-methyl-pentan-3-ol (l.Og, lOmmol) and fluorine (lOmmol) gave a crude yellow oil containing 2-methyl-pentan-3-one; GC/MS (46% conversion; 97% yield). Reaction with 2,4- dinitrophenylhydrazine (0.9g, 4.5mmol) gave the 2,4- dinitrophenylhydrazone of 2-methyl-pentan-3-one as an
orange solid (1.2g, 93% yield based on 46% conversion) ; m.p. 110°C (lit. 112°C) ; (Found: C, 51.1; H, 5.8; N, 20.4. C12H16N40 requires C, 51.4; H, 5.7; N, 20.0%); δH (200MHz, CDC13, Me4Si) 11.21ppm (br s, 1 H, NH) , 9.15 (d, J=2.57 Hz, 1 H, aryl), 8.29 (dd, J=2.57 Hz, 9.60 Hz, 1 H, aryl) 7.98 (d, J=9.60 Hz, 1 H, aryl), 2.45 (m, 1H, CHMe2) , 1.31-1.25 (m, 5H, CH2CH3) , 1.23 (d, J=3.0 Hz, 3H, CH3) and 1.21 (d, J=3.0 Hz, 3H, CH3,); δc (100MHz, CDC13, Me4Si) 160.41ppm, 143.31, 139.51, 138.01, 130.42, 124.06, 116.96, 36.45, 22.03, 20.56, 19.05 and 18.01; m / z (Cl+, NH3) 281 (M++l, 77%), 124 (17%) and 100 (31%). Example 5: Oxidation of hexan-2-ol
By a similar process to that described in Example 1, hexan-2-ol (l.Og, lOmmol) and fluorine (lOmmol) gave a crude yellow oil of hexan-2-one; GC/MS showed (100% conversion; 100% yield) . Reaction with 2,4- dinitrophenylhydrazine (2.0g, lOmmol) gave the 2,4- dinitrophenylhydrazone of hexan-2-one as an orange solid (2.7g, 97% yield based on 100% conversion); m.p. 107°C (lit. 106°C) ; (Found: C, 51.5; H, 5.6; N, 23.1. C12H16N404 requires C, 51.4; H, 5.7; N, 20.0%); δH (200MHz, CDC13, Me4Si) 11.21ppm (br s, 1 H, NH) , 9.13 (d, J=2.56 Hz, 1 H, aryl), 8.29 (dd, J=2.56 Hz, 9.59 Hz, 1 H, aryl), 7.89 (d, J=9.59 Hz, 1H, aryl), 2.42-1.51 (m, 6H, CH2CH2CH2) , 1.07 (s, 3H, CH3) and 0.92 (t, J=6.02 Hz, 3H, CH3) ; δc (100MHz, CDC13, Me4Si) 160.39ppm (C=N) , 146.03, 136.93, 135.01, 128.95, 122.61, 116.14, 31.03, 24.01, 23.91, 20.19 and 18.32; m / z (Cl+, NH3) 281 (M++l, 34%) and 100 (9%) . Example 6: Oxidation of hexane-1.2-diol
By a similar process .to that described in Example l, hexane-l,2-diol (0.6g, 5mmol) and fluorine (5mmol) gave a crude yellow oil l-hydroxy-hexan-2-one; GC/MS (91% conversion; 95% yield). Reaction with 2,4- dinitrophenylhydrazine (0.9g, 4.3mmol) gave the 2,4- dinitrophenylhydrazone of l-hydroxy-hexan-2-one as an
orange solid (1.2g, 89% yield based on 91% conversion) ; m.p. 179°C; (Found: C, 48.8; H, 5.6; N, 18.9. C12H16N405 requires C, 48.6; H, 5.4; N, 18.5%); δH (200MHz, CDC13, Me Si) 11.02ppm (br s, 1 H, NH) , 9.14 (d, J=2.59 Hz, 1 H, aryl), 8.33 (dd, J=2.59 Hz, 9.60 Hz, 1 H, aryl) 7.25 (br s, OH), 7.92 (d, J=9.60 Hz, 1H, aryl), 4.19 (s, 2H, CH2) , 2.95-0.90 (m, 9H, CH2 and CH3) ; δc (100MHz, CDC13, Me4Si) 159.28ppm (C=N) , 146.49, 144.89, 138.15, 130.19 (CH) , 123.52 (CH) , 115.91 (CH) , 64.50 (CH2OH) , 28.02 (CH2) , 26.98 (CH2) , 23.01 (CH2) and 13.62 (CH3) ; m / z (Cl+, NH3) 297 (M++l, 100%), 279 (25%) and 261 (10%). Example 7: Oxidation of butane-l .3-diol
By a similar process .to that described in Example 1, butane-l, 3-diol (0.9g, lOmmol) and fluorine (lOmmol) gave a crude yellow oil containing l-hydroxy-butan-3-one; GC/MS (98% conversion; 53% yield) . Reaction with 2,4- dinitrophenylhydrazine (l.Og, 5.2mmol) gave the 2,4- dinitrophenylhydrazone of l-hydroxy-butan-3-one as an orange solid (1.2g, 46% yield based on 98% conversion); m.p. 158°C; (Found: C, 45.0; H, 4.8; N, 21.0. C10H12N4O5 requires C, 44.8; H, 4.5; N, 20.9%); δH (200MHz, CDC13, Me4Si) 11.12ppm (br s, 1 H, NH) , 9.14 (d, J=2.60 Hz, 1 H, aryl), 8.20 (dd, J=2.60 Hz, 9.62Hz, 1H, aryl), 7.88 (d, J=9.60 Hz, 1H, aryl), 4.02 (m, 2H, CH2OH) and 2.20-2.01 (m, 5 H) ; δc (100MHz, CDC13, Me4Si) 156.44ppm (C=N) , 144.91, 130.30, 130.17, 123.56, 123.07, 116.03, 59.22 (CH2OH) , 45.21 and 16.76; m / z (Cl+, NH3) 269 (M++l, 100%), 251 (84%) and 249 -(84%) . Example 8: Oxidation of tetrahvdro-4H-pyran-4-ol
By a similar process to that described in Example 1, tetrahydro-4H-pyran-4-ol (l.Og, lOmmol) and fluorine (lOmmol) gave a crude yellow oil containing tetrahydro-4H- pyran-4-one. Reaction with 2,4-dinitrophenylhydrazine (2.0g, lOmmol) gave the 2 ,4-dinitrophenylhydrazone of tetrahydro-4H-pyran-4-one as an orange solid (l.25g, 45% yield); m.p. 188°C (lit. 186°C) ; (Found: C, 45.0; H, 4.8;
N, 21.0. C10H12N4θ5 requires C, 44.8; H, 4.5; N, 20.9%); δH (200MHz, CDC13, Me Si) 11.12ppm (br s, 1 H, NH) , 9.14 (br s, IH, aryl) , 8.29 (br d, J=9.60 Hz, IH, aryl) , 7.96 (d, J=9.60 Hz, IH, aryl), 3.93-3.90 (m, 4H, CH2OCH2) and 2.20-2.00 ( , 4H) ; δc (100MHz, CDC13, Me Si) 156.23ppm (C=N) , 145.13, 137.62, 129.99, 128.92, 116.36, 68.30 (C- O) , 66.25 (C-O) , 28.43 and 25.53; m / z (Cl+, NH3) 269 (M++l, 100%), 251 (84%) and 249 (84%).
Claims
1. A method for the oxidation of one or more hydroxyl groups in an organic compound to one or more carbonyl groups which comprises reacting the organic compound with elemental fluorine.
2. A method as in Claim 1 and wherein the said organic compound is an aliphatic or aromatic alcohol, diol or polyol.
3. A method as in Claim 2 and wherein the said organic compound which is treated by the method is a compound of any one of formulae (7) , (8) , (9) or (10) specified herein.
4. A method as in Claim 1, 2 or 3 and wherein the organic compound is contained in a liquid into which the fluorine is passed as a gas.
5. A method as in Claim 4 and wherein the liquid comprises an inert, neutral solvent.
6. A method as in Claim 5 and wherein the inert, neutral solvent comprises water.
7. A method as in Claim 6 and wherein the water forms from 5% to 25% by volume of the solvent system to which the organic compound is added.
8. A method as in claim 5, 6, or 7 and wherein the solvent also comprises a fluorinated or perfluorinated organic solvent.
9. A method as in any one Claims 4, 5, 6, 7 or 8 and wherein the fluorine gas is diluted before application to the said organic compound with an inert gas.
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GB9415312A GB9415312D0 (en) | 1994-07-29 | 1994-07-29 | The preparation of organic compounds |
GB9415312.9 | 1994-07-29 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6242653B1 (en) | 1998-08-21 | 2001-06-05 | Basf Aktiengesellschaft | Process for the preparation of α-diketones from ketols or ketals from ketols |
JP2008308419A (en) * | 2007-06-13 | 2008-12-25 | Ube Ind Ltd | Method for producing tetrahydropyran-4-one |
RU2838317C1 (en) * | 2024-09-16 | 2025-04-14 | Федеральное государственное бюджетное учреждение науки Институт органического синтеза им. И.Я. Постовского Уральского отделения Российской академии наук (ИОС УрО РАН) | Method of producing cyclohexanone |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3038941A (en) * | 1959-03-23 | 1962-06-12 | Du Pont | Process for preparing polyfluoroaldehydes |
US3165554A (en) * | 1962-07-25 | 1965-01-12 | Dow Chemical Co | Oxidation of cyclic and aliphatic alcohols |
-
1994
- 1994-07-29 GB GB9415312A patent/GB9415312D0/en active Pending
-
1995
- 1995-07-26 WO PCT/GB1995/001764 patent/WO1996004229A1/en active Application Filing
- 1995-07-28 ZA ZA956322A patent/ZA956322B/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3038941A (en) * | 1959-03-23 | 1962-06-12 | Du Pont | Process for preparing polyfluoroaldehydes |
US3165554A (en) * | 1962-07-25 | 1965-01-12 | Dow Chemical Co | Oxidation of cyclic and aliphatic alcohols |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6242653B1 (en) | 1998-08-21 | 2001-06-05 | Basf Aktiengesellschaft | Process for the preparation of α-diketones from ketols or ketals from ketols |
US6316676B1 (en) | 1998-08-21 | 2001-11-13 | Basf Aktiengesellschaft | Process for the preparation of α-diketones from ketols or ketals from ketols |
JP2008308419A (en) * | 2007-06-13 | 2008-12-25 | Ube Ind Ltd | Method for producing tetrahydropyran-4-one |
RU2838317C1 (en) * | 2024-09-16 | 2025-04-14 | Федеральное государственное бюджетное учреждение науки Институт органического синтеза им. И.Я. Постовского Уральского отделения Российской академии наук (ИОС УрО РАН) | Method of producing cyclohexanone |
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ZA956322B (en) | 1996-03-14 |
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