EP4258868A1 - Lactam composition and use - Google Patents
Lactam composition and useInfo
- Publication number
- EP4258868A1 EP4258868A1 EP21802747.2A EP21802747A EP4258868A1 EP 4258868 A1 EP4258868 A1 EP 4258868A1 EP 21802747 A EP21802747 A EP 21802747A EP 4258868 A1 EP4258868 A1 EP 4258868A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- lactam
- composition
- lactate
- solvent
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 79
- 150000003951 lactams Chemical class 0.000 title claims abstract description 67
- 239000002904 solvent Substances 0.000 claims abstract description 45
- 230000001580 bacterial effect Effects 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 40
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 30
- GMEONFUTDYJSNV-UHFFFAOYSA-N Ethyl levulinate Chemical compound CCOC(=O)CCC(C)=O GMEONFUTDYJSNV-UHFFFAOYSA-N 0.000 claims description 22
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims description 22
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 13
- MRABAEUHTLLEML-UHFFFAOYSA-N Butyl lactate Chemical compound CCCCOC(=O)C(C)O MRABAEUHTLLEML-UHFFFAOYSA-N 0.000 claims description 12
- 239000001191 butyl (2R)-2-hydroxypropanoate Substances 0.000 claims description 12
- 229940116333 ethyl lactate Drugs 0.000 claims description 11
- 150000004730 levulinic acid derivatives Chemical class 0.000 claims description 11
- 150000003903 lactic acid esters Chemical class 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 230000003139 buffering effect Effects 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000004033 plastic Substances 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 239000004753 textile Substances 0.000 claims description 2
- 239000002023 wood Substances 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 14
- 239000007787 solid Substances 0.000 description 11
- 239000004094 surface-active agent Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- HHCPGPHTKXVNHA-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-methylidenepyrrol-2-one Chemical compound C1=CC(Cl)=CC=C1C1=CC(=O)NC1=C HHCPGPHTKXVNHA-UHFFFAOYSA-N 0.000 description 5
- YSZWLEFVAJQHJS-UHFFFAOYSA-N 5-methylidene-4-(4-methylphenyl)pyrrol-2-one Chemical compound C1=CC(C)=CC=C1C1=CC(=O)NC1=C YSZWLEFVAJQHJS-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- PZQOWENOZPCUSJ-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1H-pyrrol-2-one Chemical compound CC1(O)NC(=O)C=C1C1=CC=C(Cl)C=C1 PZQOWENOZPCUSJ-UHFFFAOYSA-N 0.000 description 3
- CPAOXJPVYYJEAF-UHFFFAOYSA-N 5-hydroxy-5-methyl-4-(4-methylphenyl)-1H-pyrrol-2-one Chemical compound CC1=CC=C(C=C1)C1=CC(=O)NC1(C)O CPAOXJPVYYJEAF-UHFFFAOYSA-N 0.000 description 3
- JTBGHWGTJYXHMI-UHFFFAOYSA-N 5-hydroxy-5-methyl-4-(4-methylphenyl)furan-2-one Chemical compound CC1=CC=C(C=C1)C1=CC(=O)OC1(C)O JTBGHWGTJYXHMI-UHFFFAOYSA-N 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- OVLMWAKWSBFBBQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-hydroxy-5-methylfuran-2-one Chemical compound CC1(O)OC(=O)C=C1C1=CC=C(Cl)C=C1 OVLMWAKWSBFBBQ-UHFFFAOYSA-N 0.000 description 2
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002280 amphoteric surfactant Substances 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000003093 cationic surfactant Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- WEJRYKSUUFKMBC-UHFFFAOYSA-N 1-(4-chlorophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=C(Cl)C=C1 WEJRYKSUUFKMBC-UHFFFAOYSA-N 0.000 description 1
- NOXKUHSBIXPZBJ-UHFFFAOYSA-N 1-(4-methylphenyl)propan-2-one Chemical compound CC(=O)CC1=CC=C(C)C=C1 NOXKUHSBIXPZBJ-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- KVZLHPXEUGJPAH-UHFFFAOYSA-N 2-oxidanylpropanoic acid Chemical class CC(O)C(O)=O.CC(O)C(O)=O KVZLHPXEUGJPAH-UHFFFAOYSA-N 0.000 description 1
- JOOXCMJARBKPKM-UHFFFAOYSA-M 4-oxopentanoate Chemical class CC(=O)CCC([O-])=O JOOXCMJARBKPKM-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 150000003950 cyclic amides Chemical class 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000010903 husk Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940058352 levulinate Drugs 0.000 description 1
- 229940040102 levulinic acid Drugs 0.000 description 1
- 239000002029 lignocellulosic biomass Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
Definitions
- the invention relates to an improvement in the field of hygiene, in particular to a composition comprising a lactam which displays improved solubility and stability of the lactam.
- Hygiene in particular inhibition of bacterial species, is important to consumers.
- Lactams are known as inhibitors of bacterial species. They may be applied to surfaces to inhibit bacterial species.
- the invention relates in a first aspect to a composition
- a composition comprising:-
- composition has a pH of from 4 to 6.50, preferably pH 4 to 6.25, more preferably 4.50 to 6.00; wherein the lactam is selected from:
- the pH is from 4 to 5.40, more preferably from 4.50 to 5.40.
- lactam is selected from:
- lactam is:
- the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water.
- the solvent is selected from the group: alcohol; levulinate derivatives; lactate derivatives; and solvents with a dielectric constant of 15 of higher, preferably the solvent is selected from the group: alcohol, levulinate derivatives; and lactate derivatives; more preferably the solvent is selected from the group: levulinate derivatives and lactate derivatives.
- solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
- alcohols preferably a C1-C4 alcohol, more preferably ethanol
- lactate derivatives preferably ethyl lactate and/or butyl lactate
- levulinate derivatives preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK)
- LGK ethyl levulinate glycerol ketal
- the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
- the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
- the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
- the solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%.
- the solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%.
- the solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
- the composition comprises one or more surfactants.
- the surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
- the surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
- the surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants.
- Preferred surfactants are nonionic surfactants.
- the composition preferably comprises a buffer.
- the invention relates in a second aspect to a method of treatment of a surface, to improve resistance of said surface to bacterial fouling, by treatment with a composition according to the first aspect of the invention.
- the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes.
- the lactam is selected from:
- the invention further relates in a third aspect to the use in a lactam composition, of a combination of a solvent and application of pH at from 4 to 6.5, preferably 4 to 6.25, more preferably 4.50 to 6.00 to said composition, to improve the solubility and stability of said lactam in the composition.
- the lactam is selected from:
- Figure 1 is a photograph showing the solubility of the lactam 488 at pH 5, pH 7 and pH 8
- Figure 2 demonstrates the pH effect on the solubility and stability of the lactam 488. Lactam initial solubility (Left hand axis and circular data points) and stability (right hand axis and square data points) vs buffer pH, with lactam delivered in ethanol, to a total of 2% solvent and 100 ppm lactam in solution
- a lactam is a cyclic amide.
- the lactam is a lactam selected from:
- lactam is selected from: Most preferably the lactam is:
- the lactam is cationic in nature
- the cation can be used or with a suitable counterion (e.g. iodide).
- the lactam is present at a level of from 0.0001 to 2.5 wt.%, preferably from 0.0001 to 1 wt.%.
- the lactam may be suitably present at levels of 0.001 to 1 wt.%, or even 0.01 to 1 wt.%, or even 0.01 to 0.5 wt.%.
- the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water.
- the composition may comprise any amount of water ranging from lower amounts of 0.1 , 0.5, 1, 1.5, 2 or even 5 wt.% water up to 30, 40, 50, 60, 70, 75, 80, 85, 90, 95, 96, 97, 98, or even 99 wt.% water.
- the composition comprises a solvent.
- Preferred solvents are selected from the group: alcohol; levulinate derivatives; lactate derivatives; and, solvents with a dielectric constant of 15 of higher.
- Preferred examples of solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
- DMSO dimethyl sulfoxide
- the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran (2Me-THF), ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
- the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
- the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
- 2Me-THF, ethyl levulinate and LGK can be classed as levulinic acid derivatives (or levulinate derivatives).
- Levulinic acid may be derived from lignocellulosic biomass (i.e. corn husks, sugar cane waste etc), and can be converted in to 2Me-THF in a cyclisation reaction, ethyl levulinate in one step esterification, and LGK in 2 steps (esterification and ketal synthesis).
- Ethyl lactate and butyl lactate are lactic acid (lactate) derivatives. Lactic acid is a byproduct of fermentation which is then reacted with ethanol or butanol to generate ethyl and butyl lactate.
- the solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%.
- the solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%.
- the solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
- the solvent may be present at a level of from 1 to 80 wt.%, preferably from 1 to 50 wt.%, more preferably from 1 to 40 wt.%.
- the solvent level may also be from 1 to 30 wt.%, 1 to 20 wt.%, or even 1 to 15 wt.% or 1 to 10 wt.%.
- the composition comprises one or more surfactants.
- the surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
- the surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants.
- Preferred surfactants are nonionic surfactants.
- the composition may preferably comprise a buffer to assist in maintaining any resulting composition within a specified pH range.
- Buffering systems may be any usual buffering system known in the art. These may for example include citrate, acetate, phosphate, and or carbonate buffers, or mixtures thereof.
- composition may comprise further ingredients such as surfactants, chelating agents, thickeners, pH modifiers, and perfumes.
- 1-(4-Chlorophenyl)propan-2-one (40.00 g, 34.75 mL, 237.2 mmol), glyoxylic acid monohydrate (32.75 g, 355.8 mmol) and phosphoric acid (69.74 g, 711.7 mmol) were combined at room temperature before heating to 85 °C overnight. After cooling to room temperature, the mixture was poured into a mixture of water (500 mL) and ethyl acetate (500 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (500 mL).
- aqueous layer was extracted with dichloromethane (100 mL), and the combined organic layers washed with a 1 :1 mixture of water and saturated aqueous sodium hydrogen carbonate solution (100 mL), dried (MgSC and filtered. Silica was added to the filtrate and the mixture stirred for 10 minutes before filtering through a plug of silica, washing through with dichloromethane followed by a 3:1 mixture of dichloromethane:diethyl ether. Fractions containing the desired product were combined and concentrated under reduced pressure.
- lactam used was lactam 488.
- This example shows the effect of the pH on the solubility of the lactam in an aqueous based composition with a solvent included.
- a targeted 10,000 ppm stock of lactam 488 in EtOH was prepared and left on the bottle rollers for 24 hrs, before filtration through a syringe filter to yield a saturated solution (likely around 8000 ppm in EtOH).
- This stock solution was mixed in a 1 :2 ratio with 0.1 M acetate buffer at pH 5.2, or with 0.1M phosphate buffer at pH 7 or 8, agitated in vial and observed visually for any precipitate formed, indicating insolubility.
- Figure 1 glass picture
- the lactam was mostly solubilised to an acceptable level at 5, while at pH 7 and 8, the solubility was greatly reduced.
- Example 3 This example demonstrates the lack of stability of the lactam composition at pH below pH 4 and above pH 6.5.
- Lactam 488 was dissolved to maximum concentration ( ⁇ 10 mg/mL) in d6-DMSO, and mixed in a 2:1 ratio with a range of pH buffers (pH 7.4 0.2M phosphate buffer, pH 6 0.1 M citrate buffer, pH 5.2 0.1M acetate buffer, 4, 2) and water. These samples were then filtered and studied by water suppression 1 H NMR a weekly time points for 4 weeks. Relative %lactam remaining was quantified using the integration of the buffer peak compared to the lactam resonance at 5.22 ppm.
- the lactam is only initially solubilised and displays long term stability (4 weeks) for compositions where the pH is from 4 to 6.5. Above this pH, the composition does not solubilise well enough and is also not stable, and below pH 4, the composition is not stable.
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Abstract
The invention relates to a composition comprising: (a) from 0.0001 to 5 wt.% of a lactam; and, (b) 1 to 80 wt.%, of a solvent; wherein the composition has a pH of from 4 to 6.50; wherein the lactam is selected from the formulae. The invention also relates to a method of treatment of a surface, to improve resistance of said surface to bacterial fouling; and also to the use in a lactam composition, of a combination of a solvent and application of pH at from 4 to 6.50 to said composition, to improve the solubility and stability of said lactam in the composition.
Description
LACTAM COMPOSITION AND USE
Field of Invention
The invention relates to an improvement in the field of hygiene, in particular to a composition comprising a lactam which displays improved solubility and stability of the lactam.
Background of the Invention
Hygiene, in particular inhibition of bacterial species, is important to consumers.
Lactams are known as inhibitors of bacterial species. They may be applied to surfaces to inhibit bacterial species.
There is a wish to improve the availability of the lactam and provide a formulation that displays improved solubility and stability of the lactam.
Summary of the Invention
We have found that by formulating a composition comprising a lactam in combination with a solvent at pH 4 to 6.50, the resulting formulation displays improved solubility and stability of the lactam.
The invention relates in a first aspect to a composition comprising:-
(a) from 0.0001 to 5 wt.%, preferably from 0.0001 to 2.5 wt.%, more preferably from 0.0001 to 1 wt.%, more preferably from 0.001 to 1 wt.% of a lactam; and,
(b) from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.% of a solvent; wherein the composition has a pH of from 4 to 6.50, preferably pH 4 to 6.25, more preferably 4.50 to 6.00; wherein the lactam is selected from:
Preferably the pH is from 4 to 5.40, more preferably from 4.50 to 5.40.
More preferably the lactam is selected from:
Most preferably the lactam is:
4-(4-chlorophenyl)-5-methylene-pyrrol-2-one
Preferably the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water.
The solvent is selected from the group: alcohol; levulinate derivatives; lactate derivatives; and solvents with a dielectric constant of 15 of higher, preferably the solvent is selected from the group: alcohol, levulinate derivatives; and lactate derivatives; more preferably the solvent is selected from the group: levulinate derivatives and lactate derivatives.
Preferred examples of solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate
derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
Preferably the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
Preferably the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
Most preferably the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
The solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%. The solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%. The solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
Preferably the composition comprises one or more surfactants. The surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
The surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
The surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants. Preferred surfactants are nonionic surfactants.
The composition preferably comprises a buffer.
The invention relates in a second aspect to a method of treatment of a surface, to improve resistance of said surface to bacterial fouling, by treatment with a composition according to the first aspect of the invention.
Preferably the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes.
Preferably in the method, the lactam is selected from:
The invention further relates in a third aspect to the use in a lactam composition, of a combination of a solvent and application of pH at from 4 to 6.5, preferably 4 to 6.25, more preferably 4.50 to 6.00 to said composition, to improve the solubility and stability of said lactam in the composition.
Preferably in the use, the lactam is selected from:
Brief Description of the Figures
Figure 1 Figure 1 is a photograph showing the solubility of the lactam 488 at pH 5, pH 7 and pH 8
Figure 2 Figure 2 demonstrates the pH effect on the solubility and stability of the lactam 488. Lactam initial solubility (Left hand axis and circular data points) and stability
(right hand axis and square data points) vs buffer pH, with lactam delivered in ethanol, to a total of 2% solvent and 100 ppm lactam in solution
Detailed Description of the Invention The indefinite article "a" or "an" and its corresponding definite article "the" as used herein means at least one, or one or more, unless specified otherwise.
It will be appreciated that, except where expressly provided otherwise, all preferences are combinable.
Lactam
A lactam is a cyclic amide. The lactam is a lactam selected from:
More preferably the lactam is selected from:
Most preferably the lactam is:
4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.
Where the lactam is cationic in nature, the cation can be used or with a suitable counterion (e.g. iodide).
Levels of lactam
Preferably the lactam is present at a level of from 0.0001 to 2.5 wt.%, preferably from 0.0001 to 1 wt.%. For example, the lactam may be suitably present at levels of 0.001 to 1 wt.%, or even 0.01 to 1 wt.%, or even 0.01 to 0.5 wt.%.
Compositions
Preferably the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water. The composition may comprise any amount of water ranging from lower amounts of 0.1 , 0.5, 1, 1.5, 2 or even 5 wt.% water up to 30, 40, 50, 60, 70, 75, 80, 85, 90, 95, 96, 97, 98, or even 99 wt.% water.
Solvents
The composition comprises a solvent.
Preferred solvents are selected from the group: alcohol; levulinate derivatives; lactate derivatives; and, solvents with a dielectric constant of 15 of higher. Preferred examples of solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
Preferably the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran (2Me-THF), ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
Preferably the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
Most preferably the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
2Me-THF, ethyl levulinate and LGK can be classed as levulinic acid derivatives (or levulinate derivatives). Levulinic acid may be derived from lignocellulosic biomass (i.e. corn husks, sugar cane waste etc), and can be converted in to 2Me-THF in a cyclisation reaction, ethyl levulinate in one step esterification, and LGK in 2 steps (esterification and ketal synthesis). Ethyl lactate and butyl lactate are lactic acid (lactate) derivatives. Lactic acid is a byproduct of fermentation which is then reacted with ethanol or butanol to generate ethyl and butyl lactate.
The solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%. The solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%. The solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
The solvent may be present at a level of from 1 to 80 wt.%, preferably from 1 to 50 wt.%, more preferably from 1 to 40 wt.%. The solvent level may also be from 1 to 30 wt.%, 1 to 20 wt.%, or even 1 to 15 wt.% or 1 to 10 wt.%.
Preferably the composition comprises one or more surfactants. The surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
The surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants. Preferred surfactants are nonionic surfactants.
The composition may preferably comprise a buffer to assist in maintaining any resulting composition within a specified pH range. Buffering systems may be any usual buffering system known in the art. These may for example include citrate, acetate, phosphate, and or carbonate buffers, or mixtures thereof.
Further Ingredients
The composition may comprise further ingredients such as surfactants, chelating agents, thickeners, pH modifiers, and perfumes.
The invention will be further described with the following non-limiting examples.
Examples
Example 1 - Preparation of examples of preferred lactams
Preparation of 4-(4-chlorophenyl)-5-hvdroxy-5-methylfuran-2(5H)-one
1-(4-Chlorophenyl)propan-2-one (40.00 g, 34.75 mL, 237.2 mmol), glyoxylic acid monohydrate (32.75 g, 355.8 mmol) and phosphoric acid (69.74 g, 711.7 mmol) were combined at room temperature before heating to 85 °C overnight. After cooling to room temperature, the mixture was poured into a mixture of water (500 mL) and ethyl acetate (500 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (500 mL). The combined organic layers were washed with a 1:1 mixture of water and brine (2 x 500 mL), dried (MgSO4) and concentrated under reduced pressure to yield 4-(4- chlorophenyl)-5-hydroxy-5-methylfuran-2(5H)-one (66.00 g, >100% yield) as a brown oil. The material was used in the next step without further purification.
Preparation of 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1 H-pyrrol-2(5H)-one
4-(4-Chlorophenyl)-5-hydroxy-5-methylfuran-2(5H)-one (66.00 g, 293.8 mmol) was dissolved in thionyl chloride (196.8 g, 120.0 mL, 1654 mmol) and heated at 40 °C for 1 hour, then 80 °C for 2 hours. The mixture was concentrated under reduced pressure and azeotroped with 2-methyltetrahydrofuran (200 mL). The residue was diluted with 2-methyltetrahydrofuran (160 mL) and this solution added to a cooled stirring mixture of 28% ammonia in water (180 mL) in 2-methyltetrahydrofuran (20 mL) at 0 °C. The mixture was warmed to room temperature and stirred overnight. Water (100 mL) and ethyl acetate (200 mL) were added and the layers separated. The aqueous phase was extracted with ethyl acetate (200 mL), and the combined organic extracts dried (MgSC ) and concentrated under reduced pressure. Purification by dry flash column chromatography (5-60% ethyl acetate in heptane) yielded 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1H-pyrrol-2(5H)-one (23.18 g, 35% yield) as a cream coloured solid.
1H NMR (400 MHz, d6-DMSO) 8.55 (brs, 1 H), 7.88-7.83 (m, 2H), 7.51-7.46 (m, 2H), 6.37 (d, 1 H), 6.32 (s, 1H), 1.45 (s, 3H)
UPLC (Basic) 1.51/5.00 min, 100% purity, M+H+ 224 MP 177 °C
Preparation of 4-(4-chlorophenyl)-5-methylene-1 H-pyrrol-2(5H)-one
To a cooled solution of 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1H-pyrrol-2(5H)-one (10.00 g, 44.51 mmol) in dry dichloromethane (100 mL) at 0 °C was added a solution of boron trifluoride diethyl etherate (8.213 g, 7.142 mL, 57.87 mmol) in dry dichloromethane (45 mL) over 15 minutes. The mixture was stirred at 0 °C, before slowly warming to room temperature and stirring for 2 hours. The reaction was quenched with ice-water (100 mL) and the layers separated. The aqueous layer was extracted with dichloromethane (100 mL), and the combined organic layers washed with a 1 :1 mixture of water and saturated aqueous
sodium hydrogen carbonate solution (100 mL), dried (MgSC and filtered. Silica was added to the filtrate and the mixture stirred for 10 minutes before filtering through a plug of silica, washing through with dichloromethane followed by a 3:1 mixture of dichloromethane:diethyl ether. Fractions containing the desired product were combined and concentrated under reduced pressure. Upon concentration a precipitate formed, which was collected by filtration, washing with diethyl ether, to yield 4-(4-chlorophenyl)-5-methylene-1 H-pyrrol-2(5H)-one (5.25 g, 57% yield) as a cream coloured solid.
1H NMR (400 MHz, d6-DMSO) 10.10 (s, 1H), 7.54-7.47 (m, 4H), 6.36 (s, 1H), 5.04 (t, 1H), 4.85 (s, 1 H)
UPLC (Basic) 1.87/5.00 min, 100% purity, M+H+ 206 MP 182 °C
Preparation of 5-hydroxy-5-methyl-4-(p-tolyl)furan-2(5H)-one
1-(p-Tolyl)propan-2-one (25.00 g, 24.00 mL, 168.7 mmol), glyoxylic acid monohydrate (23.29 g, 253.0 mmol) and phosphoric acid (49.60 g, 506.1 mmol) were combined at room temperature before heating at 90 °C overnight. After cooling to room temperature, the mixture was poured into a stirring mixture of ice-water (400 mL) and ethyl acetate (400 mL). The layers were separated and the organic phase washed with water (100 mL), dried (MgSC ) and concentrated under reduced pressure. The mixture was azeotroped with 2- methyltetrahydrofuran (50 mL) to yield 5-hydroxy-5-methyl-4-(p-tolyl)furan-2(5H)-one (16.50 g, 48% yield) as a brown solid.
1H NMR (400 MHz, de-DMSO) 7.86 (s, 1 H), 7.75 (d, 2H), 7.28 (d, 2H), 6.59 (s, 1 H), 2.32 (s, 3H), 1.61 (s, 3H)
Preparation of 5-hydroxy-5-methyl-4-(p-tolyl)-1 H-pyrrol-2(5H)-one
50 - 80 C
5-Hydroxy-5-methyl-4-(p-tolyl)furan-2(5H)-one (16.50 g, 80.80 mmol) was dissolved in thionyl chloride (48.06 g, 29.47 mL, 404.0 mmol) and heated at 50 °C for 1 hour, before heating at reflux for 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure and azeotroped with 2-methyltetra-hydrofuran (2 x 50 mL). The residue was diluted with 2-methyltetrahydrofuran (60 mL) and this solution added to a cooled stirring mixture of 28% ammonia in water (55 mL, 808.0 mol) in 2-methyltetrahydrofuran (10 mL) at 0 °C. The mixture was warmed to room temperature and stirred overnight. 2- Methyltetrahydrofuran was removed under reduced pressure, and the residue diluted with water (200 mL) and diethyl ether (100 mL) and the mixture stirred for 20 minutes at room temperature. The solids were collected by filtration and stirred in water (100 mL) and diethyl ether (50 mL) at room temperature for 10 minutes. The solids were collected by filtration and washed with water, diethyl ether and dried under vacuum at 50 °C to yield 5-hydroxy-5- methyl-4-(p-tolyl)-1H-pyrrol-2(5H)-one (10.49 g, 31% yield) as a light beige solid.
1H NMR (400 MHz, d6-DMSO) 8.44 (brs, 1H), 7.73 (d, 2H), 7.21 (d, 2H), 6.24 (s, 2H), 2.29 (s, 3H), 1.45 (s, 3H)
13C NMR (400 MHz, d6-DMSO) 170.4 (s, 1C), 161.1 (s, 1C), 139.8 (s, 1C), 129.7 (s, 2C), 128.9 (s, 1C), 128.2 (s, 2C), 119.1 (s, 1C), 87.8 (s, 1C), 26.7 (s, 1C), 21.5 (s, 1C) UPLC (Basic) 1.41/5.00 min, 100% purity, M+H+ 204 MP 178 °C Decomposition
Preparation of 5-methylene-4-(p-tolyl)-1H-pyrrol-2(5H)-one
To a cooled solution of 5-hydroxy-5-methyl-4-(p-tolyl)-1H-pyrrol-2(5H)-one (8.68 g, 42.7 mmol) in dry dichloromethane (87 mL) at 0 °C was added a solution of boron trifluoride diethyl etherate (6.85 g, 5.96 mL, 55.5 mmol) in dry dichloromethane (40 mL) over 15 minutes. After 1 hour the mixture was allowed to slowly warm to room temperature. After a further 3 hours, the reaction was diluted with dichloromethane (50 mL) and ice-water (100 mL) and stirred for 10 minutes. The layers were separated and the organic layer washed with water (100 mL), a 1:1 mixture of water and saturated aqueous sodium hydrogen carbonate solution (100 mL) and brine (100 mL) and the organic layer filtered through Celite, washing with dichloromethane. Any excess water was removed by pipette before drying the filtrate (MgSCU) and concentrating under reduced pressure to a brown solid. The solids
were stirred in hot dichloromethane (120 mL) for 15 minutes before slowly cooling to room temperature and then 0 °C. The solids were collected by filtration to yield 5-methylene-4-(p- tolyl)-1H-pyrrol-2(5H)-one (3.87 g, 49% yield) as a yellow solid. Silica was added to the filtrate and the mixture stirred for 10 minutes before filtering through a plug of silica, washing through with dichloromethane and then a 4:1 mixture of dichloromethane:diethyl ether. The filtrate was concentrated under reduced pressure to yield 5-methylene-4-(p-tolyl)-1H-pyrrol- 2(5H)-one (0.58 g, 7%) as a yellow solid. Total yield of 5-methylene-4-(p-tolyl)-1H-pyrrol- 2(5H)-one (4.45 g, 56% yield).
1H NMR (400 MHz, d6-DMSO) 10.11 (brs, 1 H), 7.35 (d, 2H), 7.25 (d, 2H), 6.25 (s, 1 H), 5.01 (s, 1 H), 4.85 (s, 1 H), 2.31 (s, 3H)
UPLC (Basic) 1.83/5.00 min, 100% purity, M+H+ 186
MP 200 °C Decomposition
Materials Used
In the following examples, the lactam used was lactam 488.
This is 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one and the structure is shown below:-
Example 2
This example shows the effect of the pH on the solubility of the lactam in an aqueous based composition with a solvent included. A targeted 10,000 ppm stock of lactam 488 in EtOH was prepared and left on the bottle rollers for 24 hrs, before filtration through a syringe filter to yield a saturated solution (likely around 8000 ppm in EtOH). This stock solution was mixed in a 1 :2 ratio with 0.1 M acetate buffer at pH 5.2, or with 0.1M phosphate buffer at pH 7 or 8, agitated in vial and observed visually for any precipitate formed, indicating insolubility. As can be seen from Figure 1 (glass picture), the lactam was mostly solubilised to an acceptable level at 5, while at pH 7 and 8, the solubility was greatly reduced.
Example 3
This example demonstrates the lack of stability of the lactam composition at pH below pH 4 and above pH 6.5.
Initial lactam solubility (3 hrs) was measured by preparing a 5 mg/ml solution of lactam 488 in ethanol. A 0.1M Phosphate/Citrate/Carbonate mixed buffer was prepared and adjusted to a pH range between 2-10 (exact values are in Figure 2 and Table 1), then the lactam 488/EtOH stock was added to a total of 2%, corresponding to a theoretical 100 ppm lactam concentration in solution.
The solutions were left to equilibrate for 3 hrs, then 7 repeats of 200pl of each was dispensed into a 96 well microtitre plates (Greiner, UV-Star), with an 8th well as a non-lactam containing background. On a Varioskan Lux UV/Vis plate reader, a UV absorbance spectra were recorded at a range of 200-450nm in order to quantify the intensity of the lactam peak (Amax = 280 nm), and against a calibration of known EtOH/Lactam solutions the signal was converted to ppm lactam in solution.
Long term lactam stability was measured using solution-state 1H NMR. Lactam 488 was dissolved to maximum concentration (~10 mg/mL) in d6-DMSO, and mixed in a 2:1 ratio with a range of pH buffers (pH 7.4 0.2M phosphate buffer, pH 6 0.1 M citrate buffer, pH 5.2 0.1M acetate buffer, 4, 2) and water. These samples were then filtered and studied by water suppression 1H NMR a weekly time points for 4 weeks. Relative %lactam remaining was quantified using the integration of the buffer peak compared to the lactam resonance at 5.22 ppm.
The results for the lactam stability and solubility are shown for the UV/Vis and 1H NMR data in Figure 2. The values in figure 2 are also shown in table 1 .
Table 1 Initial concentration calculated using UVA/is spectroscopy, decay measured by NMR spectroscopy - values with * were not measured, but estimated by extrapolation from the graph
The lactam is only initially solubilised and displays long term stability (4 weeks) for compositions where the pH is from 4 to 6.5. Above this pH, the composition does not solubilise well enough and is also not stable, and below pH 4, the composition is not stable.
Claims
1. A composition comprising:
(a) from 0.0001 to 5 wt.%, preferably from 0.0001 to 2.5 wt.%, more preferably from 0.0001 to 1 wt.%, more preferably from 0.001 to 1 wt.% of a lactam; and,
(b) from 1 to 80 wt.%, preferably from 1 to 50 wt.%, more preferably from 1 to 40 wt.% of a solvent; wherein the composition has a pH of from 4 to 6.50, preferably pH 4 to 6.25, more preferably 4.50 to 6.00; wherein the lactam is selected from:
2. A composition according to claim 1 , wherein the pH is from 4 to 5.40, preferably 4.50 to 5.40.
3. A composition according to claim 1 or claim 2, wherein the lactam is selected from:
A composition according to any preceding claim, wherein the lactam is:
chlorophenyl)-5-methylene-pyrrol-2-one. A composition according to any preceding claim, wherein the composition is an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water. A composition according to any preceding claim, wherein the solvent is selected from the group: alcohol; levulinate derivatives; lactate derivatives; and solvents with a dielectric constant of 15 of higher; preferably the solvents are: alcohols, preferably a C1-C4 alcohol, more preferably ethanol; lactate derivatives, preferably ethyl lactate and/or butyl lactate; levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO). A composition according to any preceding claim, wherein the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof; preferably ethyl lactate, butyl lactate; 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof. A composition according to any preceding claim, wherein the solvent is selected from the group: ethyl lactate, butyl lactate; 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof. A composition according to any preceding claim, wherein the composition comprises a buffering system. A method of treatment of a surface, to improve resistance of said surface to bacterial fouling, by treatment with a composition according to any one of claims 1 to 9.
17
11. A method according to claim 10, wherein the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes.
12. A method according to claim 10 or claim 11 , wherein the lactam is selected from:
13. Use in a lactam composition, of a combination of a solvent and application of pH at from 4 to 6.50, preferably from pH 4 to 6, more preferably 4.50 to 5.50, to said composition, to improve the solubility and stability of said lactam in the composition.
14. Use according to claim 14, wherein the lactam is selected from:
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