Patent Application
20100031452
The present invention relates to new azo dyes, preparation methods for these azo dyes and formulations for dyeing fibers, such as, keratine fibers for example, human hair, wool or furs, comprising these compounds.
The European Commission started on July 2007 a new EU regulatory framework for chemicals. Under this new system called REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), enterprises that manufacture or import more than one ton of a chemical substance per year would be required to register it in a central database. This enhances the constraints for the color industry. Many dyes have demonstrated toxicity in the past. The new dyes developed have to prove their safety through adequate toxicity studies. Indeed, several parameters have to be tested as dyes present on the market (not cytotoxic) were recently proved to be mutagenic (Jager et al Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2004. 561(1-2): 35-44; Jager et al. Melliand English 2005: E12-E14; Schneider et al. Journal of Applied Toxicology 2004. 24: 83-91).
Azo dyes constitute the largest group of dyes, both with reference to the number of different chemical structures and to the total production volume (Zollinger H, Color Chemistry: syntheses, properties and applications of organic dyes and pigments. 2003, Weinheim: VCH). They are extensively used in textile dyeing and paper printing because of their great color variety. They generally present high molar extinction coefficients and medium to high light and wet fastness properties (Zollinger 2003). A survey of oral acute toxicity of 4461 dyes as measured by the 50% lethal dose has revealed that azo and cationic dyes are the most toxic, and there is ample evidence of the mutagenicity of certain dyes, especially azo dyes.
Developing new less toxic and non mutagenic azo dyes is therefore needed.
Additional problems are that the chemical synthesis pathways of traditional azo dyes are usually non worker-friendly processes and non environmental friendly processes.
Azo dyes are generally synthesized through diazotization followed by azo coupling. In general, diazotization of an aromatic or heteroaromatic primary amine is usually carried out at 0° C., due to the explosive character of the compounds, in presence of sodium nitrite and with an excess of mineral acid such as HCl, H2SO4, or HBF4. In the second step, the coupling to basic components requires higher pH. Such syntheses pose an environmental problem as high amounts of electrolytes are produced for the neutralization of the reaction mixture and purification of the dye, and sometimes, low yields result in highly colored effluents. Furthermore, the use of strong mineral acids is non worker friendly and the cooling under 5° C. required during the first step results in high energy consumption.
U.S. Pat. No. 4,709,019 describes anthraquinone azo pyridine containing compounds, and the synthesis thereof. The reactions are performed in nitrosylsulfuric acid or sulfuric acid in a sodium nitrite solution. These reactions are not worker friendly conditions and include steps at 0° C. and steps between 70° C. and 90° C., which is energivoracious and not environmental friendly.
GB 330644 describes the synthesis of azoanthraquinone. The azoanthraquinone is formed from diaminoanthraquinone derivatives by oxidation using chromic acid, which is a non environmental friendly process. Chromium (IV) compound are carcinogenic and toxic. For this reason chromic acid oxidation is not used at the industrial scale.
There is therefore a need to find improved methods for the preparation of azo dye, which are worker and environmentally friendly. It is accordingly one of the objects of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.
An objective of the present invention is therefore to provide new azo dyes, wherein at least one of the above mentioned drawbacks is overcome. In particular, it is an object of the present invention to provide new azo dyes amongst which some are less toxic than prior art dyes. It is a further object of the invention to provide method for the preparation of azo dyes which solves at least one of the above mentioned drawbacks.
The present invention concerns a compound having the structural Formula (I) or (II), a tautomer, a quaternary form, or a salt thereof,
wherein
R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-12arylene-hydroxyl, —N═N—C6-12arylene-SO3H, and —SO2—CH═CH2;
R2a is hydrogen or —SO3H;
R2b is hydrogen or —SO3H;
wherein at least one of R2a or R2b is —SO3H;
R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, aryloxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, C1-6alkylaminocarbonyl, and —NH-phenylene-SO2—CH═CH2;
R4 is selected from the group consisting of hydrogen, halogen, amino, —SO3H, C1-6alkyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R6 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R7 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, C1-6alkylaminocarbonyl, —C(OH)═CH—OH, and —NH-phenylene-SO2—CH═CH2;
R8 is hydrogen or —SO3H;
R9 is hydrogen or —SO3H;
R10 is selected from the group consisting of hydrogen, halogen, C1-6alkyl, amino, hydroxyl, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; and
R11 is selected from the group consisting of hydrogen, C1-6alkyl, amino, halogen, hydroxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl.
In an particular embodiment, the present invention concerns a compound having the structural Formula (I) or (II), a tautomer, a quaternary form, or a salt thereof,
wherein
R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-12arylene-hydroxyl, —N═N—C6-12arylene-SO3H, and —SO2—CH═CH2;
R2a is hydrogen or —SO3H;
R2b is hydrogen or —SO3H;
wherein at least one of R2a or R2b is —SO3H;
R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, C1-6alkylaminocarbonyl, and —NH-phenylene-SO2—CH═CH2;
R4 is selected from the group consisting of hydrogen, halogen, amino, —SO3H, C1-6alkyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R6 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R7 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, C1-6alkylaminocarbonyl, —C(OH)═CH—OH, and —NH-phenylene-SO2—CH═CH2;
R8 is hydrogen or —SO3H;
R9 is hydrogen or —SO3H;
R10 is selected from the group consisting of hydrogen, halogen, C1-6alkyl, amino, hydroxyl, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; and
R11 is selected from the group consisting of hydrogen, C1-6alkyl, amino, halogen, hydroxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl.
Some of the compounds according to the present invention have the advantage of being non mutagenic, and present a low cytoxicity and low ecotoxicity in the range of conditions tested. Some of the compounds have also a good optical density at the maximum wavelength.
Their method of production is preferably based on coupling by an oxidoreductase of precursors with aromatic amines structures in mild conditions. They provide the advantages of being safer and environmentally friend routes to azo dyes.
In particular, the present invention also concerns a process for the production of a compound of the invention, comprising the step of: coupling an amine of formula (Ia) with a compound of formula (Ib) or (IIb) in the presence of an oxidoreductase;
wherein R16 is selected from the group comprising hydrogen, C1-6cycloalkyl, C6-10aryl, haloC6-10aryl, 9,10-dioxoanthracenyl, or 4-p-tolyloxysulfonyloxy-phenyl;
R17 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, carboxyl and —NH-phenylene-SO2—CH═CH2; and
R18 is selected from hydrogen, or C6-12aryl; or
NH—R18 and R17 together with the carbon atom to which they are attached form a 5 membered heteroaryl or heterocyclyl ring, each ring being optionally substituted with one or two substituents selected from C1-6alkylcarbonyloxy or carboxyl;
wherein R1, R2a, R2b, R3, R4, R5, R6, R8, R9, R10, and R11 have the same meaning as defined herein.
The present invention provides a process that can be applied at reduced reaction temperature comparing to prior art conditions. In an embodiment, the pH of the present process is also milder than traditional chemical synthesis. The present process has the advantages of avoiding the use of dangerous reactant or the production of dangerous or explosive component and therefore provides advantage towards the reduction of the ecological footprint in industrial processes.
The compounds of the present invention can be used as dyes for textile, leather, hair, cosmetic or paper applications, or for biological staining. Beside the synthesis of new compounds, these findings open the way towards safe and environmentally friend routes to azo dyes.
The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
The present invention concerns azo compounds of Formula (I) or (II), a tautomer, a quaternary amine, or a salt thereof, wherein
R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-12arylene-hydroxyl, —N═N—C6-12arylene-SO3H, and —SO2—CH═CH2; preferably, R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-12arylene-hydroxyl, and —N═N—C6-12arylene-SO3H; preferably R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-10arylamino, haloC6-10arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-10arylene-hydroxyl, —N═N—C6-10arylene-SO3H, and —SO2—CH═CH2; preferably R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-10arylamino, haloC6-10arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-10arylene-hydroxyl, and —N═N—C6-10arylene-SO3H; preferably, R1 is selected from the group consisting of hydrogen, C1-4alkyl, C4-6cycloalkylamino, amino, hydroxyl, C1-4alkylamino, C6-10arylamino, haloC6-10arylamino, C1-4alkoxy, C1-4alkoxyC1-6alkyl, C1-4alkoxycarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, —N═N—CH═CH—C6-12arylene-hydroxyl, —N═N—C6-10arylene-SO3H, and —SO2—CH═CH2; preferably, R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-12arylene-hydroxyl, and —N═N—C6-12arylene-SO3H; more preferably, R1 is selected from the group consisting of hydrogen, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-10arylene-hydroxyl, and —N═N—C6-10arylene-SO3H; more preferably, R1 is selected from the group consisting of hydrogen, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—CH═CH—C6-10arylene-hydroxyl, and —N═N—C6-10arylene-SO3H; more preferably , R1 is selected from the group consisting of hydrogen, cyclohexylamino, amino, C1-6alkylamino, phenylamino, halophenylamino, aminocarbonyl, —N═N—CH═CH-phenylene-hydroxyl, and —N═N-phenylene-SO3H; more preferably, R1 is selected from the group consisting of hydrogen, cyclohexylamino, amino, C1-6alkylamino, phenylamino, aminocarbonyl, —N═N—CH═CH-phenylene-hydroxyl, and —N═N-phenylene-SO3H;
R2a is hydrogen or —SO3H; R2b is hydrogen or —SO3H; wherein at least one of R2a or R2b is —SO3H; for example when R2a is —SO3H; R2b is hydrogen, or when R2a is hydrogen; R2b is —SO3H;
R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C6-10aryloxy, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, C1-6alkylaminocarbonyl, and —NH-phenylene-SO2—CH═CH2; preferably, R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, and carboxyl; preferably, R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-4alkyl, amino, C1-4alkylamino, C6-10arylamino, C1-4alkoxy, C1-4alkoxyC1-6alkyl, C1-4alkoxycarbonyl, and carboxyl; preferably, R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-4alkyl, amino, C1-4alkylamino, phenylamino, C1-4alkoxy, C1-4alkoxyC1-6alkyl, C1-4alkoxycarbonyl, and carboxyl;
R4 is selected from the group consisting of hydrogen, halogen, amino, —SO3H, C1-6alkyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R4 is selected from the group consisting of hydrogen, halogen, amino, —SO3H, C1-6alkyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, and C1-6alkoxyC1-6alkyl; preferably, R4 is selected from the group consisting of hydrogen, halogen, amino, —SO3H, C1-4alkyl, carboxyl, C1-4alkylamino, C6-10arylamino, C1-4alkoxy, and C1-4alkoxyC1-6alkyl;
R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R5 is selected from the group consisting of hydrogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-4alkyl, hydroxyl, carboxyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, aminocarbonyl, and C1-4alkylaminocarbonyl; preferably, R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-4alkyl, hydroxyl, carboxyl, C1-4alkoxy, and C1-4alkoxyC1-4alkyl; preferably, R5 is selected from the group consisting of hydrogen, amino, nitro, —SO3H, C1-4alkyl, hydroxyl, carboxyl, C1-4alkoxy, and C1-4alkoxyC1-4alkyl;
R6 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R6 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkoxy, and aminocarbonyl; preferably, R6 is selected from the group consisting of hydrogen, halogen, amino, C1-4alkyl, and C1-4alkoxy; preferably, R6 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, and C1-4alkoxy; more preferably R6 is hydrogen;
R7 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, carboxyl, —C(OH)═CH—OH, and —NH-phenylene-SO2—CH═CH2; preferably, R7 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, —C(OH)═CH—OH, and aminocarbonyl; preferably R7 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, carboxyl, —C(OH)═CH—OH, and aminocarbonyl; preferably R7 is selected from the group consisting of hydrogen, halogen, amino, C1-4alkyl, C1-4alkylamino, C1-4alkoxy, C1-4alkoxyC1-6alkyl, carboxyl, —C(OH)═CH—OH, and aminocarbonyl; more preferably R7 is selected from the group consisting of hydrogen, halogen, amino, C1-4alkyl, carboxyl, —C(OH)═CH—OH, and C1-4alkoxy; more preferably R7 is hydrogen, halogen, carboxyl or —C(OH)═CH—OH;
R8 is hydrogen or —SO3H;
R9 is hydrogen or —SO3H;
preferably at least one of R8 and R9 is —SO3H; for example when R8 is —SO3H; R9 is hydrogen, or when R8 is hydrogen; R9 is —SO3H;
R10 is selected from the group consisting of hydrogen, halogen, C1-6alkyl, amino, hydroxyl, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R10 is selected from the group consisting of hydrogen, halogen, C1-6alkyl, amino, hydroxyl, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, and aminocarbonyl; preferably, R10 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, amino, hydroxyl, C1-4alkylamino, C4-6cycloalkylamino, phenylamino, C1-4alkoxy, and aminocarbonyl; preferably, R10 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, amino, hydroxyl, C1-4alkylamino, C4-6cycloalkylamino, and phenylamino; and
R11 is selected from the group consisting of hydrogen, C1-6alkyl, amino, halogen, hydroxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably, R11 is selected from the group consisting of hydrogen, C1-6alkyl, amino, halogen, hydroxyl, C1-6alkylamino, and C1-6alkoxy; preferably, R11 is selected from the group consisting of hydrogen, C1-4alkyl, amino, halogen, hydroxyl, C1-4alkylamino, and C1-4alkoxy; preferably, R11 is selected from the group consisting of hydrogen, C1-4alkyl, halogen, and C1-4alkoxy; more preferably, R11 is hydrogen.
As used in the foregoing and hereinafter, the following definitions apply unless otherwise noted.
The term “salt thereof” as used encompasses the fact that compounds of Formula (I) or (II) contain an acidic proton which can also be converted into their non-toxic metal or amine addition salt forms by treatment with appropriate organic and inorganic bases. Appropriate base salt forms comprise, for example, the ammonium salts, the alkali and earth alkaline metal salts, e.g. the lithium, sodium, potassium, magnesium, calcium salts and the like, salts with organic bases, e.g. primary, secondary and tertiary aliphatic and aromatic amines such as methylamine, ethylamine, propylamine, isopropylamine, the four butylamine isomers, dimethylamine, diethylamine, diethanolamine, dipropylamine, diisopropylamine, di-n-butylamine, pyrrolidine, piperidine, morpholine, trimethylamine, triethylamine, tripropylamine, quinuclidine, pyridine, quinoline and isoquinoline; the benzathine, N-methyl-D-glucamine, hydrabamine salts, and salts with amino acids such as, for example, arginine, lysine and the like. Conversely the salt form can be converted by treatment with acid into the free acid form.
The term “quaternary amine” as used hereinbefore defines the quaternary ammonium salts which the compounds of Formula (I) or (II) are able to form by reaction between a basic nitrogen of a compound of Formula (I) or (II) and an appropriate quaternizing agent, such as, for example, an optionally substituted alkylhalide, arylhalide or arylalkylhalide, e.g. methyliodide or benzyliodide. Other reactants with good leaving groups may also be used, such as alkyl trifluoromethanesulfonates, alkyl methanesulfonates, and alkyl p-toluenesulfonates. A quaternary amine has a positively charged nitrogen.
The term halo or halogen is generic to fluoro, chloro, bromo and iodo.
As used herein “C1-6alkyl”, as a group or part of a group, defines straight or branched chain saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as for example methyl, ethyl, prop-1-yl, prop-2-yl, but-1-yl, but-2-yl, isobutyl, 2-methyl-prop-1-yl; pent-1-yl, pent-2-yl, pent-3-yl, hex-1-yl, hex-2-yl, 2-methylbut-1-yl, 2-methylpent-1-yl, 2-ethylbut-1-yl, 3-methylpent-2-yl, and the like. Of interest amongst C1-6alkyl is C1-4alkyl.
Where C1-6alkyl groups as defined are divalent, i.e., with two single bonds for attachment to two other groups, they are termed “C1-6alkylene” groups. Non-limiting examples of alkylene groups includes methylene, ethylene, methylmethylene, propylene, ethylethylene, 1,2-dimethylethylene, and the like.
The term “C3-8cycloalkyl”, as a group or part of a group, is a cyclic alkyl group, that is to say, a monovalent, saturated hydrocarbyl group comprising from 3 to 8 carbon atoms and having 1, 2 or 3 cyclic structure. Examples of C3-8cycloalkyl groups include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl. When the suffix “ene” is used in conjunction with a cyclic group, this is intended to mean the cyclic group as defined herein having two single bonds as points of attachment to other groups.
The term “C6-12aryl”, as a group or part of a group, refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (i.e. phenyl) or multiple aromatic rings fused together (e.g. naphthalene), or linked covalently, typically containing 6 to 12 atoms; wherein at least one ring is aromatic. Non-limiting examples of C6-12aryl comprise phenyl, biphenylyl, biphenylenyl, or 1- or 2-naphthanelyl.
Where C6-12aryl groups as defined are divalent, i.e., with two single bonds for attachment to two other groups, they are termed “C1-6arylene” groups. Non-limiting examples of arylene groups includes phenylene and the like.
The term “amino” refers to the group —NH2.
The term “C1-6alkylamino”, as a group or part of a group, refers to a group of formula —N(Ra)(Rb) wherein Ra is hydrogen or C1-6alkyl as defined above, and Rb is C1-6alkyl as defined above. C1-6alkylamino include mono-C1-6alkylamino group such as methylamino and ethylamino and di-C1-6alkylamino group such as dimethylamino and diethylamino. Non-limiting examples of C1-6alkylamino groups include methylamino (NHCH3), ethylamino (NHCH2CH3), n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, n-hexylamino, dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, ethylmethylamino, methyl-n-propylamino, methyl-i-propylamino, n-butylmethylamino, i-butylmethylamino, t-butylmethylamino, ethyl-n-propylamino, ethyl-i-propylamino, n-butylethylamino, i-butylethylamino, t-butylethylamino, di-n-butylamino, di-t-butylamino, di-i-butylamino, methylpentylamino, methylhexylamino, ethylpentylamino, ethylhexylamino, propylpentylamino, propylhexylamino, and the like.
The term “C3-8cycloalkylamino”, as a group or part of a group, refers to a group of formula —N(Rg)(Rh) wherein Rg is hydrogen, C3-8cycloalkyl or C1-6alkyl as defined above, and Rh is C3-8cycloalkyl as defined above.
The term “C6-12arylamino”, as a group or part of a group, refers to a group of formula —N(Rd)(Rc) wherein Rd is hydrogen, C6-12aryl or C1-6alkyl as defined above, and Rc is C6-12aryl as defined above.
The term “C1-6alkoxy” or “C1-6alkyloxy”, as a group or part of a group, refers to a radical having the Formula —ORb wherein Rb is C1-6alkyl as defined above. Non-limiting examples of suitable C1-6alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy.
The term “C1-6alkoxyC1-6alkyl” or “C1-6alkyloxyC1-6alkyl”, as a group or part of a group, refers to a radical having the Formula —Re—ORb wherein Re is a C1-6alkylene, and Rb is C1-6alkyl as defined above.
The term “C1-6alkoxycarbonyl” or “C1-6alkyloxycarbonyl”, as a group or part of a group, refers to a group of formula —C(═O)—O—Rb, wherein Rb is C1-6alkyl as defined above.
The term “aminocarbonyl” refers to the group —(C═O)—NH2.
The term “C1-6alkylaminocarbonyl”, as a group or part of a group, refers to a group −(C═O)—NRaRb wherein Ra is hydrogen or C1-6alkyl as defined above, and Rb is C1-6alkyl as defined above.
The term “C6-12arylaminocarbonyl”, as a group or part of a group, refers to a group of formula —C(═O)—N(Rd)(Rc) wherein Rd is hydrogen, C6-12aryl or C1-6alkyl as defined above, and Rc is C6-12aryl as defined above.
The term “carboxy” or “carboxyl”, as a group or part of a group, refers to the group —CO2H.
The term “haloC6-12aryl”, as a group or part of a group, refers to a C6-12aryl radical having the meaning as defined above wherein one or more hydrogens are replaced with one or more halogens as defined above.
It should be noted that the group positions on any molecular moiety used in the definitions may be anywhere on such moiety as long as it is chemically stable.
Groups used in the definitions of the variables include all possible isomers unless otherwise indicated. For instance naphthalenyl includes naphthalen-1-yl and naphthalen-2-yl.
When any variable occurs more than one time in any constituent, each definition is independent.
As used in the specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. By way of example, “a compound” means one compound or more than one compound.
Some of the compounds of formula (I) may exist in their tautomeric form. Such forms although not explicitly indicated in the above formula are intended to be included within the scope of the present invention.
Preferred features of the compounds of this invention are now set forth.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein at least one of R8 and R9 is —SO3H, and R1, R2a, R2b, R3, R4, R5, R7, R10, R11 have the same meaning as defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R2a is —SO3H; and R2b is hydrogen and R1, R3, R4, R5, R3, R7, R8, R9, R10, R11 have the same meaning as defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R8 is —SO3H; and R9 is hydrogen, and R1, R2a, R2b, R3, R4, R5, R3, R7, R10, R11 have the same meaning as defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R2a is —SO3H; and R2b is hydrogen and wherein R8 is —SO3H; and R9 is hydrogen and R1, R3, R4, R5, R3, R7, R10, R11 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R2a is hydrogen; and R2b is —SO3H, and R1, R3, R4, R5, R3, R7, R8, R10, R11 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R8 is hydrogen; and R9 is —SO3H, and R1, R2a, R2b, R3, R4, R5, R3, R7, R10, R11 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R2a is hydrogen; and R2b is —SO3H and wherein R8 is hydrogen; and R9 is —SO3H and R1, R3, R4, R5, R3, R7, R10, R11 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R10 is selected from the group consisting of C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, —N═N—CH═CH—C6-12arylene-hydroxyl, and —N═N—C6-12arylene-SO3H, and R1, R2a, R2b, R3, R4, R5, R3, R7, R8, R9, R11 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R11 is hydrogen and R1, R2a, R2b, R3, R4, R5, R3, R7, R8, R9, R10 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, —N═N—C6-12arylene-SO3H, and —SO2—CH═CH2; preferably R1 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkylamino, amino, hydroxyl, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, and —N═N—C6-12arylene-SO3H;
R2a is hydrogen or —SO3H;
R2b is hydrogen or —SO3H;
wherein at least one of R2a or R2b is —SO3H;
R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, C1-6alkylaminocarbonyl, and —NH-phenylene-SO2—CH═CH2; preferably R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, carboxyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R4 is selected from the group consisting of hydrogen, halogen, amino, —SO3H, C1-6alkyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R5 is selected from the group consisting of hydrogen, halogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably R5 is selected from the group consisting of hydrogen, amino, nitro, —SO3H, C1-6alkyl, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R6 is selected from the group consisting of hydrogen, halogen, amino, and C1-6alkyl;
R7 is selected from the group consisting of hydrogen, halogen, amino, carboxyl, —C(OH)═CH—OH, and C1-6alkyl;
R8 is hydrogen or —SO3H;
R9 is hydrogen or —SO3H; wherein at least one of R8 or R9 is —SO3H;
R10 is selected from the group consisting of hydrogen, amino, hydroxyl, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; and
R11 is hydrogen.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R6 is hydrogen.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R1 is selected from the group consisting of hydrogen, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, —N═N—CH═CH—C6-12arylene-hydroxyl, and —N═N—C6-12arylene-SO3H; preferably hydrogen, cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, amino, C1-4alkylamino, phenylamino, naphthalenylamino, halophenylamino, —N═N—CH═CH-phenylenyl-hydroxyl, and —N═N-phenylenyl-SO3H; and R2a, R2b, R3, R4, R5, R3, R7, R8, R9, R10, R11 have the same meaning as that defined herein.
According to an embodiment, the present invention provides compounds of Formula (I) or (II), wherein R1 is selected from the group consisting of hydrogen, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, —N═N—CH═CH—C6-12arylene-hydroxyl and —N═N—C6-12arylene-SO3H;
R2a is —SO3H; and R2b is hydrogen;
R3 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, and carboxyl;
R4 is selected from the group consisting of hydrogen, —SO3H, C1-6alkyl, amino, halogen, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R5 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, nitro, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably R5 is selected from the group consisting of hydrogen, —SO3H, C1-6alkyl, amino, nitro, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R6 is hydrogen;
R7 is hydrogen, carboxyl or —C(OH)═CH—OH;
R8 is hydrogen or —SO3H;
R9 is hydrogen or —SO3H;
R10 is selected from the group consisting of hydrogen, halogen, C1-6alkyl, amino, hydroxyl, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; and
R11 is hydrogen.
According to an embodiment, the present invention provides compounds of Formula (I) wherein
R1 is selected from the group consisting of hydrogen, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, —N═N—CH═CH—C6-12arylene-hydroxyl, and —N═N—C6-12arylene-SO3H;
R2a is hydrogen or —SO3H;
R2b is hydrogen or —SO3H;
wherein at least one of R2a or R2b is —SO3H;
R3 is selected from the group consisting of hydrogen, —SO3H, C1-6alkyl, amino, halogen, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, and carboxyl;
R4 is selected from the group consisting of hydrogen, —SO3H, C1-6alkyl, amino, halogen, carboxyl, C1-6alkylamino, C6-12arylamino, and C1-6alkoxy;
R5 is selected from the group consisting of hydrogen, halogen, —SO3H, C1-6alkyl, amino, nitro, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; preferably R5 is selected from the group consisting of hydrogen, —SO3H, C1-6alkyl, amino, nitro, hydroxyl, carboxyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl;
R6 is hydrogen; and
R7 is hydrogen, carboxyl, or —C(OH)═CH—OH.
According to an embodiment, the present invention provides compounds of Formula (II), wherein
R1 is selected from the group consisting of hydrogen, C3-8cycloalkylamino, amino, C1-6alkylamino, C6-12arylamino, haloC6-12arylamino, and —N═N—C6-12arylene-SO3H;
R2a is hydrogen or —SO3H;
R2b is hydrogen or —SO3H;
wherein at least one of R2a or R2b is —SO3H;
R8 is hydrogen or —SO3H;
R9 is hydrogen or —SO3H;
R10 is selected from the group consisting of hydrogen, amino, C1-6alkylamino, C3-8cycloalkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, aminocarbonyl, and C1-6alkylaminocarbonyl; and
R11 is hydrogen.
The present invention also encompasses the compounds listed in Table 3, tautomers, salts or ammonium salts thereof.
The present invention also includes processes for the preparation of compounds of the invention.
The compounds of this invention can be prepared as described hereunder. They are generally prepared from starting materials which are either commercially available or prepared by standard means obvious to those skilled in the art. The compounds of this invention can be also prepared using standard synthetic processes commonly used by those skilled in the art of organic chemistry.
Compounds of Formula (I) or (II) can be prepared as illustrated in Schemes 1 or 2 respectively by reacting the amino moiety of a compound of formula (Ia) with the amino moieties of a compound of Formula (Ib) or (IIb) respectively,
wherein R16 is selected from the group comprising hydrogen, C1-6cycloalkyl, C6-10aryl, haloC6-10aryl, 9,10-dioxoanthracenyl, or 4-p-tolyloxysulfonyloxy-phenyl, preferably R16 is selected from the group comprising hydrogen, C1-6cycloalkyl, C6-10aryl, or haloC6-10aryl; more preferably, R16 is selected from the group comprising hydrogen, C1-6cycloalkyl, or C6-10aryl; more preferably, R16 is selected from the group comprising hydrogen or C1-6cycloalkyl;
R17 is selected from the group consisting of hydrogen, halogen, amino, C1-6alkyl, C1-6alkylamino, C6-12arylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, carboxyl and —NH-phenylene-SO2—CH═CH2; and
R18 is selected from hydrogen, or C6-12aryl; preferably hydrogen or phenyl; or
NH—R18 and R17 together with the carbon atom to which they are attached form a 5 membered heteroaryl or heterocyclyl ring, each ring being optionally substituted with one or two substituents selected from C1-6alkylcarbonyloxy or carboxyl, for example NH—R18 and R17 together with the carbon atom to which they are attached may form a pyrrolyl, said pyrrolyl being optionally substituted with one or two substituents selected from C1-6alkylcarbonyloxy or carboxyl;
and R1, R2a, R2b, R3, R4, R5, R6, R7, R8, R9, R10, R11 have the same meaning as defined herein.
Compounds of Formula (I) can also be prepared by reacting a compound of Formula (Ia) in the presence of an oxidoreductase.
The product may be readily purified from the reaction using the methods described herein.
In the reactions described, it may be necessary to protect reactive functional groups, for example hydroxy, amino, or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups can be used in accordance with standard practice, for example, see T. W. Greene and P. G. M. Wuts in “Protective Groups in Organic Chemistry”, John Wiley and Sons, 1999.
According to the present invention, compounds of Formula (I) or (II) may be may be produced through the use of oxidoreductases, for example produced by microorganisms. As compared to “whole cells” process using microorganisms which takes several days (for example three days) to synthesize the azo bond, the present process has the advantage of using isolated enzyme. This enzymatic process allowed reducing the reaction time to a few hours and is therefore an advantage. Since enzymes are produced by microorganisms (that can grow on wastes), the catalyst is therefore renewable, in contrast to traditional chemical catalysts.
According to an embodiment, the oxidoreductase enzyme suitable for use in said process is selected from the group consisting of laccase, peroxidase, cellobiose dehydrogenase, and tyrosinase.
In a preferred embodiment, laccase are used. Laccases show high potential as industrial biocatalysts. Laccases (EC 1.10.3.2) are benzenediol:oxygen oxidoreductases that oxidise a wide variety of organic compounds, causing O- and N-demethylation reactions, carbon-carbon bond cleavage or polymerizations (Burton S. Current organic chemistry 2003; 1317-1331). These biocatalysts require molecular oxygen as the electron acceptor therefore producing water (Solomon E I. et al Chemical Review 1996, 96 (17) 2563-2606). The use of this enzyme therefore represents an advantage for industrial applications. Moreover, laccases can be cheaply available as they may be secreted by some fungi in high level upon induction.
According to an embodiment, the laccase used in the present process is produced by white rot fungi.
The reaction mixture comprise a quantity of laccase either in solution or immobilized so that the resulting activity of the enzyme in the solution is equal to or greater than 1,10, 35, 50, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1150, 1200, 1250, 1300, 1400, 1500, 1600, 1700, 1800, 1900, or 2000 U.L−1 or a value in the range between any two of the aforementioned values, preferably between 1 and 1000 U.L−1. Preferably the laccase is used in a quantity of at least 10 U.L−1, preferably above 10 U.L−1, for example of at least 20 U.L−1, of at least 30 U.L−1, of at least 40 U.L−1, more preferably of at least 50 U.L−1, preferably of at least 60 U.L−1, preferably of at least 70 U.L−1, more preferably of at least 80 U.L−1, yet more preferably of at least 90 U.L−1, yet more preferably of at least 100 U.L−1.
Preferably, the enzyme for use in said process can be used as a free enzyme or as an immobilized enzyme. In an embodiment said enzyme is immobilized on a solid support. In an embodiment, said process is performed using immobilized enzyme with or without support. Suitable solid supports can be selected from the non-limiting group comprising glass beads, perlite, montmorillonite, alginate and carrageenan. Preferably said solid support is perlite.
According to an embodiment, the coupling reaction is performed in a bioreactor.
The reaction is preferably performed aerobically using common glassware (e.g. beaker or flask) agitated by magnetic stirrer, or by agitation in shaking flasks or using a fermentor, if appropriate with the introduction of air or oxygen. In an embodiment, the process also comprises the step of at least sequentially agitating or aerating, or oxygenating the reaction mixture or performing the reaction under overpressure of oxygen.
In an embodiment, said reaction is performed under overpressure of oxygen, more preferably at about 2 atmospheric bars.
According to an embodiment, the reaction is performed at a pH between about 3 and 9, preferably at a pH between about 4 and 8, more preferably at a pH between about 4 and 7, yet more preferably at a pH between about 4 and 6, yet more preferably at a pH between about 4 and 5, preferably at pH of about 4.5. According to an embodiment, the reaction is performed in a buffer selected from the group comprising tartaric buffer, acetate buffer, phosphate borate buffer. Preferably the reaction is performed in tartaric buffer.
The enzymatic reaction can be performed at temperatures ranging from about 15-60° C., preferably about 20-50° C., preferably about 20-40° C., yet more preferably about 20-30° C. In a preferred embodiment, the enzymatic reaction is performed at room temperature. Downstream processing can be through classical processes, including, but not limited to salting out, lyophilization, spray drying, air drying and the like.
The course of the reaction can be monitored with the aid of the pH measurement of the medium, the aid of HPLC method, spectrophotometric method or by thin layer chromatography. The compounds of interest are isolated from the reaction mixture by known methods, taking into account the chemical, physical and biological properties of the products.
The skilled person will appreciate that reaction products and unreacted reagents may be detected by thin layer chromatography on silica gel with polar solvent mixture, for example n-butanol/acetic acid/water or methylethylketone/acetone/water as the mobile phase. Alternatively the detection can be carried out by known liquid chromatographic methods (e.g. HPLC), and by mass spectrometry.
The compound can be further purified by appropriate filtration through a plug of reversed phase silica gel with water as the mobile phase up to a purity of about 90%. Further purification can be accomplished by known methods, for example, using semi-preparative HPLC.
The compounds of Formula (I) or (II) are particularly convenient to dye textile, leather, hair and other articles. The compounds are particularly useful as red dyes.
Also part of the invention, is the use of the compounds of the present invention as a dye for dyeing natural or synthetic materials such as paper, cellulose, polyamide, hair, leather or glass fibers.
The present invention therefore encompasses a method of dyeing an article or a substrate comprising the step of contacting said article or substrate with a compound of Formula (I) or (II) according to the invention.
Suitable articles for this dyeing method can be made of a material selected from a fabric, yarn, fiber, garment or film made of a material selected from the group consisting of fur, hair, hide, leather, silk, wool, cationic polysaccharide, synthetic polyamide, and the like.
The dye according to the invention particularly provides an even coloration on acetate, cotton, nylon, PES, acrylic and wool keratin, fibers with favorable dyeing properties such as good fastness to light, washing, rubbing and perspiration.
The present compounds according to the invention are particularly suitable for dyeing organic materials, such as keratin-containing fibers, wool, leather, silk, cellulose or polyamides, cotton or nylon, and preferably human hair.
The dyeings obtained are distinguished by their depth of shade and their good fastness properties to washing, such as, for example, fastness to light, shampooing and rubbing. The stability, in particular the storage stability of the dyes according to the invention are excellent.
The present invention also encompasses formulation containing at least one compound of Formula (I) or (II).
Formulations, containing dyes according to the invention of the structural Formula (I) or (II) provide an even coloration for example on keratin fibers, in particular human hair, with favorable dyeing properties such as good fastness to light, washing, rubbing and perspiration. Natural colorations with low selectivity can be obtained already under gentle conditions.
The dyes of the structural Formula (I) or (II) according to the invention are preferably present in the formulation according to the invention in a total amount of from about 0.01 to 10% by weight, preferablyfrom about 0.1 to 8% by weight, more preferably from 0.1 to 7% by weight, preferably from 0.3 to 6% by weight, preferably from 0.4 to 5% by weight, in particular 0.5 to 4% by weight.
To produce special color shades, besides the dyes of the structural Formula (I) or (II) according to the invention, it is possible to add to the compounds according to the invention or to the formulation according to the invention, one or more additional customary direct dye from the group consisting of acidic dyes, basic dyes, nitro dyes, azo dyes, anthraquinone dyes and triphenylmethane dyes. In addition, the formulations according to the invention can also comprise naturally occurring dyes, such as, for example, henna red, henna neutral, henna black, camomile, sandalwood, black tea, buckthorn bark, sage, logwood, madder root, catechu, sedre and alkanna root.
The abovementioned additional direct dyes and naturally occurring dyes may be present in a total amount of from about 0.01 to 5% by weight, the total content of dyes in the formulations according to the invention being preferably from about 0.01 to 10% by weight, in particular about 0.1 to 5% by weight.
The present invention also covers articles or substrate dyed with a compound of Formula (I) or (II).
The following examples are intended to illustrate the present invention and not to limit it thereto.
Compounds of Formula (I) or (II) may be prepared according to any of the protocol N to T.
The compounds may be produced by the reaction of two precursors listed in Table 1 or by the reaction of a precursor listed in Table 1 with a precursor listed in Table 2. Said reaction is preferably performed in the presence of enzymes, in particular oxidoreductase enzyme. Suitable oxidoreductase used for the preparation process can be selected from the group consisting of laccases, peroxidases, cellobiose deshydrogenases and tyrosinases, and preferably laccases.
Unless indicated otherwise, All reagents used were either obtained commercially or were prepared in a manner known per se.
Unless indicated otherwise, the enzyme activity was determined according to protocols A or B.
Protocol A:
Laccase activity was determined by oxidation of ABTS [2′,2-azino-bis-(3-ethylbenzo thiazoline-6-sulfonic acid)] (4 mM) (Sigma-Aldrich) into a stable cationic radical ABTS·+ (absorption coefficient, εM=34 220 M−1.cm−1) in tartaric buffer (100 mM) at pH 4.5. One unit was defined as the amount of enzyme that oxidizes 1 μmol of ABTS per minute. The increase in absorbance at 414 nm was monitored during about 2 min with a Beckman DU-800 spectrophotometer connected to a high performance temperature controller (Analis, Namur, Belgium), which maintained the temperature of the reaction mixture at 25° C.
Protocol B:
Cellobiose dehydrogenase activity was assessed using a modified protocol from Baminger et al. J Microbiol Meth 1999. 35:253-9. Lactose was replaced by cellobiose. One unit of enzyme activity was defined as the amount of enzyme reducing 1 μmol of DCIP (2,6-dichlorophenol-indolophenol)/min.
Unless indicated otherwise, the biocatalytic material was prepared according to protocol C.
Protocol C:
Biocatalytic material was prepared as following. Perlite Perlagri 40 was firstly silanized by immersion in acetone containing aminopropyltrimethoxysilane (APTES—4%) during 24 h at 45° C. under stirring. The supernatant was removed and carrier was dried at 45° C. during 24 h. Carrier was activated by immersion in phosphate buffer containing 5% glutaraldehyde under magnetic stirring during 2 h at 4° C. After washing, the carrier was filtered on Duran no4 filter and 1 L of water containing Enzymatic powder (125 mg) was mixed with activated carrier. The immobilized enzyme was finally stored at 4° C. in acidic water pH 4.5 before being packed in a column.
Unless indicated otherwise, the bioreactor was prepared according to protocol D.
Protocol D:
The biocatalytic material was rinsed with acid water (pH 4.5, HCl) and was used to fill the enzymatic bioreactor (Minilab, Wetlands, Belgium), following the instructions of the manufacturer.
Unless indicated otherwise, the reactions were followed up according to protocol E.
Protocol E: Spectrophotometric Follow Up of Biotransformation.
Sampling were made at interval times and scanning was realized between 300 and 700 nm with a Beckman DU-800 spectrophotometer connected to a high performance temperature controller (Analis, Namur, Belgium) at 25° C. The decrease in absorbance at the maximum wavelength was monitored. Increase at maximal wavelength of the product was also monitored.
Unless indicated otherwise, the biotransformation monitoring and compound production, isolation and/or purification were performed according to protocol F, G, H I, and/or J.
Protocol F:
Monitoring of the biotransformation was made through thin layer chromatography, using pre-coated TLC plates SIL G-25 (Macherey Nagel) with methylethylketone/acetone/water (80/20/80:v/v/v) as eluant.
Protocol G:
Capillary electrophoresis analysis was carried out with a P/ACE MDQ Beckman Coulter equipped with a photodiode array UV/Vis detector controlled by a P/ACE station software (Analis, Gent, Belgium). The fused-silica capillary (Analis, Gent, Belgium) (50 cm 75 lm ID) was maintained in a cartridge with a detection window of 100·800 lm. The separation voltage was 25 kV. The procedure consisted of an initial 1 min wash with NaOH 0.1 M under 138 kPa followed by a 1 min wash with the initiator (provided by Analis) under 138 kPa. The capillary was then flushed with the buffer MEKC 9.2 during 2 min at 138 kPa. When a constant run current was achieved, the sample was injected by hydrodynamic injection for 5 s under 3.5 kPa, followed by injection of water during 10 s under 0.7 kPa. A 20 min separation step was performed under a 25 kV potential. After the completion of the procedure, the capillary was rinsed with NaOH 0.1 M during 1 min under 138 kPa. The absorbance from 190 to 600 nm was monitored with an on-column photodiode array detector and acquisition of the electrophoregram was performed at 190 nm.
Protocol H:
HPLC follow up was performed with a system comprising a Waters pump, a Waters 996 photodiode array detector (for analytical separations) or a Waters 486 absorbance detector (for semi-preparative HPLC) (Waters, Milford, Mass., USA). Analytical separations were performed with a Waters Novapack C-18 column (4.6·250 mm). The mobile phase was acetonitrile/water (10/90 of analytical grade). The flow rate was 0.3 ml min—1. Samples were filtered and injected. Detection was performed at 220 nm and on-line UV-Vis absorbance scans were performed.
Protocol I:
Semi-preparative HPLC was performed with a Waters Novapack C-18 column (22·250 mm) (Waters, Milford, Mass., USA). The mobile phase was acetonitrile as eluent A and water as eluent B. The gradient applied was 10/90 (A/B: v/v) over 10 min, 15/85 (A/B: v/v) over 10 min, 20/80 (A/B: v/v) over 10 min and 25/75 (A/B: v/v) over 10 min. The flow rate was 20 ml min—1. On-line UV-Vis absorbance scans were performed.
Protocol J: Dye Recovery
In order to precipitate the dye, samples were treated with 0.9 M NaCl. A centrifugation was then carried out.
Unless otherwise indicated, NMR spectra were determined according to protocol K.
Protocol K:
The 1H and 13C NMR spectra were recorded using a Bruker Avance 500 spectrometer (Bruker, Wissembourg, France) in D2O or MeOD as solvent. Spectra are reported in ppm. Spectra in D2O were obtained with 2,2-dimethyl-2-silapentane-5-sulfonate sodium (DSS) as internal standard.
Unless otherwise indicated, mass spectra were acquired and analyzed according to protocol L1 or L2.
Protocol L1:
ESI/MS. The mass spectra were acquired using a Thermo Finnigan Ion Trap LCQ spectrometer, equipped with an ESI source (Thermo electron, San Jose, Calif., USA). High Resolution Mass Spectrometry (HRMS) analysis was performed at University of Mons-Hainaut (Belgium).
Protocol L2:
ESI/MS. The mass spectra were acquired using a Waters micromass ZMD MC364 spectrometer.
Unless otherwise indicated, the precursors were prepared according to protocol M.
Protocol M:
To a solution of 1-bromaminic acid, sodium salt (0.404 g, 1 mmol) in water/ethanol 9/1 (100 mL) were added the appropriate amine (2 mmol), Na2CO3, 10 H2O (0.645 g, 2.25 mmol) and CuSO4, 5 H2O (0.312 g, 1.25 mmol). The mixture was stirred at reflux during 4 hours. After evaporation, the residue was dissolved in H2O (100-150 mL). NaCl (40 g) was added and the solution was stirred at room temperature during 1-2 h and filtered. The precipitate was purified by column chromatography on RP18 silica gel using a mixture of water/methanol 1/1 as eluent.
Compounds of Formula (I) or (II) may be prepared according to any one of protocols N to T.
Protocol N:
The precursor (62.5 μM) was solubilized in phosphate borate buffer 0.05 M pH 4.5 and biotransformation was carried out in the presence of 10 U/L of Pycnoporus sanguineus laccase. The enzyme activity was determined using protocol A. Reaction was performed at 25° C. during 24 h.
Protocol O:
Precursors (500 μM each) were solubilized in tartaric buffer 0.1 M and the biotransformation was carried out in the presence of 100 U/L of laccase. Enzyme activity was determined using protocol A. Reaction was performed at about 25° C. during about 24 h. Samples were withdrawn and diluted 10 time for spectrophotometric measurement.
Protocol P:
Precursors (875 μM) were solubilized in malt extract 20 g/L. Reaction was carried out at about 25° C. during about 24 h in the presence of Cellobiose dehydrogenase. Enzyme activity was determined using protocol B.
Protocol Q:
Precursors (875 μM) were solubilized in acetate buffer 0.05 M pH 4. Reaction was carried out at about 25° C. during about 24 h in presence of 1 μg/L Tyrosinase (Sigma).
Protocol R:
Precursor was solubilized in water (2.35 mM) and in acetate buffer (50 mM pH 4.5) and a 1 liter volume of precursor was passed through the bioreactor (protocol D) containing 500 U L−1 immobilized lactase (protocol C) at a flow rate of about 100 ml/min (total: 10 min) at 25° C. After the passage, the medium was oxygenated during about 15 min, and then passed again on the bioreactor. The process was repeated about 14 times, with a total contact time between precursor and enzyme of 2 h 20 hours. A maturation phase was obtained by only letting the medium during 24 h at room temperature. Dye was recovered from the medium following protocol J.
Protocol S:
Precursor (11.85 mM) was solubilized in acetate buffer 0.1 M pH 4.5. Biotransformation was carried out in the presence 250 U L−1 laccase. Enzyme activity was determined using protocol A. The reaction was carried out at about 25° C., under agitation.
Protocol T:
Precursor (1.54 mM) was solubilized in tartaric buffer 100 mM pH 4.5. Biotransformation was carried out in the presence of 35 U.l−1 laccase. Enzyme activity was determined using protocol A. Reaction was carried out at about 25° C.
Structural formulas of suitable precursors are listed in Tables 1 and 2.
Compound 1 was synthesized, by biotransformation of Precursor I1 following protocol T. biotransformation was analyzed by CE (protocol G), HPLC (protocol H) purified by semi preparative HPLC (protocol I) and analyzed by NMR (protocol K), and ESI (protocol L1).
Results are conformed to the expected structure:
C34H24N4O10S2Na2; Preparative HPLC tR: 31 min; analytical HPLC tR: 10 min; CE tm: 13 min; IR (KBr) v 3500, 2931, 1666, 1629, 11593, 1582, 1484, 1402, 1204, 1047, 1021, 732 cm−1; MS (ESI negative mode) m/z (%) 356 (100, [M−2Na]2−), 713 (58, [M−2Na+H]−), 735 (33, [M−Na]−); HRMS (ESI positive mode) m/z found: 715.1165, calc.: 715.1169 (C34H27N4O10S2). 1H NMR δ (500.2 MHz, MeOD) 1.44 (1 H, m), 1.55 (4 H, m), 1.71 (1 H, m), 1.86 (2 H, m), 2.16 (2 H, m), 3.78 (1 H, m), 7.71 (2 H, t), 7.79 (2 H, q), 7.89 (1 H, s), 7.97 (2 H, t), 8.26 (2 H, dd), 8.65 (1 H, s); 13C NMR δ (125.8 MHz, MeOD) 25.48, 26.82, 33.93, 52.12, 114.31, 114.44, 118.00, 127.22, 127.48, 127.82, 127.85, 129.41, 132.16, 134.38, 134.52, 134.76, 134.90, 135.35, 135.49, 135.90, 136.19, 143.45, 144.52, 145.91, 150.91, 151.38, 185.40, 185.62, 186.37, 186.55
Alternatively compound 1 was synthesized through protocols N, O, P, Q, R, or S.
The bioconversion of I1 using tyrosinase or CDH (protocols P and Q) was analyzed through TLC (protocol F). rf of the product was 0.38 and was the same as the one obtained for laccase bioconversion (protocol T).
At increased substrate concentration following protocol S a yield of 70% was reached.
In an improved method, protocol C, D and R were combined and allowed, in 2 hour 30 of contact with the biocatalytic material, the production of dye free of enzyme (no risk of skin sensitivity due to the enzyme protein into the dye) as well as the reuse of the biocatalytic material.
Compound 2 was synthesized, by biotransformation of Precursor I4 following protocol N. biotransformation was followed by spectrophotometry (protocol E), TLC (protocol F) and ESI (protocol L1). m/z was 483 in negative mode.
Compound 3 was synthesized, by biotransformation of I5 (synthesized through protocol M) using protocol N. Biotransformation was followed by spectrophotometry (protocol E) TLC (protocol F) and ESI (protocol L1). m/z was 550 in negative mode.
Compound 4 was synthesized, by biotransformation of precursors I1 and I7 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L1) and TLC (protocol F). m/z was 590 (sodium adduct) in negative mode.
Compound 5 was synthesized, by biotransformation of precursors I1 and I7 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L1) and TLC (protocol F). m/z were 654 (sodium adduct) and 676 (di sodium adduct) in negative mode.
Compound 6 was synthesized, by biotransformation of precursors I1 and I10 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L1) and TLC (protocol F). m/z was 590 (sodium adduct) in negative mode.
Compound 7 was synthesized, by biotransformation of precursors I1 and I10 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L1) and TLC (protocol F). m/z were 654 (sodium adduct) and 676 (di sodium adduct) in negative mode.
Compound 8 was synthesized, by biotransformation of precursors I1 and I12 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L1) and TLC (protocol F). m/z was 546 in negative mode.
Compound 9 was synthesized, by biotransformation of precursors I1 and I21 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L1) and TLC (protocol F). m/z was 489 in negative mode.
Compound 10 was synthesized, by biotransformation of precursors I1 and I22 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 518.9 in negative mode.
Compound 11 was synthesized, by biotransformation of precursors I1 and I23 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 533 in negative mode.
Compound 12 was synthesized, by biotransformation of precursors I1 and I13 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 532 in negative mode.
Compound 13 was synthesized, by biotransformation of precursors I1 and I24 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 532 in negative mode.
Compound 14 was synthesized, by biotransformation of precursors I1 and I26 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 536 in negative mode.
Compound 15 was synthesized, by biotransformation of precursors I1 and I28 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L) and TLC (protocol F). m/z was 562 in negative mode.
Compound 16 was synthesized, by biotransformation of precursors I1 and I29 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 576 in negative mode.
Compound 17 was synthesized, by biotransformation of precursors I1 and I30 following protocol O. Biotransformation was followed by spectrophotometry (protocol E) and ESI (protocol L2) and TLC (protocol F). m/z was 580 in negative mode.
The present invention encompasses compounds as illustrated in Table 3 as well as tautomers, and salts thereof.
Table 4 shows some characteristics of compounds in their reaction medium.
Polyamide knitted fabric dyeing—Knitted polyamide 6 was immersed in a dye bath at 40° C., containing the dye solution (0.21%, 0.42%, 2.5% omf), Setacid VS-N (buffering agent—2 g L−1) and Setalan PM-8 (leveling agent—1 g L−1). The liquor ratio was 20/1. The pH was adjusted to 6.5 to 7.5 by adding sodium bicarbonate (0.2-0.3 g L−1). The temperature was raised to 105° C. over 40 min. The dyeing was continued at 105° C. for 40 min. The final pH of the dyebath was between 4.2 and 4.3. The dyed pieces were there rinsed twice at 40 and 25° C. for 5 min (liquor ratio 20/1). Fabrics dyed using 2.5% on mass of fabric (omf) were used for fastness tests as their depth corresponded to the standard depth scale as published by the society of dyers and colorists.
Shade was characterized by reflectance measurements with DataColor SF600 spectrophotometer with 10 nm band width using U.V. excluded and specular included measurements. Spectral range was from 360 to 700 nm. Light source was Pulsed Xenon filtered to appropriated to D65 and optical geometry was dual beam, the angle of viewing was 8° in 6 inches diameter sphere with an aperture size of 26 mm measured and 30 mm illuminated. The Software was Hunter Lab She Lyn.
Polyamide yarn dyeing—Polyamide 6.6 yarn was immersed in an acid dye bath (pH 5.2) containing 1% omf leveling agent Alvolan UL75 at 40° C., liquor ratio 10/1. Compound 1 was added and temperature was raised at 0.5° C. min−1 to 100° C. during 60 min. The bath was then cooled (3° C. min−1) to 60° C. The dyed pieces were there rinsed twice at 40° C. and 25° C. for 5 min (liquor ratio 10/1).
Leather dyeing—Bovine wet blue samples of approximately 30 g were neutralized to pH about 7.4 into a small glass drum using sodium formate (2% omf) and sodium bicarbonate (2.5% omf), liquor ratio 2/1, at 35° C. for 100 min. After the neutralization step, the drum was drained and the samples were retanned using mimosa (3% omf), liquor ratio 2/1 at 35° C. for 30 min. The dyeing was carried out with compound 1 (3% omf) during 30 min. The dye uptake of the leather was determined using a UV-Visible Spectrophotometer (Varian Cary 50 Bio). The samples were then fat liquored using Ombella WR (5% omf) during 40 min at 50° C. and fixed using formic acid (0.2% omf) during 30 min at 50° C.
The fastness properties of the dyeings (textile and leather) were measured in accordance with ISO standards mentioned in table 5. The results are shown in Table 5 based on visual assessment described in ISO105-A02: 1993 textiles—test for colorfastness—part A02. On this scale, a rating of 5 means no color change and a rating of 1 means a high color change.
The dyeing properties of compounds 1, 2 and 4 were tested on samples of knitted fabric.
Knitted silk was immersed in a dye bath at 40° C., containing the dye solution (2% omf) buffered at pH 6.5 with acetic acid. The liquor ratio was 20/1. The dyeing was continued at 95° C. for 1 hour. Salt was added (100% omf) and the dyeing was continued at 95° C. for 1 hour. The dyed pieces were rinsed 3 times at 40° C. with water. After drying, color of the sample was evaluated visually. The results are shown in
The toxicity of compound 1 was compared with the toxicity of disperse red 1, reactive red 4, direct red 28, and acid red 299, which are products available on the market.
Toxicity was assessed on human intestinal cells (Caco-2), bacterial cells (Lumistox assays) and fish eggs cells. Mutagenicity was assessed through classical Ames test. The results are shown in Table 6.
The results showed that the compounds presented a low toxicity and no mutagenicity in the range tested.
The toxicity of compound 4 has been measured on Caco-2 human cells as previously described, and compared with the toxicity of compound 1. The results are shown in
This application claims priority to U.S. Provisional Application No. 61/078,675, filed Jul. 7, 2008, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61078675 | Jul 2008 | US |
