Compatible-multiphase organic solvent system

Abstract

A solvent system which comprises two or more single organic solvents or two or more mixed organic solvents, characterized in that the state of the solvent system can be reversibly changed, with changing temperature conditions, from one state which is a homogeneously compatibilized mixed solvent system in which the two or more single or more mixed organic solvents constituting the solvent system have been homogeneously compatibilized and mixed to the other state which is a separated solvent system made up of two or more separated phases respectively consisting mainly of the two or more single or mixed organic solvents constituting solvent system, and that when the solvent system is the homogeneously mixed solvent system, a chemical component which is soluble in only one of the single or mixed organic solvents can be evenly dissolved in the system; and a process for producing a compound with the solvent system.

What is claim:  
     
         1 . A solvent system comprising, two or more single organic solvents or two or more mixed organic solvents, and said solvent system can change the state reversibly by changing temperature condition from one state which is a homogeneously compatibilized mixed solvent system in which two or more single organic solvents or two or more mixed organic solvents constituting the solvent system are homogeneously compatibilized and mixed to another one state which is a separated solvent system in which the solvent system is separated into two or more phases consisting mainly of the two or more single organic solvents or mixed organic solvent constituting the solvent system, and can dissolve the chemical component which is soluble in only one organic solvent or mixed organic solvent homogeneously.  
     
     
         2 . The solvent system of  claim 1 , wherein one organic solvent or mixed organic solvent is composed of cycloalkanes and another single organic solvent or mixed organic solvent is composed of at least one selected group consisting of nitroalkane, nitrile, alcohol, halogenated alkyl, amide and sulfoxide.  
     
     
         3 . The solvent system of  claim 2 , wherein carbon number of alkyl group of nitro alkane is 1, 2 or 3, carbon number of alkyl group of nitrile is 1, 2 or 3, amide is N-dialkyl or N-monoalkyl amide, the total carbon number of alkyl group and formyl group or acyl group is 6 or less, carbon number of alcohol is 8 or less, carbon number of alkyl group of sulfoxide is 1, 2 or 3 and carbon number of alkyl group of halogenated alkyl is 6 or less.  
     
     
         4 . The solvent system of  claim 1 , wherein the chemical component takes part in the reaction, and a phase whose main component is at least one organic solvent or mixed organic solvent constructing the solvent system dissolves at least one component of the chemical components which take part in the reaction, and in the state of separated solvent does not satisfy the condition which progress the substantial chemical reaction, and only in the state of homogeneous compatibilized mixed solvent system satisfies the condition which progress the substantial chemical reaction.  
     
     
         5 . The solvent system of  claim 4 , wherein one organic solvent or mixed organic solvent is composed of cycloalkanes and another organic solvent or mixed organic solvent is composed of at least one selected group consisting of nitroalkane, nitrile, alcohol, halogenated alkyl, amide and sulfoxide.  
     
     
         6 . The solvent system of  claim 5 , wherein carbon number of alkyl group of nitro alkane is 1, 2 or 3, carbon number of alkyl group of nitrile is 1, 2 or 3, amide is N-dialkyl or N-monoalkyl amide, the total carbon number of alkyl group and formyl group or acyl group is 6 or less, carbon number of alcohol is 8 or less, carbon number of alkyl group of sulfoxide is 1, 2 or 3 and carbon number of alkyl group of halogenated alkyl is 6 or less.  
     
     
         7 . A method for preparation of compound comprising, using the solvent system of two or more single organic solvents or two or more mixed organic solvents, and said solvent system can change the state reversibly by changing temperature condition from one state which is a homogeneously compatibilized mixed solvent system in which two or more single organic solvents or mixed organic solvents constituting the solvent system are homogeneously compatibilized and mixed to another one state which is a separated solvent system in which the solvent system is separated into two or more phases consisting mainly of the two or more single organic solvents or two or more mixed organic solvents constituting the solvent system, and can dissolve the chemical component which is soluble in one single organic solvent or mixed organic solvent homogeneously, using a chemical component which takes part in the reaction, after said chemical component is added, the reaction is progressed under the temperature condition realizing the state of homogeneous compatibilized mixed solvent system which satisfy the condition of chemical reaction, then the condition is changed to the temperature by which two or more single organic solvents or two or more mixed organic solvents is separated into two or more phases consisting mainly of the two or more single organic solvents or two or more mixed organic solvents, recovering by separating the generated product in one phase composing single organic solvents or mixed organic solvents as the main component as a deposit.  
     
     
         8 . The method for preparation of the compound of  claim 7 , wherein one organic solvent or mixed organic solvent is composed of cycloalkanes and another single organic solvent or mixed organic solvent is composed of at least one selected group consisting of nitroalkane, nitrile, alcohol, halogenated alkyl, amide and sulfoxide.  
     
     
         9 . The method for preparation of the compound of  claim 8 , wherein carbon number of alkyl group of nitro alkane is 1, 2 or 3, carbon number of alkyl group of nitrile is 1, 2 or 3, amide is N-dialkyl or N-monoalkyl amide, the total carbon number of alkyl group and formyl group or acyl group is 6 or less, carbon number of alcohol is 8 or less, carbon number of alkyl group of sulfoxide is 1, 2 or 3 and carbon number of alkyl group of halogenated alkyl is 6 or less.  
     
     
         10 . The method for preparation of the compound of  claim 7 , wherein electrolyte is used as the chemical component which takes part in the reaction, and the reaction is progressed by electrolysis.  
     
     
         11 . The method for preparation of the compound of  claim 10 , wherein one organic solvent or mixed organic solvent is composed of cycloalkanes and another organic solvent or mixed organic solvent is composed of at least one selected group consisting of nitroalkane, nitrile, alcohol, halogenated alkyl, amide and sulfoxide.  
     
     
         12 . The method for preparation of the compound of  claim 11 , wherein carbon number of alkyl group of nitro alkane is 1, 2 or 3, carbon number of alkyl group of nitrile is 1, 2 or 3, amide is N-dialkyl or N-monoalkyl amide, the total carbon number of alkyl group and formyl group or acyl group is 6 or less, carbon number of alcohol is 8 or less, carbon number of alkyl group of sulfoxide is 1, 2 or 3 and carbon number of alkyl group of halogenated alkyl is 6 or less.  
     
     
         13 . The method for preparation of the compound of  claim 7 , wherein the reaction is progressed by irradiating the light of ultra violet-visible light.  
     
     
         14 . The method for preparation of the compound of  claim 13 , wherein one organic solvent or mixed organic solvent is composed of cycloalkanes and another organic solvent or mixed organic solvent is composed of at least one selected group consisting of nitroalkane, nitrile, alcohol, halogenated alkyl, amide and sulfoxide.  
     
     
         15 . The method for preparation of the compound of  claim 14 , wherein carbon number of alkyl group of nitro alkane is 1, 2 or 3, carbon number of alkyl group of nitrile is 1, 2 or 3, amide is N-dialkyl or N-monoalkyl amide, the total carbon number of alkyl group and formyl group or acyl group is 6 or less, carbon number of alcohol is 8 or less, carbon number of alkyl group of sulfoxide is 1, 2 or 3 and carbon number of alkyl group of halogenated alkyl is 6 or less.  
     
     
         16 . A method for preparation of peptide utilising the solvent system of  claim 1  for preparation of peptide by liquid phase synthesis comprising, 
 using the combination with carrier induced from the compound possible to improve the solubility to one solvent composing solvent system which can control said condition or to the mixed solvent A as the constituting part of a soluble carrier to which an amino acid residue of the carboxy end of peptide to be synthesised is introduced,  
 the solubility of the compound whose peptide chain is extended by introducing amino acid gradually to peptide bonded with amino acid residue carrier of carboxy end of peptide to be synthesised or to said peptide to said solvent or mixed solvent A is improved,  
 using the solvent which dissolves various amino acid used for the extension of said peptide chain preferentially at the lower temperature than the temperature to form mentioned compatibilized condition and at the higher temperature than the temperature to form mentioned compatibilized condition forming a solvent in compatibilized condition and dissolving the peptide as another solvent to be combined with said solvent or mixed solvent A or mixed solvent B,  
 substituting above mentioned B which dissolves β-amino protected amino acid with the solvent which dissolves designed peptide in phase separated condition, then changing the condition from said separated state to the homogeneous state by heating after substitution.  
 
     
     
         17 . The method for preparation of the peptide by liquid phase synthesis of  claim 15 , wherein the carrier consists of aromatic ring moiety and alkyl chains having 10 or more carbons as a fundamental skeleton represented by general formula A which has a functional group for bond amino acid with cycloalkanephilic moiety at the end,  
       
         
           
           
               
               
           
         
       
       wherein, L 1  is hydroxyl group which bonds with amino acid, a single bond which bonds with thiol group, amino group or carbonyl group, an atomic group which bonds with said hydroxyl group, thiol group, amino group or carbonyl group or an atomic group which forms fused aromatic ring of two rings bonding with dotted line, wherein dotted line is an atomic group which forms said fused aromatic ring by bonding with H or L 1 , X is O, S, ester group, sulfide group or imino group, R is hydro carbon group of carbon number 10 or more which can contain O, S or N having a possibility to improve the solubility to cycloalkane solvents as a bonding atom, n is a integer from 1 to 5, further in the case when said hydro carbon group of carbon number 10 or more is to improve the solubility to cycloalkane solvents, R possesses a side chain with functional group which bonds with the amino group and/or substituent.  
     
     
         18 . The method for preparation of peptide by liquid phase synthesis of  claim 16 , wherein the compound represented by general formula A is the compound selected from the group of represented by general formulae B  
       
         
           
           
               
               
           
         
       
       wherein, X, R and n are same as to that of general formula A, Q is a single bond or hydro carbon group, R 2  is hydroxyl group, thiol group, amino group or carbonyl group which bonds with amino acid, R 3  and R 4  is a group represented by general formula C,  
       
         
           
           
               
               
           
         
       
       wherein, R 5  is hydroxyl group, thiol group, amino group or carbonyl group which bonds with amino acid.  
     
     
         19 . The method for preparation of peptide by liquid phase synthesis of  claim 15 , wherein the oganic solvent composing one solvent or mixed solvent is composed by cyclo alkane, and organic solvent composing another solvent or mixed solvent B to be combined with the organic solvent composing said solvent or mixed solvent A is at least one selected from the group consisting of nitroalkane, nitrile, alcohol, halogenated alkyl, amide and sulfooxide.  
     
     
         20 . The method for preparation of the peptide by liquid phase synthesis of  claim 19 , wherein the carrier consists of aromatic ring moiety and alkyl chains having 10 or more carbons as a fundamental skeleton represented by general formula A which has a functional group for bond amino acid with cycloalkanephilic moiety at the end.  
     
     
         21 . The method for preparation of peptide by liquid phase synthesis of  claim 20 , wherein the compound represented by general formula A is the compound selected from the general formulae B.  
     
     
         22 . The method for preparation of peptide by liquid phase synthesis of  claim 19 , wherein carbon number of alkyl group of nitro alkane is 1, 2 or 3, carbon number of alkyl group of nitrile is 1, 2 or 3, amide is N-dialkyl or N-monoalkyl amide, the total carbon number of alkyl group and formyl group or acyl group is 6 or less, carbon number of alcohol is 8 or less, carbon number of alkyl group of sulfoxide is 1, 2 or 3 and carbon number of alkyl group of halogenated alkyl is 6 or less.  
     
     
         23 . The method for preparation of the peptide by liquid phase synthesis of  claim 22 , wherein the carrier consists of aromatic ring moiety and alkyl chains having 10 or more carbons as a fundamental skeleton represented by general formula A which has a functional group for bond amino acid with cycloalkanephilic moiety at the end.  
     
     
         24 . The method for preparation of peptide by liquid phase synthesis of  claim 23 , wherein the compound represented by general formula A is the compound selected from the group of represented by general formulae B.