Adamantane derivatives and process for producing them

Abstract

In the presence of an imide compound (e.g., N-hydroxyphthalimide) shown by the formula (2): wherein R 1 and R 2 independently represents a hydrogen atom, a halogen atom, an alkyl group, an aryl group, a cycloalkyl group; or R 1 and R 2 may bond together to form a double bond or an aromatic or non-aromatic ring; Y is O or OH and n=1 to 3; or the imide compound and a co-catalyst (e.g., a transition metal compound), an adamantane derivative having a functional group such as a nitro group, an amino group, a hydroxyl group, a carboxyl group, a hydroxymethyl group and an isocyanato group is oxidized with oxygen. According to the above method, an adamantane derivative having a hydroxyl group together with a functional group such as a nitro group, an amino group, a hydroxyl group, a carboxyl group, a hydroxymethyl group and an isocyanato group is efficiently obtained.

1. An adamantane derivative shown by the following formula (1): 
                 
 wherein X 1  represents a hydroxyl group which may be protected by a protective group, X 2  represents nitro group, an amino group or N-substituted amino group which may be protected by a protective group, a hydroxyl group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or isocyanato group;  
 (i) when X 2  is nitro group, X 3  and X 4  are the same or different from each other and each represents a hydrogen atom, an alkyl group, a nitro group, a hydroxyl group which may be protected by a protective group, an amino group or N-substituted amino group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group, excluding the case where X 3  and X 4  are both hydrogen atoms when X 1  is hydroxyl group and excluding 1,3,5-trinitro-7-adamantanol;  
 (ii) when X 2  is an amino group or N-substituted amino group which may be protected by a protective group, X 1    is a hydroxyl group,  X 3  and X 4  are the same or different from each other and each represents a hydrogen atom, an alkyl group, an amino group or N-substituted amino group which may be protected by a protective group, a hydroxyl group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group, excluding the case where X 3  and X 4  are both hydrogen atoms or alkyl groups when X 1  is hydroxyl group ;  
 (iii) when X 2  is a hydroxyl group which may be protected by a protective group, X 3  and X 4  are the same or different from each other and each represents a hydrogen atom, an alkyl group, a hydroxyl group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group, excluding the case where X 3  and X 4  are both hydrogen atoms or alkyl groups when X 1  is hydroxyl group or a saturated aliphatic acyloxy group and X 2  is hydroxyl group or a saturated aliphatic acyloxy group and the case where X 3  and X 4  are a combination of hydrogen atom and a carboxyl group which may be protected by a protective group when X 1  and X 2  are both hydroxyl groups and excluding the case where each of X 1 , X 2 , X 3 , and X 4  are all a hydroxyl group, or all a hydroxyl group protected by an acetyl group;  
 (iv) when X 2  is a carboxyl group which may be protected by a protective group, X 3  and X 4  are the same or different from each other and each represents a hydrogen atom, an alkyl group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group, excluding the case where X 3  and X 4  are both hydrogen atoms or alkyl groups or a combination of a hydrogen atom and an alkyl group when X 1  is a hydroxyl group or a saturated aliphatic acyloxy group;  
 (v) when X 2  is a hydroxymethyl group which may be protected by a protective group, X 3  and X 4  are the same or different from each other and each represents a hydrogen atom, an alkyl group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group, excluding the case where, X 3  and X 4  are both hydrogen atoms when X 1  is hydroxyl group; and  
 (vi) when X 2  is isocyanato group, X 3  and X 4  are the same or different from each other and each represents a hydrogen atom, an alkyl group or an isocyanato group, excluding the case where, X 3  and X 4  are both hydrogen atoms when X 1  is hydroxyl group; or a salt thereof.  
 
     
     
       2. An adamantane derivative or a salt thereof according to claim w, wherein X 1  is hydroxyl group, a saturated C 2-6 aliphatic acyloxy group, a C 1-6 -alkoxy-carbonyloxy group or a carbamoyloxy group which may have a substituent and X 2  is nitro group, amino group, a C 2-6 acylamino group, a C 1-6 alkoxy-carbonylamino group, a saturated C 2-6 aliphatic acyloxy group, a C 1-6 alkoxy-carbonyloxy group, a carbamoyloxy group which may have a substituent, carboxyl group, a C 1-6 alkoxy-carbonyl group, a carbamoyl group which may have a substituent, hydroxymethyl group or isocyanato group, in the formula (1). 
     
     
       3. A process for producing an adamantane derivative according to  claim 1 , which comprises, in the presence of an oxidation catalyst comprising an imide compound shown by the following formula (2): 
                 
 wherein R 1  and R 2  are the same or different from each other and each represents a hydrogen atom, a halogen atom, an alkyl group, an aryl group, a cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group, or an acyl group; or R 1  and R 2  may bond together to form a double bond or an aromatic or non-aromatic ring; Y represents oxygen atom or hydroxyl group; and n denotes an integer of 1 to 3; contacting an adamantane derivative shown by the 
                 
 
 wherein X 2  represents an amino group or N-substituted amino group which may be protected by a protective group, a hydroxyl group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or isocyanato group; X 3a  and X 4a  are the same or different from each other and each represents a hydrogen atom, an alkyl group, a hydroxyl group which may be protected by a protective group, an amino group or N-substituted amino group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group; with oxygen.  
 
     
     
       4. A process according to  claim 3 , in the imide compound shown by the formula (2) R 1  and R 2  bond together to form a cycloalkane ring which may have a substituent, a cycloalkene ring which may have a substituent, a bridged hydrocarbon ring which may have a substituent or an aromatic ring which may have a substituent. 
     
     
       5. A process according to  claim 3 , wherein the imide compound shown by the formula (2) is a compound shown by the following formulae (2a) to (2f): 
                 
 wherein R 3  to R 6  are the same or different from each other, and each represents a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group, an acyl group, a nitro group, a cyano group, an amino group or a halogen atom; and R 1 , R 2 , Y and n have the same meanings as defined above.  
 
     
     
       6. A process according to  claim 3 , wherein the imide compound shown by the formula (2) is at least one compound selected from the group consisting of N-hydroxysuccinimide, N-hydroxymaleimide, N-hydroxyhexahydrophthalimide, N,N′-dihydroxycyclohexanetetracarboximide, N-hydroxyphthalimide, N-hydroxytetrabromophthalimide, N-hydroxytetrachlorophthalimide, N-hydroxyhetimide, N-hydroxyhimimide, N-hydroxytrimellitimide, N,N′-dihydroxypyromellitimide and N,N′-dihydroxynaphthalenetetracarboximide. 
     
     
       7. A process according to  claim 3 , wherein said oxidation catalyst comprises the imide compound shown by the formula (2) and a co-catalyst. 
     
     
       8. A process according to  claim 7 , wherein said co-catalyst is a compound containing at least one element selected from the group consisting of a Group 2A element of the Periodic Table, a transition metal element and a Group 3B element of the Periodic Table. 
     
     
       9. A process according to  claim 7 , wherein said co-catalyst is a compound containing at least one element selected from the group consisting of a Group 3A element, a Group 4A element, a Group 5A element, a Group 6A element, a Group 7A element, a Group 8 element and a Group 1B element of the Periodic Table. 
     
     
       10. A process for producing an adamantane derivative according to  claim 1 , wherein the adamantane derivative has at least a hydroxyl group which comprises subjecting an adamantane derivative shown by the following formula (1a): 
                 
 wherein X 2  represents nitro group, an amino group or N-substituted amino group which may be protected by a protective group, a hydroxyl group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or isocyanato group; X 3a  and X 4a  are the same or different from each other and each represents a hydrogen atom, an alkyl group, a nitro group, a hydroxyl group which may be protected by a protective group, an amino group or N-substituted amino group which may be protected by a protective group, a carboxyl group which may be protected by a protective group, a hydroxymethyl group which may be protected by a protective group, or an isocyanato group;  
 
       to at least one step selected from the following oxidation step (i), nitration step (ii) and carboxylation step (iii):
 (i) an oxidation step by oxygen in the presence of a catalyst comprising an imide compound shown by the following formula (2): 
                 
 
 wherein R 1  and R 2  are the same or different from each other and each represents a hydrogen atom, a halogen atom, an alkyl group, an aryl group, a cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxyl group, an alkoxycarbonyl group, or an acyl group; or R 1  and R 2  may bond together to form a double bond or an aromatic or non-aromatic ring; Y represents oxygen atom or hydroxyl group; and n denotes an integer of 1 to 3  
 provided that in the oxidation step each of X 2 , X 3a  and X 4a  in the formula (1a) is not nitro group;  
 (ii) at least one nitration step of the following (iia) and (iib): 
 (iia) a nitration step by a nitrogen oxide in the presence of a catalyst comprising the imide compound shown by the formula (2); and  
 (iib) a nitration step by oxygen and at least one nitrogen oxide selected from dinitrogen oxide and nitrogen monoxide; and  
 
 (iii) a carboxylation step by carbon monoxide and oxygen in the presence of a catalyst comprising the imide compound shown by the formula (2).  
 
     
     
       11. A process according to  claim 10 , which comprises further subjecting a reaction product to a reduction step after being subjected to at least one step selected from said nitration step (ii) and said carboxylation step (iii) to form at least one group selected from an amino group and a hydroxymethyl group. 
     
     
       12. The compound  1 , 3 , 5 - tricarboxyadamantane.   
     
     
       13. A composition comprising the compound  1 , 3 , 5 - tricarboxyadamantane.