Sapphyrins, derivatives and syntheses
First Claim
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1. A method for synthesizing sapphyrins comprising the steps of:
- (A) reacting an alkyl derivativea aldehyde and an n-nitromethylenealkyl derivativeb to produce beta-hydroxynitroalkyl derivativec ;
(B) reacting the beta-hydroxynitroalkyl derivativec with acetic anhydride to form beta-acetoxynitroalkyl derivativec ;
(C) reacting the beta-acetoxynitroalkyl derivativec with ethyl isocyanoacetate in the presence of a nonnucleophilic base to form ethyl 3-alkyl derivativea -4-alkyl derivativeb pyrrole-2-carboxylate;
(D) reacting ethyl 3-alkyl derivativea -4-alkyl derivativeb pyrrole-2-carboxylate with iodine and iodide to form ethyl 3-alkyl derivativea -4-alkyl derivativeb -5-iodopyrrole-2-carboxylate;
(E) coupling two molecular equivalents of ethyl 3-alkyl derivativea -4-alkyl derivativeb -5-iodo-pyrrole-2-carboxylate in the presence of copper bronze and heat to produce diethyl 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate;
(F) converting diethyl 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate to 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole by saponification and decarboxylation;
(G) reacting 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole with dimethylformamide and phosphorus oxychloride to form 4,4'"'"'-dialkyl derivativea -5,5'"'"'-diformyl-3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole;
(H) treating benzyl 4-alkyl derivatived -3,5-dimethylpyrrole-2-carboxylate with an oxidizing agent to produce benzyl 5-(X-methyl)-4-alkyl derivatived -3-methylpyrrole-2-carboxylate;
(I) condensing two molecular equivalents of benzyl 5-(X-methyl)-4-alkyl derivatived -3-methylpyrrole-2-carboxylate with 3-alkyl derivativee -4-alkyl derivativef pyrrole under acidic conditions to produce 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole;
(J) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole to produce 2,5-bis(5-carboxy-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole; and
(K) condensing 4,4'"'"'-dialkyl derivativea -5,5'"'"'-diformyl-3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole with 2,5-bis(5-carboxy-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole under acidic oxidizing conditions to produce a 2,23-dialkyl derivativeb -3,22-dialkyl derivativea -7,18-dimethyl-8,17-dialkyl derivatived -12-alkyl derivativee -13-alkyl derivativef sapphyrin;
wherein alkyl derivativea, alkyl derivativeb, alkyl derivativec, alkyl derivatived, alkyl derivativee and alkyl derivativef are independently alkane, functionalized alkane, derivatized alkane or derivatized functional alkane and x is a substituent capable of leaving as an anionically stable moiety.
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Abstract
The present invention involves, in addition to many unique substituted sapphyrins, a novel method for synthesizing sapphyrins with good efficiency and high yield. An improved 9-step synthesis of substituted sapphyrins, e.g., the two C2 symmetric sapphyrins, compounds 2 and 4 of FIG. 1C, is described herein. This synthesis involves as an important step the condensation between a tripyrrane diacid and a diformyl bipyrrole. The key tripyrrane component is prepared in three high-yield steps from readily available pyrrolic precursors and the bipyrrole portion is prepared in four steps from ethyl 3-methyl-4-methylpyrrole-2-carboxylate in roughly 33% yield overall.
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Citations
10 Claims
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1. A method for synthesizing sapphyrins comprising the steps of:
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(A) reacting an alkyl derivativea aldehyde and an n-nitromethylenealkyl derivativeb to produce beta-hydroxynitroalkyl derivativec ; (B) reacting the beta-hydroxynitroalkyl derivativec with acetic anhydride to form beta-acetoxynitroalkyl derivativec ; (C) reacting the beta-acetoxynitroalkyl derivativec with ethyl isocyanoacetate in the presence of a nonnucleophilic base to form ethyl 3-alkyl derivativea -4-alkyl derivativeb pyrrole-2-carboxylate; (D) reacting ethyl 3-alkyl derivativea -4-alkyl derivativeb pyrrole-2-carboxylate with iodine and iodide to form ethyl 3-alkyl derivativea -4-alkyl derivativeb -5-iodopyrrole-2-carboxylate; (E) coupling two molecular equivalents of ethyl 3-alkyl derivativea -4-alkyl derivativeb -5-iodo-pyrrole-2-carboxylate in the presence of copper bronze and heat to produce diethyl 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate; (F) converting diethyl 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate to 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole by saponification and decarboxylation; (G) reacting 4,4'"'"'-dialkyl derivativea -3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole with dimethylformamide and phosphorus oxychloride to form 4,4'"'"'-dialkyl derivativea -5,5'"'"'-diformyl-3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole; (H) treating benzyl 4-alkyl derivatived -3,5-dimethylpyrrole-2-carboxylate with an oxidizing agent to produce benzyl 5-(X-methyl)-4-alkyl derivatived -3-methylpyrrole-2-carboxylate; (I) condensing two molecular equivalents of benzyl 5-(X-methyl)-4-alkyl derivatived -3-methylpyrrole-2-carboxylate with 3-alkyl derivativee -4-alkyl derivativef pyrrole under acidic conditions to produce 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole; (J) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole to produce 2,5-bis(5-carboxy-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole; and (K) condensing 4,4'"'"'-dialkyl derivativea -5,5'"'"'-diformyl-3,3'"'"'-dialkyl derivativeb -2,2'"'"'-bipyrrole with 2,5-bis(5-carboxy-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole under acidic oxidizing conditions to produce a 2,23-dialkyl derivativeb -3,22-dialkyl derivativea -7,18-dimethyl-8,17-dialkyl derivatived -12-alkyl derivativee -13-alkyl derivativef sapphyrin; wherein alkyl derivativea, alkyl derivativeb, alkyl derivativec, alkyl derivatived, alkyl derivativee and alkyl derivativef are independently alkane, functionalized alkane, derivatized alkane or derivatized functional alkane and x is a substituent capable of leaving as an anionically stable moiety. - View Dependent Claims (2, 3, 4)
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5. A method for producing an alkyl substituted sapphyrin, the method comprising:
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(A) reacting propionaldehyde and nitroethane to produce 4-nitro-3-pentanol; (B) reacting 4-nitro-3-pentanol with acetic anhydride to form 3-acetoxy-2-nitropentane; (C) reacting 3-acetoxy-2-nitropentane with ethyl isocyanoacetate in the presence of a nonnucleophilic base to form ethyl 3-ethyl-4-methylpyrrole-2-carboxylate; (D) reacting ethyl 3-ethyl-4-methylpyrrole-2-carboxylate with iodine and iodide to form ethyl 3-ethyl-5-iodo-4-methylpyrrole-2-carboxylate; (E) coupling two molecular equivalents of ethyl 3-ethyl-5-iodo-4-methylpyrrole-2-carboxylate in the presence of copper-bronze and heat to produce diethyl 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate; (F) converting diethyl 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate to 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole by saponification and decarboxylation; (G) reacting 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole with dimethylformamide and phosphorus oxychloride to form 4,4'"'"'-diethyl-5,5'"'"'-diformyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole; (H) condensing 3,4-diethylpyrrole with two molecular equivalents of benzyl 5-(acetoxymethyl)-4-ethyl-3-methylpyrrole-2-carboxylate to produce 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole; (I) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole to produce 2,5-bis(5-carboxy-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole; and (J) condensing 4,4'"'"'-diethyl-5,5'"'"'-diformyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole and 2,5-bis(5-carboxy-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethyl-pyrrole under acidic oxidizing conditions to produce 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin.
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6. A method for producing a carboxy substituted sapphyrin, the method comprising:
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(A) reacting propionaldehyde and nitroethane to produce 4-nitro-3-pentanol; (B) reacting 4-nitro-3-pentanol with acetic anhydride to form 3-acetoxy-2-nitropentane; (C) reacting 3-acetoxy-2-nitropentane with ethyl isocyanoacetate in the presence of a nonnucleophilic base to form ethyl 3-ethyl-4-methylpyrrole-2-carboxylate; (D) reacting ethyl 3-ethyl-4-methylpyrrole-2-carboxylate with iodine and iodide to form ethyl 3-ethyl-5-iodo-4-methylpyrrole-2-carboxylate; (E) coupling two molecular equivalents of ethyl 3-ethyl-5-iodo-4-methylpyrrole-2-carboxylate in the presence of copper bronze and heat to produce diethyl 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate; (F) converting diethyl 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole-5,5'"'"'-dicarboxylate to 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole by saponification and decarboxylation; (G) reacting 4,4'"'"'-diethyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole with dimethylformamide and phosphorus oxychloride to form 4,4'"'"'-diethyl-5,5'"'"'-diformyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole; (H) reacting benzyl 4-ethoxycarboxylmethyl-3,5-dimethylpyrrole-2-carboxylate with lead tetraacetate to produce benzyl 5-(acetoxymethyl)-4-ethoxycarbonylmethyl-3-methylpyrrole-2-carboxylate; (I) condensing 3,4-diethylpyrrole with two molecular equivalents of benzyl 5-(acetoxymethyl)-3-ethoxycarbonylmethyl-4-methylpyrrole-2-carboxylate under acidic conditions to produce 2,5-bis(5-benzyloxycarbonyl-3-ethoxycarbonylmethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole; (J) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-ethoxycarbonylmethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole to produce 2,5-bis(5-carboxy-3-ethoxycarbonylmethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole; (K) (a) condensing 4,4'"'"'-diethyl-5,5'"'"'-diformyl-3,3'"'"'-dimethyl-2,2'"'"'-bipyrrole and 2,5-bis(5-carboxy-3-ethoxycarbonylmethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole under acidic oxidizing conditions to produce 3,12,13,22-tetraethyl-8,17-di(ethoxycarbonylmethyl)-2,7,19,23-tetramethylsapphyrin; and (b) producing 3,12,13,22-tetraethyl-8,17-di(ethoxycarbonylmethyl)-2,7,18,23-tetramethylsapphyrin as described in step (K) (a) and saponifying it to produce 3,12,13,22-tetraethyl-8,17-di(carboxymethyl)-2,7,18,23-tetramethylsapphyrin;
or(c) producing 3,12,13,22-tetraethyl-8,17-di(ethoxycarbonylmethyl)-2,7,18,23-tetramethylsapphyrin as described in step (K) (a) and partially saponifying it to produce 3,12,13,22-tetraethyl-8-(ethoxy-carbonylmethyl)-17-(carboxymethyl)-2,17,18,23-tetramethylsapphyrin.
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7. A method for synthesizing dioxosapphyrins comprising the steps of:
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(A) reacting benzyl 4-alkyl derivatived -3,5-dimethylpyrrole-2-carboxylate with an oxidizing agent to produce benzyl 5-(X-methyl)-4-alkyl derivatived -3-methylpyrrole-2-carboxylate; (B) condensing two molecular equivalents of benzyl 5-(X-methyl)-4-alkyl derivatived -3-methylpyrrole-2-carboxylates with 3-alkyl derivativee -4-alkyl derivativef pyrrole under acidic conditions to produce 2,5 -bis(5-benzyloxycarbonyl-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole; (C) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole to produce 2,5-bis(5-carboxy-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole; and (D) reacting furfuraldehyde and palladium acetate to produce 5,5'"'"'-diformyl-2,2'"'"'-bifuran; (E) condensing 5,5'"'"'-diformyl-2,2'"'"'-bifuran and 2,5-bis(5-carboxy-3-alkyl derivatived -4-methylpyrrol-2-ylmethyl)-3-alkyl derivativee -4-alkyl derivativef pyrrole under acidic oxidizing conditions to produce 8,17-dialkyl derivatived -12-alkyl derivativee -13-alkyl derivativef -7,18-dimethyldioxosapphyrin; wherein alkyl derivatived, alkyl derivativee and alkyl derivativef are independently alkane, functionalized alkane, derivatized alkane or derivatized functional alkane and X represents a substituent which may leave as an anionically stable moiety. - View Dependent Claims (8, 9, 10)
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Specification