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US 5,302,714 AGranted
Sapphyrins, derivatives and syntheses
AssigneeBoard of Regents, The University of Texas System
InventorsJonathan L. Sessler, Michael J. Cyr
Life of this patent
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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 C.sub.2 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.
Claims10
A method for synthesizing sapphyrins comprising the steps of:
- (A) reacting an alkyl derivative.sub.a aldehyde and an n-nitromethylenealkyl derivative.sub.b to produce beta-hydroxynitroalkyl derivative.sub.c ;
- (B) reacting the beta-hydroxynitroalkyl derivative.sub.c with acetic anhydride to form beta-acetoxynitroalkyl derivative.sub.c ;
- (C) reacting the beta-acetoxynitroalkyl derivative.sub.c with ethyl isocyanoacetate in the presence of a nonnucleophilic base to form ethyl 3-alkyl derivative.sub.a -4-alkyl derivative.sub.b pyrrole-2-carboxylate;
- (D) reacting ethyl 3-alkyl derivative.sub.a -4-alkyl derivative.sub.b pyrrole-2-carboxylate with iodine and iodide to form ethyl 3-alkyl derivative.sub.a -4-alkyl derivative.sub.b -5-iodopyrrole-2-carboxylate;
- (E) coupling two molecular equivalents of ethyl 3-alkyl derivative.sub.a -4-alkyl derivative.sub.b -5-iodo-pyrrole-2-carboxylate in the presence of copper bronze and heat to produce diethyl 4,4'-dialkyl derivative.sub.a -3,3'-dialkyl derivative.sub.b -2,2'-bipyrrole-5,5'-dicarboxylate;
- (F) converting diethyl 4,4'-dialkyl derivative.sub.a -3,3'-dialkyl derivative.sub.b -2,2'-bipyrrole-5,5'-dicarboxylate to 4,4'-dialkyl derivative.sub.a -3,3'-dialkyl derivative.sub.b -2,2'-bipyrrole by saponification and decarboxylation;
- (G) reacting 4,4'-dialkyl derivative.sub.a -3,3'-dialkyl derivative.sub.b -2,2'-bipyrrole with dimethylformamide and phosphorus oxychloride to form 4,4'-dialkyl derivative.sub.a -5,5'-diformyl-3,3'-dialkyl derivative.sub.b -2,2'-bipyrrole;
- (H) treating benzyl 4-alkyl derivative.sub.d -3,5-dimethylpyrrole-2-carboxylate with an oxidizing agent to produce benzyl 5-(X-methyl)-4-alkyl derivative.sub.d -3-methylpyrrole-2-carboxylate;
- (I) condensing two molecular equivalents of benzyl 5-(X-methyl)-4-alkyl derivative.sub.d -3-methylpyrrole-2-carboxylate with 3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole under acidic conditions to produce 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole;
- (J) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole to produce 2,5-bis(5-carboxy-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole;
- and
- (K) condensing 4,4'-dialkyl derivative.sub.a -5,5'-diformyl-3,3'-dialkyl derivative.sub.b -2,2'-bipyrrole with 2,5-bis(5-carboxy-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole under acidic oxidizing conditions to produce a 2,23-dialkyl derivative.sub.b -3,22-dialkyl derivative.sub.a -7,18-dimethyl-8,17-dialkyl derivative.sub.d -12-alkyl derivative.sub.e -13-alkyl derivative.sub.f sapphyrin;
- wherein alkyl derivative.sub.a, alkyl derivative.sub.b, alkyl derivative.sub.c, alkyl derivative.sub.d, alkyl derivative.sub.e and alkyl derivative.sub.f are independently alkane, functionalized alkane, derivatized alkane or derivatized functional alkane and x is a substituent capable of leaving as an anionically stable moiety.
10 more elements
A method for producing an alkyl substituted sapphyrin, the method comprising:
- (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-diethyl pyrrole;
- (I) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethyl pyrrole 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.
8 more elements
A method for producing a carboxy substituted sapphyrin, the method comprising:
- (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-ylmeth yl)-3,4-diethylpyrrole;
- (J) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-ethoxycarbonylmethyl-4-methylpyrrol-2-ylmeth yl)-3,4-diethylpyrrole to produce 2,5-bis(5-carboxy-3-ethoxycarbonylmethyl-4-methylpyrrol-2-ylmethyl)-3,4-di ethylpyrrole;
- (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-di ethylpyrrole under acidic oxidizing conditions to produce 3,12,13,22-tetraethyl-8,17-di(ethoxycarbonylmethyl)-2,7,19,23-tetramethyls apphyrin;
- and
- (b) producing 3,12,13,22-tetraethyl-8,17-di(ethoxycarbonylmethyl)-2,7,18,23-tetramethyls apphyrin as described in step (K) (a) and saponifying it to produce 3,12,13,22-tetraethyl-8,17-di(carboxymethyl)-2,7,18,23-tetramethylsapphyri n;
- or
- (c) producing 3,12,13,22-tetraethyl-8,17-di(ethoxycarbonylmethyl)-2,7,18,23-tetramethyls apphyrin 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.
13 more elements
A method for synthesizing dioxosapphyrins comprising the steps of:
- (A) reacting benzyl 4-alkyl derivative.sub.d -3,5-dimethylpyrrole-2-carboxylate with an oxidizing agent to produce benzyl 5-(X-methyl)-4-alkyl derivative.sub.d -3-methylpyrrole-2-carboxylate;
- (B) condensing two molecular equivalents of benzyl 5-(X-methyl)-4-alkyl derivative.sub.d -3-methylpyrrole-2-carboxylates with 3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole under acidic conditions to produce 2,5 -bis(5-benzyloxycarbonyl-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole;
- (C) hydrogenating 2,5-bis(5-benzyloxycarbonyl-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole to produce 2,5-bis(5-carboxy-3-alkyl derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f 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 derivative.sub.d -4-methylpyrrol-2-ylmethyl)-3-alkyl derivative.sub.e -4-alkyl derivative.sub.f pyrrole under acidic oxidizing conditions to produce 8,17-dialkyl derivative.sub.d -12-alkyl derivative.sub.e -13-alkyl derivative.sub.f -7,18-dimethyldioxosapphyrin;
- wherein alkyl derivative.sub.d, alkyl derivative.sub.e and alkyl derivative.sub.f are independently alkane, functionalized alkane, derivatized alkane or derivatized functional alkane and X represents a substituent which may leave as an anionically stable moiety.
4 more elements
Dependencies are inferred from the claim text.