Fiesselmann thiophene synthesis: Difference between revisions
Content deleted Content added
Citation bot (talk | contribs) Alter: pages. Add: pmid, hdl, series. Formatted dashes. | Use this bot. Report bugs. | Suggested by Graeme Bartlett | #UCB_toolbar |
added Mechanism and applications |
||
| Line 8: | Line 8: | ||
}} |
}} |
||
The '''Fiesselmann thiophene synthesis''' is a [[name reaction]] in [[organic chemistry]] that allows for the generation of 3-hydroxy-2-thiophenecarboxylic acid derivatives from α,β-acetylenic esters with [[thioglycolic acid]] and its derivatives under the presence of a base.<ref name="Fiesselmann1">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Schipprak|first2=Peter|date=1954-06-01|title=Über Oxythiophencarbonsäureester, I. Mitteil.: Über die Anlagerung von Thioglykolsäureester an Fumarsäure-, Maleinsäure- und Acetylendicarbonsäureester|url= |journal=Chemische Berichte|volume=87|issue=6|pages=835–841|doi=10.1002/cber.19540870608|access-date=}}</ref><ref name="Fiesselmann2">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Schipprak|first2=Peter|last3=Zeitler|first3=Lorenz|date=1954-06-01|title=Über Oxythiophen-carbonsäureester, II. Mitteil.): Synthese und Reaktionen von 3-Oxy-thiophen-carbonsäure-(2)-estern|url= |journal=Chemische Berichte|volume=87|issue=6|pages=841–848|doi=10.1002/cber.19540870609|access-date=}}</ref><ref name="Fiesselmann3">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Pfeiffer|first2=Gerhard|date=1954-06-01|title=Über Oxythiophencarbonsäureester, III. Mitteil.): Die Einwirkung von Thioglykolsäureester auf β-Ketosäureester (Mitbearbeitet von Ferdinand Memmel)|url= |journal=Chemische Berichte|volume=87|issue=6|pages=848–856|doi=10.1002/cber.19540870610|access-date=}}</ref><ref name="Fiesselmann4">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Schipprak|first2=Peter|date=1956-08-01|title=Über Hydroxythiophencarbonsäureester, IV. Mitteil.: Eine einfache Darstellungsweise von 3-Hydroxy-thiophen- dicarbonsäure-(2.5)-estern|url= |journal=Chemische Berichte|volume=89|issue=8|pages=1897–1902|doi=10.1002/cber.19560890814|access-date=}}</ref><ref name="Fiesselmann5">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Thoma|first2=Fritz|date=1956-08-01|title=Über Hydroxythiophencarbonsäureester, VI. Mitteil.: Darstellung von 3-Hydroxy-thiophencarbonsäure-(2)-estern aus β-Ketosäureestern|url= |journal=Chemische Berichte|volume=89|issue=8|pages=1907–1912|doi=10.1002/cber.19560890816|access-date=}}</ref><ref name="Gronowitz">{{cite book |last=Gronowitz|first=Salo|author-link= |date=1991-01-01|title=Chemistry of Heterocyclic Compounds: Thiophene and Its Derivatives, Part Four, Volume 44|series=Chemistry of Heterocyclic Compounds: A Series of Monographs|url= |location= |publisher=John Wiley & Sons, Inc.|page=88-125|isbn=9780470187265|doi=10.1002/9780470187265|hdl=2027/mdp.39015078685115 |
The '''Fiesselmann thiophene synthesis''' is a [[name reaction]] in [[organic chemistry]] that allows for the generation of 3-hydroxy-2-thiophenecarboxylic acid derivatives from α,β-acetylenic esters with [[thioglycolic acid]] and its derivatives under the presence of a base. The reaction was developed by Hans Fiesselmann in the 1950s.<ref name="Fiesselmann1">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Schipprak|first2=Peter|date=1954-06-01|title=Über Oxythiophencarbonsäureester, I. Mitteil.: Über die Anlagerung von Thioglykolsäureester an Fumarsäure-, Maleinsäure- und Acetylendicarbonsäureester|url= |journal=Chemische Berichte|volume=87|issue=6|pages=835–841|doi=10.1002/cber.19540870608|access-date=}}</ref><ref name="Fiesselmann2">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Schipprak|first2=Peter|last3=Zeitler|first3=Lorenz|date=1954-06-01|title=Über Oxythiophen-carbonsäureester, II. Mitteil.): Synthese und Reaktionen von 3-Oxy-thiophen-carbonsäure-(2)-estern|url= |journal=Chemische Berichte|volume=87|issue=6|pages=841–848|doi=10.1002/cber.19540870609|access-date=}}</ref><ref name="Fiesselmann3">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Pfeiffer|first2=Gerhard|date=1954-06-01|title=Über Oxythiophencarbonsäureester, III. Mitteil.): Die Einwirkung von Thioglykolsäureester auf β-Ketosäureester (Mitbearbeitet von Ferdinand Memmel)|url= |journal=Chemische Berichte|volume=87|issue=6|pages=848–856|doi=10.1002/cber.19540870610|access-date=}}</ref><ref name="Fiesselmann4">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Schipprak|first2=Peter|date=1956-08-01|title=Über Hydroxythiophencarbonsäureester, IV. Mitteil.: Eine einfache Darstellungsweise von 3-Hydroxy-thiophen- dicarbonsäure-(2.5)-estern|url= |journal=Chemische Berichte|volume=89|issue=8|pages=1897–1902|doi=10.1002/cber.19560890814|access-date=}}</ref><ref name="Fiesselmann5">{{cite journal |last1=Fiesselmann|first1=Hans|last2=Thoma|first2=Fritz|date=1956-08-01|title=Über Hydroxythiophencarbonsäureester, VI. Mitteil.: Darstellung von 3-Hydroxy-thiophencarbonsäure-(2)-estern aus β-Ketosäureestern|url= |journal=Chemische Berichte|volume=89|issue=8|pages=1907–1912|doi=10.1002/cber.19560890816|access-date=}}</ref><ref name="Gronowitz">{{cite book |last=Gronowitz|first=Salo|author-link= |date=1991-01-01|title=Chemistry of Heterocyclic Compounds: Thiophene and Its Derivatives, Part Four, Volume 44|series=Chemistry of Heterocyclic Compounds: A Series of Monographs|url= |location= |publisher=John Wiley & Sons, Inc.|page=88-125|isbn=9780470187265|doi=10.1002/9780470187265|hdl=2027/mdp.39015078685115}}</ref> |
||
[[File:Fiesselmann Übersicht.svg]] |
|||
== Mechanism == |
|||
[[file:Fiesselmann mechanism.svg]] |
|||
After deprotonation the thioglycolic acid ester attacks the tripel bond of the alkyne. Another addition takes place on the resulting double bond. Via deprotonation of a thioglycolic acid ester moiety the cyclization is initialized. From the resulting [[thiolane]] an alcoholate is eliminated to yield a ketone. Elimination of a thioglycolic acid ester results in an α,β-unsatuated ketone. Tautomerization leads to the desired product.<ref>{{cite book |last=Li|first=Jie Jack|date=2014|title=Name Reactions |publisher=Springer International Publishing |isbn=978-3-319-03978-7 |page=250–251 |DOI=10.1007/978-3-319-03979-4_104}}</ref> |
|||
== Applications == |
|||
[[file:Fiesselmann Lissavetzky.svg]] |
|||
A variation of the Fiesselmann synthesis by Lissavetzky starts from a cyclic β-ketoester and thioglycolic acid. In combination with an alcohol (R<sup>4</sup>OH) the monoadduct is the main product. Without the addition of alcohol a [[thioacetal]] is generated. In presence of [[potassium hydroxide]] it can be esterificated and cyclisized. To cyclisize the mono adduct a sodium alcoholate is used.<ref>{{cite journal |last1=Donoso|first1=R.|last2=Jordán de Urríes|first2=P.|last3=Lissavetzky|first3=J. |title=Synthesis of [b]-Condensed Alkyl 3-Hydroxythiophene-2-carboxylates |journal=Synthesis |volume=1992 |issue=06 |date=1992 |page=526–528 |ISSN=0039-7881 |DOI=10.1055/s-1992-26152}}</ref> |
|||
[[file:Fiesselmann Scott.svg]] |
|||
If the substrate contains an nitrile instead of an ester group the reaction will result in 3-aminothiophenes. Scott used this approach to synthesis a p38 kinase inhibitor.<ref name="Redman">{{cite journal |last1=Redman|first1=Anikó M.|last2=Johnson|first2=Jeffrey S.|last3=Dally|first3=Robert|last4=Swartz|first4=Steve|last5=Wild|first5=Hanno|last6=Paulsen|first6=Holger|last7=Caringal|first7=Yolanda|last8=Gunn|first8=David|last9=Renick|first9=Joel|last10=Osterhout|first10=Martin|last11=Kingery-Wood|first11=Jill|last12=Smith|first12=Roger A.|last13=Lee|first13=Wendy|last14=Dumas|first14=Jacques|last15=Wilhelm|first15=Scott M.|last16=Housley|first16=Timothy J.|last17=Bhargava|first17=Ajay|last18=Ranges|first18=Gerald E.|last19=Shrikhande|first19=Alka|last20=Young|first20=Deborah|last21=Bombara|first21=Michael|last22=Scott|first22=William J.|date=2001-01-08|title=p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: thienyl, furyl, and pyrrolyl ureas|url= |journal=Bioorganic & Medicinal Chemistry Letters|volume=11|issue=1|pages=9–12|doi=10.1016/S0960-894X(00)00574-6|pmid=11140741|access-date=}}</ref> |
|||
[[file:Fiesselmann Fry.svg]] |
|||
The reaction also works with aromatic derivates. Fry used this variation for the synthesis of tyrosinkinase inhibitors, starting from a substituted [[pyridine]].<ref name="Showalter">{{cite journal |last1=Showalter|first1=H. D. Hollis|last2=Bridges|first2=Alexander J.|last3=Zhou|first3=Hairong|last4=Sercel|first4=Anthony D.|last5=McMichael|first5=Amy|last6=Fry|first6=David W.|date=1999-12-09|title=Tyrosine Kinase Inhibitors. 16. 6,5,6-Tricyclic Benzothieno[3,2-d]pyrimidines and Pyrimido[5,4-b]- and -[4,5-b]indoles as Potent Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase|url= |journal= Journal of Medicinal Chemistry|volume=42|issue=26|pages=5464–5474|doi=10.1021/jm9903949|pmid=10639288|access-date=}}</ref> |
|||
[[file:golfomycin A Fiesselmann.svg]] |
|||
Nicolaou used the conditions of the Fiesselmann thiophene synthesis to show potential DNA cleaving properties of golfomycin A, a cyclic alkyne with potential antitumor activity.<ref name="Nicolaou">{{cite journal |last1=Nicolaou|first1=Kyriacos Costa|author-link1=K. C. Nicolaou|last2=Skokotas|first2=Golfo|last3=Furuya|first3=S.|last4=Suemune|first4=H.|last5=Nicolaou|first5=D. Colette|date=September 1990|title=Golfomycin A, a Novel Designed Molecule with DNA-Cleaving Properties and Antitumor Activity|url= |journal=Angewandte Chemie International Edition|volume=29|issue=9|pages=1064–1067|doi=10.1002/anie.199010641|access-date=}}</ref> The Fiesselmann synthesis is also used to produce potential antiallergy agents<ref name="Mullican">{{cite journal |last1=Mullican|first1=Michael D.|last2=Sorenson|first2=Roderick J.|last3=Connor|first3=David T.|last4=Thueson|first4=David O.|last5=Kennedy|first5=John A.|last6=Conroy|first6=Mary Carol|date=1991-07-01|title=Novel thiophene-, pyrrole-, furan-, and benzene carboxamidotetrazoles as potential antiallergy agents|url= |journal= Journal of Medicinal Chemistry|volume=34|issue=7|pages=2186–2194|doi=10.1021/jm00111a039|pmid=1712394|access-date=}}</ref>, antileishmanial and antifungal agents<ref name="Ram">{{cite journal |last1=Ram|first1=Vishnu J.|last2=Goel|first2=Atul|last3=Shukla|first3=P. K.|last4=Kapil|first4=A.|date=1997-12-16|title=Synthesis of thiophenes and thieno[3,2-c]pyran-4-ones as antileishmanial and antifungal agents|url= |journal=Bioorganic & Medicinal Chemistry Letters|volume=7|issue=24|pages=3101–3106|doi=10.1016/S0960-894X(97)10153-6|access-date=}}</ref> and thieno[''b'']azepinediones.<ref name="Migianu">{{cite journal |last1=Migianu|first1=Evelyne|last2=Kirsch|first2=Gilbert|date=2002|title=Synthesis of New Thieno[b]azepinediones from α-Methylene Ketones|url= |journal=Synthesis|volume=2002|issue=8|pages=1096–1100|doi=10.1055/s-2002-31963|access-date=}}</ref> |
|||
==References== |
==References== |
||
{{Reflist}} |
{{Reflist}} |
||
Revision as of 14:08, 23 June 2022
| Fiesselmann thiophene synthesis | |
|---|---|
| Named after | Hans Fiesselmann |
| Reaction type | Ring forming reaction |
The Fiesselmann thiophene synthesis is a name reaction in organic chemistry that allows for the generation of 3-hydroxy-2-thiophenecarboxylic acid derivatives from α,β-acetylenic esters with thioglycolic acid and its derivatives under the presence of a base. The reaction was developed by Hans Fiesselmann in the 1950s.[1][2][3][4][5][6]
Mechanism
After deprotonation the thioglycolic acid ester attacks the tripel bond of the alkyne. Another addition takes place on the resulting double bond. Via deprotonation of a thioglycolic acid ester moiety the cyclization is initialized. From the resulting thiolane an alcoholate is eliminated to yield a ketone. Elimination of a thioglycolic acid ester results in an α,β-unsatuated ketone. Tautomerization leads to the desired product.[7]
Applications
A variation of the Fiesselmann synthesis by Lissavetzky starts from a cyclic β-ketoester and thioglycolic acid. In combination with an alcohol (R4OH) the monoadduct is the main product. Without the addition of alcohol a thioacetal is generated. In presence of potassium hydroxide it can be esterificated and cyclisized. To cyclisize the mono adduct a sodium alcoholate is used.[8]
If the substrate contains an nitrile instead of an ester group the reaction will result in 3-aminothiophenes. Scott used this approach to synthesis a p38 kinase inhibitor.[9]
The reaction also works with aromatic derivates. Fry used this variation for the synthesis of tyrosinkinase inhibitors, starting from a substituted pyridine.[10]
Nicolaou used the conditions of the Fiesselmann thiophene synthesis to show potential DNA cleaving properties of golfomycin A, a cyclic alkyne with potential antitumor activity.[11] The Fiesselmann synthesis is also used to produce potential antiallergy agents[12], antileishmanial and antifungal agents[13] and thieno[b]azepinediones.[14]
References
- ^ Fiesselmann, Hans; Schipprak, Peter (1954-06-01). "Über Oxythiophencarbonsäureester, I. Mitteil.: Über die Anlagerung von Thioglykolsäureester an Fumarsäure-, Maleinsäure- und Acetylendicarbonsäureester". Chemische Berichte. 87 (6): 835–841. doi:10.1002/cber.19540870608.
- ^ Fiesselmann, Hans; Schipprak, Peter; Zeitler, Lorenz (1954-06-01). "Über Oxythiophen-carbonsäureester, II. Mitteil.): Synthese und Reaktionen von 3-Oxy-thiophen-carbonsäure-(2)-estern". Chemische Berichte. 87 (6): 841–848. doi:10.1002/cber.19540870609.
- ^ Fiesselmann, Hans; Pfeiffer, Gerhard (1954-06-01). "Über Oxythiophencarbonsäureester, III. Mitteil.): Die Einwirkung von Thioglykolsäureester auf β-Ketosäureester (Mitbearbeitet von Ferdinand Memmel)". Chemische Berichte. 87 (6): 848–856. doi:10.1002/cber.19540870610.
- ^ Fiesselmann, Hans; Schipprak, Peter (1956-08-01). "Über Hydroxythiophencarbonsäureester, IV. Mitteil.: Eine einfache Darstellungsweise von 3-Hydroxy-thiophen- dicarbonsäure-(2.5)-estern". Chemische Berichte. 89 (8): 1897–1902. doi:10.1002/cber.19560890814.
- ^ Fiesselmann, Hans; Thoma, Fritz (1956-08-01). "Über Hydroxythiophencarbonsäureester, VI. Mitteil.: Darstellung von 3-Hydroxy-thiophencarbonsäure-(2)-estern aus β-Ketosäureestern". Chemische Berichte. 89 (8): 1907–1912. doi:10.1002/cber.19560890816.
- ^ Gronowitz, Salo (1991-01-01). Chemistry of Heterocyclic Compounds: Thiophene and Its Derivatives, Part Four, Volume 44. Chemistry of Heterocyclic Compounds: A Series of Monographs. John Wiley & Sons, Inc. p. 88-125. doi:10.1002/9780470187265. hdl:2027/mdp.39015078685115. ISBN 9780470187265.
- ^ Li, Jie Jack (2014). Name Reactions. Springer International Publishing. p. 250–251. doi:10.1007/978-3-319-03979-4_104. ISBN 978-3-319-03978-7.
- ^ Donoso, R.; Jordán de Urríes, P.; Lissavetzky, J. (1992). "Synthesis of [b]-Condensed Alkyl 3-Hydroxythiophene-2-carboxylates". Synthesis. 1992 (06): 526–528. doi:10.1055/s-1992-26152. ISSN 0039-7881.
- ^ Redman, Anikó M.; Johnson, Jeffrey S.; Dally, Robert; Swartz, Steve; Wild, Hanno; Paulsen, Holger; Caringal, Yolanda; Gunn, David; Renick, Joel; Osterhout, Martin; Kingery-Wood, Jill; Smith, Roger A.; Lee, Wendy; Dumas, Jacques; Wilhelm, Scott M.; Housley, Timothy J.; Bhargava, Ajay; Ranges, Gerald E.; Shrikhande, Alka; Young, Deborah; Bombara, Michael; Scott, William J. (2001-01-08). "p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: thienyl, furyl, and pyrrolyl ureas". Bioorganic & Medicinal Chemistry Letters. 11 (1): 9–12. doi:10.1016/S0960-894X(00)00574-6. PMID 11140741.
- ^ Showalter, H. D. Hollis; Bridges, Alexander J.; Zhou, Hairong; Sercel, Anthony D.; McMichael, Amy; Fry, David W. (1999-12-09). "Tyrosine Kinase Inhibitors. 16. 6,5,6-Tricyclic Benzothieno[3,2-d]pyrimidines and Pyrimido[5,4-b]- and -[4,5-b]indoles as Potent Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase". Journal of Medicinal Chemistry. 42 (26): 5464–5474. doi:10.1021/jm9903949. PMID 10639288.
- ^ Nicolaou, Kyriacos Costa; Skokotas, Golfo; Furuya, S.; Suemune, H.; Nicolaou, D. Colette (September 1990). "Golfomycin A, a Novel Designed Molecule with DNA-Cleaving Properties and Antitumor Activity". Angewandte Chemie International Edition. 29 (9): 1064–1067. doi:10.1002/anie.199010641.
- ^ Mullican, Michael D.; Sorenson, Roderick J.; Connor, David T.; Thueson, David O.; Kennedy, John A.; Conroy, Mary Carol (1991-07-01). "Novel thiophene-, pyrrole-, furan-, and benzene carboxamidotetrazoles as potential antiallergy agents". Journal of Medicinal Chemistry. 34 (7): 2186–2194. doi:10.1021/jm00111a039. PMID 1712394.
- ^ Ram, Vishnu J.; Goel, Atul; Shukla, P. K.; Kapil, A. (1997-12-16). "Synthesis of thiophenes and thieno[3,2-c]pyran-4-ones as antileishmanial and antifungal agents". Bioorganic & Medicinal Chemistry Letters. 7 (24): 3101–3106. doi:10.1016/S0960-894X(97)10153-6.
- ^ Migianu, Evelyne; Kirsch, Gilbert (2002). "Synthesis of New Thieno[b]azepinediones from α-Methylene Ketones". Synthesis. 2002 (8): 1096–1100. doi:10.1055/s-2002-31963.
 | This chemistry-related article is a stub. You can help Wikipedia by expanding it. |