Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction
A short and economical synthesis of various 2-methylaminopyidine amides (MAPA) from 2-bromopyridine has been developed using the catalytic Goldberg reaction. The effective catalyst was formed in situ by the reaction of CuI and 1,10-phenanthroline in a 1/1 ratio with a final loading of 0.5–3 mol%. Th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/6/1833 |
| _version_ | 1827627355351285760 |
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| author | Daniel L. Comins |
| author_facet | Daniel L. Comins |
| author_sort | Daniel L. Comins |
| collection | DOAJ |
| description | A short and economical synthesis of various 2-methylaminopyidine amides (MAPA) from 2-bromopyridine has been developed using the catalytic Goldberg reaction. The effective catalyst was formed in situ by the reaction of CuI and 1,10-phenanthroline in a 1/1 ratio with a final loading of 0.5–3 mol%. The process affords high yields and can accommodate multigram-scale reactions. A modification of this method provides a new preparation of 2-<i>N</i>-substituted aminopyridines from various secondary <i>N</i>-alkyl(aryl)formamides and 2-bromopyridine. The intermediate aminopyridine formamide is cleaved in situ through methanolysis or hydrolysis to give 2-alkyl(aryl)aminopyridines in high yields. |
| first_indexed | 2024-03-09T13:11:08Z |
| format | Article |
| id | doaj.art-f0902edabf514695a538b20157866b65 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T13:11:08Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f0902edabf514695a538b20157866b652023-11-30T21:41:54ZengMDPI AGMolecules1420-30492022-03-01276183310.3390/molecules27061833Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg ReactionDaniel L. Comins0Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USAA short and economical synthesis of various 2-methylaminopyidine amides (MAPA) from 2-bromopyridine has been developed using the catalytic Goldberg reaction. The effective catalyst was formed in situ by the reaction of CuI and 1,10-phenanthroline in a 1/1 ratio with a final loading of 0.5–3 mol%. The process affords high yields and can accommodate multigram-scale reactions. A modification of this method provides a new preparation of 2-<i>N</i>-substituted aminopyridines from various secondary <i>N</i>-alkyl(aryl)formamides and 2-bromopyridine. The intermediate aminopyridine formamide is cleaved in situ through methanolysis or hydrolysis to give 2-alkyl(aryl)aminopyridines in high yields.https://www.mdpi.com/1420-3049/27/6/1833<i>N</i>-methyl-<i>N</i>-(2-pyridyl)formamide2-methylaminopyridine amides2-alkyl(aryl)aminopyridinesGoldberg reactioncopper-catalyzed reactionscross-coupling reactions |
| spellingShingle | Daniel L. Comins Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction Molecules <i>N</i>-methyl-<i>N</i>-(2-pyridyl)formamide 2-methylaminopyridine amides 2-alkyl(aryl)aminopyridines Goldberg reaction copper-catalyzed reactions cross-coupling reactions |
| title | Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction |
| title_full | Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction |
| title_fullStr | Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction |
| title_full_unstemmed | Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction |
| title_short | Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction |
| title_sort | synthesis of mapa reagents and 2 alkyl aryl aminopyridines from 2 bromopyridine using the goldberg reaction |
| topic | <i>N</i>-methyl-<i>N</i>-(2-pyridyl)formamide 2-methylaminopyridine amides 2-alkyl(aryl)aminopyridines Goldberg reaction copper-catalyzed reactions cross-coupling reactions |
| url | https://www.mdpi.com/1420-3049/27/6/1833 |
| work_keys_str_mv | AT daniellcomins synthesisofmapareagentsand2alkylarylaminopyridinesfrom2bromopyridineusingthegoldbergreaction |