Photochemical Synthesis of Substituted Indan-1-ones Related to Donepezil

POSPÍŠIL, Tomáš, Aneesh TAZHE VEETIL, Lovely ANGEL P. A a Petr KLÁN. Photochemical Synthesis of Substituted Indan-1-ones Related to Donepezil. Photochemical & Photobiological Sciences. Cambridge, UK: Royal Society of Chemistry, 2008, roč. 7, č. 5, s. 625–632. ISSN 1474-905X.

Základní údaje

• Originální název: Photochemical Synthesis of Substituted Indan-1-ones Related to Donepezil
• Název česky: Fotochemická syntéza substituovaných indan-1-onů jako derivátů donepezilu
• Autoři: POSPÍŠIL, Tomáš (203 Česká republika), Aneesh TAZHE VEETIL (356 Indie, domácí), Lovely ANGEL P. A (356 Indie, domácí) a Petr KLÁN (203 Česká republika, garant, domácí).
• Vydání: Photochemical & Photobiological Sciences, Cambridge, UK, Royal Society of Chemistry, 2008, 1474-905X.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 10401 Organic chemistry
• Stát vydavatele: Velká Británie a Severní Irsko
• Utajení: není předmětem státního či obchodního tajemství
• Impakt faktor: Impact factor: 2.144
• Kód RIV: RIV/00216224:14310/08:00026021
• Organizační jednotka: Přírodovědecká fakulta
• UT WoS: 000255743700015
• Klíčová slova anglicky: Photochemistry; donepezil; photoenolization
• Štítky: donepezil, Photochemistry, photoenolization
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

A photoenolization reaction is shown to be the key reaction step in the preparation of substituted indan-1-ones as convenient precursors for the synthesis of donepezil, a well known acetylcholinesterase inhibitor. Model 2,5-dialkylphenacyl chlorides, differently substituted in the alpha carbon position, were found to produce indan-1-ones upon irradiation in non-nucleophilic solvents in high chemical yields via hydrogen chloride release. While direct excitation of 4,5-dimethoxy-2-methylphenacyl chloride led to a complex mixture of photoproducts, photolysis of the corresponding benzoate was found to form 5,6-dimethoxyindan-1-one in 62-72% chemical yields and a relatively low quantum efficiency (F = 0.02). This compound can then be easily converted to donepezil by standard synthetic steps described in the literature. Isotopic exchange and quenching experiments revealed that the product is obtained by the photoenolization process via the triplet excited state, while minor side-photoproducts originate from the singlet excited state. Irradiation of the reactant in neat acetone, used both as a triplet sensitizer and solvent at the same time, was found to form 5,6-dimethoxyindan-1-one exclusively in high (90%)chemical yield.

Anotace česky

A photoenolization reaction is shown to be the key reaction step in the preparation of substituted indan-1-ones as convenient precursors for the synthesis of donepezil, a well known acetylcholinesterase inhibitor. Model 2,5-dialkylphenacyl chlorides, differently substituted in the alpha carbon position, were found to produce indan-1-ones upon irradiation in non-nucleophilic solvents in high chemical yields via hydrogen chloride release. While direct excitation of 4,5-dimethoxy-2-methylphenacyl chloride led to a complex mixture of photoproducts, photolysis of the corresponding benzoate was found to form 5,6-dimethoxyindan-1-one in 62-72% chemical yields and a relatively low quantum efficiency (F = 0.02). This compound can then be easily converted to donepezil by standard synthetic steps described in the literature. Isotopic exchange and quenching experiments revealed that the product is obtained by the photoenolization process via the triplet excited state, while minor side-photoproducts originate from the singlet excited state. Irradiation of the reactant in neat acetone, used both as a triplet sensitizer and solvent at the same time, was found to form 5,6-dimethoxyindan-1-one exclusively in high (90%)chemical yield.

Návaznosti

• GA203/05/0641, projekt VaV: Název: Vývoj a aplikace fotolabilních chránících skupin

Investor: Grantová agentura ČR, Vývoj a aplikace fotolabilních chránících skupin

• MSM0021622413, záměr: Název: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím