Efficient Synthesis of 2,9‐Disubstituted 8‐Hydroxyadenine Derivatives.

Abstract

Purine derivativesPurine derivatives R 0540 Efficient Synthesis of 2,9-Disubstituted 8-Hydroxyadenine Derivatives. -A novel synthesis of 8-hydroxyadenine derivatives is developed using compounds (IV) as key intermediates. Treatment of (XXI) with urea and subsequent alkylation results in the formation of (XIX) in an alternative method. Under mild conditions, various types of substituents are directly introduced at the 2-and 9-positions of the 8-hydroxyadenine nucleus. -(HIROTA*, K.; KAZAOKA, K.; NIIMOTO, I.; SAJIKI, H.; Org.

Die Renaissance des H/D‐Austausches

“…Chemie einem Eintopfverfahren weiterentwickelt, [104] bei dem eine In-situ-Aktivierung des Pd/C-Katalysators durch Wasserstoff stattfindet. [105] Folgerichtig wurde in wasserstofffreier Atmosphäre bei der Modellverbindung Diphenylmethan (99) Weiterführende Untersuchungen von Sajiki et al an 5-Phenylvaleriansäure (102) offenbarten darüber hinaus einen starken Einfluss der Reaktionstemperatur auf Regioselektivität und Deuteriumeinbau beim H/D-Austausch.…”

Efficient C−H/C−D Exchange Reaction on the Alkyl Side Chain of Aromatic Compounds Using Heterogeneous Pd/C in D2O

“…However, such conventional procedures for the incorporation of deuterium into the C−H bonds of organic compounds are often limited to activated positions of the molecules, leading to low levels of deuterium incorporation, and usually require a vast amount of the catalyst, addition of acidic or basic additives, and/or deuterium atmosphere. Although, most recently, Matsubara et al, reported a remarkable H−D exchange transformation with 10% Pd/C in subcritical D 2 O (250 °C) in the absence of hydrogen, we independently found that hydrogen gas is essential for the 10% Pd/C-catalyzed H−D exchange reaction below 180 °C. , …”

“…18 we independently found that hydrogen gas is essential for the 10% Pd/C-catalyzed H-D exchange reaction below 180 °C. 19,20 We report here that a heterogeneous Pd/C-D 2 O-H 2 system efficiently catalyzes the exchange of deuterium from D 2 O into organic compounds, including nonactivated positions of the molecules.…”

“…While no exchange was observed in the absence of hydrogen gas (entry 3) or 10% Pd/C (entry 4), hydrogen was found to dramatically activate the reactivity of the Pd/C-catalyzed H-D exchange reaction. 19 Additional optimization revealed that the efficiency of H-D exchange reaction can be greatly enhanced with a rise in temperature up to 160 °C using a sealed tube (entry 7). Although the Pd/C-D 2 O-H 2 system catalyzed extensive deuterium incorporation into the benzylic and unactivated methylene positions, the deuterium efficiency at the benzene ring was lower.…”

“…The deuterium efficiency into the side chain (C 1 −C 4 ) of 1a and 1b decreases with increasing distance from the benzene ring. While no exchange was observed in the absence of hydrogen gas (entry 3) or 10% Pd/C (entry 4), hydrogen was found to dramatically activate the reactivity of the Pd/C-catalyzed H−D exchange reaction . Additional optimization revealed that the efficiency of H−D exchange reaction can be greatly enhanced with a rise in temperature up to 160 °C using a sealed tube (entry 7).…”