Abstract:1,2-Bis(N-alkoxy-N-nitroso)amines 7 obtained by nitrosation of the corresponding 1,2-bisalkoxyamines 4 were smoothly converted into 1-alkoxy-4,5-dihydro-1,2,3-triazole 2-oxides 8 under reflux in methanol in high yields. 4H-1,2,3-Triazole 2-oxides 9, a novel type of triazole oxides, and 2-hydroxy-2H-1,2,3-triazoles 10 were obtained by the reaction of 1-alkoxy-4,5-dihydro-1,2,3-triazole 2-oxides 8 with sodium methoxide.
“…While O 2 -alkylation produces stable derivatives which do not release NO (until removal of the “protecting” group), , O 1 -alkylation produces compounds that can still generate NO via a radical pathway involving homolytic cleavage of the N−N bond. This radical formation has also been implicated in the release of NO during the formation of triazoles from vicinal bisdiazeniumdiolates (eq 46). …”
Section: Reactions Leading To Nitric Oxide Releasementioning
Joseph A. Hrabie received his entire education in the New York City public school system, including his Ph.D. degree in Chemistry (1981) under the guidance of Professor William F. Berkowitz at Queens College of the City University of New York. After postdoctoral research with Professor Herbert O. House at the Georgia Institute of Technology, he moved to the National Cancer Institute at Frederick and is currently a Senior Scientist with SAIC−Frederick, the primary NCI contractor at the site. In addition to many scientific publications, his continuing interest in nitric oxide chemistry has resulted in 15 U.S. patents. Larry K. Keefer received his B.A. degree from Oberlin College and his Ph.D. degree in Chemistry (1965) under the guidance of Professor Gloria G. Lyle at the University of New Hampshire. He held research positions at the Chicago Medical School and the University of Nebraska College of Medicine before coming to the National Cancer Institute in 1971. He and his colleagues in the NCI's Chemistry Section, Laboratory of Comparative Carcinogenesis, are intensively studying the chemistry and pharmacology of the diazeniumdiolates as nitric oxide sources for biomedical applications.This section contains a description of reactions that are used preparatively as well as those that do not
“…While O 2 -alkylation produces stable derivatives which do not release NO (until removal of the “protecting” group), , O 1 -alkylation produces compounds that can still generate NO via a radical pathway involving homolytic cleavage of the N−N bond. This radical formation has also been implicated in the release of NO during the formation of triazoles from vicinal bisdiazeniumdiolates (eq 46). …”
Section: Reactions Leading To Nitric Oxide Releasementioning
Joseph A. Hrabie received his entire education in the New York City public school system, including his Ph.D. degree in Chemistry (1981) under the guidance of Professor William F. Berkowitz at Queens College of the City University of New York. After postdoctoral research with Professor Herbert O. House at the Georgia Institute of Technology, he moved to the National Cancer Institute at Frederick and is currently a Senior Scientist with SAIC−Frederick, the primary NCI contractor at the site. In addition to many scientific publications, his continuing interest in nitric oxide chemistry has resulted in 15 U.S. patents. Larry K. Keefer received his B.A. degree from Oberlin College and his Ph.D. degree in Chemistry (1965) under the guidance of Professor Gloria G. Lyle at the University of New Hampshire. He held research positions at the Chicago Medical School and the University of Nebraska College of Medicine before coming to the National Cancer Institute in 1971. He and his colleagues in the NCI's Chemistry Section, Laboratory of Comparative Carcinogenesis, are intensively studying the chemistry and pharmacology of the diazeniumdiolates as nitric oxide sources for biomedical applications.This section contains a description of reactions that are used preparatively as well as those that do not
“…Hydroxylamine and hydroxylamine ether systems possess a more nucleophilic nitrogen compared to the amide-type systems mentioned above and can therefore be readily nitrosated with sodium nitrite in aqueous acid leading to Nnitrosohydroxylamines and N-nitrosohydroxylamine ethers, respectively (Scheme 11 and Scheme 12). 26,27 Likewise, hydrazines, hydrazones, and hydrazides have been reported as suitable systems for N-nitrosation with sodium nitrite in aqueous acidic conditions. 28,29,50−52 Hydrazides generally undergo N-nitrosation beta to the carbonyl, whereas hydrazines appear to undergo N-nitrosation if both nitrogens are functionalized (Scheme 13) 28 or via an N−N cleavage/ nitrosation process for N,N-disubstituted hydrazines (Scheme 13).…”
Section: Nitrosating Agentsmentioning
confidence: 99%
“…Other secondary NH-containing systems have also been shown to undergo N -nitrosation. These include, in order of decreasing reporting frequency: amides, ureas, − carbamates, heteroamides, , hydroxylamines, , hydroxylamine ethers, hydrazines, , hydrazones, hydrazides, and guanidines. , In general, these systems are less used, and their reactivity is typically lower compared to secondary amines due to the weaker nucleophilic character of the NH moiety. Hydroxylamine- and hydrazine-type compounds are an exception as they are typically as nucleophilic as amines.…”
Section: N–n Bond Formationmentioning
confidence: 99%
“…Hydroxylamine and hydroxylamine ether systems possess a more nucleophilic nitrogen compared to the amide-type systems mentioned above and can therefore be readily nitrosated with sodium nitrite in aqueous acid leading to N -nitrosohydroxylamines and N -nitrosohydroxylamine ethers, respectively (Scheme and Scheme ). , …”
Recent drug recalls (e.g., valsartan and ranitidine) linked to
the discovery of nitrosamine impurities have led to increased regulatory
scrutiny in the manufacturing process of marketed medicines, notably
for determining any sources of risk for nitrosamine (or related N-nitroso compound) formation within the manufacturing process.
This review seeks to aid the risk assessment process through identifying
known conditions and reactants through which N-nitroso
compounds can be formed.
“…However, regioselective construction of 1,2,3triazoles 2-oxides has been challenging due to the unmanageable regioselectivity of the conventional synthetic reactions. Both intramolecular cyclization of azido-nitrosamines 10 and bisnitrosoamines 11 and intermolecular cyclization of diaminopyridines with nitric acid 12 are the usually used methods to access 1,2,3-triazoles 2-oxides (Scheme 1a). Involvement of explosive azides or concentrated acids leads to potential hazards, and multistep processes result in poor efficiency.…”
The direct synthesis of triazole 2-oxides has posed a
challenge
in the field of N-heterocyclic chemistry. A novel
copper(I)-catalyzed nitrosylation/annulation cascade of enaminones
provides a straightforward route to 1H-1,2,3-triazole
2-oxides by forming new C–N, N=N, and N–N bonds using
noncorrosive tert-butyl nitrite (TBN) as both the
N and NO sources. The synthetic protocol features easily accessible
starting materials, wide substrate scopes, and good tolerance toward
various functional groups while avoiding use of explosive azides.
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