Studies on pyrazines. 35. An improved synthesis of bromopyrazines from hydroxypyrazines

Sato, Nobuhiro; Narita, Nobuhiko

doi:10.1002/jhet.5570360334

Cited by 13 publications

(5 citation statements)

References 15 publications

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“…This same transformation can be effected via generation of the O-silylated pyrazinones with phosphorus(III) halide or phosphorus(V) chloride under mild conditions and without the need for isolation of the silyl intermediate (Scheme 19.224) [247]. The iodo adducts were obtained in low yield.…”

Section: Hydroxydiazinesmentioning

confidence: 97%

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Six‐Membered Heterocycles: 1,2‐, 1,3‐, and 1,4‐Diazines and Related Systems

Cabal

2011

Modern Heterocyclic Chemistry

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Section: Hydroxydiazinesmentioning

confidence: 97%

“…Sato and Narita have provided an improved synthesis of halopyrazines 149 in which hydroxypyrazines 148 were activated with TMSCl to give silyl ethers [178]. Subsequent treatment with the appropriate phosphorus-based halogen source provided halopyrazines in 46-94% overall yield (Scheme 19.160).…”

Section: Pyrazines (14-diazines)mentioning

confidence: 99%

Six‐Membered Heterocycles: 1,2‐, 1,3‐, and 1,4‐Diazines and Related Systems

Cabal

2011

Modern Heterocyclic Chemistry

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“…[19,20] The 2-hydroxypyridines can be further functionalized into different 2-substituted pyridine derivatives. [21][22][23][24][25][26] N-oxidants Different N-oxidants are well known in the literature for heteroatom oxidation. In our studies, the reactions were carried out with m-CPBA in DCM or with aqueous H 2 O 2 in acetic acid, so these compounds were described in detail regarding their safety aspect.…”

Section: N-oxide Derivativesmentioning

confidence: 99%

Preparation of Pyridine N-oxide Derivatives in Microreactor

Vörös

Timári

Baan

et al. 2014

Period. Polytech. Chem. Eng.

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Introduction Microflow technologyIn the recent years the importance of microreactors are continuously growing in R&D and industrial applications as well. This popularity originates from the unique properties of this technology such as: very precise temperature control, outstanding mixing and heat exchange due to the high surface to volume ratio. With an extremely low active reactor volume, 'safety concern' chemicals and chemical processes can be handled in safe manner under inert conditions. Based on evidence gained from several examples, the scale-up of microreactors is also expected to be less problematic compared to batch processes, due to the reduced amount of critical scale-up parameters. [1] In this paper, we describe our recent results on the N-oxidation of different pyridine derivatives, quinoline and isoquinoline with m-CPBA in DCM or aqueous H 2 O 2 in acetic acid using microreactor technology.

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“…When toluene 2 was used as the solvent instead of MeCN, the yield of 3a decreased to 72%. The effects of Pd-catalyst, CuI and triethylamine can be realized from the experiments lacking each additive (entries [4][5][6][7][8][9]. Without the Pdcatalyst, the coupling proceeded only slightly.…”

mentioning

confidence: 99%

“…We first examined Pd-catalysts in the cross-coupling of 2-bromo-5-phenylpyrazine (1a) 9 with tributyl(1-ethoxyvinyl)tin (2), in which 5 mol% each of Pd catalyst and CuI were employed in refluxing MeCN containing triethylamine (Table 1, entries 1-3) according to our previous procedure. 1 Consequently, PdCl 2 (Ph 3 P) 2 induced the best yield (81%) of 2-acetyl-5-phenylpyrazine (3a).…”

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confidence: 99%

Studies on Pyrazines; 38: Acylation of Bromopyrazines and 2-Bromopyridine via Copper-Cocatalytic Stille Reaction

Sato¹,

Narita²

2004

Synthesis

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Synthesis of acetylpyrazines 3 and propionylpyrazines 5 was achieved by copper-cocatalytic Stille reaction of bromopyrazines 1 with tributyl(1-ethoxyalkenyl)tin and then acidic hydrolysis. The optimal reaction conditions involve the combination of 15 mol% CuI with 5 mol% of PdCl 2 (Ph 3 P) 2 . Similarly, 2-acylpyridines and propionylbenzenes were prepared from the corresponding aryl bromides.The Stille cross-coupling of bromobenzenes with trialkyl(1-ethoxyvinyl)tin followed by acidic hydrolysis has been shown as a convenient method for the synthesis of acetophenones. 2,3 In a preceding paper, we reported this methodology to be also effective in the dehalogenative acylation of electron-deficient nitrogen heteroaromatics, thus high yields of 1,3-dihydro-6-propionylpterin-2,4-diones were synthesized via Pd-catalyzed reaction of the 6-bromopteridines with tributyl(1-ethoxyprop-1-enyl)tin. 1 The key for the successful transformation was the use of CuI under the traditional Stille conditions, in other words the cross-coupling did not proceed at all without the additive. The cocatalytic effect of CuI in the Stille coupling was first reported by Liebeskind and Fengl, 4 and the many subsequent applications have stimulated a considerable development in this chemistry. 5 Much less is known, however, about the couplings of aryl halides with trialkyl(1-ethoxyalkenyl)tin in the presence of CuI. 6 On the other hand, acylpyrazines are of interest as the constituents in foodstuffs or pheromones, which have been often prepared by the Minisci-type radical reaction of pyrazines 7 or lithiation followed by reaction of the resultant lithiopyrazines with N,N-dialkylamides. 8 These methods suffer from some drawbacks, especially the regioselectivity of aromatic substitution. In this respect, acylation via displacement of halogeno substituent is a promising synthetic route to the desired acylpyrazines. We are currently investigating the acylation of bromopyrazines through copper-cocatalytic Stille reaction with 1-ethoxyvinyl or 1-ethoxypropenyl tin compounds (Scheme 1). Additionally, the cross-coupling of halogenopyridines and bromobenzenes was carried out under similar conditions for comparison of reactivity with pyrazine series.We first examined Pd-catalysts in the cross-coupling of 2-bromo-5-phenylpyrazine (1a) 9 with tributyl(1-ethoxyvinyl)tin (2), in which 5 mol% each of Pd catalyst and CuI were employed in refluxing MeCN containing triethylamine (Table 1, entries 1-3) according to our previous procedure. 1 Consequently, PdCl 2 (Ph 3 P) 2 induced the best yield (81%) of 2-acetyl-5-phenylpyrazine (3a). When toluene 2 was used as the solvent instead of MeCN, the yield of 3a decreased to 72%. The effects of Pd-catalyst, CuI and triethylamine can be realized from the experiments lacking each additive (entries 4-9). Without the Pdcatalyst, the coupling proceeded only slightly. The addition of CuI unexpectedly led to an appreciable increase in the yield of acetylpyrazine 3a. Our previous cross-coupling of bromopteridines necessitated cat...

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Studies on pyrazines. 35. An improved synthesis of bromopyrazines from hydroxypyrazines

Abstract: The synthesis of bromopyrazines from hydroxypyrazines was successfully effected by the procedure via trimethylsilyloxypyrazines, the sequence of which proceeds under mild conditions and does not require the isolation of intermediate.

Cited by 13 publications

References 15 publications

Six‐Membered Heterocycles: 1,2‐, 1,3‐, and 1,4‐Diazines and Related Systems

Six‐Membered Heterocycles: 1,2‐, 1,3‐, and 1,4‐Diazines and Related Systems

Preparation of Pyridine N-oxide Derivatives in Microreactor

Studies on Pyrazines; 38: Acylation of Bromopyrazines and 2-Bromopyridine via Copper-Cocatalytic Stille Reaction

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