Multicomponent Synthesis of Structurally Diverse Imidazoles Featuring Azirines, Amines and Aldehydes

Rossa, Thaís A.; Fantinel, Mariane; Bortoluzzi, Adaílton J.; Sá, Marcus M.

doi:10.1002/ejoc.201800687

Cited by 17 publications

(7 citation statements)

References 33 publications

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“…Thusly, the behavior of imidazole towards OPs seems to follow a trend: with less reactive OPs, imidazole tends to prefer other electrophilic centers other than the phosphorus. This gives important insights concerning the challenging chemistry of imidazole 41 and its feasible alkylation. The synthesis of 1-methylimidazole and 1-ethylimidazole can be accomplished in an aqueous weakly basic medium, a breakthrough for organic synthesis.…”

Section: Imidazoles: Versatile or Promiscuous?mentioning

confidence: 99%

Are Imidazoles Versatile or Promiscuous in Reactions With Organophosphates? Insights From the Case of Parathion

Silva

Orth

2019

J. Braz. Chem. Soc.

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Is the broad mechanistic versatility of imidazole towards organophosphates (OPs), that has inspired many catalysts and sensors, beneficial? Herein, a thorough analysis is given seeking to unravel this puzzle. For OPs from the P=O family, imidazole attacks the phosphorus atom exclusively (N-phosphorylates). With the P=S family which are less reactive, an unusual N-alkylation predominates. Surprisingly, imidazole reacts with methyl parathion exclusively at the aliphatic carbon, whilst for the ethylated analogue parathion, imidazole reacts by two pathways: at both the phosphorus and aliphatic carbon, with predominance for the latter. The preference for the electrophilic center can be modulated by the pH. Overall, a mechanistic structure-related trend is observed: imidazole tends to prefer other electrophilic centers than the phosphorus for less reactive OPs. Moreover, this gives important insights concerning the challenging chemistry of imidazole alkylation and the outcomes for monitoring systems that depend on the detection of degradation products. Finally, a thorough comparison with the literature is presented seeking to understand how imidazole reacts towards various OPs. We suggest that the promiscuity of imidazole boosts up its versatility.

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Section: Imidazoles: Versatile or Promiscuous?mentioning

confidence: 99%

Are Imidazoles Versatile or Promiscuous in Reactions With Organophosphates? Insights From the Case of Parathion

Silva

Orth

2019

J. Braz. Chem. Soc.

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“…Pyridotriazole 1f was prepared by the reported procedure. [14b] Azirines 2a , 2b , 2c , 2d , 2e , 2f , and 2g were prepared by the reported procedures.…”

Section: Methodsmentioning

confidence: 99%

Pseudopericyclic Dearomative 1,6‐Cyclization of 1‐(2‐Pyridyl)‐2‐azabuta‐1,3‐dienes: Synthesis and Ring–Chain Valence Equilibria of 4H‐Pyrido[1,2‐a]pyrazines

et al. 2020

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The 1,6-electrocyclization of 1-(2-pyridyl)-2-azabuta-1,3-dienes obtained by Rh II -catalyzed reaction of pyridotriazoles with 2H-azirines affords stable non-aromatic 4H-pyrido[1,2-a]pyrazines despite the fact that the reaction proceeds with irreversible dearomatization of the pyridine aromatic system. This pseudopericyclic cyclization occurs when the 2-azabutadiene contains H, alkyl, or Ph at the C4 atom and an electron-withdrawing substituent at the C1 atom. A number of stable 4H-[a] I. 2904 pyrido[1,2-a]pyrazines as well as 1H-pyrazino[1,2-a]quinoline and 4H-benzo[4,5]oxazolo[3,2-a]pyrazine derivatives were synthesized. Whereas 4-alkyl-substituted pyridopyrazines are stable at room temperature, 4-phenyl-substituted pyridopyrazines exist in ring-chain valence equilibrium with 1-(2-pyridyl)-2-azabutadienes. Thermodynamic stability of the 4H-pyrido[1,2-a]pyrazine decreases with increasing size of the substituent at the C6 atom. Scheme 1. 1,6-Electrocyclizations of aza-and diazahexa-1,3,5-trienes. 2905 Scheme 2. The reaction of pyridotriazole 1a with azirine 2a.Scheme 4. The reaction of 3-benzoylpyridotriazole 1g with azirine 2b.sium hydroxide (4 equiv.) in methanol at room temperature for 24 h followed by chromatographic purification on silica gel.Compound 3d: (mixture of Z and E isomers in 1.9:1 ratio). Unstable yellow oil which is rapidly transformed to 5d. 1 H NMR (400 MHz, CDCl 3 ) δ: 1.72 (d, J = 7.1 Hz, 5.7H, Z), 1.79 (d, J = 7.2 Hz, 3H, E), 3.73 (s, 3.7H, Z), 3.81 (s, 3H, E), 3.91 (s, 3H, E), 3.92 (s, 5.7H, Z), 5.42 (q, J = 7.2 Hz, 1H, E), 5.52 (q, J = 7.0 Hz, 1.9H, Z), 6.82 (d, J = 8.1 Hz, 1H, E), 6.89 (d, J = 8.2 Hz, 1.9H, Z), 7.31-7.46 (m, 16H), 7.63-7.67 (m, 1H, E), 7.71-7.77 (m, 3H), 7.93 (d, J = 7.3 Hz, 1H, Z). Compound 5d: Orange solid, m.p. 175-177°C. 1 H NMR (400 MHz, CDCl 3 ) δ: 1.20 (d, J = 6.7 Hz, 3H), 3.89 (s, 3H), 3.96 (s, 3H), 5.78 (dd, J = 7.5, 0.9 Hz, 1H), 6.23 (q, J = 6.7 Hz, 1H), 7.11 (dd, J = 9.3, 7.5 Hz, 1H), 7.29-7.34 (m, 1H), 7.37-7.42 (m, 2H), 7.88-7.91 (m, 2H), 8.09 (dd, J = 9.3, 0.8 Hz, 1H). 13 Methyl 4-{[1-(6-Chloropyridin-2-yl)-2-methoxy-2-oxoethylidene]amino}but-3-enoate (3e) and Methyl 6-Chloro-4-(2-methoxy-2-oxoethyl)-3-phenyl-4H-pyrido[1,2-a]pyrazine-1-carboxylate (5e): Azadiene 3e (114 mg, yield 63 %) and pyridopyrazine 5e (28 mg, yield 15 %) were obtained according to the general procedure from pyridotriazole 1b (116 mg, 0.55 mmol) and azirine 2c (89 mg, 0.5 mmol) [110°C, 15 min, Rh 2 (OAc) 4 (2 mol-%, 4.4 mg), eluent for chromatography EtOAc/hexane, 1:5]. Compound 3e: (mixture of Z and E isomers in 1:1.6 ratio). Unstable orange oil which is rapidly transformed to 5e. 1 H NMR (400 MHz, CDCl 3 ) δ: 3.16-3.20 (m, 5.2H), 3.71-3.73 (m, 11H), 3.92 (s, 5H, E), 5.41 (t, Compound 5e: Red solid, m.p. 132-134°C. 1 H NMR (400 MHz, CDCl 3 ) δ: 2.33 (dd, J = 15.6, 4.0 Hz, 1H), 2.83 (dd, J = 15.6, 9.7 Hz, 1H), 3.60 (s, 3H), 3.93 (s, 3H), 6.55 (dd, J = 6.9, 1.1 Hz, 1H), 6.73 (dd, J = 9.7, 4.0 Hz, 1H), 6.99 (dd, J = 9.4, 7.0 Hz, 1H), 7. 1H), 7.46 (t, J = 7.4 Hz, 2H), 2H), 1H). 13 C C...

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“…In recent years, the synthesis of imidazoles employing azirines or their equivalents as N1À C4À C5 unit has been actively studied. [69] Complementally, Sa et al [70] report the selective synthesis of tetrasubstituted imidazoles through a three-component reaction involving azirines, aldehydes and amines without any additive or metal catalyst (Scheme 43). The reaction proceeds involving nucleophilic addition of amine to C=N bond of 2Harizine to generate cyclic amine, as a nucleophilic reagent to imine came from aldehydes and amines.…”

Section: Synthesis Of Nn-containing Heterocylcesmentioning

confidence: 99%

2H‐Azirines: Recent Progress in Synthesis and Applications

Xu,

Zeng,

Luo

et al. 2024

Eur J Org Chem

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2H‐arizines are important three‐membered heterocycles in organic chemistry. Recently, many advances in the synthesis and functionalization of 2H‐arizines have been reported. Neber rearrangement, isomerization of isoxazole, oxidation of enamine, C–H bond activation, decomposition of vinyl azide, functionalization of alkyne, and multi‐step synthesis have been developed for the efficient assembly of 2H‐azirines. As versatile and highly strained three‐membered unsaturated heterocycles, 2H‐azirines can be used as distinctive building blocks towards significant functional groups, and have attracted extensive attention for the fabrication of numerous heterocycles. Recent studies have focused on [3+n] ring‐expansion reactions, nucleophilic addition of C=N double bond or continuous nucleophilic addition followed by cyclization, ring‐opening of 2H‐azirines to acyclic compounds, and substitution of sp3‐C‐H of 2H‐azirines. One of the most critical challenges is seeking for a selective opening of the specific three bonds of the strained azirine circle, some of what can be achieved on the basis of metal catalyst, photocatalysis, or combination of metal catalyst and photocatalysis. In this review, recent advances involving the synthesis and reactivity of 2H‐arizines accompanied with challenges and breakthroughs are summarized. The review mainly covers the period from 2019 to 2023.

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Multicomponent Synthesis of Structurally Diverse Imidazoles Featuring Azirines, Amines and Aldehydes

Cited by 17 publications

References 33 publications

Are Imidazoles Versatile or Promiscuous in Reactions With Organophosphates? Insights From the Case of Parathion

Are Imidazoles Versatile or Promiscuous in Reactions With Organophosphates? Insights From the Case of Parathion

Pseudopericyclic Dearomative 1,6‐Cyclization of 1‐(2‐Pyridyl)‐2‐azabuta‐1,3‐dienes: Synthesis and Ring–Chain Valence Equilibria of 4H‐Pyrido[1,2‐a]pyrazines

2H‐Azirines: Recent Progress in Synthesis and Applications

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