Pyrrole | EPFL Graph Search

Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula . It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, . Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme. Pyrroles are components of more complex macrocycles, including the porphyrinogens and products derived therefrom, including porphyrins of heme, the chlorins, bacteriochlorins, and chlorophylls. Properties Pyrrole is a colorless volatile liquid that darkens readily upon exposure to air, and is usually purified by distillation immediately before use. Pyrrole has a nutty odor. Pyrrole is a 5-membered aromatic heterocycle, like furan and thiophene. Unlike furan and thiophene, it has a dipole in which the positive end lies on the side of the heteroatom, with a dipole moment of 1.58 D. In CDCl3, it has chemical shifts at 6.

Reactions of nitrogen-containing compounds with ozone: kinetics and mechanisms

Sung Eun Lim

Nitrogen-containing moieties are widespread in natural waters in dissolved organic nitrogen and micropollu-tants. They are often susceptible to an electrophilic attack of ozone because of the electron-rich nature of the neutral form of nitrogen in organic compounds. This indicates that reactions of nitrogen-containing compounds with ozone inevitably occur in water and wastewater treatment where ozonation is applied for disinfection or oxidation. Despite the relevance to ozone chemistry, the knowledge on reactions of ozone with some principal nitrogen-containing functional groups is limited. The aim of this thesis was to elucidate reaction mechanisms of nitrogen-containing compounds with ozone for common nitrogen-containing functional groups: aliphatic amines and azoles. The primary objectives were (1) to determine the second-order rate constants for the reactions of nitrogen-containing compounds with ozone (kO3), (2) to identify/quantify transformation products and reactive oxygen species, (3) to perform kinetic simulations and quantum chemical computations to supplement or corroborate empirical evidences. Reaction mechanisms were proposed by compiling the results from all aspects, providing a better understanding of nitrogen-ozone chemistry. The investigation of triethylamine, diethylamine, and ethylamine yielded kO3 of the neutral form of amines ranging from 9.310^4 M-1 s-1 to 2.210^6 M-1 s-1. The apparent kO3 at pH 7 for potential or identified transformation products were 6.810^5 M-1 s-1 for N,N-diethylhydroxylamine, ~10^5 M-1 s-1 for N-ethylhydroxylamine, 1.910^3 M-1 s-1 for N-ethylethanimine oxide, and 3.4 M-1 s-1 for nitroethane. All amines predominantly underwent oxygen-transfer pathways to form major transformation products containing nitrogen-oxygen bonds: triethylamine N-oxide (88% per abated triethylamine) and nitroethane (69% per abated diethylamine and 100% per abate ethylamine). N,N-diethylhydroxylamine was a potential primary transformation product during the diethylamine-ozone reaction. Its formation was not confirmed due to its high ozone reactivity, but supported by measurements of reactive oxygen species, kinetic simulations, and quantum chemical computations. Pyrrole and imidazole reacted fast (kO3 > 10^3 M-1 s-1 at pH 1 â 12), whereas pyrazole reacted moderately fast with ozone (kO3 = 56 M-1 s-1 at pH 7). All studied azoles underwent an addition of ozone to the C-C double bond in the ring. Subsequent pathways after the initial ozone addition varied considerably among the azoles. Pyrrole reacted with ozone via a Criegee-type and an oxygen-addition mechanism. The major identified products (yield per abated pyrrole) were maleimide (34%), formamide (14%) and formate (54%). Imidazole predominantly reacted via a Criegee-type mechanism with ring cleavage and formation of the three fragments, formamide, cyanate, and formate (~100 % yields, respectively), completely closing the mass balance. For pyrazole, only carbonous products were identified (126% formate and 34% glyoxal per abated pyrazole). Products containing hydroxypyrazole and hydrazide moieties were postulated, possibly formed via an oxygen addition and a Criegee-type mechanism, respectively. The nitrogenous transformation products identified during this study may have different environmental implications. Some of them (e.g., nitroalkanes, N-formyl compounds) require further efforts to understand their impact on the aquatic environment and human health.

EPFL2020

Synthesis of Alkynylated Heterocycles by Direct C-H Alkynylation or Domino Alkynylation Reactions

Yifan Li

Heterocycles are important compounds in organic chemistry. To introduce functional groups on heterocycles or synthesize functionalized heterocycles stays a hot topic of research. Among all the functional groups, alkynes attracted a lot of attention not only because of their occurrence in organic compounds, like synthetic pharmaceuticals, natural products and organic materials, but also because of their versatile chemistry, such as metal catalyzed cyclization and [3+2] annulation reactions. Therefore, it is of great importance to introduce alkynes on heterocycles or synthesize alkynylated heterocycles in an efficient and regioselective manner. The Sonogashira reaction has dominated the introduction of alkynes on heterocycles. Even though the method is well established, there are several shortcomings such as stoichiometric waste production and poor stability or accessibility of the starting materials. To introduce alkynes on heterocycles in an efficient fashion, direct C-H alkynylation has been intensiely investigated as an alternative in the last decades. Based on the previous work in our group, direct C-H alkynylation was extended to access C2- alkynylated furans using a gold catalyst and triisopropylsilyl ethynyl benziodoxolone (TIPS-EBX). For less nucleophilic substrates like benzofurans, the use of Zn(OTf)2 was necessary to activate the EBX reagent. Although direct C-H alkynylation provides a straightforward way to access alkynylated heterocycles, it is limited to the inherently more reactive positions such as the C2 position of five-membered heterocycles or the heterocyclic ring of benzofused heterocycles. It is therefore challenging to find pathways to obtain heterocycles functionalized at other positions. Domino reactions could provide a solution to this challenge, as the metal-carbon bond could be installed on positions different from the ones obtained via a direct metallation approach. Based on this concept, unprecedented cyclization-alkynylation domino reactions were developed to access alkynylated heterocycles. Starting from easily prepared allenic ketones or ortho- ethynylated phenols or thioanisoles, C3 alkynylated furans, benzofurans and benzothiophenes can be rapidly accessed. This is a breakthrough as it allows for the introduction of alkynes on less nucleophilic positions. These products are difficult to obtain via direct C-H alkynylation as it occurred exclusively on C2 position of furans, benzofurans and benzothiophenes. Nevertheless, this approach was still limited to more reactive heterocycles. We then turned our efforts to develop domino reactions to functionalize the less reactive benzene ring. We found that with C2 or C3-substituted pyrroles as starting materials, C5 or C6 alkynylated indoles can be easily formed when combining a platinum catalyst with a bistrifluoromethyl benziodoxole reagent. In summary, a series of alkynylated heterocycles were obtained via direct alkynylation or domino reactions combining hypervalent iodine reagents and metal catalysts. This discovery is expected to find broad application to access diverse alkynylated heterocycles. It also set the bases for the development of new domino processes with different metal catalysts and electrophilic reagents in the future.

EPFL2016

Catalytic Atropenantioselective Heteroannulation between Isocyanoacetates and Alkynyl Ketones: Synthesis of Enantioenriched Axially Chiral 3-Arylpyrroles

Qian Wang, Sheng-Cai Zheng, Jieping Zhu

We report herein the first examples of catalytic enantioselective synthesis of axially chiral 3-arylpyrroles. Reaction of a-isocyanoacetates with b-aryl-a,b-alkynic ketones in the presence of silver oxide and a phosphine ligand derived from Cinchona alkaloid occurred chemoselectively to afford enantioenriched 3-arylpyrroles in high yields with excellent enantiomeric excesses. The pyrrole ring was constructed de novo in this process.