Synthesis of 6-Amino-5-cyano-1,4-disubstituted-2(1H)-Pyrimidinones via Copper-(I)-catalyzed Alkyne-azide ‘Click Chemistry’ and Their Reactivity

Najahi, Ennaji; Sudor, Ján; Chabchoub, Fakher; Nepveu, Françoise; Zribi, Fethi; Duval, Romain

doi:10.3390/molecules1512884

Cited by 4 publications

(5 citation statements)

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“…The 2(1 H )-pyrimidinones 5a – 5f were synthesized in good yields by the condensation of ethyl 2,2-dicyanovinylcarbamate derivatives 7 with primary aromatic amines ( o -tolylamine or naphthalen-1-ylamine) . Starting from the methyl N -(aminothiocarbonyl)imidates 8 and malononitrile, the 2(1 H )-pyrimidinethiones 6a and 6b were obtained in acceptable yield (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…X-ray crystallographic analyses of N -(1-naphthyl)-2(1 H )-pyrimidinone 5d revealed that the pyrimidinone crystallized in the monoclinic and centrosymmetric space group P 21/ c . Each single crystal of pyrimidinone 5d is composed of both enantiomers (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…Preparation of 6-amino-5-cyano-1- o -tolyl-4-substituted-2(1 H )-pyrimidinones ( 5a – 5c ). The 2(1 H )-pyrimidinones 5a – 5c were prepared according to the reported procedure . The 2(1 H )-pyrimidinones 5d – 5f have been already described …”

Section: Experimental Sectionmentioning

confidence: 99%

“…The 2(1 H )-pyrimidinones 5a – 5c were prepared according to the reported procedure . The 2(1 H )-pyrimidinones 5d – 5f have been already described …”

Section: Experimental Sectionmentioning

confidence: 99%

“…Clearly, further experimental data and appropriate calculations were mandatory in this domain. In the course of our studies on a series of N -aryl-2(1 H )-pyrimidin-(thi)ones, we report herein the barriers of racemization in 6-amino-5-cyano-1,4-disubstituted-pyrimidinones 5a – 5f and the 6-amino-5-cyano-4- p -tolyl-1-substituted-pyrimidinethiones 6a and 6b . If one considers the substitution pattern around the pivotal N -aryl bond, compounds 5a – 5f to 6a – 6b differ from the previous studies in the field of atropisomeric 2(1 H )-pyrimidin-(thi)ones by the introduction of a NH 2 substituent at the place of a Me group in compounds 1 – 4 .…”

Section: Introductionmentioning

confidence: 99%

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Atropisomerization inN-aryl-2(1H)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

et al. 2013

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Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in N-aryl-2(1H)-pyrimidin-(thi)ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 5a−5f and two 6-amino-5-cyano-4-p-tolyl-1-substituted-2(1H)-pyrimidinethiones 6a and 6b were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6amino-5-cyano-1-o-tolyl-4-p-tolyl-2(1H)-pyrimidinone (5b) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-p-tolyl-2(1H)-pyrimidinone (5e) were found to be 120.4 and 125.1 kJ•mol −1 (n-BuOH, 117 °C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ•mol −1 (EtOH, 78 °C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and o-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in N-aryl-2(1H)-pyrimidinethiones.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%

“…The 2(1 H )-pyrimidinones 5a – 5c were prepared according to the reported procedure . The 2(1 H )-pyrimidinones 5d – 5f have been already described …”

Section: Experimental Sectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Atropisomerization inN-aryl-2(1H)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

et al. 2013

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Chiroptical Detectors for the Study of Unusual Phenomena in Chiral Chromatography

Vanthuyne

Roussel

2013

Topics in Current Chemistry

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Differentiation of enantiomers in chromatography requires specific detectors, based on polarimetry or circular dichroism. Their use is limited to chiral HPLC and SFC. We explain the operating principles of the different chiroptical detectors available and stress the influence of working wavelength and mobile phase on the output signal. Current and relevant applications of chiroptical detectors are absolute configuration assignment, measurement of enantiomeric excesses in complex mixtures and determination of elution order. We focus on the reversals of enantiomeric elution order, an important subject for the understanding of the chiral recognition mechanisms. We review the main parameters which can induce a reversal, show the usefulness of chiroptical detectors to easily identify reversals and emphasize the significance of the isoenantioselective temperature. The aim of this chapter is to highlight the valuable information provided by chiroptical detectors to study unusual behaviour in chiral HPLC and SFC, reversals of enantiomeric elution order and exchange phenomena as dynamic chromatography and self-disproportionation on achiral columns.

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Atropisomerism and Axial Chirality in Heteroaromatic Compounds

Alkorta

Elguero

Roussel³

et al. 2012

Advances in Heterocyclic Chemistry

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Synthesis of 6-Amino-5-cyano-1,4-disubstituted-2(1H)-Pyrimidinones via Copper-(I)-catalyzed Alkyne-azide ‘Click Chemistry’ and Their Reactivity

Cited by 4 publications

References 22 publications

Atropisomerization inN-aryl-2(1H)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

Atropisomerization inN-aryl-2(1H)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

Chiroptical Detectors for the Study of Unusual Phenomena in Chiral Chromatography

Atropisomerism and Axial Chirality in Heteroaromatic Compounds

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