1,3-Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4-Dihydroisoquinoline toward Aryl Iso(thio)cyanates

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1,3-Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4-Dihydroisoquinoline toward Aryl Iso(thio)cyanates. / Penney, Alexander A.; Efremova, Mariia M.; Molchanov, Alexander P.; Kryukova, Mariya A.; Kudinov, Andrey Yu; Bunev, Alexander S.; Keresten, Valentina M.; Kuznetsov, Mikhail A.

In: ChemistrySelect, Vol. 7, No. 30, e202202627, 12.08.2022.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{dc209788559f48aebfca4954a7e90f31,

title = "1,3-Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4-Dihydroisoquinoline toward Aryl Iso(thio)cyanates",

abstract = "Unsubstituted and 1-methyl-substituted 1,3,4,8b-tetrahydrodiazirino[3,1-a]isoquinolines (diaziridines 1 and 2) demonstrate different reactivities toward aryl isocyanates and aryl isothiocyanates. Diaziridine 1 reacts with aryl isocyanates as a nucleophile to afford novel 1,5,6,10b-tetrahydro[1,2,4]triazolo[5,1-a]isoquinolines. The addition of a Lewis or Br{\o}nsted acid switches the reaction pathway, producing seven-membered 2,3-benzodiazepines. In reactions of diaziridine 1 with aryl isothiocyanates, unusual zwitterionic compounds – 2-thioxo-5,6-dihydro-2H-[1,2,4]triazolo[5,1-a]isoquinolin-1-ium-3-ides – and products of the addition of two molecules of diaziridine 1 to one molecule of aryl isothiocyanate are obtained. However, in reactions with aryl iso(thio)cyanates under heating or acid catalysis, diaziridine 2 is first converted into an azomethine imine, the 1,3-dipolar cycloaddition of which to the dipolarophile produces substituted triazolo[5,1-a]isoquinolin-2(3H)-(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Br{\o}nsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts.",

keywords = "azomethine imines, cycloaddition, diaziridines, isocyanates, isothiocyanates",

author = "Penney, {Alexander A.} and Efremova, {Mariia M.} and Molchanov, {Alexander P.} and Kryukova, {Mariya A.} and Kudinov, {Andrey Yu} and Bunev, {Alexander S.} and Keresten, {Valentina M.} and Kuznetsov, {Mikhail A.}",

note = "Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2022",

month = aug,

day = "12",

doi = "10.1002/slct.202202627",

language = "English",

volume = "7",

journal = "ChemistrySelect",

issn = "2365-6549",

publisher = "Wiley-Blackwell",

number = "30",

}

RIS

TY - JOUR

T1 - 1,3-Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4-Dihydroisoquinoline toward Aryl Iso(thio)cyanates

AU - Penney, Alexander A.

AU - Efremova, Mariia M.

AU - Molchanov, Alexander P.

AU - Kryukova, Mariya A.

AU - Kudinov, Andrey Yu

AU - Bunev, Alexander S.

AU - Keresten, Valentina M.

AU - Kuznetsov, Mikhail A.

PY - 2022/8/12

Y1 - 2022/8/12

N2 - Unsubstituted and 1-methyl-substituted 1,3,4,8b-tetrahydrodiazirino[3,1-a]isoquinolines (diaziridines 1 and 2) demonstrate different reactivities toward aryl isocyanates and aryl isothiocyanates. Diaziridine 1 reacts with aryl isocyanates as a nucleophile to afford novel 1,5,6,10b-tetrahydro[1,2,4]triazolo[5,1-a]isoquinolines. The addition of a Lewis or Brønsted acid switches the reaction pathway, producing seven-membered 2,3-benzodiazepines. In reactions of diaziridine 1 with aryl isothiocyanates, unusual zwitterionic compounds – 2-thioxo-5,6-dihydro-2H-[1,2,4]triazolo[5,1-a]isoquinolin-1-ium-3-ides – and products of the addition of two molecules of diaziridine 1 to one molecule of aryl isothiocyanate are obtained. However, in reactions with aryl iso(thio)cyanates under heating or acid catalysis, diaziridine 2 is first converted into an azomethine imine, the 1,3-dipolar cycloaddition of which to the dipolarophile produces substituted triazolo[5,1-a]isoquinolin-2(3H)-(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Brønsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts.

AB - Unsubstituted and 1-methyl-substituted 1,3,4,8b-tetrahydrodiazirino[3,1-a]isoquinolines (diaziridines 1 and 2) demonstrate different reactivities toward aryl isocyanates and aryl isothiocyanates. Diaziridine 1 reacts with aryl isocyanates as a nucleophile to afford novel 1,5,6,10b-tetrahydro[1,2,4]triazolo[5,1-a]isoquinolines. The addition of a Lewis or Brønsted acid switches the reaction pathway, producing seven-membered 2,3-benzodiazepines. In reactions of diaziridine 1 with aryl isothiocyanates, unusual zwitterionic compounds – 2-thioxo-5,6-dihydro-2H-[1,2,4]triazolo[5,1-a]isoquinolin-1-ium-3-ides – and products of the addition of two molecules of diaziridine 1 to one molecule of aryl isothiocyanate are obtained. However, in reactions with aryl iso(thio)cyanates under heating or acid catalysis, diaziridine 2 is first converted into an azomethine imine, the 1,3-dipolar cycloaddition of which to the dipolarophile produces substituted triazolo[5,1-a]isoquinolin-2(3H)-(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Brønsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts.

KW - azomethine imines

KW - cycloaddition

KW - diaziridines

KW - isocyanates

KW - isothiocyanates

UR - http://www.scopus.com/inward/record.url?scp=85136189968&partnerID=8YFLogxK

U2 - 10.1002/slct.202202627

DO - 10.1002/slct.202202627

M3 - Article

AN - SCOPUS:85136189968

VL - 7

JO - ChemistrySelect

JF - ChemistrySelect

SN - 2365-6549

IS - 30

M1 - e202202627

ER -

ID: 98766745