Studies on intramolecular 1,3-dipolar cycloaddition reactions: III. The synthesis of a novel heterocyclic ring system by regiospecific cycloaddition

We have discovered and studied a telesubstitution reaction in a biologically important heterocyclic ring system. Conditions that favour the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base, or the use of softer nucleophiles, less polar solvents and larger halogens on the electrophile. Using results from X-ray crystallography and isotope labelling experiments a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active anti-plasmodium compounds of Series 4 of the Open Source Malaria consortium. Archive of the electronic laboratory notebook with the description of all conducted experiments and raw NMR data could be accessed via following link <a href="https://ses.library.usyd.edu.au/handle/2123/21890">https://ses.library.usyd.edu.au/handle/2123/21890</a> . For navigation between entries of laboratory notebook please use file "Strings for compounds in the article.pdf" that works as a reference between article codes and notebook codes, also this file contain SMILES for these compounds.

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Multicomponent 1,3-Dipolar Cycloaddition Reactions in the Construction of Hybrid Spiroheterocycles

Current Organic Chemistry ◽

10.2174/13852728113179990091 ◽

2013 ◽

Vol 17 (18) ◽

pp. 1929-1956 ◽

Cited By ~ 16

Author(s):

Natarajan Arumugam ◽

Raju Kumar ◽

Abdulrahman Almansour ◽

Subbu Perumal

Keyword(s):

Dipolar Cycloaddition ◽

Cycloaddition Reactions

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The Chemistry of Triazine Isomers: Structures, Reactions, Synthesis and Applications

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200729160720 ◽

2020 ◽

Vol 20 ◽

Author(s):

Neelottama Kushwaha ◽

C S Sharma

Keyword(s):

Basic Property ◽

Electrophilic Substitution ◽

Antimicrobial Agents ◽

Resonance Energy ◽

Heterocyclic Ring ◽

Ring System ◽

Agricultural Fields ◽

Substitution Reactions ◽

Anti Cancer ◽

Benzene Structure

: Triazine is the six-membered heterocyclic ring containing three nitrogen which replaces carbon-hydrogen unit in the benzene ring. Based on nitrogen position present in the ring system, it is categorized in three isomeric forms i.e.1, 2, 3-triazine (vicinal triazine), 1, 2, 4-triazine (asymmetrical triazine or isotriazine) and 1, 3, 5-triazine (symmetrical or s-triazine or cyanidine). Triazines have weakly basic property. Its isomers have much weaker resonance energy than benzene structure, so nucleophilic substitution reactions are more preferred than electrophilic substitution reactions. Triazine isomers and their derivatives are known to play important roles possessing various activities in medicinal and agricultural fields such as anti-cancer, antiviral, fungicidal, insecticidal, bactericidal, herbicidal, antimalarial and antimicrobial agents.

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Resolving the Mystery of Ring Opening in the Synthesis of Benzo[d][1, 3]oxazin-4-one and Quinazolin-4(3H)-one

Letters in Organic Chemistry ◽

10.2174/1570178616666181217114030 ◽

2019 ◽

Vol 16 (11) ◽

pp. 898-905

Author(s):

Harun Patel ◽

Rahul Pawara ◽

Sanjay Surana

Keyword(s):

Characteristic Feature ◽

Ring Opening ◽

Biological Activities ◽

Heterocyclic Ring ◽

Ring System ◽

Time Saving ◽

Fusion Strategy ◽

Good Template ◽

Lead Generation

Quinazoline is the six-membered heterocyclic ring system reported for its versatile biological activities. This characteristic feature of quinazoline makes it a good template for a lead generation library. Ring opening is one of the major concerns in the synthesis of quinazolin-4(3H)-one that results in diamide formation. Here, alternative fusion strategy is reported, which is a time-saving and costeffective method to overcome the ring opening problem associated with the synthesis of benzo[ d][1,3]oxazin-4-one and quinazolin-4(3H)-one.

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Synthesis of New Aryl(Hetaryl)-Substituted Tandospirones Under Reductive Heck Type Hydroarylations and Isoxazoline Derivatives via 1,3-Dipolar Cycloaddition Reactions with Expected Anxiolytic Activity†

Current Organic Synthesis ◽

10.2174/1570179411310030010 ◽

2013 ◽

Vol 10 (3) ◽

pp. 481-485 ◽

Cited By ~ 2

Author(s):

Irem Kulu ◽

Asli Kopruceli ◽

Gokce Goksu ◽

Nuket Ocal

Keyword(s):

Anxiolytic Activity ◽

Dipolar Cycloaddition ◽

Cycloaddition Reactions

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π-Facial Selectivity in 1,3-Dipolar Cycloaddition Reactions of α-Methylidene-γ-lactone Substituted by 4-Methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl Group in γ-Position

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20020353 ◽

2002 ◽

Vol 67 (3) ◽

pp. 353-364 ◽

Cited By ~ 3

Author(s):

Petr Melša ◽

Ctibor Mazal

Keyword(s):

Double Bond ◽

Carboxylic Acid ◽

Nitrile Oxide ◽

Dipolar Cycloaddition ◽

Cycloaddition Reactions ◽

Enantiomerically Pure ◽

Nitrile Imine ◽

Facial Selectivity ◽

Excellent Selectivity

Diastereoselectivity of 1,3-dipolar cycloaddition reactions of benzyl azide, diazomethane, a nitrile oxide and a nitrile imine to α-methylidene-γ-lactone dipolarophile was effectively controlled by a bulky γ-substituent, 4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl in γ-position of the dipolarophile. The dipoles added from the less hindered face of the double bond with an excellent selectivity. Enantiomerically pure dipolarophile was prepared from the easily available (S)-5-oxotetrahydrohydrofuran-2-carboxylic acid.

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