Consecutive Utilization of Mechanochemical and Microwave Methods for the Synthesis of Boc‐2‐amino‐quinazolin‐4(3<i>H</i>)‐ones and DFT Study of Mechanism 6π‐Diazaelectrocyclization Process

Antol, Ivana; Glasovac, Zoran; Murata, Yasujiro; Hashikawa, Yoshifumi; Margetić, Davor

doi:10.1002/slct.202200633

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…Here, we should note that the calculated barrier relates to the intramolecular proton transfer that involves the fourmembered cyclic TS structure which is known to be highly unfavorable. The elimination of methanol is a process that can be assisted by the external molecule(s) of water or the other proton-donating molecules which can significantly reduce the reaction barriers as shown by Antol et al [44]. Indeed, assuming the guanidine itself as the catalyst for the conversion of 15b_t1 to 17b_t1, the calculated barrier for the elimination of methanol was lowered from 88 kJ mol −1 to −72 kJ mol −1 (see Section S3 in the Supplementary Materials).…”

Section: Guandinesmentioning

confidence: 99%

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

2023

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A proposed mechanism of the reaction of guanidinium chlorides with dimethyl acetylenedicarboxylate in a tandem aza-Michael addition reaction/intramolecular cyclization was investigated by DFT M06-2X and B3LYP computational approaches. The energies of the products were compared against the G3, M08-HX, M11, and wB97xD data or experimentally obtained product ratios. The structural diversity of the products was interpreted by the concurrent formation of different tautomers formed in situ upon deprotonation with a 2-chlorofumarate anion. A comparison of relative energies of the characteristic stationary points along the examined reaction paths indicated that the initial nucleophilic addition is energetically the most demanding process. The overall reaction is strongly exergonic, as predicted by both methods, which is primarily due to methanol elimination during the intramolecular cyclization step producing cyclic amide structures. Formation of a five-membered ring upon intramolecular cyclization is highly favored for the acyclic guanidine, while optimal product structure for the cyclic guanidines is based on a 1,5,7-triaza [4.3.0]-bicyclononane skeleton. Relative stabilities of the possible products calculated by the employed DFT methods were compared against the experimental product ratio. The best agreement was obtained for the M08-HX approach while the B3LYP approach provided somewhat better results than the M06-2X and M11 methods.

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Section: Guandinesmentioning

confidence: 99%

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

2023

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“…The N,N-Boc-protected N-amidinylpyrrole 28 [31] and 1-guanidinoanthracene (29) [10,32] have functional groups which were not tolerated under the debromination conditions and intractable mixtures of products were obtained. Carbomethoxypyrrole (30) was less susceptible to the reaction conditions, but unreactive.…”

Section: Scope Of the Reactionmentioning

confidence: 99%

“…Instead, small amounts of another cycloadduct were obtained. It was found that this is the product arising from anthraquinone (32), which was present as an impurity in 31. Independent milling of 10 with anthraquinone afforded dihydroxy cycloadduct 33 (in 35% yield) indicating that in the reaction conditions of the anthraquinone ↔ 9,10-dihydroxyanthracene (DHA) equilibrium is shifted towards DHA [34,35].…”

Section: Scope Of the Reactionmentioning

confidence: 99%

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

Štrbac¹,

Margetić²

2022

Beilstein J. Org. Chem.

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The solution phase 1,2-debromination of polycyclic imides using the Zn/Ag couple was successfully transferred to solid state mechanochemical conditions. The Zn/Ag couple was replaced by the Zn/Cu couple which was prepared without any metal activation by in situ ball milling of zinc and copper dusts. The advantage of the ball milling process is that the whole procedure is operationally very simplified. The reactive alkene generated was trapped in situ by several dienes and the respective Diels−Alder cycloadducts were obtained. It was demonstrated that mechanochemical milling offers complementary conditions to solution (thermal) reaction by allowing chemical transformations to proceed which were not possible in solution and vice versa.

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Mechanochemical and Microwave Multistep Organic Reactions

Margetic

2024

CGC

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The development of more sustainable chemical reactions and processes has been the focus of recent research activities. Advances in the field of organic synthesis have led to the emergence of new methodologies and techniques involving non-conventional energy sources. These include the applications of mechanical energy (mechanochemistry) and microwave radiation (MW) methods. This article reviews the advances in multistep organic synthesis of biologically relevant organic molecules using mechanochemistry and microwave techniques. Among them, various heterocyclic molecules (with nitrogen, oxygen, and sulphur atoms), amides, and peptides have been synthesized by multistep mechanochemical or MW reactions. Performing multiple synthetic steps using more sustainable methods shows cumulative advantages over multistep processes under conventional conditions in terms of reduced solvent use, shorter reaction times, better turnovers, and reaction yields. Simplification of protocols by carrying out two or more reaction steps in the same reaction vessel is another advantage of multistep syntheses.

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Consecutive Utilization of Mechanochemical and Microwave Methods for the Synthesis of Boc‐2‐amino‐quinazolin‐4(3H)‐ones and DFT Study of Mechanism 6π‐Diazaelectrocyclization Process

Cited by 3 publications

References 42 publications

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

Mechanochemical and Microwave Multistep Organic Reactions

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