An Overview on the Synthetic Routes and Properties of Ammonium Dinitramide (ADN) and other Dinitramide Salts

The systematic exploration of synthetic pathways to afford a desired product through quantum chemical calculations remains a considerable challenge. In 2013, Maeda et al. introduced ‘quantum chemistry aided retrosynthetic analysis’ (QCaRA), which uses quantum chemical calculations to search systematically for decomposition paths of the target product and propose a synthesis method. However, until now, no new reactions suggested by QCaRA have been reported to lead to experimental discoveries. Using a difluoroglycine derivative as a target, this study investigated the ability of QCaRA to suggest various synthetic paths to the target without relying on previous data or the knowledge and experience of chemists. Furthermore, experimental verification of the seemingly most promising path led to the discovery of a synthesis method for the difluoroglycine derivative. The extent of the hands-on expertise of chemists required during the verification process was also evaluated. These insights are expected to advance the applicability of QCaRA to the discovery of viable experimental synthetic routes.

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Discovery of a Difluoroglycine Synthesis Method through Quantum Chemical Calculations

10.26434/chemrxiv.11550057 ◽

2020 ◽

Author(s):

Tsuyoshi Mita ◽

Yu Harabuchi ◽

Satoshi Maeda

Keyword(s):

Quantum Chemical Calculations ◽

Experimental Verification ◽

Quantum Chemical ◽

Synthesis Method ◽

Target Product ◽

Systematic Exploration ◽

Hands On ◽

Retrosynthetic Analysis ◽

Synthetic Routes ◽

Verification Process

The systematic exploration of synthetic pathways to afford a desired product through quantum chemical calculations remains a considerable challenge. In 2013, Maeda et al. introduced ‘quantum chemistry aided retrosynthetic analysis’ (QCaRA), which uses quantum chemical calculations to search systematically for decomposition paths of the target product and propose a synthesis method. However, until now, no new reactions suggested by QCaRA have been reported to lead to experimental discoveries. Using a difluoroglycine derivative as a target, this study investigated the ability of QCaRA to suggest various synthetic paths to the target without relying on previous data or the knowledge and experience of chemists. Furthermore, experimental verification of the seemingly most promising path led to the discovery of a synthesis method for the difluoroglycine derivative. The extent of the hands-on expertise of chemists required during the verification process was also evaluated. These insights are expected to advance the applicability of QCaRA to the discovery of viable experimental synthetic routes.

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Three-Component [1+1+1] Cyclopropanation with Ruthenium(II)

10.26434/chemrxiv.6025772 ◽

2018 ◽

Author(s):

Tanner C. Jankins ◽

Robert R. Fayzullin ◽

Eugene Khaskin

Keyword(s):

Quaternary Carbon ◽

Poor Control ◽

One Step ◽

Synthetic Routes ◽

Mechanistic Investigations ◽

Chiral Centers ◽

Metal Catalyzed ◽

The Right ◽

Substituted Cyclopropanes

We report a one-step, Ru(II)-catalyzed cyclopropanation reaction that is conceptually different from the previously reported protocols that include Corey-Chaykovsky, Simmons-Smith, and metal catalyzed carbene attack on olefins. Under the current protocol, various alcohols are transformed into sulfone substituted cyclopropanes with excellent isolated yields and diastereoselectivities. This new reaction forms highly congested cyclopropane products with three new C–C bonds, three or two new chiral centers and one new quaternary carbon center. 22 examples of isolated substrates are given. Previously reported synthetic routes for similar substrates are all multi-step, linear routes that proceed with overall low yields and poor control of stereochemistry. Experimental mechanistic investigations suggest initial metal-catalyzed dehydrogenation of the alcohol substrate and catalyst independent stepwise attack of two equivalents of sulfone on the aldehyde under basic conditions. While the Ru(II) is only responsible for the initial dehydrogenation step, the rate of aldehyde formation is crucial to maintaining the right balance of intermediates needed to afford the cyclopropane product.

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Computational Analysis of Some Aspects of a Synthetic Route to Ammonium Dinitramide

10.21236/ada274648 ◽

1993 ◽

Author(s):

Tore Brinck ◽

Peter Politzer

Keyword(s):

Computational Analysis ◽

Synthetic Route ◽

Ammonium Dinitramide

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Voltage Gated Sodium Channel Blockers: Synthesis of Mexiletine Analogues and Homologues

Current Medicinal Chemistry ◽

10.2174/0929867327666200504080530 ◽

2020 ◽

Vol 27 ◽

Author(s):

Alessia Catalano ◽

Carlo Franchini ◽

Alessia Carocci

Keyword(s):

Sodium Channel ◽

Channel Blocker ◽

Parent Compound ◽

Channel Blockers ◽

Sodium Channel Blocker ◽

Starting Point ◽

Channel Blocking ◽

Blocking Activity ◽

Synthetic Routes ◽

Lateral Sclerosis

: Mexiletine is an antiarrhythmic drug belonging to IB class, acting as sodium channel blocker. Besides its well-known activity on arrhythmias, its usefulness in the treatment of myotonia, myotonic distrophy and amyotrophic lateral sclerosis is now widely recognized. Nevertheless, it has been retired from the market in several countries because of its undesired effects. Thus, several papers were reported in the last years about analogues and homologues of mexiletine being endowed with a wider therapeutic ratio and a more selectivity of action. Some of them showed sodium channel blocking activity higher than the parent compound. It is noteworthy that mexiletine is used in therapy as a racemate even though a difference in the activities of the two enantiomers were widely demonstrated, with (–)-(R)-enantiomer being more active: this finding led several research groups to study mexiletine and its analogues and homologues in their optically active forms. This review summarizes the different synthetic routes used to obtain these compounds. They could represent an interesting starting point to new mexiletine-like compounds without common side effects related to the use of mexiletine.

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