A System Fusing Computational and Information Chemistry for Developing New Synthesis Routes of Compounds

Hori, Kenzi; Yamaguchi, Toru; Okano, Katsuhiko

doi:10.2751/jcac.5.26

Cited by 6 publications

(4 citation statements)

References 8 publications

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“…We have been developing synthesis routes for compounds by fusing computational chemistry and chemoinformatics . In these studies, TOSP and KOSP, the synthesis route design systems (SRDSs) developed by Satoh and Funatsu and Fujitsu, were used to create synthesis routes.…”

Section: Introductionmentioning

confidence: 99%

Predicting experimental yields as an index to rank synthesis routes II: application to the Curtius rearrangement

Yoshimura

Okano

Ishikawa

et al. 2011

J of Physical Organic Chem

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Synthesis yields of organic reactions are one of the most important factors in ranking synthesis routes created by synthesis route design systems such as Transform-Oriented Synthesis Planning and Knowledge base-Oriented Synthesis Planning. If it is possible to predict the yields of synthesis reactions before starting experiments, one can easily determine an order of synthesis routes for experimental works. In the present study, the reaction profiles of the Curtius rearrangement with different substituents were calculated to generate an equation predicting experimental yields of this reaction. Reactions followed by the formation of isocyanates were also analyzed to consider the relationship between reaction times and experimental yields. A partial least squares (PLS) regression was used to correlate the experimental yields with the calculated activation energies, E a (calc), together with experimental conditions such as dielectric constants of solvents, reaction times, and reaction temperatures as explanatory variables. Although the PLS regression using all the data gave very poor results, we succeeded in making a model equation with R 2 = 0.887 using a modified data set. However, there is a conflict between the predictability and the interpretability on the reaction time. This discrepancy mainly comes from unnecessarily long reaction times in the experiments for azides with calculated E a values of less than 33 kcal mol -1 . To construct a good model equation for the experimental yields of the Curtius reaction, we have to use data sets obtained from within 90 min of the reaction for the PLS regression.

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Section: Introductionmentioning

confidence: 99%

Predicting experimental yields as an index to rank synthesis routes II: application to the Curtius rearrangement

Yoshimura

Okano

Ishikawa

et al. 2011

J of Physical Organic Chem

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“…In particular, it is necessary to check whether side reactions are likely to proceed by comparison with the main reaction. We have been investigating these computational procedures to analyze synthetic routes, which are referred to as “ in silico screenings” [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Towards the Development of Synthetic Routes Using Theoretical Calculations: An Application of In Silico Screening to 2,6-Dimethylchroman-4-one

Hori

Sadatomi²,

Miyamoto

et al. 2010

Molecules

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This study describes an attempt to develop a synthetic route using theoretical calculations, i.e., in silico synthesis route development. The KOSP program created four potential synthetic routes for generating 2,6-dimethylchroman-4-one. In silico screening of these four synthetic routes was then performed. In silico screening involves theoretical analysis of synthetic routes prior to actual experimental work. A synthetic route using the Mitsunobu reaction had already been reported by Hoddgets et al. Theoretical investigations were also conducted on two SNAr reactions as well as a Michael reaction before they were examined experimentally. In silico screening using DFT calculations indicated that only the Michael reaction was likely to produce the target. Experimental work confirmed that the target was obtained in a yield of 76.4% using the Michael reaction. The other two routes, except for the Mitsunobu reaction, failed to generate the target. Our results demonstrate that theoretical calculations can be used to narrow down the number of experiments that need to be conducted when developing novel synthetic routes.

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“…combined data analysis such as artificial intelligence or machine learning with quantum chemical calculation, have been developing. [1][2][3] They are limited to a certain type of reaction and are not readily available when a synthetic organic chemist wants to use them. This paper is concerned with the simple prediction based on a correlation between the literature yield and reduced mass of raw materials.…”

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confidence: 99%

“…Fourth, a regression analysis was performed on the Sonogashira coupling shown in Scheme 4. Three examples of the single-fold coupling from the literature and 19examples of the four-fold coupling from the other literature were selected in the same way as for the case of the coppercatalyzed C-N couping,14,20,21 and applied for the regression equation(3). A correlation between the literature and predicted yield is shown in Figure6(β= 0.84, R 2 = 0.90).…”

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Correlation Between Yield and Reduced Mass of Raw Materials in Coupling Reactions

Kawashima¹

2020

Preprint

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Product yields in various organic reactions such as C-N, C-C, and C-O coupling reactions were found to be correlated with reduced mass of raw materials. The product yields decreased gradually with increasing the reduced mass according to a regression equation, yield = − 0.2047(MAB/n) + 104.2, where MAB is the reduced mass per mole and n is the number of reaction sites.

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A System Fusing Computational and Information Chemistry for Developing New Synthesis Routes of Compounds

Cited by 6 publications

References 8 publications

Predicting experimental yields as an index to rank synthesis routes II: application to the Curtius rearrangement

Predicting experimental yields as an index to rank synthesis routes II: application to the Curtius rearrangement

Towards the Development of Synthetic Routes Using Theoretical Calculations: An Application of In Silico Screening to 2,6-Dimethylchroman-4-one

Correlation Between Yield and Reduced Mass of Raw Materials in Coupling Reactions

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