Virtual Chemist

Uses Reactant Lewis Formulas as Inputs to Predict Organic Reaction Mechanisms, Regiochemistry, and Stereochemistry

About


Software that can predict organic reaction products is a hotly pursued but unsolved challenge because of its obvious potential. However, regiochemistry and stereochemistry are not included in the vast majority of the previous efforts, although their control is often the most challenging and interesting part of organic reactions. This is not an accidental omission but maybe an inherent problem with data structures of computer molecular representation.

VirtualChemist is an atom-based organic reaction software focusing on regiochemistry and stereochemistry. Using reactant Lewis structure as the only user input, it can (1) describe detailed reaction mechanisms at the level of electron flows in elementary reaction steps, ensuring that all reaction steps are not only atom and electron balanced but also atom-mapped; and (2) track molecular 3-D structure changes in every elementary reaction steps. In each reaction step, users can start animation and look at 3-D structures from different perspectives for each molecules and isomers, to aid the understanding of stereochemistry. For the compounds with tetrahedral carbon stereocenters and compounds with carbon-carbon double bond stereocenters, all possible stereocenters and stereoisomers are identified. The trial version of the software can be downloaded free.

The software application cases, in which the reactant Lewis formulas are stored, are arranged that parallel the contents of organic chemistry textbooks. They can be downloaded free too.

The demo videos show the basic graphic user interfaces of the software and its basic functionalities.

Partners are welcome.

Software


VirtualChemist

It translates reactant Lewis formulas to machine readable format data, predicts and presents organic reaction mechanism, stereochemistry, and regiochemistry. Bug Fix (2021-04-18).

Stereochemistry


C3H5Br2

One isomer has a chiral center, another one does not.

C5H11Br

Some isomers have chiral centers, some does not.

C7H11O

It has two chiral centers.

methyl-cyclohexane

It has no chiral center.

C8H15OH

It has a chiral center.

C8H15OH

It has no chiral center.

C9H10O

It has a chiral center.

chlorohexane

Some isomers have one, some has two chiral centers.

CPI rule-1

Cahn-Ingold-Prelog sequence rules

CPI rule-2

Cahn-Ingold-Prelog sequence rules

Tautomerism


isopropyl-methyl-ketone

Catalyst: acid or base. One step, two tautomers can be found.

2-methyl-propanamide

Catalyst: acid or base. Two tautomers can be found.

3-cyclohexene-1-one

(1). Catalyst: acid. Two tautomers are found. (2). Catalyst: base. Three tautomers are found.

Substrate: 3-methyl-2-penten-2-ol

Catalyst: acid or base. Two tautomers.

Substrate: 1-amino-2-methyl-1-butanol

Catalyst: acid/base. Two tautomers.

Substrate: 4-pyridone

Catalyst: acid. One tautomer.

Substrate: 4-hydroxypyridine

Catalyst: base. One Tautomer.

Substrate: 2-hydroxypyridone

Catalyst: base. One Tautomer.

Substrate: 2-pyridone

Catalyst: acid. One Tautomer.

Substrate: pyridine-2-thiol

Catalyst: base. One Tautomer.

Halohydrocarbon


Substrate: (S/R)2-bromobutane

(1). Reagent: CH3OK; Medium: CH3OH. (2). Reagent: CH3OH.

Substrate: (S/R)-2-chloro-1-methylcyclohexane

(1). Reagent: CH3OK; Medium: CH3OH. (2). Reagent: CH3OH.

Substrate: 1-bromopentane

(1). Reagent: NaOH; Medium: water. (2). Reagent: water.

Substrate: 2-bromo-2-methylpropane

(1). Reagent: CH3CH2OH.

Substrate: ter-butyl bromide

Reagent: CH3Ch2OH. The major reaction is solvolysis.

Substrate: (R/S)-1-bromo-2-methyl-cyclohexane

(1). Reagent: CH3OK, Medium: CH3OH. Major E2 product is ... (2). Reagent: CH3OH. Major SN1 product is (R/S) mixture.

Substrate: (R/S)-1-bromo-3-methyl-cyclohexane

(1). Reagent: CH3OK, Medium: CH3OH. Major E2 product is ... (2). Reagent: CH3OH. Major SN1 product is (R/S) mixture.

Substrate: 1-bromo-4-methyl-cyclohexane

(1). Reagent: CH3OK, Medium: CH3OH. Major E2 product is ... (2). Reagent: CH3OH. Major SN1 product is (R/S) mixture.

Substrate: (R/S)-1-bromo-5-ethyl-2-methyl-cyclohexane

(1). Reagent: CH3OK, Medium: CH3OH. Major E2 product is ... (2). Reagent: CH3OH. Major SN1 product is (R/S) mixture.

Substrate: 1-chloro-3-methyl-butane

Reagent: water. SN1/E1 competition

Alcohols and Ethers


Substrate: (R/S)-1-phenyl-2-propanol

Reagent: H2SO4. Rearrangement, Zaitsev rule, (Z/E) products.

Substrate: (R/S)-2-phenyl-3-butanol

Reagent: HCl. Rearrangement, (R/S) products.

Substrate: 1-methyl-cyclohexanol

Reagent: HBr. Temperature effect on elimination-substitution competition.

Substrate: cyclohexyl-methyl-methanol

Reagent: HBr. Rearrangement, (R/S) products.

Substrate: 3-methyl-2-butanol

Reagent: HBr. Rearrangement, (R/S) products.

Substrate: 3-methyl-2-butanol

Reagent: HBr. Temperature effect on elimination-substitution competition

Substrate: (R/S)-4,4-dimethyl-3-pentanol

Reagent: H2SO4. Rearrangement, Zaitsev rule, (Z/E) products.

Substrate: (R/S)4-ethyl-4-methyl-3-pentanol

Reagent: H2SO4. Rearrangement, Zaitsev rule, (Z/E) products.

Substrate: 2, 2-dimethyl-1-pentanol

Reagent: HBr. Hindered primary alcohol SN1, rearrangement.

Substrate : 3, 3-dimethyl-1-pentanol

Reagent: HBr. primary alcohol SN2.

Alkene


Substrate: (R/S)-2,3-dimethyl-cyclohexene

Reagent: HBr. Markovnikov rule, Br is axial in major stereoisomer.

Substrate: (R/S)-3,4-dimethyl-cyclohexene

Reagent: HCl. carbocation rearrangement, Markovnikov rule, (R/S)product, Cl is axial in major stereoisomer.

Substrate: 1-methyl-cyclohexene

Reagent: HBr. Markovnikov rule, Br is axial.

Substrate: 3-methyl-3-hexene

Reagent: HBr. Markovnikov rule, (R/S)product

Substrate: (R/S)-3-methyl-4-phenyl-1-butene

Reagent: HBr. carbocation rearrangement, Markovnikov rule, (R/S)product.

Substrate: (R/S)-1,3-dimethyl-cyclohexene

Reagent: HCl. Markovnikov rule, (R/S)product, Cl is axial in major stereoisomer.

Substrate: (Z/E)-1-phenylpropene

Reagent: HBr. regioselectivity, (R/S)product.

Substrate: 2-methyl-1-phenyl--1-propene

Reagent: HCl. regioselectivity, (R/S)product

Substrate: 2-butene

(1). Reagent: Cl2; (2). Reagent: Br2; (3). Reagent: I2. stereospecific anti-addition.

Substrate: phenyl ethylene

(1). Reagent: Cl2. (2). Reagent: Br2. (3). Reagent: I2. Size matters here.

Conjugated Alkene


Substrate: (s-cis/trans)-1,3-pentadiene

Reagent: HBr. Markovnikov rule, resonance, (R/S)product

Substrate: (E/Z)1,3,5-hexatriene

Reagent: HBr. Regioselectivity, resonance, (R/S)product.

Substrate: 2,5-dimethyl-2,4-hexadiene

Reagent: HBr, regioselectivity, resonance, (R/S)product

Substrate: (s-cis/trans)-1,3-pentadiene

Reagent: 2-propenal. Only s-cis- diene does Diels-Alder reaction, regioselectivity. However stereoselectivity?

Substrate: (s-cis/trans)2-methyl-1,3-butadiene

Reagent: 2-propenal. Only (s-cis)-dien does Diels-Alder reaction. regioselectivity. However stereoselectivity?

Substrate: (s-cis/trans)-1,3-butadienyl-methyl-ether

Reagent: 2-propenal, Only (s-cis)-diene does Diels-Alder reaction. regioselectivity. However, stereoselectivity?

Substrate: (s-cis/trans)-1,3-pentadiene

Reagent: acrylic acid. Only (s-cis)-diene does Diels-Alder reaction. Regioselectivity. However, stereoselectivity?

Substrate: (s-cis/trans)-1,3-butadiene

Reagent: butanedioic acid. Only (s-cis)-diene does Diels-Alder reaction. Both regioselectivity and stereoselectivity.

Substrate: 2-methyl-1,3-butadiene

Reagent: HBr. Regioselectivity

Substrate: 2-propenal

No reagent. Not very reactive but quite regioselective.

Aldehyde, Ketone


Substrate: isopropenyl-propenyl ketone

(1). Reagent: Cl2, Catalyst: acid. (2). Reagent: Cl2, Catalyst: base.

Substrate: isopropenyl-isopropenyl ketone

(1). Reagent: Br2, Catalyst: acid. (2). Reagent: Br2, Catalyst: base.

Substrate: propenyl-propenyl ketone

(1). Reagent: I2, Catalyst: acid. (2). Reagent: I2, Catalyst: base.

Substrate: cyclohexenyl-phenyl ketone

(1). Reagent: Grignard reagent (then water).

Substrate: cyclohexenyl-ethyl ketone

(1). Reagent: Organolithium (then water).

Substrate: pent-3-en-2-one

(1). Reagent: HBr.

Substrate: 4-methyl, hexe-3-en-2-one

(1). Reagent: methanol, Catalyst: acid.

Substrate: 4-methyl, pent-3-en-2-one

(1). Reagent: water, Catalyst: acid.

Substrate: pent-3-en-2-one

(1). Reagent: Br2. (2). Reagent: Br2, Medium: water. (3). Reagent: water, Catalyst: acid.

Substrate: pent-3-en-2-one

(1). Reagent: H2SO4.

Carboxylic Acid


Substrate: 2-methyl-5-hexenoic Acid

Reagent: Br2. Iodolactonization results in 6-membered rings, O and I are anti.

Substrate: 4-pentenoic acid

Reagent: I2. It produces 5-membered rings. O and I are anti.

Substrate: 3-methyl-5-hexenoic acid

Reagent: I2. It produces 6-membered rings. O and I are anti.

Substrate: Propanoic Acid

Reagent: (R/S)-1-methyl-1-propanol, Catalyst: acid. The stereochemistry of the alcohol is maintained.

Substrate: 2-methyl-propanoic Acid

Reagent: 2-methyl-1-propanol, Catalyst: acid. The esterification follows addition-elimination mechanism.

Substrate: (R/S)-4-hydroxy-pentanoic acid

Catalyst: acid. Intramolecular esterification yields lactone

Substrate: (R/S)-5-hydroxy-hexanoic acid

Catalyst: acid. Intramolecular esterification results in lactone.

Substrate: 4-hexenoic acid

Reagent: I2. Forming 5-membered ring and 6-membered ring. In one of the 6-membered ring, O and I are not Anti.

Substrate: 2-methyl-propanoic acid

Reagent: primary amine. Equilibrium favored at lower temperature.

Substrate: (R/S)-2-methyl-butanoic acid

Reagent: secondary amine. Equilibrium favored at lower temperature.

Aromatics Substitution


Substrate: Ethylbenzene or Toluene or Benzene or Benzaldehyde

Reagent: HNO3. Catalyst: acid. Nitration and substituent directing effect. Temperature is low at the last case.

Substrate: Ethylbenzene, Toluene or Benzene

Reagent: Br2 or Cl2. Catalyst: AlCl3. Lewis acid catalyzed halogenation.

Substrate: Ethylbenzene or Toluene or Benzene

Reagent: HOCl or HOBr or ICl. Halogenation.

Substrate: Ethylbenzene or Toluene or Benzene

Reagent: 1-bromobutane or 2-bromobutane. Catalyst: Lewis acid. Halogenation.

Substrate: Ethylbenzene or toluene or benzene

Reagent: 1-chloro-propane or 2-chloro-propane. Catalyst: Lewis acid. Reactivity order is F>Cl>Br>I.

Substrate: Ethylbenzene or Toluene or benzene

Reagent: 2-chloro-4-fluoro-hexane or 2-chloro-4-fluoro-pentane. Catalyst: Lewis acid. Friedel-Crafts alkylation. Reactivity order: F>Cl>Br>I.

Substrate: Ethylbenzene or Toluene or Benzene

Reagent: 2-chloro-5-fluoro-Hexane or 2-chloro-5-fluoro-heptane. Catalyst: Lewis acid. (entangled rings not done in 3D)

Substrate: ethylbenzene or toluene or benzene

Reagent: 2-propanol or 1-propanol or 2-butanol or 1-butanol or phenol. Catalyst: acid. Friedel-Crafts alkylation.

Substrate: Ethylbenzene or Toluene or benzene

Reagent: 3-methyl-butene or butane, propane or cyclohexene or 1-methylcyclohexene. Catalyst: acid. Friedel-Crafts alkylation.

Substrate: Ethylbenzene or Toluene or Benzene

Reagent: CH3Cl or CH2Cl2 or CHCl3 or CCl4. Catalyst: Lewis acid. C6H6 with CH3Cl gives PhCH3, with CH2Cl2 gives Ph2CH2, with CHCl3 gives PH3CH, with CCl4 gives PH3CCl.

Forum


Comments and suggestions are welcome. Your input is very valuable for the future's development of the software. 

Contact


  • Calgary, Alberta, Canada

The developer, Ming Yu, is a process engineer working in Canadian petrochemical industry. He attended schools in China and has degrees of BS, MS, and PhD all in chemical engineering. His earlier careers included thermodynamic calculations and engineering software development, his industrial experiences included plant design, operation, and technical services.