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Structure of 3-Methyl-2-butenal
CAS No.: 107-86-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Zhang, Yueteng ; Ji, Peng ; Meng, Xiang ; Gao, Feng ; Zeng, Fanxun ; Wang, Wei
Abstract: A simple arylamine-catalyzed Mannich-cyclization cascade reaction was developed for facile synthesis of substituted 2H-benzo[h]chromenes, e.g., I (R1 = Ph, 2-MeOC6H4, furan-2-yl, 2-bromopyridin-3-yl, etc.; R2 = H, Cl, O2N, AcNH, etc.). The notable feature of the process includes the efficient generation of ortho-quinone methides (o-QMs) catalyzed by o-phenylenediamine. The mild reaction conditions allows for a broad spectrum of 1- and 2-naphthols and trans-cinnamaldehydes R1CH:CHCHO to engage in the cascade sequence with high efficiency.
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Keywords: aminocatalysis ; cascade reaction ; chromenes ; organocatalysis ; quinone methide
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CAS No. : | 107-86-8 |
Formula : | C5H8O |
M.W : | 84.12 |
SMILES Code : | CC(C)=CC=O |
MDL No. : | MFCD00010291 |
InChI Key : | SEPQTYODOKLVSB-UHFFFAOYSA-N |
Pubchem ID : | 61020 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H226-H302-H313-H314-H317-H331-H402 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P261-P264-P270-P271-P272-P273-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P312-P333+P313-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501 |
Class: | 8(3) |
UN#: | 2920 |
Packing Group: | Ⅱ |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 25.87 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.17 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.83 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.03 |
Solubility | 7.8 mg/ml ; 0.0928 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.12 |
Solubility | 6.33 mg/ml ; 0.0752 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.58 |
Solubility | 22.0 mg/ml ; 0.261 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.98 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.55 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In tetrahydrofuran; for 24h;Heating / reflux; | To a solution of 4-pyridin-3-yl-imidazole (1 g) in THF (34 ML) was added acetic acid (1.6 ML) and 3-methyl-2-butenal (3.3 ML) and the resulting solution was heated under gentle reflux for 24 hours. THF was then removed in vacuo and the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2 to give the title compound as slightly yellow oil. MS: m/z 230 (M+H). | |
With acetic acid; In tetrahydrofuran; | EXAMPLE 15 3,3-Dimethyl-3(4-Pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (1 g) in THF (34 mL) was added acetic acid (1.6 mL) and 3-methyl-2-butenal (3.3 mL) and the resulting solution was heated under gentle reflux for 24 hours. THF was then removed in vacuo and the residue was purified on a Flash 75 (silica gel column made by Biotage Division of Dyax Corp, U.S.) long column eluding with MeOH-CH2Cl2 to give the title compound as slightly yellow oil. MS: m/z 230 (M+H). | |
With acetic acid; In tetrahydrofuran; | Example 15 3,3-Dimethyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (1 g) in THF (34 mL) was added acetic acid (1.6 mL) and 3-methyl-2-butenal (3.3 mL) and the resulting solution was heated under gentle reflux for 24 hours. THF was then removed in vacuoand the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2to give the title compound as slightly yellow oil. MS: m/z 230 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In ethanol; para-xylene; | Production of 6-acetyl-2,2-dimethyl-2H-1-benzopyran 60 mg undried catalyst KP-10 (Sud-Chemie) and 35.8 g triethyl orthoformate were placed in a flask in 45 ml absolute ethanol in an argon atmosphere. While cooling 19.56 g 3-methyl-crotonaldehyde was added in drops over 30 minutes at 5 C. Then the reaction mixture was stirred for a further hour at 5 C. After adding 195 mg potassium carbonate, 100 ml xylol and 20.95 g 4-hydroxy-acetophenone, the reaction mixture was heated for an hour to 140 C. and the ethanol formed was continuously distilled off. The solution was stirred for a further 4 hours at 140 C. After cooling, the organic phase was washed with NaOH (5%) and concentrated. The raw product was distilled under high vacuum (0.5mbar/98 C.). The fractions of the said compound obtained had a content of 76.4% (0.91 g) and 94.3% (15.8 g) (51.8% yield). |