Structure of 3-Chlorobenzaldehyde
CAS No.: 587-04-2
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Hydrazinated geraniol derivatives as potential broad-spectrum antiprotozoal agents
Jooste, Joelien ; Legoabe, Lesetja J ; Ilbeigi, Kayhan ; Caljon, Guy ; Beteck, Richard M ;
Abstract: Geraniol, a primary component of several essential oils, has been associated with broad-spectrum antiprotozoal activities, although moderate to weak. This study primarily concentrated on the synthesis of hydrazinated geraniol derivatives aspotential antiprotozoal agents. The synthesised compounds were tested in vitro against different parasitic protozoans of clinical relevance, including Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania infantum. Compounds 6, 8, 13, 14 and 15 demonstrated low micromolar activity against the different parasites. Compounds 8, 13, 14 and 15 had the highest efficacy against Trypanosoma brucei rhodesiense, as indicated by their respective IC50 values of 0.74, 0.56, 1.26 and 1.00 μM. Compounds 6, 14 and 15 displayed the best activity against Trypanosoma brucei brucei, with IC50 values of 1.49, 1.48 and 1.85 μM, respectively. The activity of compounds 6, 14 and 15 also extended to intracellular Trypanosoma cruzi, with IC50 values of 5.14, 6.30 and 4.90 μM, respectively. Compound 6, with an IC50 value of 11.73 μM, and compound 14, with an IC50 value of 8.14 μM, demonstrated some modest antileishmanial activity.
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Keywords: geraniol ; Leishmania infantum ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense ; Trypanosoma cruzi
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Design and synthesis of imidazo[1,2-a]pyridine-chalcone conjugates as antikinetoplastid agents
Agarwal, Devesh S. ; Beteck, Richard M. ; Ilbeigi, Kayhan ; Caljon, Guy ; Legoabe, Lesetja J. ;
Abstract: A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized using 1H NMR,13C NMR and HRMS. The synthesized analogs were screened for their antikinetoplastid activity against Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. The analogs were also tested for their cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all screened derivatives, (E)-N-(4-(3-(2-chlorophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active against T. cruzi and T. b. brucei exhibiting IC50 values of 8.5 and 1.35 μM, resp. Against T. b. rhodesiense, (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active with an IC50 value of 1.13 μM. All synthesized active analogs were found to be non-cytotoxic against MRC-5 and PMM with selectivity indexes of up to more than 50.
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Keywords: antikinetoplastid ; chalcone ; drug likeliness properties ; imidazo[1,2-a]pyridine ; neglected tropical diseases (NTDs) ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense
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Are β-Lactones Involved in Carbon-Based Olefination Reactions?
Jan Nowak ; Michał Tryniszewski ; Michał Barbasiewicz ;
Abstract: Heteroatom-based olefinating reagents (e.g., organic phosphonates, sulfonates, etc.) are used to transform carbonyl compounds into alkenes, and their mechanism of action involves aldol-type addition, cyclization, and fragmentation of four-membered ring intermediates. We have developed an analogous process using ethyl 1,1,1,3,3,3-hexafluoroisopropyl methylmalonate, which converts electrophilic aryl aldehydes into α-methylcinnamates in up to 70% yield. The reaction plausibly proceeds through the formation of β-lactone that spontaneously decarboxylates under the reaction conditions. The results shed light on the Knoevenagel–Doebner olefination, for which decarboxylative anti-fragmentation of aldol-type adducts is usually considered.
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Keywords: olefination ; carbonyl compounds ; reaction mechanism ; lactones ; malonates ; Knoevenagel ; Doebner reaction
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Nitrothiazole-Thiazolidinone Hybrids: Synthesis and in Vitro Antimicrobial Evaluation
Dylan Hart ; Lesetja J. Legoabe ; Omobolanle J. Jesumoroti ; Audrey Jordaan ; Digby F. Warner ; Rebecca Steventon , et al.
Abstract: Herein we report the synthesis of novel compounds inspired by the antimicrobial activities of nitroazole and thiazolidin-4-one based compounds reported in the literature. Target compounds were investigated in vitro for antitubercular, antibacterial, antifungal, and overt cell toxicity properties. All compounds exhibited potent antitubercular activity. Most compounds exhibited low micromolar activity against S. aureus and C. albicans with no overt cell toxicity against HEK-293 cells nor haemolysis against human red blood cells. Notably, compound 3b exhibited low to sub-micromolar activities against Mtb, MRSA, and C. albicans. 3b showed superior activity (0.25 μg/ml) against MRSA compared to vancomycin (1 μg/ml).
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CAS No. : | 587-04-2 |
Formula : | C7H5ClO |
M.W : | 140.57 |
SMILES Code : | O=CC1=CC=CC(Cl)=C1 |
MDL No. : | MFCD00003350 |
InChI Key : | SRWILAKSARHZPR-UHFFFAOYSA-N |
Pubchem ID : | 11477 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.56 |
Solubility | 0.385 mg/ml ; 0.00274 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.25 |
Solubility | 0.782 mg/ml ; 0.00556 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.94 |
Solubility | 0.163 mg/ml ; 0.00116 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) |
Yes |
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 |
-5.55 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 |
1.0 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) |
1.0 |
* 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 |
---|---|---|
In tetrahydrofuran; at 0 - 20℃; for 3.16667h;Inert atmosphere; | General procedure: To a solution of aldehyde 11 (4mmol) in THF (12mL) at 0C under nitrogen, was dropwise added methylmagnesium bromide (1.0M in THF, 5mmol). After stirring for 10min the reaction mixture was allowed to warm to room temperature and was stirred for 3h. Upon completion, the reaction was quenched with saturated NH4Cl solution and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure. The crude residue was used directly. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 231 3-(3-Chloro-benzylamino)-4-methoxy-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 3-chlorobenzaldehyde as starting materials, which are commercially available from Aldrich; m.p. 203-205 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | at 90℃; for 8h;Neat (no solvent); | Aldehyde 1 (1 mmol), dihydrothiophen-3(2H)-one-1,1-dioxide 2 (0.134 g, 1 mmol), enaminone 3 (1 mmol) and were triturated together in an agate mortar for 5 minutes. Then the mixture was kept at 90 C for a certain time (monitored by TLC). The result mixture was washed with water and recrystallized from ethanol (95 %) to give pure product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.8% | In ethanol;Reflux; | General procedure: solutionof acid hydrazide (0.01 mol) and appropriate benzaldehyde/acetophenone (0.01 mol) in ethanol was refluxed for 5-6 h. The precipitated title compounds were then filtered off, washed with water and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: SI, Figure 4. General procedure of the reductive amination reactions: synthesis of AA9-AA24 compounds (Tables 1 and 2). The <strong>[347174-05-4]ethyl 3-amino-4-(cyclohexylamino)benzoate</strong> (AA1) and derivatives (1 equiv.)and benzaldehyde (1 equiv) were heated in DCE for 1h at 80 oC in the presence of molecular sieves (4 A), then the mixture was cooled down to room temperature before addition of the NaBH(OAc)3 (1.6 equiv.) in small portions over 3h. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 17h. The reaction mixture was quenched with aqueous saturated NaHCO3, and the product was extracted with EtOAc. The EtOAc extract was dried (MgSO4), and the solvent was evaporated. The residue was purified by flash-column chromatography on silica gel, using a mixture of solvent of DCM: MeOH (50:1), to provide the desired AA9-AA24 compounds (Tables 1-2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 70 - 80℃; for 3h; | General procedure: The mixture of <strong>[78364-55-3]6-fluoro-2-hydrazinylbenzo[d]thiazole</strong> (2) (0.01 mol) and benzalde-hyde/substituted benzaldehyde (0.01 mol) was reuxed in ethanol (15 ml) at 70?80 °C for 3 h. The separated product obtained was ltered off, washed withdistilled water and recrystallized from methanol to give the correspondinghydrazone. The product obtained was further dissolved in acetic acid (20 ml) atroom temperature followed by the addition of sodium acetate (0.5 g). Bromine(2 mmol) in acetic acid (10 ml) was added dropwise to the reuxing reactionmixture. After 1 h, the mixture was poured onto crushed ice (100 g). The precipitateobtained was ltered off and crystallized from ethanol-dimethylformamide (1:1) togive crystals of (3a?3t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | at 160℃; for 0.25h; | General procedure: 3a (141mg, 0.5mmol) and benzaldehyde (106mg, 0.75mmol) were placed in a microwave-proof glass tube and heated for 15 min at 160C in a commercial microwave apparatus. The reaction was cooled to room temperature. The reaction product was precipitated by addition of ethyl acetate and hexane, collected by filtration, and recrystallized from hexane and ethyl acetate. The title compound was obtained as an orange solid (93mg, 0.30mmol, 59%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With 3-((1'R,2'R)-2-hydroxy-1',2'-diphenylethoxy)phthalonitrile; In dichloromethane; at 20℃; for 24h;Inert atmosphere; | General procedure: Under an argon atmosphere, chiral ligand (0.1 mmol) was dissolvedin dry solvent, Ti(OiPr)4 (0.94 mmol) was added and stirredfor 1 h for the Ti-mediated reactions. Et2Zn (2 mmol, 1 M in hexane)was added, and the resulting yellow solution was stirred for20 min at rt. Aldehyde (1 mmol) was then added dropwise in 10min and the reaction was stirred for another 24 h at room temperature.After quenching with 1 mL saturated NH4Cl solution, 25 mLof H2O was added and then extracted with CH2Cl2 (3 25 mL). Thecombined organic phases were dried over Na2SO4 and evaporatedin vacuo. The crude product was purified by flash chromatographyto give the corresponding alcohol. Enantiomeric excesses weredetermined by GC analysis with chiral HP-CHIRAL-B20 column. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With piperidine; In ethanol; at 80℃; for 16h;Inert atmosphere; | General procedure: To a mixture of 9 (100mg, 0.74mmol) (the general procedure for the synthesis of intermediate 9 was presented in supporting information), 3-chlorobenzaldehyde (104mg, 0.74mmol) and ethyl 2-cyanoacetate (83μL, 0.78mmol) in anhydrous EtOH (5mL) was added piperdine (136μL, 1.48mmol). The reaction mixture was stirred for 16hat 80C under N2 atmosphere. The resulting reaction mixture was evaporated to dryness under reduced pressure. The residue was purified by flash column chromatography eluting with CH2Cl2/MeOH (200:1-100:1, v/v) to afford the title compound (9a) as a slight yellow solid (210mg, 77% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With piperidine; In ethanol; at 80℃; for 16h;Inert atmosphere; | General procedure: To a mixture of 9 (100mg, 0.74mmol) (the general procedure for the synthesis of intermediate 9 was presented in supporting information), 3-chlorobenzaldehyde (104mg, 0.74mmol) and ethyl 2-cyanoacetate (83muL, 0.78mmol) in anhydrous EtOH (5mL) was added piperdine (136muL, 1.48mmol). The reaction mixture was stirred for 16hat 80C under N2 atmosphere. The resulting reaction mixture was evaporated to dryness under reduced pressure. The residue was purified by flash column chromatography eluting with CH2Cl2/MeOH (200:1-100:1, v/v) to afford the title compound (9a) as a slight yellow solid (210mg, 77% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With toluene-4-sulfonic acid; In methanol; for 4.0h;Reflux; | General procedure: p-Toluenesulfonic acid (PTSA) (0.1mmol, 10mol%) was added to a mixture of aminopyrazolone 1 (1mmol) and benzaldehyde 2a (2.5mmol) in methanol (5mL) and the mixture was stirred at reflux for 4h. Upon reaction completion (TLC), the solvent was removed under reduced pressure and the residue purified by silica gel column chromatography (n-hexane/EtOAc, 3:1). (3aR*,4S*,8aR*,9S*)-2,4,7,9,11-Pentaphenyl-5,7,9,10-tetrahydro-3a,8a-methanodipyrazolo[3,4-b:3?,4?-f][1,5]diazocine-3,8(2H,4H)-dione (3a). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | General procedure: The aldehyde (0.8 equivalent) and amine (0.7 equivalent) were dissolved in methanol (2.0 mL) and stirred for two to 3 h depending upon the starting material. The acid (100 mg, 1 equivalent) and isocyanide (0.7 equivalent) were added in the reaction mixture and further stirred. The reaction mixture was monitored using TLC analysis.Water (4 mL) was added upon completion of the reaction.The resulted solid was filtered off and dissolved in ethyl acetate(10 mL), washed with water (2 3 mL) and dried over sodium sulphate. The crude product was purified using silica gel column chromatography. The ethyl acetate:hexane (6:4) solvent system was used for the purification of these compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | for 0.116667h;Microwave irradiation; | General procedure: Second step consists of condensation of <strong>[6761-52-0]3-aminopyrazine-2-carbohydrazide</strong> (0.5 gm, 0.003 mol) with aromatic aldehydes (0.5 gm, 0.008 mol) using microwaveirradiation (8 - 10 min, 350 W). After cooling and filtration,the product was recrystallized using ethanol [6, 9] (Fig. 1). |
Tags: 587-04-2 synthesis path| 587-04-2 SDS| 587-04-2 COA| 587-04-2 purity| 587-04-2 application| 587-04-2 NMR| 587-04-2 COA| 587-04-2 structure
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P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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