2420-26-0

Basic information

• Product Name: 4-Chloro-2-hydroxybenzaldehyde
• Synonyms: 4-CHLORO-2-HYDROXY-BENZALDEHYDE;4-Chloro-2-hydroxy-benzaldehyde ,97%;4-chloro-2-hydoxybenzaldehyde;4-chloro-2-hydoxybenzaldehye;4-chlorosalicylaldehyde;2-hydroxy-4-chlorobenzaldehyde;4-Chlorosalicylaldehyde, 5-Chloro-2-formylphenol;4-Chloro-2-hydroxybenzaldehyde, 95+%
• CAS NO: 2420-26-0
• Molecular Formula: C₇H₅ClO₂
• Molecular Weight: 156.57
• EINECS: 1533716-785-6
• Product Categories: Aromatic Aldehydes & Derivatives (substituted);Aldehydes;Phenyls & Phenyl-Het
• Mol File: 2420-26-0.mol

Chemical Properties

• Melting Point: 45.0 to 49.0 °C
• Boiling Point: 229.1 °C at 760 mmHg
• Flash Point: 92.4 °C
• Appearance: /
• Density: 1.404 g/cm³
• Vapor Pressure: 0.0468mmHg at 25°C
• Refractive Index: 1.632
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 7.21±0.10(Predicted)
• CAS DataBase Reference: 4-Chloro-2-hydroxybenzaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-2-hydroxybenzaldehyde(2420-26-0)
• EPA Substance Registry System: 4-Chloro-2-hydroxybenzaldehyde(2420-26-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 2420-26-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-2-hydroxybenzaldehyde is used as an intermediate for the preparation of benzodiazepine diones, which serve as Hdm2 antagonists. These antagonists are important in the development of drugs targeting the regulation of the cell cycle and have potential applications in cancer therapy.
Additionally, 4-Chloro-2-hydroxybenzaldehyde is used to synthesize hydroxy-dimethyl-oxo-cyclohexenyl-dimethyl-tetrahydro-xanthenone, which is an oral neuropeptide Y5 receptor antagonist. 4-Chloro-2-hydroxybenzaldehyde has potential applications in the treatment of obesity and related metabolic disorders by modulating the neuropeptide Y system, which is involved in appetite regulation and energy homeostasis.

InChI:InChI=1/C7H5ClO2/c8-6-2-1-5(4-9)7(10)3-6/h1-4,10H

Upstream product

• 88-33-5 5-chloro-2-formyl-benzenesulfonic acid 
• 874-42-0 2,4-dichlorobenzaldeyhde 
• 108-43-0 3-monochlorophenol 
• 76-03-9 trichloroacetic acid 
• 67-66-3 chloroform 
• 5306-98-9 5-chloro-2-methyl-phenol 
• 106-43-4 para-chlorotoluene 
• 50-00-0 formaldehyd 
• 75-25-2 Bromoform 
• 7732-18-5 water 
• 82944-19-2 7-chloro-2,2-dimethyl-benzo[1,3]dioxin-4-one 
• 64917-81-3 4-chloro-2-hydroxybenzyl alcohol 
• 5106-98-9 4-chlorosalicylic acid 
• 925-90-6 ethylmagnesium bromide 

Downstream Products

• 20300-58-7 7-chloro-2-oxo-2H-chromene-3-carboxylic acid 
• 30818-28-1 5-chloro-2-cyanophenol 
• 52112-68-2 6-chloro-1,3-benzoxazol-2-amine 
• 17487-76-2 7-chloro-1',3',3'-trimethyl-1',3'-dihydro-spiro[chromene-2,2'-indole] 
• 442125-04-4 6-chloro-1-benzofuran-2-carboxylic acid 
• 89130-16-5 N,N'-ethylenebis(2-hydroxy-5-chlorophenyleneimine) 
• 20536-95-2 5-chloro-2-((phenylimino)methyl)phenol 
• 53581-86-5 4-chloro-2-methoxybenzaldehyde 
• 74334-00-2 N-benzothiazol-2-yl-4-(4-chloro-2-hydroxy-benzylideneamino)-benzenesulfonamide 
• 80055-55-6 7-Chloro-2,2-dimethyl-2H-chromene 
• 148228-50-6 C₂₄H₂₈Cl₂N₄O₄ 
• 133900-94-4 1-(4-{[1-(4-Chloro-2-hydroxy-phenyl)-meth-(Z)-ylidene]-amino}-benzoyl)-1,3-dicyclohexyl-urea 
• 67897-17-0 C₁₇H₁₉ClO₂ 
• 96126-91-9 4-chloro-2-hydroxy-α-isopropyl-benzylalcohol 

Relevant articles and documents

Imine or Enamine? Insights and Predictive Guidelines from the Electronic Effect of Substituents in H-Bonded Salicylimines

Imine and enamine bonds decorate the skeleton of numerous reagents, catalysts, and organic materials. However, it is difficult to isolate at will a single tautomer, as dynamic equilibria occur easily, even in the solid state, and are sensitive to electronic and steric effect, including π-conjugation and H-bonding. Here, using as model Schiff bases generated from salicylaldehydes and TRIS in a set of linear free energy relationships (LFER), we disclose how the formation of either imines or enamines can be controlled and provide a comprehensive framework that captures the structural underpinning of this prediction. This work highlights the potentiality of tailor-made designs en route to compounds with desirable functionality.

Efficient synthesis of 4-sulfanylcoumarins from 3-bromo-coumarins: Via a highly selective DABCO-mediated one-pot thia-Michael addition/elimination process

A facile and efficient protocol for the highly selective direct sulfanylation of 3-bromocoumarins under DABCO promotion, was developed. The transformation took place with aromatic and aliphatic thiols as well as with α,ω-dithiols, affording the expected products in very good to excellent yields. Simple and convenient ways to access 4-((ω-mercaptoalkyl) thio)coumarins and the dimeric 4,4′-(alkane-1,4-diylbis(sulfanediyl))bis(coumarins) were also devised with the use of α,ω-alkanedithiols in different ratios with regards to the starting 3-bromocoumarin. The transformation seems to proceed through the DABCO-mediated thia-Michael stereoselective addition of the thiolate anion to the α,β-unsaturated carbonyl system of the coumarin, followed by a DABCO-assisted stereoselective dehydrobromination of the resulting α-bromo carbonyl intermediate.

Phosphine-Catalyzed [3+2] Annulation of β-Sulfonamido-Substituted Enones with Sulfamate-Derived Cyclic Imines

Phosphine-catalyzed [3+2] annulation of β-sulfonamido-substituted enones and sulfamate-derived cyclic imines has been developed, giving a series of imidazoline derivatives in moderate to excellent yields with good to excellent diastereoselectivities. A scale-up reaction worked well under mild reaction conditions. A possible mechanism was proposed on the basis of the results obtained.

MgBr2 supported on Fe3O4@SiO2?~?urea nanoparticle: An efficient catalyst for ortho-formylation of phenols and oxidation of benzylic alcohols

Urea was successfully immobilized on the surface of chloropropyl-modified Fe3O4@SiO2 core–shell magnetic nanoparticles, then supported by MgBr2 and acts as a unique catalyst for oxidation of benzylic alcohols to aldehydes and ketones, and ortho-formylation of phenols to salicylaldehydes. The prepared catalyst was characterized by FT-IR, transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, dispersive X-ray spectroscopy, CHN and TGA. It was found that Fe3O4@SiO2?~?urea/MgBr2 showed higher catalytic activity than homogenous MgBr2, and could be reused several times without significant loss of activity.

Enantioselective Construction of Tetrahydroquinazoline Motifs via Palladium-Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinones with Sulfamate-Derived Cyclic Imines

A palladium-catalyzed enantioselective [4 + 2] cycloaddition reaction of vinyl benzoxazinones with sulfamate-derived cyclic imines is described, affording the tetrahydroquinazolines bearing several functional rings in high yields (up to 99% yield) with good to excellent diastereoselectivities and excellent enantioselectivities (up to 96% ee). This reaction represents the first Pd-catalyzed asymmetric decarboxylative cycloaddition of vinyl benzoxazinones with imines.

Metabolic epoxidation is a critical step for the development of benzbromarone-induced hepatotoxicity

Benzbromarone (BBR) is effective in the treatment of gout; however, clinical findings have shown it can also cause fatal hepatic failure. Our early studies demonstrated that CYP3A catalyzed the biotransformation of BBR to epoxide intermediate(s) that reacted with sulfur nucleophiles of protein to form protein covalent binding both in vitro and in vivo. The present study attempted to define the correlation between metabolic epoxidation and hepatotoxicity of BBR by manipulating the structure of BBR. We rationally designed and synthesized three halogenated BBR derivatives, fluorinated BBR (6-F-BBR), chlorinated BBR (6-Cl-BBR), and brominated BBR (6-Br-BBR), to decrease the potential for cytochrome P450-mediated metabolic activation. Both in vitro and in vivo uricosuric activity assays showed that 6-F-BBR achieved favorable uricosuric effect, while 6-Cl-BBR and 6-Br-BBR showed weak uricosuric efficacy. Additionally, 6-F-BBR elicited much lower hepatotoxicity in mice. Fluorination of BBR offered advantage to metabolic stability in liver microsomes, almost completely blocked the formation of epoxide metabolite(s) and protein covalent binding, and attenuated hepatic and plasma glutathione depletion. Moreover, the structural manipulation did not alter the efficacy of BBR. This work provided solid evidence that the formation of the epoxide(s) is a key step in the development of BBR-induced hepatotoxicity.

Efficient synthesis of chiral benzofuryl β-amino alcohols via a catalytic asymmetric Henry reaction

Chiral β-amino alcohol ligands were found effective for the copper(ii)-catalyzed asymmetric Henry reaction of benzofuran-2-carbaldehydes with nitromethane, which led to the formation of (S)-enriched benzofuryl β-nitro alcohols with satisfactory enantioselectivities (up to 98% ee). Using this catalytic protocol, bioactive (S)-benzofuryl β-amino alcohols could be conveniently prepared in short steps.

Phosphine-Catalyzed [4 + 2] Annulation of Allenoate with Sulfamate-Derived Cyclic Imines: A Reaction Mode Involving γ′-Carbon of α-Substituted Allenoate

A phosphine-catalyzed [4 + 2] cycloaddition of cyclic α-substituted allenoates with sulfamate-derived cyclic imines has been reported. Using dibenzylphenylphosphine as the nucleophilic catalyst, the reaction worked efficiently to yield various fused multicyclic heterocyclic compounds in high yields with excellent diastereoselectivities. It undergoes a new reaction mode involving γ′-carbon of α-substituted allenoate.

Enantioselective synthesis of 2,3-disubstituted: Trans -2,3-dihydrobenzofurans using a Br?nsted base/thiourea bifunctional catalyst

The diastereo- and enantioselective synthesis of 2,3-disubstituted trans-2,3-dihydrobenzofuran derivatives (15 examples, up to 96 : 4 dr, 95 : 5 er) via intramolecular Michael addition has been developed using keto-enone substrates and a bifunctional tertiary amine-thiourea catalyst. This methodology was extended to include non-activated ketone pro-nucleophiles for the synthesis of 2,3-disubstituted indane and 3,4-disubstituted tetrahydrofuran derivatives.

Selective Aromatic Hydroxylation with Dioxygen and Simple Copper Imine Complexes

The formation of a bis(μ-oxido)dicopper complex with the ligand 2-(diethylaminoethyl)-6-phenylpyridine (PPN) and its subsequent hydroxylation of the pendant phenyl group (studied earlier by Holland et al., Angew. Chem. Int. Ed. 1999, 38, 1139-1142) has been reinvestigated to gain a better understanding of such systems in view of the development of new synthetic applications. To this end, we prepared a simple copper imine complex system that also affords selective o-hydroxylation of aromatic aldehydes by using dioxygen as the oxidant: Applying the ligand N′-benzylidene-N,N-diethylethylenediamine (BDED), salicylaldehyde was prepared in good yields and we show that this reaction also occurs through an intermediate bis-μ-oxido copper complex. The underlying reaction mechanism for the PPN-supported complex was studied at the BLYP-D/TZVP level of density functional theory and the results for representative stationary points along reaction paths of the BDED-supported complex reveal a closely related mechanistic scenario. The results demonstrate a new facile synthetic way to introduce OH groups into aromatic aldehydes.