4903-09-7

Basic information

• Product Name: 3-CHLORO-4-METHOXYBENZALDEHYDE
• Synonyms: TIMTEC-BB SBB003854;AKOS B029259;3-CHLORO-4-METHOXYBENZALDEHYDE;3-CHLORO-4-METHOXYBENZENECARBALDEHYDE;3-CHLORO-P-ANISALDEHYDE;CHEMBRDG-BB 6945816;3-chloroanisaldehyde;3-CHLORO-P-ANISALDEHYDE, 98+% GC
• CAS NO: 4903-09-7
• Molecular Formula: C₈H₇ClO₂
• Molecular Weight: 170.59
• EINECS: 225-532-2
• Product Categories: Aromatic Aldehydes & Derivatives (substituted);Benzaldehyde;Adehydes, Acetals & Ketones;Anisoles, Alkyloxy Compounds & Phenylacetates;Chlorine Compounds
• Mol File: 4903-09-7.mol

Chemical Properties

• Melting Point: 56-60 °C(lit.)
• Boiling Point: 269.1 °C at 760 mmHg
• Flash Point: 120.7 °C
• Appearance: /
• Density: 1.244 g/cm³
• Vapor Pressure: 0.00738mmHg at 25°C
• Refractive Index: 1.564
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• Sensitive: Air Sensitive
• CAS DataBase Reference: 3-CHLORO-4-METHOXYBENZALDEHYDE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-CHLORO-4-METHOXYBENZALDEHYDE(4903-09-7)
• EPA Substance Registry System: 3-CHLORO-4-METHOXYBENZALDEHYDE(4903-09-7)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 4903-09-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-CHLORO-4-METHOXYBENZALDEHYDE is used as a key intermediate in the synthesis of various pharmaceuticals for its ability to contribute to the development of new drugs and enhance the properties of existing ones.
Used in Agrochemical Industry:
3-CHLORO-4-METHOXYBENZALDEHYDE is used as a precursor in the production of agrochemicals, playing a crucial role in the development of pesticides and other agricultural chemicals to improve crop protection and yield.
Used in Dye Industry:
3-CHLORO-4-METHOXYBENZALDEHYDE is used as an intermediate in the synthesis of dyes, contributing to the creation of a wide range of colorants for various applications, including textiles, plastics, and printing inks.
Used in Perfume Industry:
3-CHLORO-4-METHOXYBENZALDEHYDE is used as a component in the formulation of perfumes, adding to the complexity and richness of fragrances due to its aromatic properties.
It is important to handle 3-CHLORO-4-METHOXYBENZALDEHYDE with care, as it can be harmful if ingested or inhaled, and can cause skin and respiratory irritation upon contact.

InChI:InChI=1/C8H7ClO2/c1-11-8-3-2-6(5-10)4-7(8)9/h2-5H,1H3

Upstream product

• 74-90-8 hydrogen cyanide 
• 766-51-8 2-Chloroanisole 
• 473-34-7 N,N-dichloro-p-toluenesulfonamide 
• 123-11-5 4-methoxy-benzaldehyde 
• 507-40-4 tert-butylhypochlorite 
• 64-19-7 acetic acid 
• 14503-45-8 3-chloro-4-methoxybenzyl alcohol 
• 105-13-5 4-Methoxybenzyl alcohol 
• 37908-96-6 3-chloro-4-methoxy benzoic acid 
• 50638-47-6 4-bromo-2-chloro-1-methoxybenzene 
• 93-61-8 N-methyl-N-phenylformamide 
• 37908-98-8 methyl 3-chloro-p-anisate 
• 3964-58-7 3-chloro-4-hydroxybenzoic acid 
• 3964-57-6 methyl 4-hydroxy-3-chlorobenzoate 

Downstream Products

• 58236-76-3 3-chloro-4-methoxycinnamic acid 
• 14503-45-8 3-chloro-4-methoxybenzyl alcohol 
• 860000-28-8 3-chloro-4-methoxy-4'-methyl-trans-chalcone 
• 861207-97-8 4-(3-chloro-4-methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one 
• 865660-26-0 [1-(3-Chloro-4-methoxy-phenyl)-meth-(E)-ylidene]-(2,2-dimethoxy-ethyl)-amine 
• 213470-63-4 (+/-)-1-(3'-chloro-4'-methoxyphenyl)-1-propanol 
• 212576-67-5 N-(3-chloro-4-methoxybenzyl)formamide 
• 372103-23-6 (E)-1-(3-bromo-2-hydroxy-5-methylphenyl)-3-(3-chloro-4-methoxyphenyl)-2-propen-1-one 
• 37908-98-8 methyl 3-chloro-p-anisate 
• 50638-47-6 4-bromo-2-chloro-1-methoxybenzene 
• 1857-56-3 3-(3-chloro-4-methoxyphenyl)propionic acid 
• 6396-53-8 (Z)-2-chloro-4-(1'-propenyl)anisole 
• 1027906-68-8 [1-(3-Chloro-4-methoxy-phenyl)-meth-(E)-ylidene]-(4-methanesulfonyl-phenyl)-amine 
• 909784-34-5 2-[3,5-bis(trifluoromethyl)phenyldimethylsilyl]-1-(3-chloro-4-methoxyphenyl)ethanol 

Relevant articles and documents

Activator free, expeditious and eco-friendly chlorination of activated arenes by N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI)

N-Chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI) has been explored for the first time as a chlorinating reagent for direct chlorination of various activated arenes and heterocycles without any activator. A comparative in-silico study was performed to determine the electrophilic character for NCBSI and commercially available N-chloro reagents to reveal the reactivity on a theoretical viewpoint. The reagent was prepared by an improved method avoiding the use of hazardous t-butyl hypochlorite. This reagent was proved to be very reactive compared to other N-chloro reagents. The precursor of the reagent N-(phenylsulfonyl)benzene sulfonamide was recovered from aqueous spent, which can be recycled to synthesize NCBSI. The eco-friendly protocol was equally applicable for the synthesis of industrially important chloroxylenol as an antibacterial agent.

C70Fullerene Catalyzed Photoinduced Aerobic Oxidation of Benzylamines to Imines and Aldehydes

C70 fullerene catalyzed photoinduced oxidation of benzylic amines at ambient conditions has been explored here. The developed strategy's main feature includes the additive/oxidant-free conversion of benzylic amine to corresponding imine and aldehydes. The reaction manifests broad substrate scope with excellent function group leniency and is applicable up to the gram scale. Further, symmetrical secondary amines can also be synthesized from benzylic amine in a one-pot two-step process. Various experiments and density functional theory studies revealed that the current reaction involves the generation of reactive oxygen species, single electron transfer reaction, and benzyl radical formation as key steps under photocatalytic conditions.

Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells

Cancer cells reprogram their metabolism to support growth and to mitigate cellular stressors. The serine synthesis pathway has been identified as a metabolic pathway frequently altered in cancers and there has been considerable interest in developing pharmacological agents to target this pathway. Here, we report a series of indole amides that inhibit human 3-phosphoglycerate dehydrogenase (PHGDH), the enzyme that catalyzes the first committed step of the serine synthesis pathway. Using X-ray crystallography, we show that the indole amides bind the NAD+ pocket of PHGDH. Through structure-based optimization we were able to develop compounds with low nanomolar affinities for PHGDH in an enzymatic IC50 assay. In cellular assays, the most potent compounds inhibited de novo serine synthesis with low micromolar to sub-micromolar activities and these compounds successfully abrogated the proliferation of cancer cells in serine free media. The indole amide series reported here represent an important improvement over previously published PHGDH inhibitors as they are markedly more potent and their mechanism of action is better defined.

Amplification of Trichloroisocyanuric Acid (TCCA) Reactivity for Chlorination of Arenes and Heteroarenes via Catalytic Organic Dye Activation

Heteroarenes and arenes that contain electron-withdrawing groups are chlorinated in good to excellent yields (scalable to gram scale) using trichloroisocyanuric acid (TCCA) and catalytic Brilliant Green (BG). Visible-light activation of BG serves to amplify the electrophilic nature of TCCA, providing a mild alternative approach to acid-promoted chlorination of deactivated (hetero)aromatic substrates. The utility of the TCCA/BG system is demonstrated through comparison to other chlorinating reagents and by the chlorination of pharmaceuticals including caffeine, lidocaine, and phenazone.

Visible-light photocatalytic activation of N-chlorosuccinimide by organic dyes for the chlorination of arenes and heteroarenes

A variety of arenes and heteroarenes are chlorinated in moderate to excellent yields using N-chlorosuccinimide (NCS) under visible-light activated conditions. A screening of known organic dye photocatalysts resulted in the identification of methylene green as the most efficient catalyst to use with NCS. According to mechanistic studies described within, the reaction is speculated to proceed via a single electron oxidation of NCS utilizing methylene green under visible-light photoredox pathway. The photo-oxidation of NCS amplifies the electrophilicity of the chlorine atom of the NCS, thus leading to enhanced reactivity as a chlorinating reagent with aromatic substrates.

Amino-TEMPO Grafted on Magnetic Multi-Walled Nanotubes: An Efficient and Recyclable Heterogeneous Oxidation Catalyst

An efficient and easy recyclable heterogeneous oxidation catalyst was prepared by grafting TEMPO–NH2 moieties on the surface of magnetic multi-walled carbon nanotubes (MWCNT), first by a radical reaction introducing butyric acid moieties on carbon nanotube surface. Subsequently, carboxylic acid moieties were submitted for amidation using TEMPO–NH2. The functionalized nanotubes [MWCNT-{(CH2)3-CO-NH-TEMPO}n] were investigated as a (pre-)catalyst for the oxidation of primary and secondary alcohols for the production of aldehydes and ketones in a Montanari-type catalytic oxidation using the cheap and readily available 1,3-dichloro-5,5-dimethylhydantoin as the terminal oxidant.

In Situ Formed IIII-Based Reagent for the Electrophilic ortho-Chlorination of Phenols and Phenol Ethers: The Use of PIFA-AlCl3 System

A new and in situ formed reagent generated by mixing PIFA {bis[(trifluoroacetoxy)iodobenzene]} and AlCl3 was introduced in the organic synthesis for the direct and highly regioselective ortho-chlorination of phenols and phenol ethers. An efficient electrophilic chlorination for these electron-rich arenes as well as the scope of the reaction are described herein. An easy, practical, and open-flask reaction allowed us to introduce a chlorine atom, which is a highly important functional group in organic synthesis. The reproducibility of our method has been demonstrated on gram-scale by carrying out the reaction in 6-bromo-2-naphthol. This halogenation reaction also proceeds in excellent conditions by first preparing the iodine(III)-based chlorinating reagent. Our new chlorinating reagent can be stored at least for two weeks at 4 °C without losing its reactivity.

Iron(III)-Catalyzed Chlorination of Activated Arenes

A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.

Aggregation-induced emission enhancement in halochalcones

A family of push-pull fluorophores, consisting of a chalcone core decorated with electron-donating substituents and halogen atoms, was designed and synthesized. Luminescence studies were performed in solution, aggregate form and in the solid state. Although some compounds are only weakly fluorescent in solution, all are emissive in the solid state showing aggregation-induced emission enhancement. In the crystalline state, the halogen atoms are not involved in halogen bonds but their presence strongly influences the aggregation-induced emission properties of the fluorophores.

Aromatic stacking interactions govern catalysis in aryl-alcohol oxidase

Aryl-alcohol oxidase (AAO, EC 1.1.3.7) generates H2O2 for lignin degradation at the expense of benzylic and other π system-containing primary alcohols, which are oxidized to the corresponding aldehydes. Ligand diffusion studies on Pleurotus eryngii AAO showed a T-shaped stacking interaction between the Tyr92 side chain and the alcohol substrate at the catalytically competent position for concerted hydride and proton transfers. Bi-substrate kinetics analysis revealed that reactions with 3-chloro- or 3-fluorobenzyl alcohols (halogen substituents) proceed via a ping-pong mechanism. However, mono- and dimethoxylated substituents (in 4-methoxybenzyl and 3,4-dimethoxybenzyl alcohols) altered the mechanism and a ternary complex was formed. Electron-withdrawing substituents resulted in lower quantum mechanics stacking energies between aldehyde and the tyrosine side chain, contributing to product release, in agreement with the ping-pong mechanism observed in 3-chloro- and 3-fluorobenzyl alcohol kinetics analysis. In contrast, the higher stacking energies when electron donor substituents are present result in reaction of O2 with the flavin through a ternary complex, in agreement with the kinetics of methoxylated alcohols. The contribution of Tyr92 to the AAO reaction mechanism was investigated by calculation of stacking interaction energies and site-directed mutagenesis. Replacement of Tyr92 by phenylalanine does not alter the AAO kinetic constants (on 4-methoxybenzyl alcohol), most probably because the stacking interaction is still possible. However, introduction of a tryptophan residue at this position strongly reduced the affinity for the substrate (i.e. the pre-steady state Kd and steady-state Km increase by 150-fold and 75-fold, respectively), and therefore the steady-state catalytic efficiency, suggesting that proper stacking is impossible with this bulky residue. The above results confirm the role of Tyr92 in substrate binding, thus governing the kinetic mechanism in AAO.