635-93-8

Usage

Synthesis Reference(s)

Synthetic Communications, 20, p. 609, 1990 DOI: 10.1080/00397919008244911Tetrahedron Letters, 15, p. 3463, 1974

Purification Methods

Steam distil it, then crystallise it from aqueous EtOH or *C6H6 (m 100o). It forms complexes with Cu2+ and Fe2+ . [Beilstein 8 H 53, 8 II 45, 8 III 181, 8 IV 224.]

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

Upstream product

• 90-02-8 salicylaldehyde 
• 302-17-0 chloral hydrate 
• 106-48-9 4-chloro-phenol 
• 67-66-3 chloroform 
• 1121-74-0 potassium 4-chlorophenoxide 
• 76-03-9 trichloroacetic acid 
• 50-00-0 formaldehyd 
• 868-85-9 Dimethyl phosphite 
• 60315-73-3 4-chloro-2-formylphenyl acetate 
• 7791-25-5 sulfuryl dichloride 
• 7647-01-0 hydrogenchloride 
• 60-29-7 diethyl ether 
• 15454-33-8 chloromethanol 
• 7782-50-5 chlorine 

Downstream Products

• 6116-07-0 2-hydroxy-5-piperidin-1-ylmethyl-benzaldehyde 
• 111163-12-3 4-chloro-2-[(3-piperidino-propylamino)-methyl]-phenol 
• 107523-06-8 N-(5-chloro-2-hydroxy-benzylidene)-sulfanilic acid-[2]pyridylamide 
• 92596-90-2 N-(5-chloro-2-hydroxybenzylidene)-4-hydroxyaniline 
• 132972-13-5 (E)-3-(5-chloro-2-hydroxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one 
• 79567-37-6 4-chloro-2-[(2,4-dichloro-phenylimino)-methyl]-phenol 
• 3542-65-2 6-chloro-3-(phenylcarbonyl)-2H-chromen-2-one 
• 36043-76-2 4-chloro-2-(p-tolylimino-methyl)-phenol 
• 38544-16-0 2-(benzyloxy)-5-chlorobenzaldehyde 
• 96583-20-9 N-(5′-chlorosalicylidene)-4-chloroaniline 
• 115820-15-0 4-chloro-2-[(4-methoxy-phenylimino)-methyl]-phenol 
• 115820-16-1 (E)-4-chloro-2-(((4-(dimethylamino)phenyl)imino)methyl)phenol 
• 53451-80-2 4-chloro-2-[(4-nitro-phenylimino)-methyl]-phenol 
• 118110-23-9 (E)-3-(5-chloro-2-hydroxyphenyl)-1-phenylprop-2-en-1-one 

Relevant academic research and scientific papers

The X-ray structure of 5-chlorosalicylaldehyde

5-Chlorosalicylaldehyde [monoclinic, a = 3.800(2), b = 5.595(4), c = 15.174(11) ?, β = 93.221(17), space group P21] exhibits an unusual crystal structure with both intramolecular and intermolecular OH to CH=O hydrogen bonding, the latter leading to chains of molecules aligned along the b axis. A survey of previous substituted salicylaldehyde structures shows three main hydrogen bonding patterns: intramolecular only (14), intramolecular and intermolecular dimeric (5), and intramolecular and intermolecular polymeric (3).

Phosphine-catalyzed sequential (2+3)/(2+4) annulation of γ-vinyl allenoates: Access to the synthesis of chromeno[4,3-: B] pyrroles

A phosphine-catalyzed cascade (2+3)/(2+4) cyclization reaction of γ-vinyl allenoates with aldimine esters has been developed to provide a series of chromeno[4,3-b]pyrrole derivatives that contain three contiguous stereogenic centers. The method gives a good yield, excellent chemoselectivity and diastereoselectivity under mild conditions.

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.

Driving the Emission Towards Blue by Controlling the HOMO-LUMO Energy Gap in BF2-Functionalized 2-(Imidazo[1,5-a]pyridin-3-yl)phenols

Several boron compounds with 2-(imidazo[1,5-a]pyridin-3-yl)phenols, differentiated by the nature of the substituent (R) in the para position of the hydroxy group, have been synthesized and thoroughly characterized both in solution (1H, 13C, 11B, 19F NMR) and in the solid state (X-ray). All derivatives displayed attractive photophysical properties like very high Stokes shift, high fluorescence quantum yields and a good photostability in solution. Time-Dependent Density Functional Theory (TD-DFT) calculations allowed to define the main electronic transitions as intra ligand transitions (1ILT), which was corroborated by the Natural Transition Orbitals (NTOs) shapes. The HOMO-LUMO energy gap was correlated to the electronic properties of the substituent R on the phenolic ring, as quantified by its σp Hammett constant.

Copper(II) N, N, O-Chelating Complexes as Potential Anticancer Agents

Three novel dinuclear Cu(II) complexes based on a N,N,O-chelating salphen-like ligand scaffold and bearing varying aromatic substituents (-H, -Cl, and -Br) have been synthesized and characterized. The experimental and computational data obtained suggest that all three complexes exist in the dimeric form in the solid state and adopt the same conformation. The mass spectrometry and electron paramagnetic resonance results indicate that the dimeric structure coexists with the monomeric form in solution upon solvent (dimethyl sulfoxide and water) coordination. The three synthesized Cu(II) complexes exhibit high potentiality as ROS generators, with the Cu(II)/Cu(I) redox potential inside the biological redox window, and thus being able to biologically undergo Cu(II)/Cu(I) redox cycling. The formation of ROS is one of the most promising reported cell death mechanisms for metal complexes to offer an inherent selectivity to cancer cells. In vitro cytotoxic studies in two different cancer cell lines (HeLa and MCF7) and in a normal fibroblast cell line show promising selective cytotoxicity for cancer cells (IC50 about 25 μM in HeLa cells, which is in the range of cisplatin and improved with respect to carboplatin), hence placing this N,N,O-chelating salphen-like metallic core as a promising scaffold to be explored in the design of future tailor-made Cu(II) cytotoxic compounds.

Complete chemical shift assignment and molecular modeling studies of two chromene derivatives as potential leads for new anticancer drugs

The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (5) and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (7), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance (NMR) from 1H, 13C, APT, COSY, HSQC, and HMBC spectra. Additional HOMO-LUMO DFT calculations corroborated the NMR results and pointed to the most stable stereoisomers of each compound. Besides, further docking and molecular dynamic studies suggest that the stereoisomers (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, and 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione of these compounds may act as DNA intercalators and qualify as potential leads for the development of new anticancer drugs. Communicated by Ramaswamy H. Sarma.

Directed Structural Transformations of Coordination Polymers Supported Single-Site Cu(II) Catalysts to Control the Site Selectivity of C-H Halogenation

A main difficulty in C-H bond functionalization is to undertake the catalyst control accurately where the reaction takes place. In this work, to achieve highly effective and regioselective single-site catalysts, a three-dimensional (3D) rhombus-like framework of {[Mn(Hidbt)DMF]·H2O}n (1) [H3idbt = 5,5′-(1H-imidazole-4,5-diyl)-bis(2H-tetrazole)] containing coordinated DMF molecules was constructed. For the dissolution-recrystallization structural transformation process, attractive structural transformations proceeded from 1 to a new crystalline species formulated as {[Mn3(idbt)2(H2O)2]·3H2O}n (2) with a 3D windowlike architecture, and then the Mn ions in 2 could be exchanged with Cu ions through cation exchange in a single-crystal to single-crystal fashion to produce the Cu-exchanged product {[Mn2Cu(idbt)2(H2O)2]·3H2O}n (2a), which had a windowlike framework like that of 2. Furthermore, 2 and 2a were used as heterogeneous catalysts for the regioselective C-H halogenation of phenols with N-halosuccinimides (NCS and NBS) to produce the site selective single monohalogenated products. It was found that the catalytic activity and site selectivity of 2a were much higher than those of 2, because the unique structural features of 2a with the uniformly dispersed CuII active centers served as a single-site catalyst with a site-isolated and well-defined platform to promote the C-H halogenation reaction in regiocontrol and guide an orientation that favored the para selectivity during the reaction process.

Thiocyanate radical mediated dehydration of aldoximes with visible light and air

We developed a new means of activating aldoximes by an in situ generated thiocyanate radical from ammonium thiocyanate and molecular oxygen at room temperature. With a catalytic amount of organic dye aizenuranine as the photocatalyst, the dehydration of aldoximes proceeds smoothly under visible light irradiation, providing a simple to handle, excellent functional group tolerance, and metal-free protocol for a wide range of nitriles.

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.

Synthesis, anti-inflammatory evaluation in vivo and docking studies of some new 5-(benzo[b]furan-2-ylmethyl)-6-methyl-pyridazin-3(2H)-one derivatives

Seven novel 5-(benzo[b]furan-2-ylmethyl)-6-methyl-pyridazin-3(2H)-one derivatives (6a to 6g) have been synthesized by the condensation of appropriate 3-(benzofuran-2-ylmethylene)-4-oxopentanoic acid and hydrazine hydrate in ethanol. Structures of all compounds were elucidated by elemental analysis, IR, 1H NMR and 13C NMR. These compounds were tested for their anti-inflammatory activity in carrageenan-induced rat paw edema model. In silico molecular docking study has been executed to study the binding interactions of the synthesized compounds with COX-2 protein. Compounds 6a, 6b, 6e and 6g showed a good anti-inflammatory activity at 50 mg/kg compared with the indometacin at 10 mg/kg and the aspirin at 150 mg/kg and good binding affinity with COX-2.