Improved Synthesis of 2‐Chloro‐3‐amino‐4‐methylpyridine

2‐Chloro‐3‐amino‐4‐methylpyridine ( 1 ), a key intermediate in the synthesis of nervirapine, was prepared from 2‐cyanoacetamide and 4,4‐dimethoxyl‐2‐butanone via condensation, cyclization, one‐pot reaction of chlorination and hydrolysis, and Hofmann reaction. Utilization of the quadratic orthogonal test resulted in a high yield (62.1%) of the whole process.     

Chemical Reduction and Dimerization of 1‐Chloro‐2,3,4,5‐tetraphenylborole

As neutral isoelectronic analogues of the elusive cyclopentadienyl cation, boroles have been of interest for their prospective applications as strong Lewis acids, chromophores, and electron acceptors. Recently our group discovered a π‐nucleophilic boryl anion based on the borole system. In an effort to extend borole chemistry, we now report the molecular structure of 1‐chloro‐2,3,4,5‐tetraphenylborole ( 1 ) and its corresponding borole dianion resulting from the two‐electron reduction of 1 with KC₈. The thermally induced dimerization of 1 yields an unprecedented boracyclohexadiene/borolene spiro‐bicyclic compound and the resulting dimer was fully characterized including a single‐crystal X‐ray analysis.     

2‐Chloro‐3‐(pyrrolidin‐1‐yl)‐1,4‐naphtho­quinone

The structure of the title compound, C₁₄H₁₂ClNO₂, (I), comprises essentially planar mol­ecules which crystallize in a monoclinic lattice. C—H?O interactions exist to both naphtho­quinone O atoms and the Cl atom.     

4‐Chloro‐N‐(4‐cyano‐2‐nitro­phenyl)‐3‐nitro­benz­amide

The structure of the title compound, C₁₄H₇ClN₄O₅, comprises two nearly coplanar phenyl rings connected via an amido moiety.     

Synthesis of Novel Phthalazine Derivatives as Potential Anticancer and Antioxidant Agents Based on 1‐Chloro‐4‐(4‐phenoxyphenyl)phthalazine

A new series of phthalazine derivatives was synthesized from the reaction of 1‐chloro‐4‐(4‐phenoxyphenyl)phthalazine as a reactive starting material with different carbon, nitrogen, oxygen, and sulfur nucleophiles. The structural formulae of all products were confirmed and characterized by elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and mass spectra). Some of the synthesized derivatives were screened for their antitumor activity against four human tumor cell lines using MTT assay. In comparison with doxorubicin as standard drug, compounds 1 , 20 , and 25 showed the most potent cytotoxic effect. In addition, investigation of antioxidant activity revealed that hydrazinylphthalazine 20 has the highest activity.     

Synthesis and Transformations of 5‐Chloro‐2,2′‐Dipyrrins and Their Boron Complexes, 8‐Chloro‐BODIPYs

Symmetric dipyrrylketones 1 a , b were synthesized in two steps from the corresponding α‐free pyrroles, by reaction with thiophosgene followed by oxidative hydrolysis under basic conditions. The dipyrrylketones produced the corresponding 5‐chloro‐dipyrrinium salts or 5‐ethoxy‐dipyrrins on reaction with phosgene or Meerwein’s salt, respectively. Boron complexation of the dipyrrins afforded the corresponding 8‐functionalized BODIPYs (borondipyrromethenes) in high yields. The 5‐chloro‐dipyrrinium salts reacted with methoxide or ethoxide ions to produce monopyrrole esters, presumably via a 5,5‐dialkoxy‐dipyrromethane intermediate. In contrast, 8‐chloro‐BODIPYs underwent a variety of nucleophilic substitutions of the chloro group in the presence of alkoxide ions, Grignard reagents, and thiols. In the presence of excess alkoxide or Grignard reagent, at room temperature or above, substitution at the boron center also occurred. The 8‐chloro‐BODIPY was a particularly useful reagent for the preparation of 8‐aryl‐, 8‐alkyl‐, and 8‐vinyl‐substituted BODIPYs in very high yields, using Pd⁰‐catalyzed Stille cross‐coupling reactions. The X‐ray structures of eleven BODIPYs and two pyrroles are presented, and the spectroscopic properties of the synthesized BODIPYs are discussed.     

First synthesis of 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol from 1‐ and 2‐naphthol derivatives

Two new structurally isomeric, 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol ( 1 ) and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol ( 3 ) have been synthesized from 2‐acetyl‐1‐naphthol and ethyl‐3‐hydroxy‐2‐naphthoate, respectively, involving Grignard reaction, dehydration of the corresponding tertiary alcohols, and hetero Diels–Alder dimerization. The two benzochromenes ( 1 and 3 ) have been fully characterized by IR, NMR, and HRESIMS data. Their structures are further supported by crystallography of their corresponding acetates ( 2 and 4 ). J. Heterocyclic Chem., (2011).     

2‐Chloro‐3‐morpholino‐1,4‐naphtho­quinone

The structure of the title compound, C₁₄H₁₂ClNO₃, (I), comprises essentially planar mol­ecules stacked parallel to the a axis. C—H?O hydrogen‐bonding interactions exist to both naphtho­quinone O atoms and the Cl atom, but not to the morpholine O atom.     

2‐Chloro‐4,6‐di­methoxy‐1,3,5‐triazine

The mol­ecules of 2‐chloro‐4,6‐di­methoxy‐1,3,5‐triazine, C₅H₆ClN₃O₂, lie on a crystallographic mirror plane. There is a close contact of 3.180 (3) Å between one of the methyl C atoms and the N atom of a neighboring mol­ecule. Differential scanning calorimetry measurements show that methyl rearrangement does not take place in the solid state, despite the close proximity of the methyl group to the N atom.     

Steady‐State Spectroscopy of the 2‐(N‐methylacetimidoyl)‐1‐naphthol Molecule

The steady‐state spectroscopy of 2‐(N‐methylacetimidoyl)‐1‐naphthol (MAN) reveals composite absorption and emission spectra from 298 to 193 K in hexane. The ground electronic state (So) absorption can be assigned to the sum of three molecular structures: the OH normal tautomer, and two NH proton transfer tautomers. The NH‐structures are the most stable ones in equilibrium with the OH tautomer for the S₀ state. On photoexcitation of the OH tautomer the excited state intramolecular proton transfer is undergone, and the corresponding NH emission is monitored at 470 nm. On photoexcitation of the NH tautomers the previous emission is monitored in addition to another emission at 600 nm, which is ascribed to intramolecular hydrogen‐bonded (IHB) nonplanar NH structures generated from the IHB planar NH tautomers. A Jab?oński diagram is introduced which gathers all the experimental evidence as well as the theoretical calculations executed at the DFT‐B3LYP and TD‐DFT levels. The MAN molecule is compared with other analogs such as 1‐hydroxy‐2‐acetonaphthone (HAN), 2‐(1?‐hydroxy‐2?‐naphthyl)benzimidazole and methyl 1‐hydroxy‐2‐naphthoate to validate the theoretical calculations. Photoexcitation of MAN generates two emission bands at longer wavelengths than that of the emission band of HAN. The MAN molecule exhibits a great photostability in hydrocarbon solution which depends on the photophysics of the NH tautomers (keto forms).     

2‐Chloro‐6‐(2‐furyl)‐9‐(4‐methoxybenzyl)‐9H‐purine

The title compound, C₁₇H₁₃ClN₄O₂, displays profound and selective activity against Mycobacterium tuberculosis. In the crystal structure, there are two independent molecules in the asymmetric unit. Intermolecular hydrogen bonding between a CH group of the purine ring and the O atom of the furan ring, and also π–π stacking in another direction, builds the three‐dimensional network.     

2‐Chloro‐4‐nitrobenzoic acid as a coformer with pharmaceutical cocrystals and molecular salts

A series of five binary complexes, i.e. three cocrystals and two molecular salts, using 2‐chloro‐4‐nitrobenzoic acid as a coformer have been produced with five commonly available compounds, some of pharmaceutical relevance, namely, 2‐chloro‐4‐nitrobenzoic acid–isonicotinamide (1/1), C₇H₄ClNO₄·C₆H₆N₂O, 2‐chloro‐4‐nitrobenzoic acid–3,3‐diethylpyridine‐2,4(1H,3H)‐dione (2/1), 2C₇H₄ClNO₄·C₉H₁₃NO₂, 2‐chloro‐4‐nitrobenzoic acid–pyrrolidin‐2‐one (1/1), C₇H₄ClNO₄·C₄H₇NO, 2‐carboxypiperidinium 2‐chloro‐4‐nitrobenzoate, C₆H₁₂NO₂^?·C₇H₃ClNO₄^?, and (2‐hydroxyethyl)ammonium 2‐chloro‐4‐nitrobenzoate, C₂H₈NO⁺·C₇H₃ClNO₄^?. The coformer falls under the classification of a `generally regarded as safe' compound. All five complexes make use of a number of different heteromeric hydrogen‐bonded interactions. Intermolecular potentials were evaluated using the CSD‐Materials module.     

7‐Chloro‐3,6‐di­methyl‐1H‐indene‐2‐carb­aldehyde

In the crystal structure of C₁₂H₁₁ClO, the (planar) mol­ecules give rise to a parallel packing. A model crystal obtained by semi‐empirical and packing‐energy calculations is consistent with the observed structure.     

4‐Chloro‐3′‐methylsulfinyl‐5(6 or 8)‐nitro‐3,4′‐diquinolinyl sulfides

Reaction of 4‐chloro‐3′‐methylthio‐3,4′‐diquinolinyl sulfides 3, 9b, 9c with a nitrating mixture proceeds via the 3′‐methylthio group monooxidation and yields 3′‐methylsulfinyl diquinolinyl sulfides 4, 5b, 5c , respectively. Further treatment of 4 with a nitrating mixture followed as C₅‐ and C₈‐nitration and gives mixture of 5a and 5c. Treatment of 3′‐methylsulfinyl quinolines 6 and 7 with hydrochloric acid/potassium iodide system causes reduction of the sulfoxide group in 6 and 7 to the sulfide group yielding 8 , in case of 4‐methoxyquinolines 6 , hydrolysis of the 4‐methoxyquinoline moiety to the 4‐quinolinone moiety takes place simultaneously. The proton and carbon chemical shifts of 4 and 5a were completely assigned following COSY, HETCOR and INEPT or COLOC studies.     

1‐Chloro‐1,1‐di­fluoro‐N‐(4‐methoxy­phenyl)‐3‐(pyrrolidin‐2‐yl­idene)­propan‐2‐imine

In the title compound, C₁₄H₁₅ClF₂N₂O, the Z configuration has been confirmed. The molecular structure shows an intramolecular N—H?N hydrogen bond [H?N 2.04 (6), N?N 2.709 (6) Å and N—H?N 124 (5)°]. This interaction could be responsible for the Z configuration.     

A Novel Procedure to Synthesize 3‐Chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl Azetidin‐2‐ones and Exploration of Their Anti‐Inflammatory Activity

Some new derivatives of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl azetidin‐2‐one were synthesized through the reaction of N‐{4‐[phenyldiazenyl] phenyl}‐N‐[phenyl methylene] amine with 4‐[phenyldiazenyl] aniline. The resulting 3‐chloro‐4‐phenyl‐1‐{4‐[phenyldiazenyl] phenyl} azetidin‐2‐one intermediate in benzene was irradiated in a Pyrex vessel with 350 nm UV light in a photochemical reactor to give the desired derivatives (4a–j) . Structures of the new compounds were verified on the basis of spectral and elemental methods of analyses. Nine of the prepared compounds were tested for their anti‐inflammatory effects; most of these compounds showed potent and significant results compared with indomethacin.