Novel regioselective synthesis of 3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐one containing compounds

A variety of 3″,5″‐diaryl‐3″H,4′H‐dispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]thiadiazol]‐4′‐ones 3a‐c were synthesized regioselectively through the reaction of 4′H,5H‐trispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]oxadithiino[5,6‐c]chromene‐5″,1″′‐cyclohexan]‐4′‐one ( 1 ) with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a‐c ) in refluxing dry toluene. Single crystal X‐ray diffraction studies of 3a,b add support for the established structure. Similarly, 3′,5′‐diaryl‐2,2‐dimethyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5a‐c were obtained in a regioselective manner through the reaction of 2,2,5′,5′‐tetramethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino[5,6‐c]chromen]‐4‐one ( 4a ) with nitrilimines under similar reaction conditions. On the other hand, reaction of 2,5′‐diethyl‐2,5′‐dimethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino‐[5,6‐c]chromen]‐4‐one ( 4b ) with nitrilimines in refluxing dry toluene afforded the corresponding 3′,5′‐diaryl‐2‐ethyl‐2‐methyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5d‐f as two unisolable diastereoisomeric forms.     

Organocatalyzed Enantioselective Synthesis of 2‐Amino‐4H‐chromene Derivatives

Optically active 2‐amino‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carboxylates, 2‐amino‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carbonitriles, and 2‐amino‐8‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carbonitriles were synthesized. Using cinchona alkaloid‐derived bifunctional catalysts, the corresponding 2‐amino‐4H‐chromene derivatives were obtained in high yields and moderate to high ee values (up to 82% ee) from the tandem Michael addition–cyclization reaction between 1,3‐cyclohexanediones or 1,2‐cyclohexanediones and (E )‐3‐aryl‐2‐cyanoacrylate or alkylidene malononitrile derivatives.     

Short Synthesis of 1-(3-tert-Butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2H-chromen-8-yl) Urea Derivatives

A short and efficient synthesis of 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2H-chromen-8-yl) urea derivatives (1a–c), a novel type of p38 MAPK inhibitors, is described. The Claisen thermal rearrangement of arylpropargyl ethers was employd as a key step to synthesize the chromene core. The solvent effect on the ratio of the resultant two isomers of Claisen thermal rearrangement, namely 2-methylbenzofuran and 2H-chromen, was also investigated.     

Synthesis of 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane) from 6-(cyclopent-1-enyl)-2-methylaniline

The reaction of 6-(cyclopent-1-enyl)-N-ethoxycarbonyl-2-methylaniline with Br₂ or its reaction with NH₃ followed by the reaction with Br₂ afforded 2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentan)-2(1H)-one and 2-amino-2"-bromo-8-methylspiro(4H-3,1-benzooxazine-4,1"-cyclopentane), respectively.     

A simple two steps ytterbium triflate‐catalysed preparation of 2,2‐dimethyl‐2h‐chromenes from salicylaldehydes and 2‐methylpropene

The preparation of various 2,2‐dimethyl‐2H‐chromenes was achieved in two steps via an ytterbium triflate‐catalysed reaction between salicylaldehydes, trimethylorthoformate and 2‐methylpropene. From salicylaldehyde, two reaction products were characterised: 4‐methoxy‐2,2‐dimethylchroman and 2‐(1,3‐dimethoxy‐3‐methylbutyl)phenol. The former compound probably results from a Lewis acid‐catalysed [2+4] cycloaddition between the intermediate quinonemethide and 2‐methylpropene whereas the latter may occur via a reaction related to a carbonyl‐ene reaction between the quinonemethide and 2‐methylpropene. Both compounds were subjected to a catalytic acidic treatment leading to 2,2‐dimethyl‐2H‐chromene. Starting from various salicylaldehydes, the scope of this method was investigated.     

7‐Hydr­oxy‐6‐methoxy‐3‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]‐2H‐1‐benzopyran‐2‐one

The title compound, daphnoretin, C₁₉H₁₂O₇, was isolated from the leaves of Stellera chamaejasme L. Two independent mol­ecules are present in the asymmetric unit, with similar conformations. Each of the independent mol­ecules is composed of two chromene systems connected by an ether bridge. The dihedral angles between the mean planes of the two chromene systems are 86.9 (2) and 81.9 (3)°. Mol­ecules form chains via hydrogen bonds and adjacent chains are parallel to each other.     

Ferromagnetism, paramagnetism, and thermally induced magnetism in photomagnetic CrIII/MnII and CrIII oxalates with the 7-methyl-3,3-diphenyl-3H-pyrano[3,2-f]quinolinium cation

Single crystals of the new cationic chromene, 7-methyl-3,3-diphenyl-3H-pyrano[3,2-f-quinolinium iodide (C₂₅H₂₀NO)I (1), were synthesized. The crystal structure of the new compound was studied, and quantum chemical calculation for the open and closed forms were carried out. The bifunctional compounds containing mono- and bimetallic 3d metal (tris)oxalates with the chromenium cation, (C₂₅H₂₀NO)₃[Cr(C₂O₄)₃] · 4H₂O (2) and (C₂₅H₂₀NO)[CrMn(C₂O₄)₃] · H₂O (3), were prepared. Compound 1 is paramagnetic due to low-lying thermally excited states of the chromene molecules. At low temperatures (∼2 K), the paramagnetic states are frozen, and the compound becomes diamagnetic. Compound 2 is paramagnetic and its magnetic properties are determined mainly by the Cr³⁺ ions and the thermally induced paramagnetic states of the chromene molecules. At high temperatures, the magnetic moment of compound 3 consists of the contributions of the paramagnetic Cr³⁺ and Mn²⁺ ions and the thermally induced paramagnetic states of chromenes. At low temperatures (2–3 K), the thermally induced magnetism of organic molecules is frozen, and the magnetically ordered (and, probably, spin-glass) state is observed in the two-dimensional network of metal oxalates (T _c = 3 K in the zero magnetic field). The UV irradiation leads to an increase in the magnetic moment of the compound in the paramagnetic region due to the generation of radiation defects.     

Novel hydrazone derivatives of 7‐hydroxy‐3′,3′‐dimethyl‐3′H‐spiro[chromene‐2,1′‐isobenzofuran]‐8‐carbaldehyde

The structures of new oxaindane spiropyrans derived from 7‐hydroxy‐3′,3′‐dimethyl‐3′H‐spiro[chromene‐2,1′‐isobenzofuran]‐8‐carbaldehyde (SP1), namely N‐benzyl‐2‐[(7‐hydroxy‐3′,3′‐dimethyl‐3′H‐spiro[chromene‐2,1′‐isobenzofuran]‐8‐yl)methylidene]hydrazinecarbothioamide, C₂₇H₂₅N₃O₃S, (I), at 120 (2) K, and N′‐[(7‐hydroxy‐3′,3′‐dimethyl‐3′H‐spiro[chromene‐2,1′‐isobenzofuran]‐8‐yl)methylidene]‐4‐methylbenzohydrazide acetone monosolvate, C₂₇H₂₄N₂O₄·C₃H₆O, (II), at 100 (2) K, are reported. The photochromically active C_spiro—O bond length in (I) is close to that in the parent compound (SP1), and in (II) it is shorter. In (I), centrosymmetric pairs of molecules are bound by two equivalent N—H...S hydrogen bonds, forming an eight‐membered ring with two donors and two acceptors.     

Acetylenchemie 7. Mitt.: Mechanistische Studien zur Synthese von Pyrano-[3,2-c]chinolin-Alkaloiden aus 4-Hydroxychinolin-2-onen und 3-Chlor-3-methylbut-1-in

The pyrano-cyclisation of 4-hydroxy-(1-methyl)-1H-quinoline-2-one with 3-chlor-3-methylbut-1-yne, supposed to proceed via an ether or vinyl intermediate, is studied by alkylating different 4-hydroxyquinolines. The nine derivatives characterized favour the ether-pathway (Späth type chromene synthesis).

     

A novel chelatofore functionalized spiropyran of the 2‐oxaindane series

A novel chelatofore functionalized spiropyran of the 2‐oxaindane series, namely 8‐formyl‐7‐hydroxy‐3′,3′‐dimethylspiro[2H‐chromene‐2,1′(3′H)‐2‐benzofuran], C₁₉H₁₆O₄, is reported. In the crystalline state, dimers are formed as a result of the π–π stacking of aromatic groups of the 2H‐chromene part of the molecule and C—H...O interactions. The C_spiro—O bond length in the pyran ring is 1.4558 (10) Å, which is longer than or equal to the bond length in thermo‐ and photochromic 2‐oxaindane spiropyrans synthesized previously, except for the 7,8‐benzo/6‐NO₂ derivative, in which this bond length is 1.465 (2) Å.     

Synthesis,Crystal Structure and Characterization of a new Protonated Magnesium Borophosphate: (H3O)Mg(H2O)2[BP2O8]·H2O

A new protonated borophosphate (H₃O)Mg(H₂O)₂[BP₂O₈]·H₂O ( 1 ) was synthesized under mild hydrothermal conditions and characterized by single‐crystal X‐ray diffraction, FTIR spectroscopy and TG‐DTA. The compound crystallizes in the hexagonal system, space group P6(1)22 (No 178), a = 9.4462(7) Å, c = 15.759(2) Å, V = 1217.8(2) Å³, and Z = 6. There exist infinite helical $^1_\infty$ {[BP₂O₈]^3–} ribbons built up from corner‐sharing PO₄ and BO₄ tetrahedra, which are connected by MgO₄(H₂O)₂ leading to an infinite three‐dimensional open‐framework. The H₃O⁺ ions are located at the free thread of the helical ribbons, whereas crystallized water occupy the channels of the helical ribbons. The dehydration of the compound occurs at a higher temperature which is presumably due to the anisotropic hydrogen bonds in the crystal structure. The luminescent properties of the compound were studied.     

Synthesis and Spectrokinetic Studies of a New Family of Photochromic 2H‐Chromenes (=2H‐1‐Benzopyrans): Dimethyl 6‐Aryl‐2,2‐dimethyl‐2H‐chromene‐7,8‐dicarboxylates

A series of dimethyl 6‐aryl‐2,2‐dimethyl‐2H‐chromene‐7,8‐dicarboxylates were synthesized, and the photochromic properties of this new family of dimethyl‐2H‐chromenes were studied under continuous irradiation. The presence of the methoxycarbonyl groups was shown to stabilize the colored forms. This stabilization depended on the solvent, and in two cases the formation of long‐lived opened forms was observed. Under irradiation with a mercury lamp, this family of 2H‐chromenes showed a strong resistance to photodegradation.     

An Efficient and Chemoselective Knoevenagel/Hemiketalization Process for the Synthesis of New 2H‐Chromenes in a One‐Pot Three‐Component Reaction

A novel L ‐proline‐catalyzed mild and ecological approach towards the synthesis of 2H‐chromene derivatives was achieved by Knoevenagel reaction followed by an intramolecular hemiketalization process. In the present protocol, chemoselectivity has been successfully achieved by using L ‐proline as catalyst. This eco‐friendly and chemoselective reaction provided an alternative synthetic method to prepare previously unknown 2H‐chromene derivatives in a one‐pot reaction.     

Reactions of 3-oxo-2,3-dihydrobenzofuran with alkyl 2-cyano-3-alkoxypropenoate and alkyl 2-alkoxycarbonyl-3-alkoxypropenoate. Synthesis of pyran derivatives

3-Oxo-2,3-dihydrobenzofuran reacted with ethyl 2-cyano-3-ethoxypropenoate, methyl 2-cyano-3-methoxy-propenoate affording compounds 3 (2-(2-cyano-2-alkoxycarbonylvinyl)-3-hydroxybenzofuran) obtained as a mixture of Z + E isomers. Methyl 2-methoxycarbonyl-3-methoxypropenoate gave compound 4 . Malonic compounds added on 2-dimethylaminomethylene-3-oxo-2,3-dihydrobenzofuran 6 for giving compound 3 or 2-oxo-3-methoxycarbonyl-2H-pyrano[3,2-b]benzofuran 8 . Compound 8 was also obtained by heating compound 4 in xylene.     

Nobiletin: a citrus flavonoid displaying potent physiological activity

Nobiletin [systematic name: 2‐(3,4‐dimethoxyphenyl)‐5,6,7,8‐tetramethoxy‐4H‐chromen‐4‐one; C₂₁H₂₂O₈] is a flavonoid found in citrus peels, and has been reported to show a wide range of physiological properties, including anti‐inflammatory, anticancer and antidementia activities. We have solved the crystal structure of nobiletin, which revealed that the chromene and arene rings of its flavone moiety, as well as the two methoxy groups bound to its arene ring, were coplanar. In contrast, the C atoms of the four methoxy groups bound to the chromene ring are out of the plane, making the molecule conformationally chiral. A comparison of the crystal structures of nobiletin revealed that it could adopt a variety of different conformations through rotation of the covalent bond between the chromene and arene rings, and the orientations of methoxy groups bound to the chromene ring.     

Studies on quinazolinones. 2. Synthesis of 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3–6]quinazolin-5-one and -2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one

To search for novel antihypertensive heterocycles in the condensed quinazoline series, two representative compounds were synthesized via a suitable reaction sequences. Treating anthranilonitrile with allyl isocyanate gave 2-(allylureido)benzonitrile ( 10 ) in a quantitative yield. Compound 10 was cyclized to 3-allylquinazoline-2(1H, 4(3H)-dione ( 11 ). Bromination of 11 in carbon tetrachloride converted it into the corresponding 3-(2,3-dibromopropyl) derivative ( 12 ) in 92% yield. Ring closure of 12 was effected by the action of alkali to afford 2-bromomethyl-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one ( 13 ). The title compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one ( 7 ) could be obtained by a reaction of either 12 or 13 with 1-benzylpiperazine respectively. Starting from the readily available 3-allyl-2H-thioxoquinazolin-4(3H)-one ( 16 ) via the analogous reactions gave the 2-bromomethyl-2,3-dihydro-5H-thiazolo[2,3-b]-quinazolin-5-one ( 19 ) in good yield. However, the reaction of 19 with 1-benzylpiperazine provided another target compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one ( 8 ) only in poor yield (8%). As major product, the dehydrobrominated compound, 2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one ( 22 ) was isolated. A preliminary pharmacological evaluation revealed that both compounds 7 and 8 are devoid of the antihypertensive activity.     

One-step synthesis of substituted 2-amino-4H-chromenes and 2-amino-4H-benzo[f]chromenes. Molecular and crystal structure of 2-amino-3-cyano-6-hydroxy-4-phenyl-4H-benzo[f]chromene

Substituted 2-aminochromenes were synthesized by three-component condensation of aromatic aldehydes, derivatives of cyanoacetic acid, and phenols or naphthols. The molecular and crystal structure of 2-amino-3-cyano-6-hydroxy-4-phenyl-4H-benzo[f]chromene was established by X-ray diffraction analysis.     

Synthesis and Evaluation of 2-{[(2-Oxo-1H-quinolin-8-yl)oxy]methyl}-Substituted α-Methylidene-γ-butyrolactones

O-Alkylation of 8-hydroxy-1H-quinolin-2-one ( 1 ) afforded 8-(2-oxopropoxy)-1H-quinolin-2-one ( 2 ) which was immediately cyclized to form the tricyclic 2,3-dihydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]benzoxazine,-5-one ( 3). The Reformatsky-type condensation of 3 furnished antiplatelet 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)melhoxy]-1H-quinolin-2-one ( 4 ). Its counterparts 7a – f , Ph-substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky-type condensation. Although compound 4 was less active against platelet aggregation than 7a – f , it was the only compound which exhibited significant inhibitory activity on high-K⁺ medium, Ca²⁺-induced vasoconstriction and was more active than most of its Ph-substituted counterparts against norepinephrine-induced vasoconstrictions.     

Synthesis and Pharmacological Evaluation of Some New Chromeno[3,4‐c]pyrrole‐3,4‐dione‐based N‐Heterocycles as Antimicrobial Agents

The reaction of 2‐oxo‐2H‐chromene‐3‐carboxamide ( 1 ) with carbon disulfide afforded 1‐mercaptopyrrolo[3,4‐c ]chromene‐3,4‐dione ( 3 ). The latter compound was utilized as versatile building block for new azole systems via incorporating in a series of manipulations including cyclocondensation reactions. The structure of the newly synthesized compounds has been confirmed by IR, ¹H NMR, ¹³C NMR, mass spectral, and elemental analysis. Furthermore, some selected compounds were screened in vitro for their antimicrobial activities. The results declared that most of the synthesized compounds have high antimicrobial activity.     

Studies on reactive intermediates. Part I. An approach to the synthesis of 2-phenyl-7-carbethoxy-5H-1,3,4-thiadiazolo[2,3-a]pyrimidin-5-one

2-Phenyltetrazolo[4,5-a]-1,3,4-thiadiazole ( 4 ), in its azido form, reacted with diethyl fumarate and diethyl maleate to give 2-phenyl-7-carbethoxy-5H-1,3,4-thiadiazolo[2,3-a]pyrimidin-5-one ( 5 ). To assign the structure of compound 5 , 2-phenyl-5-carbethoxy-7H-1,3,4-thiadiazolo[2,3-a]pyrimidin-7-one ( 6 ) was prepared from the reaction of 2-amino-5-phenyl-1,3,4-thiadiazole ( 7 ) with diethylacetylene dicarboxylate. Physical properties and spectral data of compound 6 were different from compound 5 . Theoretical and experimental aspects are discussed.