A One‐Pot Organometallic Route from a 4‐Alkenylpyridine to a 4,4‐Spiro‐Linked Ethyl 1,4‐Dihydropyridine‐1‐carboxylate

In a one‐pot process without isolation of intermediates, (but‐3‐en‐1‐yl)pyridine ( 13 ) is treated sequentially with dicyclohexylborane, trimethylaluminium, and ethyl carbonochloridate yielding ethyl 1,4‐dihydro‐4,4‐(tetramethylene)pyridine‐1‐carboxylate (=ethyl 8‐azaspiro[4.5]deca‐6,9‐diene‐8‐carboxylate; 2 ) in 46% yield based on starting alkenylpyridine 13 (Scheme 5).     

New Synthesis of 7‐(3‐chloropropoxy)‐4‐hydroxy‐6‐methoxyquinoline‐3‐carbonitrile,a Key Intermediate to Bosutinib

A new and convenient synthesis of 7‐(3‐chloropropoxy)‐4‐hydroxy‐6‐methoxyquinoline‐3‐carbonitrile, the key intermediate to bosutinib, is described on a hectogram scale. 5‐Bromo‐2‐methoxyphenol is adopted as the starting material via the simple chemical process including Friedel‐Crafts reaction, alkylation, bromination, cyano substitution, and so on to give the 3‐amino‐2‐(2‐bromobenzoyl)acrylonitrile compound 25 , which underwent key intramolecular cyclization at K₂CO₃/DMF condition; the title product was obtained in 36.9% yield over 7 steps and 98.71% purity (HPLC).     

From a Phosphaketenyl‐Functionalized Germylene to 1,3‐Digerma‐2,4‐diphosphacyclobutadiene

The first 4π‐electron resonance‐stabilized 1,3‐digerma‐2,4‐diphosphacyclobutadiene [L^H₂Ge₂P₂] 4 (L^H=CH[CHNDipp]₂ Dipp=2,6‐ⁱPr₂C₆H₃) with four‐coordinate germanium supported by a β‐diketiminate ligand and two‐coordinate phosphorus atoms has been synthesized from the unprecedented phosphaketenyl‐functionalized N‐heterocyclic germylene [L^HGe‐P=C=O] 2 a prepared by salt‐metathesis reaction of sodium phosphaethynolate (P≡C?ONa) with the corresponding chlorogermylene [L^HGeCl] 1 a . Under UV/Vis light irradiation at ambient temperature, release of CO from the P=C=O group of 2 a leads to the elusive germanium–phosphorus triply bonded species [L^HGe≡P] 3 a , which dimerizes spontaneously to yield black crystals of 4 as isolable product in 67 % yield. Notably, release of CO from the bulkier substituted [L^tBuGe‐P=C=O] 2 b (L^tBu=CH[C(^tBu)N‐Dipp]₂) furnishes, under concomitant extrusion of the diimine [Dipp‐NC(^tBu)]₂, the bis‐N,P‐heterocyclic germylene [DippNC(^tBu)C(H)PGe]₂ 5 .     

The Rearrangement of 2,2‐Diphenyl‐1‐[(E)‐2‐phenylethenyl]cyclopropane to 3,4,4‐Triphenylcyclopent‐1‐ene: a DFT Analysis

A computational study on the rearrangement of 2,2‐diphenyl‐1‐[(E)‐2‐phenylethenyl]cyclopropane ( 1 ) is presented, using density functional theory (DFT), (U)B3LYP with the 6‐31G* basis set (DFT1) and (U)M05‐2X with the 6‐311+G** basis set (DFT2). In agreement with a biradical character of the transition structure (TS) or intermediate, the potential‐energy hypersurface is lowered by the influence of three conjugated Ph groups. Surprisingly, two conformations of the geminal diphenyl group (different twist angles) induce two different minimum‐energy pathways for the rearrangement. Independent of the functional used, the first hypersurface harbors true biradical intermediates, whereas the second energy surface is a flat, slightly ascending slope from the starting material to the TS. The functional (U)M05‐2X with the basis set 6‐311+G** provides realistic energies which seem to be close to experiment. The activation energy for racemization of enantiomers of 1 is lower than that of rearrangement by 2.5 kcal mol^?1, in agreement with experiment.     

Microwave‐assisted nucleophilic cleavage of 5,7‐dimethyl‐2‐phenyl‐1‐oxo‐lH‐pyrazolo[ 1,2‐a]pyrazol‐4‐ylium‐3‐olate to α‐phenylmalonamides

Three α‐phenylmalonamides have been prepared by the selective nucleophilic cleavage of 5,7‐dimethyl‐2‐phenyl‐1‐oxo‐1H‐pyrazolo[1,2‐a]pyrazol‐4‐ylium‐3‐olate in solventless microwave syntheses. The three weak nucleophiles employed were aniline, p‐chloroaniline and m‐toluidine. The α‐phenylmalonamides of these three aniline derivatives could not be prepared using the previously reported solvent syntheses via 3‐oxopyrazolo[1,2‐a]pyrazol‐8‐ylium‐1‐olates. All products were characterised using, infrared spectroscopy, ¹H nmr and electrospray mass spectrometry. The single crystal X‐ray structures of the starting pyrazolo‐[1,2‐a]pyrazole and α‐phenylmalon‐m‐toluidide are also reported.     

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3‐monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the self‐cyclization occurs. Besides the dialkylamino derivatives of 3‐monosubstituted 2‐thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3‐monosubstituted 2‐thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2‐naphthol.     

Selenium heterocycles XLIV. Syntheses of 8,9‐dihydro‐1,2,3‐thiadiazolo[4,5‐a]‐4,7‐dihydroxynaphthalene and 1,2,3‐selenadiazolo[4,5‐a]‐4,7‐dimethoxynaphthalene

The reaction of thionyl chloride with the semicarbazone 2 gave 4,5‐dihydro‐6,9‐dihydroxynaphtho‐[1,2‐d][1,2,3]thiadiazole ( 3 ) instead of 4,5‐dihydro‐6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]thiadiazole ( 4 ). Selenium dioxide oxidation of compound 2 gave 4,5‐dihydro‐6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]selenadiazole ( 5 ). Oxidation of compound 5 with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone afforded 6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]selenadiazole ( 6 ).     

Synthesis of [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine,and [1,2‐a] benzimidazol‐2‐yl amidrazone

N‐benzimidazol‐2‐yl imidate type 1 reacts with thiourea, carbon disulfide, cyanamide, and hydrazide to give, respectively, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione 2 , [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione 3 , [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine 4 , and [1,2‐a] benzimidazol‐2‐yl amidrazone 5 with good yields. Structures elucidation of all newly synthesized heterocyclic compounds was based on the data of IR, ¹H NMR, ¹³C NMR, elemental analysis, and MS of some products. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:279–283, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20618     

Preparation of 5‐methyl‐2‐sulfanyl‐7h‐1,3,4‐thiadiazolo[3,2‐a]‐pyrimidin‐7‐ones

7H‐1,3,4‐Thiadiazolo[3,2‐a]pyrimidin‐7‐ones can be prepared by the acylation of 5‐amino‐1,3,4‐thiadiazoles with diketene and subsequent ring closure (dehydration). Whereas arylthio substituents (SC₆H₅) can be introduced in 2‐position by the replacement of Br, alkylthio groups (SC₂H₅) have to be already presentin the starting 5‐amino‐1,3,4‐thiadiazole. The ambident nucleophile 2‐thiazolidinethione reacts in the Br substitution reaction on the N atom.     

Nucleophilic addition to 3‐methyl‐1‐(4‐nitrophenyl)‐2‐phenyl‐4,5‐dihydroimidazolium iodide

Reactions of the 1,2‐diaryl 4,5‐dihydroimidazolium, represented by 3‐methyl‐1‐(4‐nitrophenyl)‐2‐phenyl‐4,5‐dihydroimidazolium iodide 1 , with ethylenediamine afforded a benzylidyne unit transferred product, 2‐phenyl‐2‐imidazoline 2 ; a ring‐opened adduct 4 was produced when excess ethylenediamine was used. Reactions of 1 with hydroxylamine, malononitrile, and nitromethane anions produced ring‐opened products, 5 , 7 , and 8 respectively.     

Photocycloaddition of Cyclohex‐2‐enones to 2‐Methylbut‐1‐en‐3‐yne

Irradiation (350 nm) of 2‐alkynylcyclohex‐2‐enones 1 in benzene in the presence of an excess of 2‐methylbut‐1‐en‐3‐yne ( 2 ) affords in each case a mixture of a cis‐fused 3,4,4a,5,6,8a‐hexahydronaphthalen‐1(2H)‐one 3 and a bicyclo[4.2.0]octan‐2‐one 4 (Scheme 2), the former being formed as main product via 1,6‐cyclization of the common biradical intermediate. The (parent) cyclohex‐2‐enone and other alkylcyclohex‐2‐enones 7 also give naphthalenones 8 , albeit in lower yields, the major products being bicyclo[4.2.0]octan‐2‐ones (Scheme 4). No product derived from such a 1,6‐cyclization is observed in the irradiation of 3‐alkynylcyclohex‐2‐enone 9 in the presence of 2 (Scheme 4). Irradiation of the 2‐cyano‐substituted cyclohexenone 12 under these conditions again affords only traces of naphthalenone 13 , the main product now being the substituted bicyclo[4.2.0]oct‐7‐ene 16 (Scheme 5), resulting from [2+2] cycloaddition of the acetylenic C−C bond of 2 to excited 12 .     

Novel and one‐pot Synthesis of Tetrahydropyrrolo[1,2‐a]‐2‐Methylbenzothiazole‐3‐Spiro‐1′‐Cyclohexa‐2′,5′‐Dien‐4′‐one‐4,5‐Dicarboxylate Derivatives via a Three Component Reaction

The three component condensation reactions involving 2‐methylbenzothiazole or 2,5‐dimethylbenzothiazole, dialkyl acetylenedicarboxylate, and 2,6‐dimethyl phenol or 2,6‐di‐tert‐butylphenol constitute a novel and one‐pot synthesis of tetrahydropyrrolo[1,2‐a ]‐2‐methylbenzothiazoles‐3‐spiro‐1^′‐cyclohexa‐2^′,5^′‐dien‐4^′‐one‐4,5‐dicarboxylate derivatives in good yields. The reactions proceeded at room temperature without using any catalyst. This method is very useful to functionalize benzothiazole derivatives in a one‐pot operation.     

Photohydrodimerization of 6‐Methoxyflavone to 6,6″‐Dimethoxy‐2,2″‐Biflavanones

6‐Methoxyflavone ( 7 ) easily afforded two hydrodimers of rac‐6,6Prime;‐dimethoxy‐2,2″‐biflavanone ( 8a ) and meso‐6,6″‐dimethoxy‐2,2″‐biflavanone ( 8b ) and one reductive product of 6‐methoxyflavanone ( 9 ) by using photolysis with the electron‐donating amines including triethylamine, 2‐(N,N‐dimethylamino)ethanol or N,N‐dimethylaniline in solvents of acetonitrile, benzene or methylene dichloride. They were found to give higher yields of rac‐6,6″‐dimethoxy‐2,2″‐biflavanone ( 8a ) and meso‐6,6″‐dimethoxy‐2,2″‐biflavanone ( 8b ) (38.7% and 4.5%, 35.3% and 6.2%, respectively) in the reaction conditions of 1/10 molar ratio of 6‐methoxy‐flavone ( 7 ) to triethylamine in a solvent of acetonitrile with irradiation of twenty‐four hours by using 306 nm and 352 nm lamps.     

3,3,4,4,5,5‐Hexafluoro‐1‐(2‐methoxyphenyl)‐2‐[5‐(4‐methoxyphenyl)‐2‐methyl‐3‐thienyl]cyclopent‐1‐ene: a photochromic compound

The photochromic title compound, C₂₄H₁₈F₆O₂S, has thienyl and aryl substituents on the C=C double bond of the shallow half‐chair‐shaped cyclopentene ring. The planes of the two substituent rings are inclined to that of the cyclopentene ring, with dihedral angles between the mean plane of the cyclopentene ring and those of the phenylene and thienyl rings of 51.2 (1) and 51.3 (1)°, respectively. The molecule adopts an antiparallel conformation, with a distance between the two photoreactive C atoms of 3.717 (2) Å.     

Convenient way to 5‐substituted 4‐amino‐2,3‐dihydro‐4H‐1,2,4‐triazole‐3‐thiones

Various 4‐amino‐2,3‐dihydro‐4H‐triazoles with aromatic, aliphatic and heterocyclic substituents at the C(5) position were synthesized from corresponding esters and thiocarbohydrazide. This method allows the synthesis these heterocycles in a short time and at reduced expenses.     

Light‐Induced Cycloaddition of 2,3‐Dihydro‐2,2‐dimethyl‐4H‐thiopyran‐4‐one (a 4‐Thiacyclohex‐2‐enone) to Alkenes and Dienes

The reactivity of (thiacyclic)‐2,3‐dihydro‐2,2‐dimethyl‐4H‐thiopyran‐4‐one ( 1a ) in light‐induced cycloadditions to furan ( F ), acrylonitrile ( AN ), or 2,3‐dimethylbut‐2‐ene ( TME ) is compared to that of (carbocyclic) 5,5‐dimethylcyclohex‐2‐enone ( 1b ). Whereas for the more‐flexible thiacycle, the efficiency of [2+2]‐photocycloadduct formation with AN or TME is generally much lower, the diastereoselectivity regarding the ring fusion in the bicyclo[4.2.0]octanes is quite similar for both enones. In contrast, 1a affords exclusively trans‐fused [4+2] cycloadducts with F , while 1b gives predominantly the corresponding cis‐fused products.     

2‐Amino‐8‐(2‐deoxy‐2‐fluoro‐β‐D‐arabinofuranosyl)imidazo[1,2‐a]‐1,3,5‐triazin‐4(8H)‐one: Synthesis and Conformation of a 5‐Aza‐7‐deazaguanine Fluoronucleoside

Nucleobase‐anion glycosylation of 2‐[(2‐methyl‐1‐oxopropyl)amino]imidazo[1,2‐a]‐1,3,5‐triazin‐4(8H)‐one ( 6 ) with 3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐α‐D ‐arabinofuranosyl bromide ( 8 ) furnishes a mixture of the benzoyl‐protected anomeric 2‐amino‐8‐(2‐deoxy‐2‐fluoro‐D ‐arabinofuranosyl)imidazo[1,2‐a]‐1,3,5‐triazin‐4(8H)‐ones 9 / 10 in a ratio of ca. 1 : 1. After deprotection, the inseparable anomeric mixture 3 / 4 was silylated. The obtained 5‐O‐[(1,1‐dimethylethyl)diphenylsilyl] derivatives 11 and 12 were separated and desilylated affording the nucleoside 3 and its α‐D anomer 4 . Similar to 2′‐deoxy‐2′‐fluoroarabinoguanosine, the conformation of the sugar moiety is shifted from S towards N by the fluoro substituent in arabino configuration.     

1,2‐Bis[5‐(1,3‐dioxolan‐2‐yl)‐2‐ethyl‐3‐thien­yl]‐3,3,4,4,5,5‐hexa­fluoro­cyclo­pent‐1‐ene,a photochromic dithienylethene

The title compound, C₂₃H₂₂F₆O₄S₂, a photochromic dithienyl­ethene, is a promising material for optical storage and other optoelectrical devices. The mol­ecule adopts a photoactive antiparallel conformation in the crystalline state. The distance between the two reactive C atoms which are involved in potential ring closure is 3.829 (4) Å. The dihedral angles between the central cyclo­pentene ring and the adjacent thio­phene rings are 55.38 (7) and 54.81 (9)°. The colourless crystals turn magenta when exposed to UV radiation and the process is reversible.