Regiocontrolled Incorporation and Annulation of Glucose into Spirothiazole and Spirothiazoloxazole Derivatives

ABSTRACT

Cyclic ketones 1a-f reacted with mercaptoacetic acid in benzene and/or toluene in the presence of p-toluenesulfonic acid afforded the corresponding spiro-1,3-oxathialanone derivatives (2a-f). Compounds 2a-f reacted with glucosamine hydrochloride in a mixture of pyridine and ethanol to yield 3-(2′-glucosyl)-2-spiro[1′-cycloalkyl]thiazolidin-4-one derivatives 4a-f. Reaction of 4a-f with fused sodium acetate in a mixture of acetic anhydride and acetic acid gave annulated spirothiazoloxazologlucose derivatives 6a-f. All the synthesized spiro derivatives were identified by conventional methods (IR, ¹H NMR spectroscopy and elemental analyses).     

Über die Darstellung von substituierten 3,4-Dihydro-2(1H)-pyrimidin-iminen und 2-Aminopyrimidinen aus Guanidin und α,β-ungesättigten Ketonen

Guanidine reacts with the 2-alken-1-ones4 a-f and5 to give the unstable dihydropyrimidinimines (or-amines respectively)8 a-f (I, II or III respectively) and the hexahydroquinazolinimine (-amine)9 (I, II or III);8 a-f lose H₂, partly in the course of the reaction, partly during recrystallization to yield the 2-pyrimidinamines10 a-c, e, f, and the 4-methyl-5,6,7,8-tetrahydro-2-quinazolinamine11. With picric acid the unstable compounds8 d, f and9, resp. are converted into the stable 2-amino-3,4-dihydro-1H-2-pyrimidinylium picrates12 d and into the 2-amino-4-methyl-3,5,6,7,8,8 a-hexahydro-1H-2-quinazolinium picrate (13 resp.14, 15)¹⁸, whereas8 e reacts with HCl to give the chloride12 e. The structures of12 d-f follow from their NMR-spectra, and of10 a-c, e, f and11 by alternative syntheses by known methods^12–17 (e.g. from -diketones and guanidine). The reaction of8 d-f and9 to10 d-f and11 respectively is compared with previously described dehydrogenation and disproportionation reactions, especially of 3,4-dihydro-2(1H)-pyrimidinones (6 d ⁴,23 ²⁰) and-thiones (30 ¹) of similar structure and formulated as a base-catalysed elimination of H₂.

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HerrnA. Fuchsgruber danken wir für die Aufnahme und Hilfe bei der Interpretation der NMR-Spektren.     

Reactivity of 4-bromomethylquinoline derivatives towards glycine and thioglycolic acid. A new ring system

Condensation of 4-bromomethylquinoline derivatives1 a-1 c with glycine and thioglycolic acid gave the corresponding quinolylmethylglycine and quinolylmethylthioacetic acid derivatives2 a-2 c and2 d-2 f, respectively. Cyclization of2 a-2 f was affected either by polyphosphoric acid or concentrated sulphuric acid to give3 a-3 f. Chlorination of2 a-2 f and3 a-3 f were also accomplished.

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Die Reaktivität von 4-Brommethylchinolin-Derivaten gegenüber Glycin und Thioglycolsäure. Ein neues Ringsystem

Zusammenfassung Die Reaktion von 4-Brommethylchinolin-Derivaten1 a-c mit Glycin und Thioglycolsäure gab die entsprechenden Kondensationsprodukte2 a-c und2d-f.2 a-f konnten mit Polyphosphorsäure bzw. mit konzentrierter Schwefelsäure zu Benzo[c]-2,6-naphthyridinen3 a-f zyklisiert werden.2 a-f und3 a-f waren einer Chlorierung (POCl₃) zugängig.

     

Direct Oxidation of Primary tert-Butyldimethylsilyl Ethers to Carboxylic Acids with Jones Reagent

Treatment of the tert-butyldimethylsilyl ethers 1a-f with Jones reagent gave the carboxylic acids 2a-f in excellent yield in the absence of potassium fluoride.     

Regioselective Synthesis of Heterocycles from 3-Cyclohex-2-enyl-4-hydroxy-1-methylquinolin-2-(1H)-one

3-Cyclohex-2-enyl-4-hydroxy-1-methylquinolin-2(1H)-one (5) reacts with pyridine hydrotribromide in CH₂Cl₂ at 0–5°C for 0.75h to give a furo fused heterocycle 6 in 96% yield. Product 6 on treatment with KOH-EtOH eliminates HBr to give compound 8 which on treatement with Pd-C in refluxing diphenyl ether for 0.5h furnishes benzofuro[3,2-c]quinolone 9 in 90% yield. Substrate 5 on sequential treatment with Ac₂O-AcONa and Br₂/AcOH followed by KOH-EtOH, however produces bicyclic product 7 in excllent overall yield. Substrate 5 reacts with 1 equivalent of m-chloroperbenzoic acid in refluxing benzene to furnish bicyclic heterocycle 12 in 80% yield and with cold conc. H₂SO₄ at 0–5°C for 2h generates the bicyclic heterocycle 14 in 90% yield.     

Hypervalent Iodine in the Synthesis of Bridgehead Heterocycles: A New Synthesis of 3, 5-Diarylthiazolo[2, 3-C]-s-triazoles

The synthesis of 3, 5-diarylthiazolo{2, 3-c}-s-triazoles (3a-f) has been accomplished by using a new method involving oxidation of arenecarbaldehyde-4-arylthiazol-2-ylhydrazones (2a-f) with iodobenzene diacetate (IBD) in dichloromethane by intramolecular cyclization in high yields.     

N,N-Dimethylamination of Acid Chlorides with Dmf

A solution of acid chlorides 3a-g in DMF solvent was refluxed to give N,N-dimethylamides 4a-f and 5g in excellent yields.     

Synthesis of Azafluorenones using Zeolites.

A convenient method for the synthesis of various azafluorenones (2a-f & 4a-d) by cyclization of substituted arylpyridines (1a-f & 3a-d) using zeolites are described.     

Phase Transfer Catalyzed Synthesis of Ferrocenoylcyclopropans

1-Phenyl-2-aryl-3-ferrocenoylcyclopropanes 3a-f have been prepared in moderate yield by the cycloaddition of the ylide generated in situ from triphenylbenzylarsonium bromide 2 to 1-oxo-3-aryl-2-propenylferrocenes 1a-d and 1,1'-di(-1-oxo-3-aryl-2-propenyl)ferrocenes le-f under phase transfer catalystic conditions.     

A Convenient and Improved Procedure for the Cyanation of Enamines and 1,3-Dicarbonyl Compounds

The direct cyanation of enamines 2a-f using acylsubstituted cyanatobenzenes 1a-c and cyanatoanthraquinone 1d furnishes β-cyanoenamines 3a-f which upon hydrolysis afford the cyanoketones 4a,b. 2-Cyano-1,3-diketones 6a-c are obtained starting from compounds 5a-c and 1.     

Synthesis of Novel Spiro Tetrahydrothiapyrano-Isoxazolines and Pyrazolines

Cis 2,6-Diphenyltetrahydrothiapyranone (1) was subjected to Wittig reaction to generate exocyclic double bond (2a-c). Cycloaddition of nitrile oxides and nitrile imines to the latter led to a novel spiro tetrahydrothiapyranoisoxazolines (3a-f) and spiro tetrahydrothiapyranopyrazolines (4a-f)     

Tetralone Esters as Intermediates for the Synthesis of Podophyllotoxin Derivatives Via Cyclopropanation of Chalcones

Cyclopropyl ester (8a-f) were synthesized by the cyclopropanation of chalcones (7a-e) in dry benzene using powdered sodium in 80-85% yield. Preparation of tetralone ester (4a-e), an intermediate for the synthesis of podophyllotoxin derivatives by Lewis acid (SnCl₄) catalyzed cyclization of (8a-e) is also described here.     

SYNTHESIS OF NEW 3-SUBSTITUTED AND SPIRO 1,5-BENZODIAZEPIN-2-ONES UNDER PHASE-TRANSFER CATALYSIS CONDITIONS

1,3-Dihydro-4-phenyl-1,5-benzodiazepin-2-one 1 was treated with bromine in 1:1 molar ratio to get the corresponding 3-bromo derivative 2 which in turn reacted with different nucleophiles to get the corresponding 3-substituted derivatives 3–11. The cyclized compounds 4_a , 5_a , 7_a,b , and 9_a–c were achieved on refluxing compounds 4, 5, 6_a,b , or 8 _a–c respectively in diphenyl ether. Compound 1 was benzoylated with benzoyl chloride to give the corresponding 1-benzoyl derivative 12 which reacted with bromine in 1:2 molar ratio to yield the corresponding 3,3-dibromo derivative 13. Spiro benzodiazepines 14_a–d–16 were obtained by reacting compound 13 with the proper bidentates. Compound 1 was treated with formaldehyde and secondary amines or thiols to give Mannich bases or sulphides 17–21, respectively.     

Azo compounds and Schiff 's bases derived from 5-(4-pyridyl)-2-amino-1,3,4-thiadiazole: synthesis,mesomorphic properties and structural study by semi-empirical calculations

The synthesis and liquid crystalline properties of new Schiff 's bases (series 3a-f) and azo compounds (4a-f) incorporating pyridine and 1,3,4-thiadiazole rings are reported. The first homologues in the series of Schiff's bases (3a-c) show a monotropic mesophase and the homologues 3d-f display an enantiotropic SmA phase. The only azo compounds to exhibit liquid crystalline properties are the homologues 4e, f which show a monotropic nematic phase. These series are compared with Schiff's bases and azo compounds analogues (series 5 and 6), previously reported by us and an AM1 study of the structure/mesomorphic property relationship is described.     

Zur Kenntnis der Reaktionsfähigkeit alkylsubstituierter Thiomorpholine, 1. Mitt.

Zusammenfassung Die Darstellung einigerMannichbasen (3 a-f) bzw.Mannich-basen-hydrochloride (2 a-f) und zahlreicher s-Triazin-Derivate (4 a-d, 5 a–m, 6 a–w, 7 a–e, 8 a–d, und9 a–l) auf Basis des unsubstituierten Thiomorpholins (1 a) sowie C-mono-[2-Methylthiomorpholin (1 b) und 2-Äthylthiomorpholin (1 c)] und C-dialkylierter Thiomorpholine [2-Methyl-3-äthylthiomorpholin (1 d)] wird beschrieben.

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Concomitant action of elementary sulfur and gaseous ammonia upon ketones, LXXIX: On the reactivity of alkyl substituted thiomorpholines, I

The preparation of someMannichbases (3 a-f) andMannich base hydrochlorides (2 a-f), resp., and numerous s-triazine derivatives (4 a-d, 5 a–m, 6 a–w, 7 a–e, 8 a–d, and9 a–l) based upon unsubstituted thiomorpholine (1 a) as well as C-mono-[2-methylthiomorpholine (1 b) and 2-ethylthio-morpholine (1 c)] and C-dialkylated thiomorpholines [2-methyl-3-ethylthiomorpholine (1 d)] is described.

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HerrE. Wilms dankt der Deutschen Texaco AG. für die Gewährung eines Stipendiums herzlichst.     

Improved Synthetic Approach to Tenatoprazole

An improved synthetic approach to tenatoprazole 1 is described. It started from 2,3,5‐trimethyl‐4‐nitropyridine‐N‐oxide 2 with acetic anhydride via rearrangement and hydrolysis to give 3, Chlorination with SOCl₂ yielded 2‐chloromethyl‐3,5‐dimethyl‐4‐nitropyridine hydrochloride 4, then 4 condensed with 2‐mercapto‐5‐methoxy imidazole [4,5‐b]pyridine 5 to give 5‐methoxy‐2‐[(4‐nitro‐3,5‐dimethyl‐2‐pyridinyl)methylthio]imidazole[4,5‐b]pyridine 6. At last the title compound 1 was produced by two methods: 6 was oxidized with MCPBA and then methoxylated with CH₃ONa to give 1 and 6 was first methoxylated with CH₃ONa and then oxidized with MCPBA to give 1. The overall yield is around 26% for both five‐step syntheses.     

Imides of 2-Trifluoroacetylphenol and other Trifluoracetic acid Esters: Novel Reactions with Phosphorus(III) Derivates

Abstract

The imido derivates of 2-trifluoroacetylphenol, 1 (R¹=H, Me, iPr) react with the isocyanatophosphites (R²O)₂PNCO, 2 (R²[dbnd]Et, R²-R²[dbnd]CMe₂-CMe₂) to yield the bicyclic compounds 3, wheras in case of 1 (R¹[dbnd](CH₂)₂NMe2) the λ³σ³P compounds 4 are found. The phosphorus(III) chlorides R3PC12 (R³[dbnd]Ph, OEt) and 1 (R¹[dbnd]H, Me) give rise to furnish the tricyclic phosphoranes 5. However with 1 (R¹[dbnd]iPr) phosphite 6 is obtained, which adds hexafluoracetone to give the 1,3,2λ⁵σ⁵-dioxaphospholane 7. 2-(Trifluoracetoxy)pyridine 8. reacts with Tris(trimethylsily1)phosphite to yield the bis(phosph0nate) 10. Some molecular structures are discussed on the basis of x-ray diffraction results.     

Effect of exchange of terminal substituents on the mesophase behaviour of some azo/ester compounds

Six homologous series of 4-(4′-alkoxy phenylazo) phenyl 4″-substituted benzoates (In_a-f) were prepared in which, within each homologous series, the length of the terminal alkoxy chain varies between 6, 8, 10, and 12 carbons, while the other terminal substituent, X, is a polar group that alternatively changed from CH₃O, CH₃, H, Br, NO₂ and CN. Compounds prepared were characterised by spectroscopic methods, and their mesophase behaviour investigated by differential scanning calorimetry (DSC) and polarised optical microscopy (POM). The results were discussed in terms of mesomeric and polarisability effects. In each group of compounds, bearing the same alkoxy substituent, the nematic-to-isotropic transition temperatures (T_C) were successfully correlated with the polarisability anisotropy of bonds to the substituent X. A comparative study was made between the investigated compounds and their previously prepared isomers, namely, 4-(4′-substituted phenylazo) phenyl 4″-alkoxybenzoates (IIn_a-f) in which the two terminal (alkoxy- and X) groups are exchanged.     

Synthesis and Reactions of the Novel Diphosphine,iPrN = C[CH2P(NiPr2)2]2

Abstract

The aldimine nBuN=CHiPr and phosphorus trichloride react to give phosphorus(III) amides in a 1:1 and 2:1 molar ratio. An imine-enamine tautomerism is proposed. In a [4+1] cycloaddition reaction diacetyl-(N-n-butyl)diimine and λ³σ³P-species, RPCl₂ or EtOPCl₂, form 1,2,3λ⁵σ⁴ -diazaphospholenes¹. The same diimine and (Et₂N)₂ PCl is furnishing annellated azaphospholenes¹. A 1,3,4λ⁵ σ⁴ -diazaphospholanium is formed from a λ³σ³ -phosphenium and iPrN=CMe₂ ². Phosphorus(III) amides P(NR₂)₃ (R= Me, Et) and O-trimethylsilylated diacetyldioxime give rise to yield the first monocyclic pentaazaphosphoranes.     

Synthesis of Linearly Fused Tetracyclic Heterocycles Through a Novel Base Catalyzed Intramolecular Rearrangement Involving Scission of N-N Bond

Synthesis of s-triazolothiadiazepinoquinolines 4a-f and the base catalyzed intramolecular facile rearrangement of 4a-f to s-triazolothiazinoquinolines 5a-f involving scission of N-N bond is reported.