Synthesis of 2-aroylpiperazinyl-4-alkoxyquinazolines by phase-transfer-catalysed heteroaromatic nucleophilic substitution

A series of quinazolines, with cardiovascular activity, having 2,3-dihydroxypropoxy or 2-hydroxy-3-t- butylaminopropoxy groups substituted at the 4-position and chlorine or 2-aroylpiperazinyl groups at the 2-position have been synthesized. The introduction of the alkoxy substituent at C-4 was carried out under phase-transfer catalysis conditions.     

SOME CHLOROHYDROXYBENZENESULFONYL DERIVATIVES

Abstract

2,4-; 2,6-; 2,3-; 3,4-; 2,5-; and 3,5-dichlorophenols by reaction with chlorosulfonic acid were converted to the following substituted benzenesulfonyl chlorides: 3,5-dichloro-2-hydroxy-; 3,5-dichloro-4-hydroxy-; 2,3-dichloro-4-hydroxy-; 4,5-dichloro-2-hydroxy-; 2,5-dichloro-4-hydroxy-; and 2,6-dichloro-4-hydroxy-respectively. In addition o-chlorophenol gave 5-chloro-4-hydroxybenzene-1,3-bis-sulfonyl chloride. The various sulfonyl chlorides have been condensed with nucleophilic reagents, e.g. ammonia, amines, hydrazine, phenylhydrazine, N, N-dimethylhydrazine, and sodium azide. 3,5-Dichloro-2-hydroxybenzenesulfonyl azide has been reacted with norbornene, triphenylphosphine, dimethylsulfoxide, and cyclohexene. 3,5-Dichloro-2-hydroxybenzenesulfonyl chloride with phenylisocyanate gave the 2-(N-phenyl-carbamoyloxy) derivative which on heating gave a heterocyclic compound. The chlorohydroxybenzenesulfonyl derivatives are of interest as potential herbicides and their ir and nmr spectral characteristics are briefly discussed.     

A convenient synthesis of methyl 2-hydroxy-4-oxo-4-(substituted phenyl) butanoates from malic acid

A synthesis of methyl 2-hydroxy-4-oxo-4-(substituted phenyl)butanoates has been accomplished using Friedel-Crafts acylation of substituted benzenes with 2-acetoxybutanoyl chloride.The key feature of this strategy is that various 4-arylbutanoates can be obtained conveniently,which are important intermediates for the synthesis of biologically active compounds including ACE inhibitors.     

Room temperature ICl-induced dehydration/iodination of 1-acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles. a selective route to substituted 1-acyl-4-iodo-1H-pyrazoles

A number of new functionally substituted 1-acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles have been prepared in moderate to excellent yields from the corresponding 2-alkyn-1-ones. The resulting dihydropyrazoles undergo dehydration and iodination in the presence of ICl and Li2CO3 at room temperature to provide 1-acyl-4-iodo-1H-pyrazoles.     

Myrochromanol und Myrochromanon,zwei weitere Metaboliten von Myrothecium roridum Tode ex Fr. Verrucarine und Roridine, 25. Mitt.

From cultures of Myrothecium roridum Tode ex Fr. myrochromanol ( 1 ) and myrochromanone ( 3 ), two new substituted chromanes, have been isolated. Their structures as 2-(1-propenyl)-4-hydroxy-6-methyl-chromane and 2-(1-propenyl)-4-oxo-6-methyl-chromane respectively, have been determined using spectroscopic techniques and by degradation to 2-hydroxy-5-methylbenzoic acid ( 6 ). The stereochemistry of 1 and 2 is deduced by NMR., CD. and by partial resolution ( Horeau method).     

Functionalization at C-5 and at the C-6 methyl group of 4-methoxy-6-methyl-2-pyrone

A new entry to C-5 substituted 4-hydroxy-6-methyl-2-pyrones has been achieved. The best conditions to prepare the monobromo and the dibromo derivatives at C-3 and the C-6 methyl group of the title pyrone have been defined. The synthetic applicability of the phosphonium salts at CH₃-C-6 of both 4-methoxy-6-methyl-2-pyrone, 5 , and dehydroacetic acid, 2 , has also been evaluated.     

The preparation,spectra and tautomerism of some 4(n-arylamino)-1,2-naphthoquinones

Twelve 4(N-arylamino)-1,2-naphthoquinones (1) have been prepared by the direct addition of substituted anilines to 1,2-naphthoquinone, and their spectra have been studied. In the solid and in ethanol solution the 1,2-naphthoquinone tautomer (1a) predominates, but in trifluoroacetic acid the 2-hydroxy-1,4-naphthoquinone-4-aryliminium (2a) is the major species.     

Synthese von Plectranthonen,diterpenoiden Phenanthren-1,4-chinonen

Synthesis of Plectranthons, Diterpenoid Phenanthrene-1,4-diones The following phenanthrene-1,4-diones have been synthesized by using the photocyclization of the corresponding highly substituted stilbenes as the key step: 3-hydroxy-5,7,8-trimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 1 ), (RS)-, (R)-, and (S)-2-[3-hydroxy-5,7,8-trimethyl-1,4-dioxophenanthren-2-yl]-1-methylethyl acetate ( 2 , 31 , and 32 , resp.), 3-hydroxy-7,8-dimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 3 ), 3-hydroxy-7,8,10-tri-methyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 4 ), 5,7,8-trimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 17 ), and 3-hydroxy-2-methylphenanthrene-1,4-dione ( 42 ). The quinones 1 and 3 proved to be identical with the recently isolated plectranthons A and C. Compounds 2 , 31 , and 32 exhibited the same UV/VIS, IR, ¹H-NMR and mass spectra as natural plectranthon B , but had different melting points. This might be due either to crystal modifications or to diastereoisomerism caused by the helical structure of the phenanthrene-1,4-dione skeleton. The spectral data of synthetic 4 were not compatible with those of natural plectranthon D for which structure 4 had been proposed based mainly on ¹H-NMR arguments concerning the chemical shifts of H? C(9) and H? C(10) in 1–3. Extensive ¹H-NMR investigations have now revealed that the currently stated assignments of the H? C(9)/ H? C(10) AB system have to be reversed for highly substituted phenanthrene-1,4-diones: in the model compounds 2-methylphenanthrene-1,4-dione (41) and 2, H? C(10) resonates al lower field as expected (peri-position), whereas in the highly substituted congeners 1 , 2 , 3 , 31 , and 32 , H? C(9) is shifted paramagnetically, a fact which had lead to the erroneous assignment of structure 4 for natural plectranthon D .     

Synthesis and Properties of 3-Cynnamoyl-4-hydroxy-2-quinolone

Condensation of 3-acetyl-4-hydroxy-2-quinolone with aromatic aldehydes gave substituted 3-cynnamoyl-4-hydroxy-2-quinolones that luminesce in the solid state in the visible spectral range.     

Azabrendanes. I. Synthesis,structure and spectral parameters of N-(arylsulfonyl)-exo-2-hydroxy-4-azatricyclo[4.2.1.03,7]nonanes

A number of N-(arylsulfonyl)bicyclo[2.2.1]hept-2-enendo-5-methylamines have been synthesized from bicyclo[2.2.1]hept-2-en-endo-5-carbonitrile via reduction of the latter by lithium aluminum hydride and subsequent reactions of the resulting amine with arylsufonyl chlorides. The structures and stereochemical homogeneity of the products have been supported by the analysis of ¹H NMR spectra and by COSY-experiments. The reactions of the sulfonamides with peroxyphthalic acid are accompanied by intramolecular cyclizations and are completed by the formation of N-(arylsulfonyl)-exo-2-hydroxy-4-azatricyclo[4.2.1.0^3,7]nonanes. The structures of the substituted azabrendanes have been confirmed by spectral methods. The molecular structure of N-(p-methoxy-carbonylaminophenylsulfonyl)-exo-2-hydroxy-4-azatricyclo-[4.2.1.0^3,7]nonane 8j has been determined by X-ray diffraction analysis. © 1997 John Wiley & Sons, Inc.     

1-Hydroxy- and 1-nitroso-2,5-dimethylpiperid-4-ones and their derivatives

Derivatives of 1-hydroxy-2,5-dimethylpiperid-4-one substituted at the hydroxy and the carbonyl groups have now been prepared and the IR spectra of some of them have been studied. 1-Nitroso-2,5-dimethylpiperid-4-one has been prepared from 2,5-dimethylpiperid-4-one and subjected to various reactions at the nitroso- and the carbonyl groups. The IR spectra of the N-nitroso-compounds prepared are discussed.     

A New Route to Partially Hydrogenated Thiazolo[3,2-a]pyridine

Partially hydrogenated thiazolo[3,2-a]pyridines have been synthesized by the interaction of functionally substituted ammonium di- and tetrahydropyridine-2-thiolates with bromocyclohexanone. The structure of 6,8-dicyano-3-hydroxy-5-oxo-1,3-tetramethylene-2,3,4,5,6,7-hexahydrospiro[thiazolo[3,2-a]pyridine-7,1'-(4'-methylcyclohexane)] has been determined by X-ray crystallography.     

Modified Coumarins. II. Mannich Reaction of Substituted 4-Phenylcoumarins

Aminomethylation of 5-hydroxy- and 7-hydroxy-4-phenylcoumarins by substituted 1,1-diaminomethanes is studied. Mannich condensation of amino acids and their esters with 7-hydroxy-4-phenylcoumarin gives a series of 8-aminoacylmethylcoumarins and 4-phenyl-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones     

Preparation of 3-hydroxy- and 3-methoxy-N-heteroaryl-2-methyl-4-pyridones

A number of new 3-hydroxy- and 3-methoxy-2-methyl-4-pyridones substituted on the nitrogen atom with selected heterocycles has been prepared. Novel chelating properties of the hydroxy-compounds are expected.     

Synthesis of Some New Benzopyranopyrimidin-2-Thiol Derivatives

Reaction of 2-mercapto-4-hydroxy-5H-[1]-benzopyrano-[4,3- d ]-pyrimidin-5-one ( 3 ) with phenyl isothiocyanate and methyl acrylate yielded the corresponding 2-(substituted)thio-4-hydroxy-5H-[1]-benzopyrano-[4,3- d ]-pyrimidin-5-ones ( 4 , 5 ). Hydrolysis and hydrazinolysis of 5 gave acid derivative 6 , and hydrazone 7 . Treatment of hydrazone 7 with ethyl acetoacetate, diethyl malonate, and phenyl isothiocyanate yielded the corresponding 2-(substituted)thio-4-hydroxy-5H-[1]-benzopyrano- [4,3- d ]-pyrimidin-5-ones ( 8 , 9 , and 11 ). Cyclization of 11 with 2 N NaOH led to 12 .     

Synthesis of 3-substituted 2-amino-1-hydroxy-1<Emphasis Type="Italic">H</Emphasis>-indole-5,6-dicarbonitriles

A method of synthesizing new 3-substituted 2-amino-1-hydroxy-1H-indole-5,6-dicarbonitriles has been developed based on the reductive cyclization of substituted 4-cyanomethyl-5-nitrophthalonitriles.     

Novel One-Pot Multicomponent Synthesis of Substituted 2,3-Dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones and Substituted 3-[3-(N′-Benzylidene-hydrazino)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones

A one-pot procedure has been developed for the synthesis of substituted 2,3-dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones by reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and phthalic anhydrides in acetic acid medium. Similarly, a one-pot, three-component synthetic procedure has been developed for substituted 3-[3-(N¹-benzylidene-hydrazino)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones from 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and various aromatic aldehydes in absolute ethanol and a few drops of glacial acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis of 4-Hydroxy- and 4-Amino-2-Methyl-3-(2-Methylindol-3-Yl)methylquinolines and Their 6- and 8-Substituted Derivatives

A method has been developed for the synthesis of substituted 4-hydroxy- and 4-amino-2-methyl-3-(2-methylindol-3-yl)methylquinolines by treating the corresponding 4-hydroxy(chloro)-2-methyl-3-(3-oxobutyl)quinolines with phenylhydrazine hydrochloride. It was found that nucleophilic substitution occurred in the case of the 4-chloroquinolines together with subsequent rearrangement to give the 4-amino derivatives. The thiosemicarbazones of the corresponding 4-hydroxy-2-methyl-3-(3-oxobutyl)quinolines were also obtained.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 554–557, April, 2005.     

Noncatalytic on water aldol reaction of isatins with cyclic 1,3-diketones at room temperature without the need for subsequent chromatography

Noncatalytic on water aldol transformation of isatins and cyclic 1,3-diketones results in substituted 3-hydroxy-3-(2-hydroxy-6-oxocyclohex-1-en-1-yl)indolin-2-ones in 87–98% yields. Optimized conditions have been found and a mechanistic rationale for the reaction has been deduced. The new efficient and facile process represents a convenient way to compounds with the 3-hydroxyindolin-2-one and 3-hydroxycyclohex-2-en-1-one moieties.     

The synthesis of polymethylquinolines and 1,10-phenanthrolines

Several polymethyl-1,10-phenanthrolines were synthesized by the use of 3-methyl-3-penten-2-one in Skraup reactions. The behavior of this ketone as well as that of 4-hydroxy-2-pentanone and 4-hydroxy-3-methyl-2-bulanone with various substituted anilines was studied.