Synthesis and molecular design of 4,8‐diaryl‐ and 4,8‐di(arylethynyl)pyrido[4,3‐d]pyrimidines: Potential applications in nonlinear optics. Diazines Part 49

Using metallation and cross‐coupling reactions, we report the synthesis of a new series of push‐pull compounds with a pyrido[4,3‐d]pyrimidine system as the central core. Two of them were tested and their NLO properties highlighted. Incorporation of triple and double bonds as spacer between the central core and the substituted aryl groups has been performed to allow an extension of conjugation.     

Reaction of 3‐aminoquinoline‐2,4‐diones with isocyanates. Synthesis of novel 3‐(3′‐alkyl/arylureido)quinoline‐2,4‐diones and their cyclic carbinolamide isomers

3‐Alkyl/aryl‐3‐amino‐1H,3H‐quinoline‐2,4‐diones react with alkyl/aryl isocyanates to give novel 3‐alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones or 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones. In some cases, a mixture of both products was obtained and separated by fractional crystallization. All compounds were characterized by their ¹H, ¹³C, ir and ms data and some of them also by ¹⁵N nmr data.     

Synthesis of fluorine containing N‐benzyl‐1,2,3‐triazoles and N‐methyl‐pyrazoles from conjugated alkynes

1, 3‐Dipolar‐cycloaddition reaction of fluoro substituted 3‐aryl‐propynenitriles 1 with benzyl azide 2 afforded the expected 3‐benzyl‐5‐aryl‐3H‐[1,2,3]triazole‐4‐carbonitrile 3 and 1‐benzyl‐5‐aryl‐1H‐[1,2,3]‐triazole‐4‐carbonitrile 4 in good yield. However, 1,3‐dipolar cycloaddition of diazomethane 5 with 3‐aryl‐propynenitriles 1 resulted in the exclusive formation of N‐methyl‐pyrazole derivatives 6 and 7 .     

High yield synthesis of 4H‐1,4‐benzothiazine‐1,1‐dioxide derivatives

4H‐1,4‐Benzothiazine‐1,1‐dioxide derivatives were synthesized through a sequence of almost quantitative reactions. The commercial starting material 2‐(methylsulfanyl)aniline was Boc‐protected, N‐acylated and oxidized at the sulfur atom to obtain a sulfonyl derivative. An anionic transposition of the acyl group followed by asimultaneous deprotection‐cyclization gave the title products in excellent yields. All products and intermediates were fully characterized.     

Darstellung und Stabilität von Aroxy-fluor-silanen

Preparation and Stability of Aroxy-fluoro-silanes. Different possibilities for preparation of aroxy-fluoro-silanes (esp. substituted phenoxy-fluoro-silanes) are investigated. The reaction was proved as the best method of preparation. The aroxy-fluoro-silanes are disposed to dismutation reactions.     

1,3‐Dipolar cycloadditions of 9‐diazofluorenes and diphenyldiazomethane to 2‐acyl‐2H‐1,2,3‐diazaphospholes

A series of 2‐acyl‐2H‐1,2,3‐diazaphospholes 3 underwent ready 1,3‐dipolar cycloaddition reactions with 9‐diazofluorenes as the 1,3‐dipole, yielding the respective bicyclic phosphiranes 5 or trimers 7 depending on the reaction conditions employed. The reaction is believed to proceed via the formation of the [3+2]‐cycloaddition adducts followed by elimination of nitrogen from the cyclic azo moiety. In the case of 3c , the phosphatetraazabicyclooctadiene compound 6 has been isolated with no loss of nitrogen. Likewise, the dipolar cycloaddition reaction of diphenyldiazomethane with the >C?P‐ moiety as the 1,3‐dipolarophile gave phosphadiazabicyclohexenes 8 in 32–68% yields.     

The synthesis of 3,3‐dimethyl‐2‐(1‐aryl‐1h‐pyrazol‐4‐yl)‐3h‐indoles

2,3,3‐Trimethylindolenine and 5‐chloro‐2,3,3‐trimethylindolenine were converted into β‐diformyl compounds by the action of the Vilsmeier reagent at 50°C. The dialdehydes reacted with various arylhydrazines and 2‐pyridylhydrazine to produce mono‐hydrazones as mixtures of cis and trans isomers. Heating the hydrazones in refluxing ethanol produced 3,3‐dimethyl‐2‐(1‐aryl‐1H‐pyrazol‐4‐yl)‐3H‐indoles in excellent yields. Reaction of the β‐diformyl compounds with hydrazine itself led directly to 3,3‐dimethyl‐2‐(pyrazol‐4‐yl)‐3H‐indoles.     

The reaction of aryl and heteroarylhydrazines with aryl‐trifluoromethyl β‐diketones

We report the results obtained when five aromatic or heteroaromatic hydrazines react with six β‐diketones bearing trifluoromethyl and aryl substituents. Forty‐two compounds have been isolated corresponding to two isomeric trifluoromethyl pyrazoles and the intermediate 5‐CF₃, 5‐OH pyrazolines. The results have provided useful information for establishing the mechanism of the synthesis of pyrazoles.     

Heterogeneous “Organoclick” Derivatization of Polysaccharides: Photochemical Thiol‐ene Click Modification of Solid Cellulose

A simple and direct method for derivatization of solid polysaccharides is presented. The novel methodology is based on the combination of organic acid‐catalyzed esterification or etherification and photochemical thiol‐ene click derivatization of a heterogeneous polysaccharide. The solid cellulose was “organoclick” modified with aryl, alkyl and polyester groups, respectively. The modification allows for a highly modular and metal free surface modification of solid polysaccharides.

     

Phenacyl esters of acetic acid derivatives and their application for the synthesis of 2‐oxo‐4‐phenyl‐5‐(phenylhydrazono)‐2,5‐dihydro‐furan‐3‐derivatives

Coupling of various substituted phenacyl acetates 1 and diazonium salts 3 was studied. If the phenacyl acetates were substituted by an electronaceptor group such as CN or COOEt 3‐substituted phenyl‐5‐(phenyl‐hydrazono)‐5H‐furan‐2‐ones 4 were formed. Also synthesis of aza and diaza analogs is described. The compounds were characterized using MS and NMR spectroscopy.     

Synthesis of 2‐alkyl‐4,5‐aryl‐2H‐[1λ6,2,3,6]‐thiatriazine‐1,1‐dioxides

Sulphamoyl chlorides and chlorosulphonyl isocyanate react with monosubstituted hydrazones and alkylhydrazonates to sulphamoyl hydrazones and sulphamoyl hydrazonates respectively. Reaction of benzil monoalkylhydrazones with chlorosulphonyl isocyanate results in formation of 2‐alkyl‐4,5‐aryl‐2H‐ [1λ⁶,2,3,6]‐thiatriazine‐1,1‐dioxides.     

Vapor‐Based Synthesis of Poly[(4‐formyl‐p‐xylylene)‐co‐(p‐xylylene)] and Its Use for Biomimetic Surface Modifications

Summary: The vapor‐based synthesis and characterization of a reactive polymer, poly[(4‐formyl‐p‐xylylene)‐co‐(p‐xylylene)] ( 1 ), have been reported. The reactive polymer coating enables the immobilization of oligosaccharides via the chemoselective aldehyde‐hydrazide coupling reaction.

     

Ruthenium‐catalyzed biginelli condensation: A simple and efficient one‐pot synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones under mild reaction conditions

Ruthenium trichloride was found to be an efficient catalyst for the first time for the synthesis of a variety of 3,4‐dihydropyrimidin‐2(1H)‐ones by cyclocondensation of an aldehyde, β‐dicarbonyl compound and urea in excellent yields under mild reaction conditions.     

Three‐component,one‐pot synthesis of pyrimido[4,5‐b]‐quinoline and pyrido[2,3‐d]pyrimidine derivatives

Reaction of 6‐amino‐2‐methylthiouracil and 6‐amino‐1,3‐dimethyluracil with equimoler amounts of cyclic ketones or cyclic 1,3‐diketones and the appropriate aromatic aldehydes yielded regioselectivity a series of polycyclic pyrimido[4,5‐b]quinoline and pyrido[2,3‐d]pyrimidine derivatives in good yields.     

Microwave Accelerated Polymerization of 2‐Phenyl‐5,6‐dihydro‐4H‐1,3‐oxazine: Kinetics and Influence of End‐Groups on Glass Transition Temperature

Summary: The ring‐opening polymerizations of 2‐phenyl‐5,6‐dihydro‐4H‐1,3‐oxazine (PhOZI) with methyl tosylate (MeOTs) and butyl iodide (BuI) as initiators were performed in refluxing butyronitrile. Reaction kinetics under microwave irradiation was compared with conventional oil bath heating. The polymerization rates, under microwave irradiation, showed an acceleration by a factor of 1.8 (independently from the used initiator). The investigation of the thermal properties of the obtained poly(N‐benzoyl‐trimethyleneimine) showed the influence of molecular weight and end‐groups on the glass transition temperature.

The ring‐opening polymerizations of 2‐phenyl‐5,6‐dihydro‐4H‐1,3‐oxazine performed in refluxing butyronitrile.     

Synthesis of trifluoromethyl‐1,2,4‐triazine‐ and trifluoromethylpyrimidine‐fused uracils

A variety of trifluoromethyl‐1,2,4‐triazine‐ and trifluoromethylpyrimidine‐fused uracils ( 9 ), ( 12 ), ( 15 ) and ( 18 ) were synthesized from trifluoroacetaldehyde ethyl hemiacetal or trifluoroacetic anhydride and corresponding uracil derivatives.     

A novel one‐pot oxidative deformylation of N‐formyldihydroquinolines employing ferric chloride hexahydrate. Synthesis of 4‐chloro‐2‐phenylquinolines and 4‐chloro‐2‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)quinolines

A novel versatile one‐pot oxidative deformylation approach has been developed to synthesize 4‐chloro‐2‐phenylquinolines and 4‐chloro‐2‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)quinolines from the corresponding N‐formyldihydroquinolines.     

Synthesis and intramolecular cyclization of 2‐methylsulfany‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide

Treatment of ambident sodium salt of 2‐methylsulfanyl‐4(3H)‐quinazolinone with methyl bromoacetate resulted in N₍₃₎‐alkyl ester formation. Reaction of the resulted ester with hydrazine hydrate gave 2‐methylsulfanyl‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide, which underwent intramolecular cyclization under heating in dimethylformamide to give 1‐aminoimidazo[2,1‐b]quinazoline‐2,5(1H,3H)‐dione. The latter took place in acylation reaction and in condensation with aromatic aldehydes.     

Convenient synthesis of some 2‐substituted 4(3H)‐quinazolinone derivatives

A series of 2‐substituted‐4(3H)‐quinazolinones 13‐20 has been synthesized in good yields using the reaction of double lithiated 2‐methylquinazolinone‐4 with a variety of aromatic aldehydes. They have been easily transformed in high yields into the corresponding 2‐substituted conjugated derivatives 21‐28 bearing terminal aryl groups by F₃CCOOH mediated dehydration.     

Synthesis of alkyl 6‐methyl‐4‐(2‐pyridyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylates for evaluation as calcium channel antagonists

The Bigenelli acid catalyzed condensation of 2‐pyridylcarboxaldehyde ( 1 ), urea ( 2 ) and an alkyl acetoacetate ( 3 ) afforded the respective alkyl (Me, Et, i‐Pr, i‐Bu, t‐Bu) 6‐methyl‐4‐(2‐pyridyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylates ( 4a‐e ). The most potent calcium channel antagonist ethyl 6‐methyl‐4‐(2‐pyridyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylate ( 4b , IC₅₀ = 1.67 × 10^?5 M) wasa much weaker calcium channel antagonist than the reference drug nifedipine (Adalat®, IC₅₀ = 1.40 × 10^?8 M) on guinea pig ileal longitudinal smooth muscle (GPILSM). The alkyl 6‐methyl‐4‐(2‐pyridyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylates did not show any inotropic effect on heart since no increase, or decrease, in the contractile force of guinea pig left atrium was observed. These structure activity studies show that the alkyl 6‐methyl‐4‐(2‐pyridyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylates ( 4a‐e ) are partial bioisosteres of nifedipine with respect to calcium channel antagonist activity on guinea pig ileal longitudinal smooth muscle (GPILSM).