Organotellurium Chemistry: Remarkably Facile Preparation of Benzo‐1,3‐tellurazoles

Benzo‐1,3‐tellurazoles carrying alkyl or aryl substituents in position 2 were prepared in a facile two‐step sequence, starting with readily available 2‐haloanilines. This approach relies on the preparation of bis(2‐aminophenyl) ditellurides by nucleophilic halide displacement from 2‐haloanilines with sodium telluride in N‐methylpyrrolidone. Subsequent reductive cyclization with carboxylic acid halides or carboxylic anhydrides furnished benzo‐1,3‐tellurazoles in good yields.     

Microwave‐assisted synthesis of 1,3′‐diaza‐flavanone/flavone and their alkyl derivatives with antimicrobial activity

A simple environmentally friendly solid‐phase microwave‐assisted method was used to synthesis of the 1,3′‐diazaflavanone ( 2 ) and 1,3′‐diazaflavone ( 3 ) from the cyclization of 2′‐amino (E)‐3″‐azachalcone ( 1 ). Ten new N‐alkyl (C_5–12,14,15)‐substituted 1,3′‐diazaflavanonium bromides ( 2a–j ) were prepared from compound 2 with corresponding alkyl halides in acetonitrile under reflux. In addition, nine new N,N′‐dialkyl (C_5–12,14)‐substituted 1,3′‐diazaflavonium bromides ( 3a–i ) were also synthesized from compound 3 with corresponding alkyl halides using basic silica in acetonitrile. The antimicrobial activities of compounds 1–3 , 2a–j , and 3a–i were tested against Gram‐positive (G+) (Bacillus subtilis, Staphylococcus epidermidis, Staphylococcus aureus, and Enterococcus faecalis) and Gram‐negative (G?) (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhimirium, Yersinia pseudotuberculosis, and Enterobacter cloaceae) microorganisms. They showed good antimicrobial activity against the Gram‐positive bacteria tested with the minimal inhibitory concentration values less than 7.8 μg/mL in most cases. The optimum length of the alkyl chain for better and broader activity is situated in the range of 9–12 carbon atoms in the series of compounds 2a–j and five to six carbon atoms in the series of compounds 3a–i . The nonalkylated compounds 1–3 were not effective, as were the ones alkylated with five or six C alkyl groups ( 2a and 2b ) and 8–13 C alkyl groups for N,N′‐dialkyl compounds ( 3c–3i ). The antimicrobial activity increased as the length of the alkyl substitution increased from 8 to 12 carbons in compounds 2a–j . However, antimicrobial activity decreased as the length of the alkyl substitution increased from 7 to 13 carbons in compounds 3c–i . J. Heterocyclic Chem., (2012)     

A novel alkylation procedure using MW irradiation for the synthesis of 1,2,3-trisubstituted 1,4,5,6,7,8-hexahydro-1,3-diazocinium salts from their corresponding 1,2-diaryldiazocines

In this work, we describe the synthesis of a series of 1,2,3-trisubstituted-1,4,5,6,7,8-hexahydro-1,3-diazocinium salts (1) by alkylation of the corresponding 1,2-diaryl-1,4,5,6,7,8-hexahydro-1,3-diazocines (2). Compounds 2 were obtained by ethyl polyphosphate-promoted cyclocondensation of N-aroyl-N′-arylpentamethylenediamines (3). Reaction of compounds 2 with alkyl iodides led to 1,2,3-trisubstituted 1,4,5,6,7,8-hexahydro-1,3-diazocinium iodides (1), a new family of cyclic amidinium salts. The best yields for the alkylation were achieved using a mixture of DCM–DMSO (10:1) as solvent. The reaction times of both, the cyclocondensation of compounds 3 and the reaction of 2 with alkyl halides, are dramatically decreased when using microwave irradiation.     

2,2-disubstituierte cyclopentan-1,3-dione—2: Untersuchung der regioselektivität von alkylierungs-reaktionen an 2-methyl-cyclopentan-1,3-dion

The regioselectivity of the alkylation of alkali metal salts of 2 - methyl - cyclopentane - 1,3 - dione with alkyl halides depends significantly on the structure of the alkylating reagent and the type of solvent used in the reaction. Unsubstituted saturated primary alkyl halides with the exception of methyl iodide preferentially yield products of O-alkylation. Alkyl halides with an sp²- or sp-hybridized carbon atom in a β-position preferentially yield products of C-alkylation. Dipolar aprotic solvents favour O-alkylation; water favours C-alkylation. On the basis of these results procedures for the prepartion of 2-allyl-2-methyl-, 2-allyl-2-ethyl-, 2-methyl-2-propargyl- and 2 - benzyl - 2 - mehtyl - cyclopentane - 1,3 - dione have been developed. The alkylation of 2 - methyl - cyclopentane - 1,3 - dione with methyl bromoacetate was also intensively investigated.     

Synthesis of 2,3-disubstituted-1,3-oxazolidines

A series of 2-aryl-3-alkyl or aryl carbamoyl- and thiocarbamoyl-1,3-oxazolidines was prepared by the reactions of alkyl and aryl isocyanates and isothiocyanates with N-(2-hydroxyethyl)-benzalamincs. The nuclear magnetic resonance spectra of these compounds are discussed.     

Two-fragment α-adrenolytics

A method for the synthesis of hypotensive alkyl(phenyl)[ω-(N-phenylpiperazino)alkyl]-phosphine oxides by reacting alkyl(ω-haloalkyl)phenylphosphine oxides withN-phenylpiperazine was elaborated. Phenyl[γ-(N-phenylpiperazino)propyl]propylphosphine oxide reacts with alkyl halides to give [γ-(N-alkyl-N′-phenylpiperazinio)propyl]phenyl(propyl)oxophosphine halides. For Part 1 see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 488–492, March, 2000.     

Pyrrole-Protected β-Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino-Derivatives

Chiral β-aminoalkylzinc halides were prepared starting from optically pure commercial β-amino-alcohols. These amino-alcohols were converted to the corresponding N-pyrrolyl-protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 °C, 10–90 min). Subsequent Negishi cross-coupling or acylation reactions with acid chlorides produced amino-derivatives with retention of chirality. Diastereoselective CBS-reductions of some prepared N-pyrrolyl-ketones provided 1,3-subsituted N-pyrrolyl-alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole-ring into a formamide without loss of optical purity.     

Synthesis of the complex bridged 1,5-oxazabicycles <Emphasis Type="Italic">via</Emphasis> one-pot reactions of 4,5-diazafluoren-9-one,alkyl halides,and cyclic 1,3-diketone

An efficient and practical procedure for the preparation of the complex bridged 1,5-oxazabicycles was developed via a one-pot domino reaction of 4,5-diazafluoren-9-one, reactive alkyl halides, and cyclic 1,3-dicarbonyl compounds.     

Ind-N-alkylation of rutaecarpine and synthesis of two novel related heterocyclic ring systems: Indolo[1′,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1′,2′:3,4] [1,4] diazepino[ 1,2-α]quinazoline

The failure to obtain the N-(13)alkylrutaecarpines ( 1d,e,f ) by heating rutaecarpine ( 1a ) with neat alkyl halides at 120° is discussed in comparison with the facile reaction with methyl iodide. In contrast, with alkyl halide-potassium carbonate in acetone, the corresponding N-(13)alkyl-rutaeearpines ( 1d-l ) are obtained in good yield. By use of 1,3-diiodopropane and 1,2-dibromo-ethane, this reaction provides a facile route to 12a and 13 which are derivatives of the heretofore unknown indolo[1,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1,2 :3,4][1,4]diazepino[1,2-α]quinazoline ring systems.     

Mass spectrometry of substituted 1,3-dihydro-2H-imidazole-2-thiones

The electron impact mass spectra of the 4-formyl-1, 3-dihydro-2H-imidazole-2-thione, its six 1-methyl(n-propyl, n-hexyl)-3-methyl(phenyl)-disubstptuted derivatives, and the 1,3-dihydro-1-phenyl-2H-imidazole-2-thiome are discussed. The fragmentation pattern is strongly influenced by the alkyl or phenyl N-substituents, as well as by the length of the alkyl chain. The odd-electron ions containing an N-phenyl substituent, but not a propyl or hexyl group, eject a hydrogen atom from the phenyl ring, while the presence of a long alkyl chain greatly enhances the loss of the sulphyhydryl radical and facilitates the expulsion of several alkenes, and alkyl and alkenyl radicals.     

Synthesis of imidazo[5,4-d] [1,3]thiazines: X-ray structure of N-methyl-N′-[5-(methylamino)-3-nonylimidazo[5,4-d] [1,3]thiazin-7(3H)-ylidene]thiourea

N-Alkyl-N′-[5-(alkylamino)-3-alkylimidazo[5,4-d] [1,3]thiazin-7(3H)-ylidene]thioureas were obtained by the reaction of 1-substituted 5-amino-4-cyanoimidazoles with alkyl isothiocyanates. The structure of this heterocyclic system was confirmed by single crystal X-ray diffraction analysis.     

Synthesis of quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts

The reaction of dihydroimidazole-2-thiol with N-(3-chloro-2-oxopropyl)phthalimide gave 2-[3-(4,5-dihydroimidazol-2-ylsulfanyl)-2-oxopropyl]-1,3-dioxo-1H-isoindole which underwent intramolecular heterocyclization to dihydroimidazothiazole system by the action of a dehydrating agent. Treatment of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with concentrated hydrochloric acid led to the formation of dihydroimidazo[2,1-b]thiazol-3-ylmethanamine. Water-soluble quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts were obtained by alkylation of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with alkyl halides.     

Arsenorgano-Verbindungen : XXII. Zur synthese der 1,3-benzazarsoline

o-Aminophenylarsine is prepared by reduction of o-nitrophenylarsonic acid. Metallation and subsequent treatment with alkyl halides give the secondary o-aminophenylarsines. o-Aminophenylarsines react with aldehydes, ketones and ketoesters forming derivates of the 1,3-benzazarsoline. Exceptions are redox reactions between o-aminophenylarsine and aldehydes. The properties of the compounds are described in more detail.     

Electronic effects in the reaction of 1,3-diaryl-1,3-diketones with hydrazinopyridines

The regioselectivity of the condensation of electronically unsymmetrical 1,3-diaryl-1,3-diketones with 2-hydrazinopyridine and 2,6-bis-hydrazinopyridine to form N-(2-pyridyl)-3,5-diarylpyrazoles was studied. Significant electronic effects on regioselectivities were observed, and regioselectivities were opposite to those exhibited by perfluoroalkyl/alkyl 1,3-diketones. The electronic effects correlate well to the difference between the Hammett σ⁺ coefficients of the para substituents on the aryl rings.     

Quinazolines. VIII. Synthesis of 1,3-diaminobenzo[f]quinazolines

Twenty-one 1,3-diaminobenzo[f]quinazolines ( 2 , R = H, alkyl, halogen, methoxy) were synthesized as planar tricyclic analogs of the antimalarial agent pyrimethamine ( 1 ). The synthetic methods included i) condensation of 1-cyano-2-naphthylamines with cyanamide in the presence of pyridine hydrochloride, ii) cyclization of N¹,N⁵-bis(2-naphthyl)biguanide hydrochlorides in diphenyl ether at 250°, iii) reaction of 2-naphthylamine hydrochlorides with excess sodium dicyanamide in boiling 1-octanol, and iv) selenium dioxide dehydrogenation of 1,3-diamino-5,6-dihydrobenzo[f]quinazolines. A number of new 2-naphthols and 2-naphthylamines were synthesized as intermediates. Substituent effects on the ultraviolet absorption spectra of 1,3-diamino-benzo[f]quinazolines were investigated and found to be additive. These compounds are of interest as inhibitors of dihydrofolate reductase and as potential antimalarial and antitumor agents.     

The anionic polymerization of dialkylaminoisoprenes-5-copolymerization with 1,3-butadiene

The anionic copolymerization of 5-(N,N-dialkylamino)isoprenes and 1,3 -butadiene was investigated in hexane. We found that basicity and increasing amount of the polar monomer has a strong influence on the microstructure of polybutadiene. All tested 5-(N,N-dialkylamino)isoprenes were incorporated much faster into the copolymer than butadiene. Depending on the alkyl substituents the resulting copolymer is either a nearly perfect diblock or shows a considerable tapered structure.     

Substituent effects of N‐alkyl groups on thermally induced polymerization behavior of 1,3‐benzoxazines

Thermally induced polymerizations of a series of 1,3‐benzoxazines with a variety of substituents on the nitrogen atom were investigated in detail, particularly in the following three aspects of the polymerization: (1) N‐alkyl‐1,3‐benzoxazines are much more reactive than N‐phenyl‐1,3‐benzoxazine. (2) The polymerization rate depended on the bulkiness of the N‐substituent. The bulkier the substituent was, the slower the polymerization was. (3) The polymerizations accompanied weight loss due to the elimination of the corresponding imine (R‐N = CH₂), and its extent became larger when R was more bulky. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2777–2782, 2010     

A STUDY ON THE TRANSESTERIFICATION REACTION OF DIMETHYL AND DIETHYL PHOSPHITE WITH 1,3-DICHLOROPROPANOL-2

Abstract

The transesterification process of dimethyl and diethyl phosphite with 1,3-dichloropropanol-2 is examined. It is found that the reaction proceeds in the absence of catalyst at a temperature of 155°, whereas in the presence of morpholine as a catalyst it takes place at 126°C. The transesterification of dimethyl phosphite and diethyl phosphite with 1,3-dichloropropanol-2 is accompanied by the evolution of dimethyl and diethyl ethers and alkyl halides (methyl chloride and ethyl chloride).     

One-pot two-step synthesis of 1-position arylated 1,3-disubstituted isoquinoline N-oxides

A one-pot two-step reaction of 2-alkynylbenzaldoximes with aryl halides has been developed, which offers the 1-position arylated 1,3-disubstituted isoquinoline N-oxides in moderate to good yields in most cases. The isoquinoline N-oxide intermediate was prepared in situ without isolation.     

Reaktion von 3-(Dimethylamino)-2H-azirinen mit 1,3-Thiazolidin-2-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Thiazolidine-2-thione Reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-thiazolidine-2-thione ( 6 ) in MeCN at room temperature leads to a mixture of perhydroimidazo[4,3-b]thiazole-5-thiones 7 and N-[1-(4,5-dihydro-1,3-thiazol-2-yl)alkyl]-N′,N′-dimethylthioureas 8 (Scheme 2), whereas, in i-PrOH at ca. 60°, 8 is the only product (Scheme 4). It has been shown that, in polar solvents or under Me₂NH catalysis, the primarily formed 7 isomerizes to 8 (Scheme 4). The hydrolysis of 7 and 8 leads to the same 2-thiohydantoine 9 (Scheme 3 and 5). The structure of 7a, 8c , and 9b has been established by X-ray crystallography (Chapt. 4). Reaction mechanisms for the formation and the hydrolysis of 7 and 8 are suggested.