A New 2H‐Azirin‐3‐amine as a Synthon for 2‐Methylaspartate

The synthesis of a novel 2,2‐disubstituted 2H‐azirin‐3‐amine 3a as a building block for racemic Asp(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 3a with thiobenzoic acid and the amino acid Z‐Val‐OH yielded the racemic monothiodiamide 10a and the dipeptide 11 as a mixture of diastereoisomers, respectively (Scheme 2). In 11 , each of the protecting groups was removed selectively (Scheme 3). First attempts toward the preparation of enantiomerically pure synthons for Asp(2Me) with a chiral auxiliary group in the side chain are described. Synthons 3b with a 1‐(naphthalen‐1‐yl)ethyl ester group and 3c with a menthyl ester group were prepared and reacted with thiobenzoic acid to form monothiodiamides 10b and 10c (Scheme 2). However, the diastereoisomers of the synthons 3b and 3c could not be separated by chromatography.     

New Energetic Materials: Functionalized 1‐Ethyl‐5‐aminotetrazoles and 1‐Ethyl‐5‐nitriminotetrazoles

A new way to make a bang : Several functionalized 1‐ethyl‐5‐aminotetrazoles, 1‐ethyl‐5‐nitrimino‐tetrazoles, and copper complexes have been synthesized and their chemical and energetic properties have been comprehensively characterized. The compounds belong to all classes of “energetic materials”: explosives, propellants, and pyrotechnics.

     

A novel synthesis of some new benzoyl‐substituted heterocycles from 2‐benzoyl‐3‐phenylpent‐2‐ene‐1,5‐dinitrile

2‐Benzoyl‐3‐phenylpent‐2‐ene‐1,5‐dinitrile 1 undergoes bromination with N‐bromosuccinimide (NBS) to afford the bromo derivative 2a . This bromo derivative undergoes reactions with sodium hydrogen sulfide, ethyl thioglycollate, hydroxylamine hydrochloride, hydrazines, cyanoacetamide, cyanacetohydrazide and urea derivatives to afford the thiophene 4 , 4H‐thiopyran 6 , 4H‐1,2‐oxazine 8 , 4H‐pyridazines 10a,b , the pyridine 15 , pyrrolo[1,2‐b]pyridazine 17 and the N‐substituted‐pyrrole derivatives 19a‐c respectively.     

A New 2H‐Azirin‐3‐amine as a Synthon for α‐Methyl Glutamate

The synthesis of a novel 2,2‐disubstituted 2H‐azirin‐3‐amine 10 as a building block for racemic Glu(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 10 with thiobenzoic S‐acid and the amino acid Z‐Val‐OH yielded the racemic monothiodiamide 17 and the dipeptide 18 as a mixture of diastereoisomers, respectively (Scheme 2). From 18 , each of the protecting groups was removed selectively (Scheme 3).     

Synthesis of new bridgehead heterocycles: Pyrimido[3′,2′:3,4]‐1,2,4‐triazino[5,6‐b]indoles

A new bridgehead nitrogen hetero‐ cycle viz. 11‐carboethoxy‐9‐oxo‐pyrimido[3′2′:3,4]‐1,2,4‐triazino[5,6‐b]indole 3 has been synthesized from 3‐azido‐5H‐1,2,4‐triazino[5,6‐b]indole 2 by its reaction with diethyl fumerate. The intermediate 2 was obtained by treating 3‐hydrazino‐5H‐1,2,4‐triazino[5,6‐b]indole with NaNO₂ in presence of polyphosphoric acid. A plausible mechanism for the formation of 3 has been formulated and discussed. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:272–276, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20199     

A Simple Multistep Conversion of 1,2‐Dihydro‐1,1‐dimethoxynaphthalen‐2‐ones to (3,4‐Dihydro‐3,4‐dioxonaphthalen‐2‐yl)acetates

On irradiation (λ=350 nm) in the presence of 1,1‐dimethoxyethene, naphthalene‐1,2‐dionemonoacetals 1 regioselectively afford 1,1,4,4‐tetramethoxycyclobuta[a]naphthalen‐3‐ones 3 . Sequential deprotection of these bis‐acetals first lead to 1,1‐dimethoxycyclobuta[a]naphthalene‐3,4‐diones 4 and then to cyclobuta[a]naphthalene‐1,3,4‐triones 6 , which, in turn, are converted into (3,4‐dihydro‐3,4‐dioxonaphthalen‐2‐yl)acetates 7 by treatment with SiO₂/MeOH/air.     

A novel 3,4-dihydroisoquinoline annulation: expedient access to isoquinoline heterocycles

3,4-Dihydroisoquinoline carboxylate 1 undergoes a smooth annulation with ω-bromopropionate, butyrate or ortho-bromomethyl benzoate 2 to afford the isoquinoline heterocycle 3 upon treatment with potassium tert-butoxide in DMF at −60 °C. This novel annulation constitutes a formal direct synthesis of cyclic Reissert equivalent compounds, thus offers an expedient access towards certain medicinally important isoquinoline heterocycles and relevant natural alkaloids, that is, of berberine and erythrina types.     

Allenyl‐β‐lactams: versatile scaffolds for the synthesis of heterocycles

The hybrid allenic β‐lactam moiety represents an excellent building block for carbo‐ and heterocyclization reactions, affording a large number of cyclic structures containing different sized skeletons in a single step. This strategy has been studied under thermal and radical‐induced conditions. More recently, the use of transition‐metal catalysis has been introduced as an alternative that relies on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of bi‐ and tricyclic compounds in a regio‐ and stereoselective manner. This overview focuses on the most recently developed cyclizations on 2‐azetidinone‐tethered allenes along with remarkable early works accounting for the mechanism, as well as for the regio‐ and diastereoselectivities of the cyclizations. DOI 10.1002/tcr.201100011     

Phosphorus heterocycles from 2‐(2‐hydroxyphenyl)‐1H‐benzimidazole

Sixteen different P(III) and P(V) heterocycles derived from 2‐(2‐hydroxyphenyl)‐1H‐benzimidazole ( 1 ) are reported. In these heterocycles the phosphorus atom is part of a six‐membered unsaturated ring. They were mainly studied by multinuclear NMR. The X‐ray diffraction of 3,4‐ benzimidazole‐5,6‐benzo‐2‐dimethylamino‐2‐seleno‐ 1,3,2‐oxazaphosphorinane is reported. Phosphoranes derived from 1 and 3,5‐di‐tert‐butylcatechol, and bearing Cl, NMe₂, or phenyl as substituent at phosphorus are presented. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:307–320, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20021     

2‐Ethyl‐2‐phosphabicyclo[2.2.2]oct‐7‐ene derivatives: Synthesis and use in fragmentation‐related phosphorylations

A 2‐phosphabicyclo[2.2.2]oct‐7‐ene oxide ( 2 ) and a 2‐phosphabicyclo[2.2.2]octa‐5,7‐diene oxide ( 3 ) with ethyl substituent on the phosphorus atom was synthesized and their fragmentation properties were studied. The phosphabicyclooctadiene oxide ( 3 ) could be utilized in both the UV light‐mediated phosphorylation of simple alcohols and in the thermoinduced phosphorylation of hydroquinone giving an easy access to P‐ethylphosphinates (e.g., 4 and 6 ). The phosphabicyclooctene oxide ( 2 ) was, however, not useful in photoinduced phosphorylations; under such conditions the precursor ( 2 ) underwent dechlorination to afford 5 . © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:196–199, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20093     

Single‐Mode Microwave Ovens as New Reaction Devices: Accelerating the Living Polymerization of 2‐Ethyl‐2‐Oxazoline

Summary: The ring‐opening cationic polymerization of 2‐ethyl‐2‐oxazoline was performed in a single‐mode microwave reactor as the first example of a microwave‐assisted living polymerization. The observed increase in reaction rates by a factor of 350 (6 h → 1 min) in the range from 80 to 190 °C could be attributed solely to a temperature effect as was clearly shown by control experiments and the determined activation energy. Because of the homogenous microwave irradiation, the polymerization could be performed in bulk or with drastically reduced solvent ratios (green chemistry).

Monomer conversion, represented by the ratio ln{[M₀]/[M_t]}, plotted against time for six temperatures in the range from 80 to 180 °C, and polymerization reaction vials, showing an increase in yellow color for those reactions performed (well) above and below 140 °C, indicating side reactions.     

Synthesis of novel ladder polymers of poly(3,4‐dihydro‐2H‐pyran‐2‐methanol)

Polydi(3,4‐dihydro‐2H‐pyran‐2‐methyl) esters of oxalic, adipic, and phthalic acids were prepared at different temperatures in the presence of different cationic initiators, namely, the boron trifluoride/diethyl ether complex system, anhydrous ferric chloride, and p‐toluene sulfonic acid. The obtained polymers were hydrolyzed under basic conditions, and the polydispersity indices of these polymers were determined before and after hydrolysis. The results are discussed to shed some light on the ability to use this analysis to investigate the precise structure of the obtained polymers and to predict the ability of these polymers to form ladder or semiladder polymers. Characteristics of such polymers were dependent, to some extent, on the type of crosslinks and the cationic initiators used for polymerization as well as the reaction temperature. It seems possible to optimize the conditions leading to formation of ladder or semiladder polydi(3,4‐dihydro‐2H‐pyran‐2‐methyl) esters of oxalic acid and adipic acid, respectively. The ladder structure was confirmed through determination of the polydispersity index before and after hydrolysis of the polymer formed at different temperatures and through computer‐aided molecular modeling. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3909–3915, 2002     

Vapor‐Phase Aldolization of n‐Butyraldehyde to 2‐Ethyl‐2‐Hexenal over Solid‐Base Catalysts

Vapor‐phase aldol condensation of n‐butyraldehyde to 2‐ethyl‐2‐hexenal was studied at 1 atm and 150～ 300°C in a fixed‐bed, integral‐flow reactor by using NaX, KX, γ‐Al₂O₃ and Na/NaOH/γ‐Al₂CO₃ catalysts. Ion exchange of NaX zeolite with potassium acetate solution results in a decrease of crystallinity and apparent lowering of surface area, whereas the basic strength is enhanced. Treatment of γ‐Al₂O₃ with NaOH and Na causes a large decrease of the surface area but strong enhancement of the catalyst basicity. The catalytic activity on the basis of unit surface area is in the order Na/NaOH/γ‐Al₂O₃ < KXU < KXW < NaX >γ‐Al₂O₃, in accordance with the relative catalyst basic strength. The molar ratio of trimeric to dimeric products increases with increasing the reaction temperature and the catalyst basic strength except for Na/NaOH/γ‐Al₂O₃. Very high selectivity of 2‐ethyl‐2‐hexenal (>98.5%) was observed for reactions over NaX zeolite at 150°C. Based on the FT‐IR and the catalytic results, the reaction paths are proposed as follows: self‐aldol condensation of n‐butyraldehyde, followed by dehydration produces 2‐ethyl‐2‐hexenal, which then reacts with n‐butyraldehyde and successively dehydrates to 2,4‐diethyl‐2,4‐octadienal and 1,3,5‐triethylbenzene. For the reaction over NaX, the calculated Arrhenius frequency factor and activation energy are 314 mol/g·h and 32.6 kJ/mol, respectively.     

5‐Ethyl‐2′‐deoxy‐4′‐thiouridine (R)‐S‐oxide monohydrate

The pyrimidine ring of the title compound, C₁₁H₁₆N₂O₅S·H₂O, is planar to within 0.026 (1) Å and makes an angle of 77.73 (8)° with the mean plane of the thiosugar ring. In terms of standard nucleoside nomenclature, this ring has a C1′‐exo,C2′‐endo conformation. The O5′—C5′—C4′—C3′ torsion angle is ?167.4 (2)° and the glycosidic S4′—C1′—N1—C2 torsion angle is ?101.8 (2)° (anti).     

Automated Parallel Temperature Optimization and Determination of Activation Energy for the Living Cationic Polymerization of 2‐Ethyl‐2‐oxazoline

Sixteen parallel polymerization reactions of 2‐ethyl‐2‐oxazoline have been performed at different temperatures in an automated synthesizer that allowed individual heating of each reactor. During the reactions samples were taken automatically, which were characterized by means of both online GPC and offline GC, in order to optimize the reaction temperature and to determine the activation energy of the polymerization.

     

2,6‐Diaryl‐4,4‐disubstituted 1,4‐dihydropyridines: Source for spiro heterocycles

Novel spiro heterocycles ( 5–12 ) were obtained by the cyclocondensation of 2,6‐diaryl‐4,4‐dimethoxycarbonyl‐/4‐cyano‐4‐ethoxycarbonyl‐1,4‐dihydropyridines( 3/4 ) with hydrazine hydrate, hydroxylamine hydrochloride, urea, and thiourea. All the compounds were characterized by IR, ¹H NMR, and ¹³C NMR spectral data.© 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:513–517, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10183     

Syntheses and Fluorescent Properties of 6‐Methoxy‐2‐oxoquinoline‐3,4‐dicarbonitriles and 6,7‐Dimethoxy‐2‐oxoquinoline‐3,4‐dicarbonitriles

4‐Chlorocarbostyrils 3 , 12 , 17 , 24 , 26 with methoxy substituents in 6, 7, or 6,7‐position react with potassium cyanide in a p‐toluenesulfinate mediated reaction either to the highly fluorescent and stable 2‐oxoquinoline‐3,4‐dicarbonitriles 6 , 27 , 29 , 30 or at slightly lower temperatures to 4‐monocarbonitriles 5 , 13 , 18 . 4‐Chlorocarbostyril 3 and lithium p‐toluenesulfinate gave pure 4‐toluenesulfonylquinolone 4 , which reacted with potassium cyanide either to monocarbonitrile 5 or dicarbonitrile 6 , depending on the reaction conditions. 4‐Trifluoromethylquinolones 9 and 19 were prepared for fluorescence comparison from the appropriate methoxyaniline and 4,4,4‐trifluoroacetoacetate. The fluorescence properties such as emission wavelengths and quantum yields of 6‐methoxyderivatives 4 , 5 , 6 , 9 , 13 were studied and compared with those of 7‐methoxy derivatives 18 , 19 and 6,7‐dimethoxyderivatives 27 , 28 , 29 , 30 . 6,7‐Dimethoxy derivatives show best results, showing long‐waved fluorescence spectra up to 520 nm and acceptable quantum yields up to 0.46 for 3,4‐dicyano derivative 27 excited at 440 nm in acetonitrile.