Rearrangement reactions of aziridinylbenzaldoximes

Reactions of 2,2-dimethylaziridine with benzohydroximoyl chlorides [ArC(Cl)?NOH] give aziridinylbenzaldoximes 1 . It has been found that the aziridine ring in these compounds undergoes ring opening in hydrogen chloride-dioxane solution to give (Z)-N-hydroxy-N′-(2-chloro-2-methylpropyl)benzenecarboximidamides [ArC(NHCH₂CR¹R²Cl)?NOH, 4 ]. Treatment of 1 with hydrochloric acid followed by neutralization with aqueous sodium hydroxide gave 6,6-dimethyl-3-aryl-1,2,4-oxadiazines 2. Reaction of 4 with sodium hydride in dioxane gave 5-isopropyl-3-aryl-4,5-dihydro-1,2,4-oxadiazoles 5. Reaction of the 4,5-dihydro-1,2,4-oxadiazoles 5 with N-chlorosuccinimide gave the heteroaromatic 1,2,4-oxadiazoles 6 . It is suggested that reactions of 4 with sodium hydride in dioxane solution involve the conjugate base of 4 which undergoes a 1,2-hydride shift that is concerted with loss of chloride ion. In aqueous sodium hydroxide solution it is suggested that the conjugate base of 4 undergoes ionization of the chlorine atom followed by nucleophilic attack by the oximate anion.     

Gas-phase reaction of ozone with trans-2-hexenal,trans-2-hexenyl acetate,ethylvinyl ketone,and 6-methyl-5-hepten-2-one

The gas-phase reaction of ozone with the unsaturated oxygenates trans-2-hexenal, trans-2-hexenyl acetate, ethylvinyl ketone, and 6-methyl-5-hepten-2-one, which are components of biogenic emissions and/or close structural homologues thereof, has been investigated at atmospheric pressure and ambient temperature (286–291 K) and humidity (RH = 55 ± 10%). Reaction rate constants, in units of 10⁻¹⁸ cm³ molecule⁻¹ s⁻¹, are 1.28 ± 0.28 for trans-2-hexenal, 21.8 ± 2.8 for trans-2-hexenyl acetate, and 394 ± 40 for 6-methyl-5-hepten-2-one. Carbonyl product formation yields, measured with sufficient cyclohexane added to scavenge the hydroxyl radical, are 0.53 ± 0.06 for n-butanal and 0.56 ± 0.04 for glyoxal from trans-2-hexenal, 0.47 ± 0.02 for n-butanal and 0.58 ± 0.14 for 1-oxoethyl acetate from trans-2-hexenyl acetate, 0.55 ± 0.07 for formaldehyde and 0.44 ± 0.03 for 2-oxobutanal from ethylvinyl ketone, and 0.28 ± 0.02 for acetone from 6-methyl-5-hepten-2-one. Reaction mechanisms are outlined and the atmospheric persistence of the compounds studied is briefly discussed. © 1996 John Wiley & Sons, Inc.     

Reaktion von Phenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Basenkatalysierte Ring-Öffnung des Primäradduktes

Reaction of Phenyldiazomethane with 1,3-Thiazole-5(4H)-thiones: Base-Catalyzed Ring Opening of the Primary Adduct Reaction of 1,3-thiazole-5(4H)-thiones 1 and phenyldiazomethane ( 2a ) in toluene at room temperature yields the thiiranes trans- and cis-1,4-dithia-6-azaspiro[2.4]hept-5-enes (trans- and cis- 4 ; Scheme 2). With Ph₃P in THF at 70°, these thiiranes are transformed stereospecifically into (E)- and (Z)-5-benzylidene-4,5-dihydro-1,3-thiazoles 5 , respectively. In the presence of DBU, 1 and 2a react to give 1,3,4-thiadiazole derivatives 6 or 7 via base-catalyzed ring opening of the primary cycloadduct (Scheme 3). In the case of 2-(alkylthio)-substituted 1,3-thiazole-5(4H)-thiones 1c and 1d , this ring opening proceeds by elimination of the corresponding alkylthiolate, yielding isothiocyanate 7 . The structures of (Z)- 5c and 6b have been established by X-ray crystallography.     

Synthesis,separation, and resolution of cis- and trans-3-ethylproline

The synthesis, separation, and optical resolution of cis- and trans-3-ethylproline are described. Two different approaches were employed: (1) The Michael addition reaction of 2-pentenal with diethyl-N-carbobenzyloxyaminomalonate gave the intermediate 3-ethyl-5-hydroxy-N-benzyloxypyrrolidine. Hydrogenolysis of this intermediate followed by acid hydrolysis gave a mixture of cis- and trans-3-ethylproline. Separation of the isomers was accomplished by selective saponification of N-(p-toluenesulfonyl)-cis- and trans-3-ethylproline methyl esters using 0.25N methanolic sodium hydroxide. (2) The Michael condensation of diethyl acetamidomalonate with 2-pentenoic acid ethyl ether produced the intermediate 5,5-bis(ethoxycarbonyl)-4-ethylpyrrolidine. Partial saponification followed by decarboxylation afforded a mixture of cis- and trans-isomers of ethyl-3-ethylpyroglutamate. The diastereoisomers were separated using low temperature fractional crystallization. Reduction of these isomers and tosylation in situ afforded the corresponding N-(p-toluenesulfonyl)-cis- and trans-3-ethylprolinols. Chromic acid oxidation gave N-(p-toluenesulfonyl)-cis- and trans-3-ethylproline. Reaction of these tosylates with 30% hydrogen bromide in acetic acid gave cis- and trans-3-ethylproline. Both optically active isomers of D(+)-and L(-)-trans-3-ethylproline were successfully resolved using (+)-dibenzoyl-D -tartaric acid and (-)-dibenzoyl-L -tartaric acid as resolving agents. The absolute configurations of the optically active isomers were determined by circular dichroism spectroscopy.     

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-diones

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-dione (Ia) and its N-sub-stituted derivatives, such as 3-methyl (Ib), 3-ethyl (Ic), and 3-benzyl (Id) derivatives is described. Reaction of Ia with hydrazine hydrate gave 1-amino-6-methyluracil (II), while Id reacted with hydrazine hydrate to give 3-hydroxy-5-methylpyrazole (III). Reaction of Ia,b,d with ethyl acetoacetate in ethanol in the presence of sodium ethoxide afforded ethyl 3-acetyl-6-hydroxy-4-methyl-2(1H) pyridone-5-carboxylate derivatives (IVa,b,d). On the other hand, reaction of Ib,c,d with ethyl acetoacetate in tetrahydrofuran in the presence of sodium hydride did not give IV, but gave 3-acetyl-1-alkyl-5-(N-alkylcarbamoyl)-6-hydroxy4-methyl-2(1H) pyridone (VIb,c,d). Mechanisms for the formation of compounds IV and VI are discussed.     

Synthese und Strukturaufklärung von Pyrimidobenzimidazolen und kondensierten Derivaten, 3. Mitt. [1,2]. Decahydropyrimido[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazol-2-ole und Octahydropyrimido[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazole

Zusammenfassung.  Die Reaktion von racemischem trans-Hexahydrobenzimidazol-2-amin mit drei ausgew?hlten vinylogen Ketonen unter milden Bedingungen wurde untersucht. Nur im Fall der Umsetzung mit 4-Phenyl-3-buten-2-on konnten Cycloadditionsprodukte isoliert werden. Diese sind laut NMR-Analysen Gemische von zwei der acht m?glichen Diastereomeren, n?mlich von rac-2β-Methyl-4β-phenyl-trans-5aα- und trans-5aβ-decahydropyrimido[1,2-a]benzimidazol-2α-ol. Bei Umsetzungen des Amins mit Phenylbutenon bei erhoühten Temperatur sowie mit, 2-Methyl-1-phenyl-1-penten-3-on und 4^′-Chlorchalkon bildeten sich Gemische entsprechend substituierter rac-4α-Phenyl-trans-5aβ- und trans-5aα-octahydropyrimido[1,2-a]benzimidazole. Struktur und Stereochemie der Titelverbindungen und ihrer Hydrochloride wurden anhand NMR-spektroskopischer Untersuchungen aufgekl?rt. Die Ringschlu?reaktionen verlaufen in allen F?llen gleichgerichtet regio-, jedoch nicht diastereoselektiv. Versuche zur Beeinflussung der Regio- und/oder Diastereoselektivit?t der Cyclisierungsreaktion durch Variation der Reaktionsbedingungen hatten keinen Erfolg.

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Synthesis and Structure Elucidation of Pyrimidobenzimidazoles and Fused Derivatives III [1,2]. Decahydropyrimido[1,2- a ]benzimidazol-2-oles and Octahydropyrimido[1,2- a ]benzimidazoles

Summary.  The reaction of racemic trans-hexahydrobenzimidazol-2-amine with three vinylogous ketones under mild conditions was studied. Only in the case of 4-phenyl-3-buten-2-one cycloaddition products could be isolated. According to NMR spectroscopy they consist of mixtures of two of eight possible diastereomers: rac-2β-methyl-4β-phenyl-trans-5aα- and trans-5aβ-decahydropyrimido[1,2-a]benzimidazol-2α-ole. Reaction of the amine with the butenone at higher temperature and with, 2-methyl-1-phenyl-1-penten-3-one, and 4^′-chlorochalcone afforded mixtures of two diastereomers each, which turned out as rac-4α-phenyl-trans-5aβ- and trans-5aα-octahydropyrimido[1,2-a]benzimidazoles. Complete structural and stereochemical assignments of the title compounds and their hydrochlorides were established by NMR spectroscopic investigations. The results showed that all investigated cyclization reactions proceeded regioselectively with equal orientation of the components, but not diastereoselectively. Variation of the reaction conditions did influence neither regio- nor diastereoselectivity.

Received October 19, 2000. Accepted October 30, 2000     

Structure of 2(5)-alkyl-4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones,cyclocondensation products of benzil with aliphatic ketones

The reaction of benzil with methyl alkyl ketones gave three isomeric cyclopentenone derivatives, 2-substituted and cis- and trans-5-substituted 4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones. cis- and trans-2,5-Disubstituted 4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones were formed in analogous reaction of benzil with dialkyl ketones. The structure of the products was confirmed by ¹H NMR spectroscopy and molecularmechanics calculations.     

Synthesis, 1H- and 13C-NMR spectra,crystal structure and ring openings of 1-methyl-6,9-epoxy-9-aryl-5,6,9,10-tetrahydro-1H-imidazo [3,2-e] [2H-1,5] oxazocinium methanesulfonate

The methanesulfonic acid catalyzed reaction of 1-(4-chloro- and 2,4-dichlorophenyl)-2-(1-methyl-2-imida-zolyl)ethanones 1a and 1b with glycerol produced cis- and trans-{2-haloaryl-2-[(1-methyl-2-imidazolyl)methyl]-4-hydroxymethyl}-1,3-dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five-membered ketals, the reaction of 1a with glycerol afforded a small amount of trans-{2-(4-chlorophenyl)-2-[(1-methyl-2-imidazolyl)methyl]-5-hydroxy}-1,3-dioxane ( 3a , 7%). The reaction of methanesulfonyl chloride with cis-1 formed the corresponding methanesulfonates, cis- 4 , which rapidly cyclized to the title compounds 5 . Base-catalyzed ring opening of 5 furnished 1-methyl-5,6-dihydro-6-hydroxymethyl-8-(4-chloro- and 2,4-dichlorophenyl)-1H-imidazo[3,2-d][1,4]oxazepinium methanesulfonates 7 . Acid-catalyzed hydrolyses of 5 or 7 provided 1-methyl-2-[(4-chloro- and 2,4-dichloro)phenacyl]-3-[(2,3-dihydroxy)-1-propyl]imidazolium salts 12 . Structure proofs were based on extensive ¹H and ¹³C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X-ray crystallography.     

Synthesis and reactions of heterocyclic methyl 2-propenoates and 2,3-epoxypropanoates with nucleophiles

Reaction of 2-(3-,4-)pyridinecarboxaldehydes 5 with carbomethoxymethylene triphenylphosphorane afforded predominantly E-methyl-3-(pyridinyl)-2-propenoates 7. Oxidation of 7a-c with m-chloroperbenzoic acid gave methyl E-3-(1-oxidopyridinyl)-2-propenoates 8a-c in high yield. The Darzen's reaction of 5a-c with methyl bromoacetate yielded a mixture of stereoisomers cis- 9a-c and methyl trans-3-(pyridinyl)-2,3-epoxy-propanoates 10a-c in a ratio of 2:1. Oxidation of cis- 9a-c and trans- 10a-c afforded the corresponding cis- 11a-c and methyl trans-3-(1-oxidopyridinyl)-2,3-epoxypropanoates 12a-c in good yield. The reaction of 11a and 12a with cyclic amines as piperidine gave the respective threo- 13 and methyl erythro-2-(1-piperidino)-3-hydroxy-3-(1-oxido-2-pyridino)propanoate 14. The sodium borohydride reduction of the N-alkoxylcarbonyl pyridinium salts of 9c and 10c afforded the corresponding N-alkoxycarbonyl-1,2-dihydropyridyl derivatives 15 and 16. A number of selected compounds ( 7a-c , 9a-c , 10a , 10c , 11a-c and 12a , 12c ) were found to be inactive in the P388 Lymphocytic screen. Compounds 9-12 did not react with the model nucleophile ethanethiol in phosphate buffer at 37°.     

Syntheses and configurations of some heterocyclic amidoximes. X-Ray crystal structure of 3-phenyl-5,6-dihydro-2(1H)-pyrazinone-O-methyloxime

O-Methyl-α-ketophenylacetohydroximoyl chloride ( 1 ) was prepared by the reaction of O-methyl-α-methoxyphenylacetohydroximoyl chloride ( 5 ) with N-bromosuccinimide and concentrated hydrobromic acid. Reaction of 1 with ethylenediamine gave 3-phenyl-5,6-dihydro-2(1H)-pyrazinone-O-methyloxime ( 6 ). 3-Phenyl-5,6-cyclohexano-5,6-dihydro-2(1H)-pyrazininone-O-methyloxime ( 7 ) was prepared by reaction of 1 with trans-1,2-diaminocyclohexane. The X-ray structure of 6 has been determined. The crystals are orthorhombic, space group Pbca with a = 10.264(3), b = 18.262(4), c = 23.530(4)Å, V = 4411(2)ų, and Z = 16. The structure, which was refined to R = 0.038 using 1652 observed reflections, shows the amidoxime moiety to be the Z configuration. Reaction of benzohydroximoyl chloride with aziridine gave (Z)-aziridinylbenzaldoxime ( 16a ). Ultraviolet irradiation of a benzene solution of 16a gave a mixture of the Z and E isomers 16a and 16b . The E isomer 16b underwent thermal isomerization to 16a at 100°. Reaction of 16a with dimethyl sulfate in sodium hydroxide solution gave (Z)-O-methylaziridinylbenzaldoxime ( 17a ). Photoisomerization of a hexane solution of 17a gave a mixture of the Z and E isomers 17a and 17b which were separated by preparative glc. The isomers 17a and 17b are resistant to thermal Z = E isomerization. The mechanisms of thermal isomerization of benzamidoximes are discussed.     

BECKMANN-Umlagerung und Fragmentierung; V. Teil Mechanismus der 7-Zentren-Fragmentierung von 1-Oxo-5-oximino-9-methyl-trans-decalin. Fragmentierungsreaktionen, 22. Mitteilung

The reaction rates of heterolytic fragmentation of 5-(p, -toluenesulfonyloxyimino)-1-oxo-9-methyl-trans-decalin ( 1 ), induced by sodium hydroxide in 80% ethanol and by sodium ethoxide in 100% ethanol, has been determined. The reaction of the oxime tosylate 1 with sodium ethoxide is first order with respect to both reactants. A similar base-dependence is observed in the reaction of the oxime tosylate 1 with sodium hydroxide. These results are explained in terms of an addition-fragmentation mechanism. This involves reversible addition of NaOH or NaOC₂H₅ to the carbonyl group of the oxime tosylate 1 and concerted fragmentation of the addition compounds 5a and 5b , yielding 9-cyano-6-methyl-trans-non-5-enoic acid ( 4a ) and the corresponding ethyl ester 4b , respectively. These reaction appear to be the first cases of concerted and stereospecific 7-centre fragmentation.     

Acyclic Palladium(II)‐N‐heterocyclic Carbene Metallacrown Ether Complexes: Synthesis,Structure and Catalytic Activity

Novel acyclic Pd(II)‐N‐heterocyclic carbene (NHC) metallacrown ethers 5a , 5b have been synthesized. Reaction of the imidazolium salts bearing a long polyether chain with Ag₂O afforded Ag‐NHC complexes, which then reacted as carbene transfer agent with PdCl₂(MeCN)₂ to give the desired acyclic Pd(II)‐NHC metallacrown ether complexes 5a and 5b . The ¹H NMR and ¹³C NMR spectra show 5a and 5b exist as mixtures of cis and trans isomers in solution. The trans isomer of 5a was characterized by X‐ray diffraction, which clearly demonstrated two pseudo‐crown ether cavities in trans‐ 5a . Pd(II)‐NHC complexes 5a and 5b have been shown to be highly effective in the Suzuki‐Miyaura reactions of a variety of aryl bromides in neat water without the need of inert gas protection.     

The syntheses of 4b,5a-dihydrodibenz[3,4:5,6]anthra[1,2-b]oxirene and 4b,5a-dihydro-5H-dibenz[3,4:5,6]anthra[1,2-b]azirine

The syntheses of the K-oxide and K-imine derivatives of dibenz[a,j]anthracene ( 1 ) are described. The parent hydrocarbon 1 that was obtained as a side product in the Elbs pyrolysis of (2-methyl-1-naphthyl)-1′-naphthylmethanone ( 10 ) was oxidized to 3-(2-formylphenyl)-3-phenanthrenecarboxaldehyde ( 3 ). Treatment of the dialdehyde with tris(dimethylamino)phosphine gave 4b,5a-dihydrodibenz[3,4:5,6]anthra[1,2-b]oxirene ( 4 ). Reaction of the oxirane with sodium azide followed by triethyl phosphite cyclization of the mixture of trans azido-alcohols so formed, yielded mainly 4b,5a-dihydrodibenz[3,4:5,6]anthra[1,2-b]azirine ( 5 ).     

Syntheses of Unique Bicyclophostones and Unexpected Difference in the Reaction of Lawesson's Reagent vs. P2S5 with Cis-Bicyclophostone (1)

Abstract

The purpose of this study was to synthesize trans-l and determine the equilibriurr constant with cis-1. Oniy the synthesis¹ and x-ray structure² of the cis isomer have bcen reported. Four prior synthetic routes to make the vans isomer³ gave only cis product. For example, intrarmolecular ring closure of the cis or trains isomers of 4 (R= (CH₂)₃OH) with LiH or thermal closure of the cis or trans 4 (R= (CH₂)₂) gave only cis-1. Since both iosmers of 1,8-dioxabicyclo[4.4.0] decane are known and readily equilibrate (57% cis and 43% trans), the apparent inaccessibility of trans-1 attracted our attention. Thc preparation of trans-1 was achieved by treatment of cis-1 with Lawesson's reagent (LR) to provide cis-2. followed by oxidation with m-chloroperbenzoic acid/trifluoroacetic acid to give a 5:1 mixture of cis:trans 1, respectively. An unexpected formation of the sulfur analogue of 1 was observed on treatment of cis-1 with P₂S₅/pyridine at reflux temperatures to give a 1.6:1 mixture of cis:trans 3, respectively. Thermal quilibration of 1 at 204°C provided an equilibrium ratio of 99.5% cis and 0.5% of the trans isomer. However, equilibration of 3 at 250°C led to 82.2:17.8 ratio in favor of the cis isomr. These results are consistent with semiemperical MO calculations. The stereochemical outcome on treatment of 4 with LR was also investigated. X-ray structures for six compounds: trans-1, cis-2, cis and trans-3; cis-4 (R=Ph), and cis-5, (R = Ph) wen determined.     

Pulse-radiolysis studies on 4-pyridinemethanol and 4-pyridinecarboxaldehyde in aqueous solutions: dimer radical anion formation in the case of 4-pyridinecarboxaldehyde

Reactions of e _aq ^– , H atom and OH radicals with 4-pyridinemethanol (4-PM) and 4-pyridinecarboxaldehyde (4-PCA) have been studied at various pH values using the pulse radiolysis technique. Reaction of e _aq ^– with 4-PM and 4-PCA leads to the formation of pyridinyl and ketyl radicals of 4-PM and 4-PCA, respectively. Ketyl radicals formed from 4-PCA react with the parent molecule to give a dimeric radical species. At pH 7, the equilibrium constant for the dimer formation was determined to be 13 500 M^-1. At pH 13 also dimer radical formation was observed. Reaction of e _aq ^– with 4-PM was found to give highly reducing pyridinyl radicals. Reaction of OH radicals with 4-PM gives a mixture of species,viz., OH adducts and radicals formed by H-atom abstraction from the –CH₂OH moiety. Radicals formed by H-atom abstraction reaction from 4-PM were found to be reducing in nature. O^– radicals were found to react with 4-PM exclusively by H-abstraction pathway.     

Copolymeric cyclodextrin polysiloxane stationary phases prepared from 6A,6C- and 6A,6D-dialkenyl-substituted β-cyclodextrin

The syntheses of four new β-cyclodextrin-hexasiloxane copolymers from heptakis(2,3-di-O-methyl)-β-cyclodextrin (2) by multi-step processes are described. 6^A,6^C-Di-O-[p,p'-methylenebis(benzenesulfonyl)]hetakis(2,3-di-O-methyl)β-cyclodextrin (3) , which was prepared by the reaction of 2 with p,p'-methylenebis-(benzenesulfonyl chloride), is a key intermediate for the preparation of permethylated 6^A,6^C-bisalkenyl-β-cyclodextrins 5, 6 , and 9. Permethylated 6^A,6^C-bissulfonate ester 4 , which was obtained from 3 by a methylation reaction under mild conditions, was reacted with sodium allyloxide or sodium ω-undecenyloxide to produce permethylated 6^A,6^C-bisallyl- (or bis-ω-undecenyl)-β-cyclodextrin 5 or 6 or was hydrolyzed with 2% sodium amalgam in methanol to yield diol 7. Compound 7 was oxidized with periodinane, followed by Wittig's reaction with methyltriphenylphosphonium iodide to give permethylated 6^A,6^C-dideoxy-6^A,6^C-dimethylene-β-cyclodextrin (9). Treatment of 2 with p,p'-methylenebis(benzenesulfonyl chloride) or p,p'-biphenyldisulfonyl chloride gave bissulfonate esters 10 or 11 , respectively. Both of them were treated with sodium p-allyloxy-phenoxide in DMF, followed by methylation, to form permethylated 6^A,6^D-di-O-(p-allyloxyphenyl)-β-cyclo-dextrin (16). Bisalkenes 5, 6, 9 and 16 were copolymerized with α,ω-dioctyldecamethylhexasiloxane by a hydrosilylation process to give the cyclodextrin-containing copolymers 17–20.     

Dediazoniation of Arenediazonium Ions in Homogeneous Solutions. Part XVI. Kinetics and mechanisms of dediazoniation of p-chlorobenzenediazonium tetrafluoroborate in weakly alkaline aqueous solutions under nitrogen gas

The kinetics of reactions of p-chlorobenzenediazonium ions in aqueous buffer solutions (pH 9.0–10.6) under N₂ (< 5 ppb of O₂) have been measured between 20 and 50°C. The formation of trans-diazotate is first-order with respect to the concentration of hydroxyl ions and to the equilibrium concentration of diazonium ions, if the diazonium ion?cis-diazotate equilibrium is considered as a fast prior equilibrium. This indicates that the p-chlorobenzenediazonium ion, in contrast to all previous investigations with the p-nitrobenzenediazonium ion and benzenediazonium ions carrying similar substituents with a ?M effect, rearranges from the cis- to the trans-configuration as diazohydroxide and not as diazotate. The formation of trans-diazotate is catalyzed by carbonate and inhibited by hydrogen carbonate ions; mechanisms of these catalyses are discussed, and the solvent isotope effect K_H2O/K_D2O measured by an ¹H-NMR. technique reported. The kinetics of the dediazoniations can be analyzed as a mixture of two reactions, a relatively fast first reaction, reaction A, which is responsible for about 5% of the total reaction, and a second reaction F. Both are first-order with respect to diazonium ion; reaction A is also first-order in hydroxyl ions. There are some indications that reaction A corresponds to the hydrolysis of the diazonium ion to give eventually amine and nitrite ions. Reaction F shows a complex dependence on hydroxyl ions; it is related to the homolytic dediazoniation.     

Design and synthesis of novel quinoline derivatives bearing oxadiazole,isoxazoline, triazolothiadiazole,triazolothiadiazine, and piperazine moieties

A new series of 2,3-disubstituted quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehyde. In the reaction sequence, acetanilide was cyclized to give 2-chloroquinoline-3-carbaldehyde 1 , which was transformed to 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 by reaction with 4-phenylpiperazine in DMF-containing anhydrous K₂CO₃; then, compound 2 was oxidized by iodine in methanol, and methyl 2-(4-phenylpiperazin-1-yl)quinoline-3-carboxylate 3 was synthesized. The key intermediate 4 , 4-amino-5-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-4H-1,2,4-triazole-3-thiol, was prepared using the ester 3 by a series of step. Reaction of 5 with various aromatic carboxylic acids or phenacyl bromides yielded 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a-c and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 6a-c , respectively. Moreover, compound 2 condensed with o-phenylenediamine to give 2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-1H-benzimidazole 7 . Interaction of 7 and 2-chloromethyl-5-aryl-1,3,4-oxadiazoles in the presence of K₂CO₃ led to the title compounds 8a-c . Furthermore, 4,5-dihydroisoxazoline derivatives 9a-c were obtained by the reaction of readily accessible starting materials including 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 , 1-phenyl-2-(triphenylphosphoranylidene)ethanone and hydroximoyl chlorides under mild conditions in the presence of Et₃N. The hydrazone intermediates 10a-c were obtained by the condensation of 2 with aroylhydrazides in ethanol, then, refluxing in acetic anhydride yielded 3-acetyl-5-aryl-2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-2,3-dihydro-1,3,4-oxadiazoles 11a-c . Structures of these compounds were established by their elemental analysis, IR, ¹H NMR, and mass spectral data.     

Furopyridines. XVII . Cyanation,chlorination and nitration of furo[3,2-b]pyridine N-oxide

The N-oxide 2 of furo[3,2-b]pyridine ( 1 ) was cyanated by the Reissert-Henze reaction with potassium cyanide and benzoyl chloride to give 5-cyano derivative 3 , which was converted to the carboxamide 4 , carboxylic acid 5 , ethyl ester 6 and ethyl imidate 8 . Chlorination of 2 with phosphorus oxychloride yielded 2-9a , 3- 9b , 5- 9c and 7-chloro derivative 9d . Reaction of 9d with sodium methoxide, pyrrolidine, N,N-dimethylformamide and ethyl cyanoacetate afforded 7-methoxy- 10 , 7-(1-pyrrolidyl)- 11 and 7-dimethylaminofuro[3,2-b]pyridine ( 14 ) and 7-(1-cyano-1-ethoxy-carbonyl)methylene-4,7-dihydrofuro[3,2-b]pyridine ( 12 ). Nitration of 2 with a mixture of fuming nitric acid and sulfuric acid gave 2-nitrofuro[3,2-b]pyridine N-oxide ( 15 ).     

The preparation of 2H-1,2,3-benzothiadiazine-1,1-dioxides, 11H-11a-dihydrobenzimidazo[1,2-b] [1,2] benzisothiazole-5,5-dioxides, 6H-dibenzo[c,g] [1,2,5] thiadiazocine-5,5-dioxides and 5H-Dibenzo[c,g] [1,2,6] thiadiazocine-6,6-dioxides

o-Benzoylbenzenesulfonyl chlorides (I) were prepared conveniently from aminobenzophenones by diazotization followed by reaction with sulphur dioxide in the presence of Cu⁺, according to the general method of Meerwein. Reaction of the sulfonyl chlorides with hydrazine led to 4-phenyl-2H-1,2,3-benzothiadiazine-1,1-dioxides (II). The latter compounds could be methylated and acetylated readily in the 2-position. The 2-methyl derivative (III) could be prepared also by reaction of the sulfonyl chloride (Ia) with methylhydrazine. Catalytic hydrogenation of 6-chloro-4-phenyl-2H-1,2,3-benzothiadiazine-1,1-dioxide (IIa) gave the 3,4-dihydro derivative (V). Reaction of the sulfonyl chlorides (I) with o-phenylenediamine followed by cyclodehydration led to 11H-11,11a-dihydrobenzimidazo[1,2-b] [1,2]benzisothiazole-5,5-dioxides (VII). One of the latter compounds (VIIa) in sodium hydroxide solution in the presence of methyl iodide or benzyl chloride was transformed into 6-methyl- and 6-benzyl-5H-dibenzo[c,g] [1,2,6]thiadiazocine-5,5-dioxides (VIII), respectively. 5H-Dibenzo[c,g] [1,2,6] thiadiazocine-6,6-dioxides (XIV) were prepared also by cyclodehydration of 2-amino-2′-benzoylbenzenesulfonanilides (XIII).