Chemistry of Phosphorus Ylides. Part 22 [1]. Effect of Newly Synthesized Niclosamide Mannich Bases,Phosphopyranones, Phosphoranylidenes,and Oxaphosphinin on Some Metabolic Aspects of <Emphasis Type="Italic">Biomphalaria Alexandrina</Emphasis>

Summary. Niclosamide reacts with secondary amines and formaldehyde under the condition of Mannich reaction, to give new Mannich bases. The reaction of these niclosamide Mannich bases with active phosphacumulene ylides affords the corresponding phenyliminopyranone, pyranone, and pyranthione, respectively. When Wittig reaction was carried out on the pyranone, using p-nitrobenzaldehyde, a new arylidene and triphenylphosphine oxide were obtained. On the other hand, stabilized phosphonium ylides affect the transylidation of niclosamide Mannich bases to the corresponding phosphoranylidenes. When diphenylmethylenetriphenylphosphorane reacts with a niclosamide Mannich base, an oxaphosphinin was obtained. The molluscicidal potency of the newly synthesized derivatives against Biomphalaria alexandrina was studied, too.     

Chemistry of Phosphorus Ylides. Part 36 Reactions of 2-Hydroxyisoindole-, Isoindoline-, and Indane-1,3-Dione With Stable and Active Phosphonium Ylides

Abstract

The stabilized alkylidenephosphoranes namely, acetyl-, benzoyl-, methoxycarbonyl-, and ethoxycarbonyl-methylenetriphenylphosphorane react with 2-hydroxyisoindole-1,3-(2H)dione to give the corresponding isoindoline-ylidenes, along with triphenylphosphane oxide. On the other hand, the reaction of active phosphacumulenes, (N-phenyliminovinylidene)-, and (2-oxovinylidene)-triphenylphosphorane with hydroxyisoindole-, isoindoline-, and indane-1,3-dione afforded phosphanylidenecyclobutylidenes derivatives, together with triphenylphosphane oxide. Mechanisms accounting for the formation of the new products are discussed. The antimicrobial activities for the new compounds are also reported.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Chemistry of phosphorus ylides. Part 25 [1]. Interaction of hexaphenylcarbodiphosphorane with carbonyls, hydrazone, and Mannich bases. A synthesis of phosphoranylidenes, phosphobetaines, and oxaphosphinin

The reaction of the allylic hexaphenylcarbodiphosphorane with carbonyls afforded the corresponding phosphoranylidene derivatives. On the other hand, the stable phosphorbetaines were obtained when the bisphosphorane was allowed to react with the α-diketone and triketone. The azaphosphoranylidene was isolated from the reaction of the bisphosphorane with hydrazone. Moreover, the bisphosphorane reacted with niclosamide and quinoline Mannich bases with the formation of the oxaphosphinins. When the Wittig reaction was performed with the new phosphoranes, the corresponding exocyclic olefins were obtained. On the other hand, the oxaphosphinins were produced when the phosphoranes were treated under the condition of a Hoffmann degradation reaction. Correspondence: Medhat M. Said, Department of Organometallic and Organometalloide Chemistry, National Research Centre, El-Tahrir Street, Dokki, Cairo, Egypt.     

Polyfluorocycloalkenes. Part XVI [1]. Some addition reactions of 1-trifluoromethylnonafluorocyclohex-1-ene

Reactions with alcohols and base replaced the vinylic fluorine of 1-trifluoromethylnonafluorocyclohex-1-ene(I) by methoxy and ethoxy groups. Fluorination with cobaltic fluoride gave, from the former, a number of saturated polyfluoro-ethers. Oxidation of the alkoxy-cycloalkenes gave hexafluoroglutaric acid. Cycloalkene I gave which ammonia an imino-enamine, which was hydrolysed by dilute acid to a keto-enamine. I was defluorinated by heated iron to octafluorotoluene.     

Polyhalogenoheterocyclic compounds. Part 37 [1]. Perfluorotetrahydro-quinoline, -isoquinoline,and related compounds

The formation of perfluorotetrahydro-quinoline (3) and -isoquinoline (6) in the high temperature reaction between KF and heptachloro-quinoline and -isoquinoline is investigated and a mechanism is proposed. Compounds (3) and (6) represent unusually substituted pyridine derivatives and the orientation of substitution in reactions with nucleophiles is reported.     

Studies on the Chemistry of Thienoannelated O , N - and S , N -Containing Heterocycles, 28 [1]. Synthesis of Imidazo[1,5- d ]thieno[2,3- b ][1,4]thiazine Derivatives as GABA -Receptor Ligands

 GABA-receptor-ligands are still very interesting in drug-development. Usually benzodiazepines are used in the treatment but they have serious side-effects. Thus, a recently synthesized quioxaline derivative which showed reduced side-effects in an animal model was used as a model-substance. The cyclus was modified to optimize the pharmacological profile. Accordingly, a series of imidazo-thieno-thiazines was synthesized starting from 5-acetyl-2-chloro-3-nitrothiophene to yield 6-ethyl-2,3-dihydro-1H-thieno[2,3-b][1,4]thiazine-2-one. Reaction with potassium tert-butoxide and diethylchlorophosphate gave an intermediate, which resulted in the desired ring system after adding the corresponding isocyanides and potassium tert-butoxide.     

The Chemistry of N-substituted benzotriazoles. Part 22 [1]: Transformations of 1-(trimethylsilylmethyl)benzotriazole

1-(Trimethylsilylmethyl)benzotriazole is readily prepared from benzotriazole and chloromethyltrimethylsilane. It undergoes fluoride-catalyzed desilylation with carbonyl compounds and forms an anion that can be alkylated and acylated readily and undergoes Peterson olefination. 1-(Cyclohexylidenemethyl)benzotriazole is lithiated exclusively at the α carbon atom, and the anion can be cleanly alkylated. 1-(α-Acylalkyl)benzotriazoles are reduced to ketones with zinc and acid. The stability of 1-alkenylbenzotriazoles to hydrolysis has been studied.     

Free radical chemistry. Part 6[1]. Halogenation of polyfluoro-ethers and -borate esters

Chlorination and bromination of CH₃OCH₂CF₂CFHCF₃ gave contrasting results for the site of halogenation and a rationalisation based on the lateness of the transition-state is advanced. Direct fluorination supports the theory. Chlorination of fluorinated trialkylborates provides a new route for conversion of fluorinated alkenes to fluorinated acid chlorides.     

Polyhalogeno-allenes and -acetylenes. Part XII[1]. Further studies on routes to tetrafluoroallene and tetrafluoropropyne

Passage of the 2,3-dibromopropane CF₂BrCBr=CF₂ over hot catalytic grade silica causes it to isomerize to its 1,2-dibromo analogue CF₃CBr=CFBr. Flow pyrolysis of these dibromorpropenes over copper yields tetrafluoroallene (39%) and tetrafluoropropyne (11%). Isomerization (with catalytic grade silica, boron tribromide, or aluminium tri-bromide or -chloride) of the 3-bromopropene CF₂BrCH=CF₂ followed by KOH-dehydrohalogenation of the resulting ( )/( ) mixture of the 1-bromopropene CF₃CH=CFBr gives low yields if the propynes CF₃CCBr and CF₃CCF.     

Chemistry of phosphorus ylides. Part 24 [1]. A route for the synthesis of oxazine derivatives via the reaction of phosphacumulenes and phosphallene with di- and tri-ketone monoximes

The reaction of bifunctional di- and tri- ketone monoximes with (N-phenylimino-vinylidene)-, (oxovinylidene)-, and (thioxovinylidene)-triphenylphosphorane was performed. These phosphacumulene ylides react with the oxime OH group rather than the carbonyl group by addition to give the corresponding phosphoranylidenes. Some of these phosphoranylidenes cyclized according to an intramolecular Wittig reaction to give the oxazines along with triphenylphosphine oxide. On the other hand, the monoximes afforded only the phosphoranylidenes when they were allowed to react with the hexaphenylcarbodiphosphorane. The reaction course between the phosphacumulenes and phosphallene with monoximes was found to depend on the nature of the reactants.     

Nitroxide chemistry. Part XVII [1]. Reaction of bistrifluoromethyl nitroxide with some halogenoalkanes and related alkenes

The mono (bistrifluoromethylamino-oxy)alkanes (CF₃)₂NOCXYZ (X = Y = F, Z = Cl; X = H, Y = F or Cl, Z = CH₃; X = Y = F, Z = CH₃; X = H, Y = Cl or Br, Z = CF₃; X = Cl, Y = Br, Z = CF₃) have been synthesised by treatment of appropriate halogenoalkanes, CHXYZ, with bistrifluoromethyl nitroxide. The 1,2-bis(bistrifluoromethylamino-oxy)alkanes (CF₃)₂NOCH₂CXYON(CF₃)₂ were obtained as by-products in the reactions involving the ethanes CH₃CHXY (X = H, Y = F or Cl; X = Y = F); these products, like their analogues (CF₃)₂NOCHFCF₂ON(CF₃)₂ and (CF₃)₂NOCH₂CCl₂ON(CF₃)₂, were also prepared $\text{via}$ attack of bistrifluoromethyl nitroxide on the corresponding ethenes.     

Radical Ions in the Pentalene Series [1]. Part II. Dibenzo [b,f]pentalene and its 5, 10-dimethyl derivative

Proton hyperfine data have been determined for the radical anions and cations of dibenzo [b,f]pentalene (III) and its 5, 10-dimethyl derivative (IV) . The assignment of the coupling constants to pairs of equivalent protons follows from a simple MO model, the use of which enables one to reproduce satisfactorily the experimental values. The proton hyperfine data, a_Hμ

1 The meaning of ^aH_μis ^aH? C(x),H? C(y),whereas only x and y are given in the particular cases.

, for the radical anion III?. correlate fairly well with the π-charge populations ?_μ derived from ¹H-NMR. spectra for the carbon centres μ in the dianion III^2?. The analogous correlation is less good in the case of the radical cation III⊕. and the dication III^2⊕., presumably due to the rough approximations involved in the evaluation of the numbers ?_μ for the latter species. The coupling constants a_H5,10 for III?. and III⊕. are very close to the corresponding values a_H4,6 for the radical ions of 1,3,5-tri-t-butylpentalene (II), in accord with the prediction of the MO model. A similarity is also found between the proton hyperfine data for III?. and those for the radical anions of structurally related 1,4-diphenyl-1,3-butadiene (V). On the other hand, there are striking changes in the coupling constants of the analogous protons on passing from III?. to the radical anions of dibenzo [a,e] cyclooctene (VI) and [16] annulene (VII), as a consequence of raising the symmetry from C_2h to D_2h and D_4h, respectively.     

Chemistry of Phosphonium Ylides. Part 39: Facile Synthesis of Aziridine,Pyridine, Pyrolotriazole Chromenones and Azaphosphinin Chromenones as Antitumor Agents

The reaction of 4‐azido‐2‐oxo‐2H‐chromene‐3‐carbaldehyde with the active nucleophilic phosphacumulenes yielded the corresponding phosphanylidene‐aziridines and chromeno‐pyrolo‐triazoles. On the other hand, the reaction of the allylic phosphonium ylide, hexaphenylcarbodiphosphorane with the azido compound, was also undertaken. In this case, the phosphanylidene‐chromeno‐triazinone was obtained. Further assessment of these new compounds against (breast: MCF‐7 and liver: HPEG2) human solid tumor cell lines is necessary.     

Enantioselective Catalysis. Part 156 [1]. Ruthenium Procatalysts and 2-Pyridinealdehyde/( S)- NOBIN-Derived Cocatalysts in the Transfer Hydrogenation of Acetophenone with 2-Propanol

Several ruthenium procatalysts were tested in the transfer hydrogenation of acetophenone with 2-propanol using the chiral imine ligand (S)-2-(2-pyridinylmethyleneamino)-2-hydroxy-1,1-binaphthyl and the corresponding amine (S)-2-(2-pyridinylmethylamino)-2-hydroxy-1,1-binaphthyl. Ru(PPh ₃)₃Cl₂ was the best procatalyst. Its triphenylphosphane ligands were crucial for the catalytic activity and take part in the chirality transfer. Triphenylphosphane removing reagents such as copper(I) chloride, TEMPO, or TMAO improved the catalytic performance to enantioselectivities up to 99% ee. The findings led to a mechanistic proposal including dissociation equilibria of triphenylphosphane and chelate ring opening of the tridentate chiral binaphthyl ligand. New ligands with an additional chiral center were synthesized and tested as cocatalysts. The nature of catalytically active intermediates was examined by MS and NMR spectroscopy.     

Protoberberines from Reissert -Compounds VIII [1]. Oxazoloisoquinolines, New and Efficient Educts for the Synthesis of 8-Oxoprotoberberines

 Certain benzylated oxazoloisoquinolinones readily available from Reissert compounds provided an efficient access to 8-oxoprotoberberines in three steps. A series of these new precursors as well as several oxoprotoberberines were prepared and the scope and limitation of this procedure were investigated.     

Heterocyclic polyfluoro-compounds. Part 34 [1]. Two-way photochemical addition of hexafluoroacetone to 1,2-dichlorofluoroethylene,and the preparation of an oxete

The well-known Paterno-Büchi reaction, which involves oxetan formation by the photochemical addition of a carbonyl compound to a carbon-carbon double bond [2], was extended to the fluorocarbon field by Harris and Coffman [3], who described the photochemical addition of fluoroaldehydes, fluoroketones, and fluoroacyl fluorides to terminal perfluoroolefins and chlorotrifluoroethylene, e.g., Subsequently, Bissel and Fields reported that low yields of oxetans were obtained from acetaldehyde and the olefins, CF₂CF₂, CF₂CFCl, and CF₂CCl₂ [4]. The reaction of hexafluoroacetone with hexafluoropropene involves the triplet state of the ketone [5].