The redox behavior of gem-dihalo compounds: 9,9-dibromofluorene, 9,9-dichlorofluorene and dichlorodiphenylmethane

The redox behavior of several gem-dihalo compounds has been examined at platinum and vitreous carbon electrodes in dimethylformamide. The reduction of 9,9-dichlorofluorene is initially an overall two-electron process which involves cleavage of chloride ion and the formation of 9-chlorofluorenyl anion. The final products and their distribution are then dependent upon the relative rates of reduction of the parent compound, nucleophilic attack of 9-chlorofluorenyl anion on the parent compound, and proton availability. If reaction by substitution is permitted to predominate, 9,9′-dichlorobifluorenyl results. This species is electroactive at the applied potential and undergoes reductive dechlorination to give bifluorenylidene. In contrast, if either the rate of reduction of 9,9-dichlorofluorene of the rate of protonation of 9-chlorofluorenyl anion exceeds the rate of substitution, the predominant product becomes 9-chlorofluorene. Reduction of this species then gives a mixture of fluorene and bifluorenyl when electrolysis is effected in an aprotic medium and fluorene when electrolysis is performed in the presence of diethyl malonate, a weak proton donor. Dichlorodiphenylmethane and 9,9-dibromofluorene also undergo reductive dehalogenation to give monomeric and dimeric products by pathways analogous to those observed for dichlorofluorene. In the case of dibromofluorene, however, the product distribution is also potential dependent since the intermediate 9-bromofluorenyl radical may not be reduced at the applied potential. No evidence was obtained in these studies to support previous claims of carbenes and/or carbene radical anions in these reductions.     

Dimerization and protonation reactions of nitrosonitrobenzenes radical anions

The electrochemical behavior of 2-, 3-, and 4-nitrosonitrobenzenes (NNB) in DMF (with Bu₄NClO₄ suppoting salt) in the presence and in the absence of different proton donors (water, phenol, benzoic, acetic, chloroacetic, and sulfuric acids) is studied by the methods of cyclic voltammetry, chronoamperometry and also by electrolysis at the controlled potential. The electrochemical reduction of these compounds is shown to preferentially afford either monomeric (N-nitrophenylhydroxylamines) or dimeric (azoxy compounds) products, which is determined by the interplay between reactions of protonation and dimerization of NNB radical anions. The dimerization reactions proceed fast and reversibly to afford the corresponding dimeric dianions with the basicity much higher as compared with NNB radical anions as the result of which the monomeric products are formed in the presence of “strong” proton donors and the dimeric products form in the presence of “weak” proton donors. Like the effective rate of formation of dimeric products, the basicity of radical anions increases in the row 4- < 3- < 2-NNB.     

Voltammetric behavior of tertiary butyl bromide at mercury electrodes in dimethylformamide

Polarograms for t-butyl bromide in dimethylformamide containing tetramethylammonium perchlorate exhibit two waves which signal stepwise reduction of the starting material to the t-butyl radical and the t-butyl carbanion. Cyclic voltammograms obtained with a hanging mercury drop and at a scan rate of 50 mV s^?1 confirm that the alkyl bromide undergoes stepwise reduction; but the height of the second peak is abnormally small, indicating that t-butyl radicals engage in combination and disproportionation. At a faster scan rate (500 mV s^?1), the first wave nearly merges with the second wave. At all scan rates, two pairs of anodic-cathodic waves, associated with reversible bromide-assisted oxidation of mercury, appear at positive potentials. In addition, another set of anodic-cathodic waves is seen if the potential is scanned rapidly to a value at which the t-butyl carbanion is generated; this set of waves might be related to the formation of trimethylammonium methylide (produced when the tetramethylammonium cation donates a proton to the t-butyl carbanion). Although this latter set of waves is eliminated by addition of a proton donor (diethyl malonate) to the system, the anion of diethyl malonate is itself involved in the appearance of yet another pair of anodic-cathodic waves.     

Chemoselective Heck arylation of acrolein diethyl acetal catalyzed by an oxime-derived palladacycle

A dimeric 4-hydroxyacetophenone oxime-derived palladacycle has been used as a very efficient precatalyst for the chemoselective arylation of acrolein diethyl acetal to give either cinnamaldehyde derivatives or 3-arylpropanoate esters by proper choice of the reaction conditions. The synthesis of cinnamaldehyde derivatives can be performed by Heck reaction of acrolein diethyl acetal with iodo-, bromo- or chloroarenes in N,N-dimethylacetamide (DMA) using K₂CO₃ as base at 120 °C and tetra-n-butylammonium acetate (TBAA) and KCl as additives, followed by acid workup. In the case of 3-arylpropanoate esters the corresponding arylation of acrolein diethyl acetal with iodoarenes can be performed at 90 °C in aqueous DMA using (dicylohexyl)methylamine as base, whereas for bromoarenes the reaction has to be performed at 120 °C using tetra-n-butylammonium bromide (TBAB) as additive. Alternatively, this process can be performed under microwave irradiation. These couplings take place in good yields and with lower catalyst loading than with palladium(II) acetate as well as in shorter reaction times and with lower excess of acrolein diethyl acetal.     

Electrochemical studies of weak carbon and nitrogen acids: Fluorene and p-cyanoaniline in dimethylformamide

The electrochemical reduction of fluorene and p-cyanoaniline in DMF at a platinum electrode is initially a one-electron process which affords the corresponding readical anions. In the absence of an added proton donor, decomposition of the radical anions occurs by carbonhydrogen bond cleavage to give the conjugate bases of the starting materials; the anions subsequently slowly abstract a proton from the tetraalkylammonium cation of the supporting electrolyte to regenerate the original electroactive species. In the presence of dimethylmalonate, both radical anions rapidly electron transfer to the added proton donor. Neither self-protonation nor protonation by the added donor was observed for either radical anion. In addition to proton abstraction, 9-fluorenyl anion reacts with oxygen to give fluorene and hydroxide ion. Abstraction of a proton from fluorene by the latter species then effects a chain reaction in which 9-fluorenyl anion is the chain-carrying species. Reduction of bifluorenyl occurs with carbon-carbon bond cleavage to give 9-fluorenyl anion as the initial product. Subsequent proton transfer from bifluorenyl to 9-fluorenyl anion then yields the final products, 9-bifluorenyl anion and fluorene, in equimolar amounts.     

, B.E. Conway,J.O&#x27;M. Bockris (Eds.)Modern Aspects of Electrochemistry,No. 13, Plenum Press,New York and London (1979)

The electrochemical reductions of fluorenone hydrazone (Fl=NNH₂), fluorenone fluorenylhydrazone (FIHNHN=Fl), fluorenone azine (Fl=N?N=Fl) and benzophenone analogs have been studied at platinum cathodes in DMF?0.1 M(n-Bu)₄NClO₄ in the absence and presence of an added proton donor. Fl=NNH₂ undergoes reduction to give an unstable anion radical which decomposes by an unidentified pathway to afford Fl=NH. The latter species is electroactive at the applied potential and is reduced to the corresponding amine, FlHNH₂. Four electrons per molecule of Fl=NNH₂ are required for this process when electroreduction is effected in the presence of diethyl malonate (DEM), an electroinactive proton donor. Unreacted Fl=NNH₂ serves as the source of protons when electroreduction is conducted in the absence of DEM.Dual reaction channels are observed for the reduction of FlHNHN=Fl. If the corresponding anion radical is not protonated by either an added proton donor or unreacted starting material, decomposition occurs by carbon-nitrogen bond cleavage to give FlH₂ and Fl=NNH₂ as products. Reduction of the latter species occurs at the same potential as FlHNHN=Fl, ultimately affording FlHNH₂. The reaction channel involving carbon-nitrogen bond cleavage is replaced by a pathway involving nitrogen-nitrogen bond cleavage in the presence of an added proton donor. The final reduction product by this route is FlHNH₂.Fl=N?N=Fl is reduced stepwise and reversibly to its dianion in an aprotic medium. In the presence of a relatively strong proton donor such as hexafluoro-2-propanol, reduction gives FlHNHN=Fl. The redox behavior of the benzophenone analogs, Ph₂C=N?N=CPh₂, Ph₂CHNHN=CPh₂ and Ph₂C=NNH₂, parallels that of their counterparts in the fluorene series.     

Solid-Liquid Phase Transfer Catalytic Synthesis XII

The anion derived from diethyl malonate reacts with a series of halides readly under microwave irradiation, and the isolated yield of alkylated products varying from 64% to 86%.     

Regioselective hydroxylation of phenols by simultaneous photochemical generation of phenol cation-radical and hydroxyl radical

Substituted phenols having pendant isoquinoline N-oxide were synthesized and their photochemical and luminiscent properties studied. Photolysis in an acid medium was found to yield the related photohydroxylation products, in a regioselective process, in addition to the isoquinoline deoxygenated precursor. Photoinduced electron transfer from the donor phenols to the protonated form of the first excited singlet state (S₁) of the pendant isoquinoline N-oxide acting as acceptor leads to a red-shifted emissive charge transfer (CT) state that is in fact a radical/cation-radical pair. Homolysis of the N-OH bond restores the aromatic isoquinoline nucleus and produces a hydroxyl radical that can couple to the required ring carbon in the phenol cation-radical to give the photohydroxylation products in a regioselective process controlled by the spin density of the phenol cation-radical. These photohydroxylation processes efficiently compete with the reported tendency to deprotonation in phenol cation-radicals. The photohydroxylation process by itself, and its regioselectivity, exclude a proton-coupled electron transfer mechanism or a consecutive electron transfer/deprotonation reaction. By contrast, the phenol cation-radical exists long enough to undergo the hydroxyl radical coupling reaction that leads to the photohydroxylation products.     

On the flash photolysis of phenol derivatives in neutral aqueous solutions: effect of nitrous oxide and alcohols on transients

Flash photolysis of N₂O saturated neutral aqueous solution of tyrosine phenol and p-cresol leads to OH adduct formation. This species subsequently undergoes either unimolecular water elimination to form the phenoxyl radical or bimolecular radical-radical recombination. Alcohol addition to neutral aqueous solutions provokes the formation of hydrogen atom adduct.     

Natural product chemistry. Part 158. Reactions of ethyl 4-hydroxy-1-methyl-3-quinolin-2(1H)-onecarboxylate with 1,4-dibromo-2-methyl-2-butene

Ethyl 4-hydroxy-1-methyl-3-quinolin-2(1H)-onecarboxylate ( 1 ) which is obtained conveniently by the condensation of N-methylisatoic anhydride with diethyl malonate [4], was reacted with 1,4-dibromo-2-methyl-butene ( 2 ) to give the main products 3 and 4 and the dimeric derivatives 5 and 6 .     

5‐Unsubstituted Pyrido[3,2,1‐jk]carbazol‐6‐ones: Syntheses,Substitution, and Cyclization Reactions

The synthesis of the 5‐unsubstituted pyrido[3,2,1‐jk]carbazol‐6‐one 4 can be achieved by the reaction of carbazole ( 1 ) and malonate derivatives, either in a three‐step synthesis via 5‐acetyl‐pyridocarbazolone 3 or in a one‐step reaction from 1 and malonic acid/phosphoryl chloride. The 5‐acetyl derivative 5 can be transformed via a tosylate intermediate to 4‐azido‐pyridocarbazolone 11 , which cyclizes by thermal decomposition to the isoxazolo‐pyrido[3,2,1‐jk]carbazolone 12 . The thermolysis conditions were investigated by DSC. Nitration of pyridocarbazolone 4 and subsequent introduction of azide leads to azido derivative 23 , which cyclizes on thermolysis to furazan‐oxide derivative 24 . Again, the thermolysis conditions were investigated by DSC. 5‐Chloro‐5‐nitro‐pyrido[3,2,1‐jk]carbazole‐4,6‐dione, obtained from 4 by subsequent nitration and chlorination, forms by exchange of both 5‐substituents 5,5‐dihydroxy‐pyridocarbazoledione 17 , which acylates phenol to give 5‐hydroxy‐5‐(p‐hydroxyphenyl)‐pyridocarbazoledione 20 . Acid‐catalyzed cyclodehydration of 20 forms a highly fused benzofuro‐pyridocarbazole 21 . Another C–C coupling at position 5 starts from 4‐chloro‐5‐nitro‐pyridocarbazolone 22 and diethyl malonate 2a , which forms the diethyl (nitrocarbazolyl)malonate 25 . With dimethyl malonate 2c , the intermediate dimethyl (nitrocarbazolyl)malonate gives on thermolysis the (nitrocarbazolyl)acetate 27 by loss of one ester group.     

Reductive metalation of unsaturated compounds: the effect of allylic protons

Reductive metalation of alkali metals of hydrocarbons containing labile protons can be accompanied by proton transfer from the hydrocarbon to the derived radical anion and/or dianion. The extent of this reaction as a function of reaction conditions has been studied with trans-1,2-diphenylpropene (I). Three alkali metals, Li, Na and K, and two solvents, diethyl ether (DEE) and tetrahydrofuran (THF) were examined.No significant proton transfer was observed with the Li/DEE, Li/THF or Na/DEE system: the product (III) being the vicinal dianion of (I). In the case of Li/DEE, the limited solubility of the dianion prevented complete conversion of (I) to (III) except in dilute solutions.With Na/THF, substantial amounts of proton transfer occurred to form the substituted allylic anion (V) from (I). The extent of this reaction could be controlled by varying the temperature and was largely suppressed at 0°.Extensive proton transfer resulted with K/THF. However, in this case the allylic anion (V) so formed was further reduced with dimerization to the tetra-anion of 1,2,5,6-tetraphenylhexane, (IX).     

Diastereoselective and enantiospecific synthesis of gamma-substituted alpha,beta-unsaturated nitriles from O-protected allylic cyanohydrins

gamma-Functionalized alpha,beta-unsaturated nitriles are prepared diastereoselectively and enantiospecifically from enantioenriched cyanohydrin-O-phosphates and carbonates derived from alpha,beta-unsaturated aldehydes, either by palladium or iridium-catalyzed nucleophilic allylic substitution reactions with different nucleophiles. Appropriate reaction conditions for dibenzylamine, benzylamine, sodium azide, NaOAc, tetra-n-butylammonium acetate (TBAA), the corresponding sodium salts of phenol and N-hydroxysuccinimide and the carbonucleophile sodium dimethyl malonate are described. Different substituted O-protected cyanohydrins, such as carbonates and phosphates, derived from crotonaldehyde, (E)-hex-2-enal, oct-2-enal, 2-methylbut-2-enal, and cinnamaldehyde are used as allylic substrates. The substitution takes place with total retention of the configuration for the (E)-gamma-functionalized nitriles and with inversion of the configuration for the Z-isomers. In general, cyanohydrin-O-phosphates are the materials of choice to get the highest E-diastereoselectivity. Dibenzylamine is the best nucleophile for the synthesis of gamma-nitrogenated alpha,beta-unsaturated nitriles in the presence of either palladium or iridium catalysts when aliphatic compounds and cinnamaldehyde derivative are used (up to 98% dr). For the synthesis of gamma-oxygenated alpha,beta-unsaturated nitriles sodium or TBAA the reagents are selected to avoid epimerizations in up to 76% dr. Finally, the Tsuji-Trost reaction with sodium malonate works only under palladium catalysis in up to 70% dr.     

Palladium-catalyzed reaction of nucleophiles with diacetates of allylic 1,1-diols

The reactions of allylic 1,1-diol diacetates (I) with carbanions under the catalysis of Pd(PPh₃)₄ were studied. Sodium diethyl malonate reacted with I to form an abnormal product resulting from the attack of the diethyl malonate carbanion on the carbonyl carbon of the acetoxy group, while sodium diethyl acetylmalonate gave the normal reaction products with high regioselectivity. The mechanisms of these reactions are discussed.     

Analogs of 3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin (warfarin) prepared from substituted salicylic acids

Some derivatives of salicylic acid containing substituents meta to the carboxyl group were used to prepare analogs of the anticoagulant drug warfarin, 3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin, containing substituents in either the 6-or 8-position of the courmarin ring. When the substituent was the hydroxyl group, the resulting products are previously identified metabolites of warfarin. The substituted salicylic acid is first acetylated with acetic anhydride, then either converted to the acid chloride and condensed with diethyl malonate in the presence of sodium hydroxide or converted to the mixed anhydride with formic acid and condensed with ethoxymagnesium diethyl malonate to yield, in either case, the corresponding 3-carbethoxy-4-hydroxycoumarin substituted in the 6- or 8-position of the coumarin ring. These compounds readily condense with benzalacetone to form the corresponding substituted warfarin in the presence of 5 mole % tertiary amine catalyst. This method offers an improved route for the synthesis of 8-hydroxywarfarin.     

Reactions of Dicarbonyl(η5-Cyclopentadienyl)Iron(II)-Complexes of Two Cyclic Enol Ethers with Selected Nucleophiles

Dicarbonyl(η⁵-cyclopentadienyl)iron(II)-complexes of 2,3-dihydrofuran and 3,4-dihydro-2H-pyran rapidly react with carbanionic nucleophiles. The adducts of certain nucleophiles, such as the anion of diethyl malonate, readily isomerise to ring opened products. Ligand exchange reactions and polymerisation compete with the nucleophilic addition reactions of neutral nucleophiles such as enol ethers and indole.     

Reaction mechanism and chemical polarization of phosphorus nuclei when diethyl phenylazophosphonate is reacted with sodium ethylate

Conclusions The action of ethoxide anion on diethyl phenylazophosphonate leads to nucleophilic substitution of the phenyldiazenyl anion, the cleavage of nitrogen from it, and subsequent electron transfer from the formed phenyl anion to the starting phosphonate molecule. Singlet-triplet evolution in the singlet radical pair that is formed here and its recombination give diethyl diphenylhydrazophosphates, which exhibit the³¹P CPN effect.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2796–2799, December, 1976.     

Photoreaction between 2-benzoylthiophene and phenol or indole

Laser flash photolysis, density functional theory (DFT) calculations, and product studies have been performed to understand the mechanism of photoreduction of 2-benzoylthiophene (BT) in the presence of phenol or indole. Time-resolved experiments showed that BT ketyl (BTH) and phenoxy (PhO) or indolyl (In) radicals are generated with high rate constants and quantum yields close to 1. However, low conversions (specially in the case of indole) of the starting reagents are obtained upon prolonged lamp irradiation, indicating that recombination within the radical pairs must occur to a large extent, regenerating the starting materials. The solvent-dependence of the quenching rate constants, together with DFT theoretical studies, indicate fundamental differences between the mechanisms of the reaction of BT triplet with phenol and indole. Thus, data for phenol agree with the involvement of a hydrogen-bonded exciplex BT(.)HOPh, where concerted electron and proton transfer leads to the BTH(.)OPh radical pair. However, in the case of indole, electron transfer at the BT(.)HIn stage precedes proton transfer. Finally, C-C cross-coupling products have been isolated and characterized in the preparative irradiation of BT in the presence of phenol and indole. The structures of the products have been confirmed by alternative synthesis.     

Polybromoaromatic Compounds: IX. Reactions of Polybromobenzyl Bromides with Enolates Derived from Some Dicarbonyl Compounds

The reaction of polybromobenzyl bromides RC₆Br₄CH₂Br (R = Br, OCH₃) with diethyl malonate sodium salt in ethanol and dimethylformamide leads to formation of diethyl 2-(polybromobenzyl)malonates, whereas in aqueous ethanol ethyl polybromobenzyl malonates are formed. The same polybromobenzyl bromides react with an equimolar amount of ethyl acetoacetate sodium salt or acetylacetone sodium salt to give C-alkylation products; with excess sodium enolates ethyl 3-(polybromophenyl)propionates and 4-(polybromophenyl)-2-butanones are formed, respectively.     

Palladium Catalysed Reactions of Baylis-Hillman Products: Synthesis of Some Useful Intermediates

Acetates derived from Baylis-Hillman products were reacted with sodio dimethyl (or diethyl) malonate under Pd(0) catalysis to form E olefins as the major products. Likewise, the Heck reaction with these acetates as well as with the corresponding alcohols form a variety of useful intermediates which include trisubstituted olefinic compounds and α-benzyl β-keto esters.