Two‐step Synthesis of New γ‐Lactones via Cyclization of 7‐Chloro‐2‐(methoxycarbonyl)‐4‐6‐dimethylocta‐(2E,4E,6E)‐trienoic acid

A new rapid synthesis of γ‐lactones, cis fused with a cyclopentenic ring by thermal cyclization of 7‐chloro‐2‐(methoxycarbonyl)‐4‐6‐dimethylocta‐7‐phenyl (or methyl) (2E,4E,6E)‐trienoic acids was reported. The key step implicates an intramolecular cyclization to a cyclopentenyl cation, according to an electrocyclic π_2s + π_2a conrotatory process, published in a recent paper (from the corresponding diacids). We have investigated the thermal behavior of the corresponding half‐esters since; if the cyclization obeys to the proposed mechanism, the diacids, half‐esters must also cyclize in a similar manner. Saponification of these led to γ‐dilactones via intermediary cyclopropanes. Mechanistic pathways were investigated.     

Photoinduced and thermal reactions of α‐cyano‐β‐bromomethylcinnamide with 1‐benzyl‐1,4‐dihydronicotinamide

The photoinduced reaction of a mixture of (Z)‐α‐cyano‐β‐bromomethylcinnamide (1) and (E)‐α‐cyano‐β‐bromomethylcinnamide (2) with 1‐benzyl‐1, 4‐dihydronicotinamide produces a mixture of the (E)‐ and (Z)‐ isomers of α‐cyano‐β‐methylcinnamide (3 and 4). Using spin‐trapping technique for monitoring reactive intermediate, it is shown that the reaction proceeds via electron transfer‐debromination‐H abstraction mechanism. The thermal reaction of the same substrate with BNAH at 60°C in the dark gives three products: the (E)‐ and (Z)‐isomers of α‐cyano‐β‐methylcinnamide and a dehydrodimeric product; 2, 7‐dicyano‐3, 6‐diphenylocta‐2, 4, 6‐trien‐1, 8‐dioic amide (7). Based on product analysis, scavenger experiment and cyclic voltammetry, an electron transfer‐debromination‐disproportionation mechanism is proposed.     

Novel π2s+π2a Electrocyclization of Triethylenic‐Malonic Acids Exemplified for a One‐Pot Synthesis of New γ‐Dilactones cis‐Fused with a Cyclopentene

A new, easy and rapid synthesis of γ‐dilactones is cis‐fused with a cyclopentenic ring via cyclization of 7‐chlorotriethylenic‐malonic acids. The key step implicates an intramolecular cyclization to a cyclopentenyl cation, according to an electrocyclic π_2s + π_2a conrotatory process. This cyclopentenyl cation led to unstable γ‐lactones intermediates that are rearrange to more stable isomers. δ‐lactones (6Z and 6E‐(3‐chlorobut‐2‐en‐2‐yl)‐5‐methyl‐3,6‐dihydro‐2H‐pyran‐2‐one) were obtained as secondary products. Mechanistic pathways were considered. The structures of the newly synthesized compounds were established by elemental and spectral data.     

Enantioselective Synthesis of (E)‐δ‐Boryl‐Substituted anti‐Homoallylic Alcohols Using Palladium and a Chiral Phosphoric Acid

(E )‐δ‐Boryl‐substituted anti ‐homoallylic alcohols are synthesized in a highly diastereo‐ and enantioselective manner from 1,1‐di(boryl)alk‐3‐enes and aldehydes. Mechanistically, the reaction consists of 1) palladium‐catalyzed double‐bond transposition of the 1,1‐di(boryl)alk‐3‐enes to 1,1‐di(boryl)alk‐2‐enes, 2) chiral phosphoric acid catalyzed allylation of aldehydes, and 3) palladium‐catalyzed geometrical isomerization from the Z to E isomer. As a result, the configurations of two chiral centers and one double bond are all controlled with high selectivity in a single reaction vessel.     

Geometry‐Retentive C‐Alkenylation of Lithiated α‐Aminonitriles: Quaternary α‐Alkenyl Amino Acids and Hydantoins

α‐Amino nitriles tethered to alkenes through a urea linkage undergo intramolecular C‐alkenylation on treatment with base by attack of the lithionitrile derivatives on the N′‐alkenyl group. A geometry‐retentive alkene shift affords stereospecifically the E or Z isomer of the 5‐alkenyl‐4‐iminohydantoin products from the corresponding starting E ‐ or Z ‐N ′‐alkenyl urea, each of which may be formed from the same N ‐allyl precursor by stereodivergent alkene isomerization. The reaction, formally a nucleophilic substitution at an sp² carbon atom, allows the direct regioselective incorporation of mono‐, di‐, tri‐, and tetrasubstituted olefins at the α‐carbon of amino acid derivatives. The initially formed 5‐alkenyl iminohydantoins may be hydrolyzed and oxidatively deprotected to yield hydantoins and unsaturated α‐quaternary amino acids.     

Diepoxy[18]annulene(10.0) : (Z,E,Z,E,Z)‐Diepoxy[18]annulen(10.0) – ein hochdynamisches Annulen

Diepoxy[18]annulenes(10.0): ( Z , E , Z , E , Z )‐Diepoxy[18]annulene(10.0) – a Highly Dynamic Annulene The McMurry reaction of (all‐E)‐5,5′‐([2,2′‐bifuran]‐5,5′‐diyl)bis[penta‐2,4‐dienal] ( 13 ) only occurs intramolecularly to give a mixture of the diepoxy[18]annulenes(10.0) 6 and 7 . Tetraepoxy[36]annulene(10.0.10.0) resulting from an intermolecular McMurry reaction is not formed. According to spectroscopic data, 6 is (Z,E,Z,E,Z)‐ and 7 (Z,E,E,Z,E)‐configured. The ¹H‐NMR data confirm that in 6 the (E)‐ethene‐1,2‐diyl bonds (C(11)=C(12) and C(15)=C(16)) rotate around the adjacent σ‐bonds. Beginning at −70°, this rotation freezes, and 6 is becoming a diatropic aromatic ring system. Beside [18]annulene itself, (Z,E,Z,E,Z)‐diepoxy[18]annulene(10.0) 6 is the only hitherto known [18]annulene derivative with dynamic properties.     

Thermal [2+3]‐Cycloadditions of trans‐1‐Methyl‐2,3‐diphenylaziridine with CS and CC Dipolarophiles: An Unexpected Course with Dimethyl Dicyanofumarate

The thermal reaction of trans‐1‐methyl‐2,3‐diphenylaziridine (trans‐ 1a ) with aromatic and cycloaliphatic thioketones 2 in boiling toluene yielded the corresponding cis‐2,4‐diphenyl‐1,3‐thiazolidines cis‐ 4 via conrotatory ring opening of trans‐ 1a and a concerted [2+3]‐cycloaddition of the intermediate (E,E)‐configured azomethine ylide 3a (Scheme 1). The analogous reaction of cis‐ 1a with dimethyl acetylenedicarboxylate ( 5 ) gave dimethyl trans‐2,5‐dihydro‐1‐methyl‐2,5‐diphenylpyrrole‐3,4‐dicarboxylate (trans‐ 6 ) in accord with orbital‐symmetry‐controlled reactions (Scheme 2). On the other hand, the reactions of cis‐ 1a and trans‐ 1a with dimethyl dicyanofumarate ( 7a ), as well as that of cis‐ 1a and dimethyl dicyanomaleate ( 7b ), led to mixtures of the same two stereoisomeric dimethyl 3,4‐dicyano‐1‐methyl‐2,5‐diphenylpyrrolidine‐3,4‐dicarboxylates 8a and 8b (Scheme 3). This result has to be explained via a stepwise reaction mechanism, in which the intermediate zwitterions 11a and 11b equilibrate (Scheme 6). In contrast, cis‐1,2,3‐triphenylaziridine (cis‐ 1b ) and 7a gave only one stereoisomeric pyrrolidine‐3,4‐dicarboxylate 10 , with the configuration expected on the basis of orbital‐symmetry control, i.e., via concerted reaction steps (Scheme 10). The configuration of 8a and 10 , as well as that of a derivative of 8b , were established by X‐ray crystallography.     

Oxidation of E,E‐bis(3‐bromo‐1‐chloro‐1‐propen‐2‐yl) chalcogenides and use of E,E‐bis(3‐bromo‐1‐chloro‐1‐propen‐2‐yl)sulfone in heterocyclization with primary amines

Oxidation of E,E‐bis(3‐bromo‐1‐chloro‐1‐propen‐2‐yl) sulfide and selenide with hydrogen peroxide in chloroform/acetic acid or acetic acid affords previously unknown E,E‐bis(3‐bromo‐1‐chloro‐1‐propen‐2‐yl) sulfoxide, selenoxide, and sulfone. The reaction of E,E‐bis(3‐bromo‐1‐chloro‐1‐propen‐2‐yl) sulfone with primary amines in ethanol in the presence of NaHCO₃ or Na₂CO₃ is found to lead not only to heterocyclization but also to alcoholysis of the chloromethylidene groups in the intermediate bis(chloromethylidene) derivatives of thiomorpholine‐1,1‐dioxides to afford N‐organyl‐2(E),6(E)‐bis(ethoxymethylidene) thiomorpholine‐1,1‐dioxides as final products.     

Crystal Structure and Properties of a New 2, 2'‐Ortho(metaxylene) E‐Bridged Stilbenophane

The synthesis and characterization of novel E and Z‐2, 2'‐ortho(metaxylene)‐bridged stilbenophane 2 by reductive McMurry condensation are described and the X‐ray structure determination of the E‐isomer is reported. The structure analysis of 2 ‐E shows weak hydrogen bonding. The complexation of Na⁺ ions in 2, 2'‐ortho(metaxylene)‐Z‐bridged stilbenophane using sodium chloride and measurements of conductivity were performed. The formation constant logK was determined to 1.45.     

Behavior of 3(2‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones and 3(3‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones as alkylating agents: A comparative study

3(2‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones and 3(3‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones were prepared as a mixture of (E) and (Z) stereoisomers by condensing pyridine‐2‐carboxaldehyde and pyridine‐3‐carboxaldehyde with 3‐aroylpropionic acids. The reaction of the furanones 6 and 7 with anhydrous aluminium chloride in benzene led to the formation of 4,4‐diaryl‐1‐(2‐pyridinyl)but‐1,3‐diene ( 8 ) and 4,4‐diaryl‐1‐(3‐pyridinyl)but‐1,3‐diene ( 9 ) as mixtures of geometrical (E,E‐ and E,Z‐) stereoisomers via an intermolecular alkylation mode. When the reaction was carried out in tetrachloroethane as a solvent, the reaction of 6 gave 5‐arylquinoline‐7‐carboxylic acid via intramolecular alkylation mode. This may be considered as a novel method for the synthesis of quinoline derivatives. J. Heterocyclic Chem., (2011).     

Utility of 4‐Benzylidene‐2‐phenyl‐5(4H)‐oxazolone in Synthesis of Triazine,Oxadiazole and Imidazole Derivatives of Anticipated Biological Activity

Treatment of oxazolone 1 with hydrazine hydrate at room temperature gave the (Z)‐configurated isomer hydrazide (Z)‐ 3 (high yield). However, refluxing 1 with hydrazine hydrate yielded the (E)‐configurated isomer hydrazide (E)‐ 2 (low yield).The hydrazide derivative (Z)‐ 3 has been utilized as synthon for the synthesis of 1,2,4‐triazinone, imidazolone, and oxadiazole derivatives through appropriate routes. The thiosemicarbazide and semicarbazide derivatives are synthesized by different routes. The structures of the new compounds were established on the basis of IR, ¹H‐NMR, mass spectral data, and elemental analysis.     

Synthesis and Evaluation of Ruthenium 2‐Alkyl‐6‐mercaptophenolate Catalysts for Olefin Metathesis

A series of ruthenium carbene catalysts containing 2‐sulfidophenolate bidentate ligand with an ortho‐substituent next to the oxygen atom were synthesized. The molecular structure of ruthenium carbene complex containing 2‐isopropyl‐6‐sulfidophenolate ligand was confirmed through single crystal X‐ray diffraction. An oxygen atom can be found in the opposite position of the N‐heterocyclic carbene (NHC) based on the steric hindrance and strong trans‐effects of the NHC ligand. The ruthenium carbene catalyst can catalyze ring‐opening metathesis polymerization (ROMP) reaction of norbornene with high activity and Z‐selectivity and cross metathesis (CM) reactions of terminal alkenes with (Z)‐but‐2‐ene‐1,4‐diol to give Z‐olefin products (Z/E ratios, 70:30–89:11) in low yields (13%–38%). When AlCl₃ was added into the CM reactions, yields (51%–88%) were considerably improved and process becomes highly selective for E‐olefin products (E/Z ratios, 79:21–96:4). Similar to other ruthenium carbene catalysts, these new complexes can tolerate different functional groups.     

Cycloaddition Reactions of 7‐Benzylidenecycloocta‐1,3,5‐triene with Ethenetetracarbonitrile and 4‐Phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione

An (E)/(Z) mixture (3 : 2) of 7‐benzylidenecycloocta‐1,3,5‐triene ( 5 ) is obtained when 1‐benzylcycloocta‐1,3,5,7‐tetraene ( 7 ), prepared by an improved procedure, is treated with t‐BuOK in THF. Alternatively, a ca. 9 : 1 mixture (E)/(Z)‐ 5 can be prepared in a Wittig reaction involving benzaldehyde and cycloocta‐2,4,6‐trien‐1‐ylidenetriphenylphoshorane ( 9 ). Treatment of (E)/(Z)‐ 5 88 : 12 with ethenetetracarbonitrile (TCNE) gave a complex mixture of products, from which seven mono‐adducts and two bis‐adducts were isolated (Sect. 2.2.1). Of the mono‐adducts, four are π4+π2 adducts: two ((E)‐ and (Z)‐isomers) are derived from valence tautomers of the two isomers of (E)/(Z)‐ 5 , while it is tentatively suggested that the other two (again (E)‐ and (Z)‐isomers) are formed from the intermediacy of a pentadienyl zwitterion (Sect. 2.3). The remaining three mono‐adducts, two of which are epimers, are π8+π2 adducts. It is suggested that they are derived from the intermediacy of homotropylium zwitterions (Sect. 2.3). For the two bis‐adducts, it is postulated that they are derived from an initial π2+π2 cycloaddition involving the homotropylium zwitterions followed by π4+π2 cycloaddition to the valence tautomer of each of the π2+π2 cycloadducts. With 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione ( 6 ), (E)/(Z)‐ 5 91 : 9 yielded two π4+π2 cycloadducts ((E)‐ and (Z)‐isomers) as well as two epimeric π8+π2 cycloadducts (Sect. 2.2.2). The intermediacy of pentadienyl (tentative suggestion) and homotropylium zwitterions accounts for the formation of the products (Sect. 2.3).     

Annulenoide Tetrathiafulvalene:, 5,16‐Bis(1,3‐benzodithiol‐2‐yliden)‐5,16‐dihydrotetraepoxy‐ und 5,16‐Bis(1,3‐benzodithiol‐2‐yliden)‐5,16‐dihydrotetraepithio[22]annulene(2.1.2.1)

Annulenoid Tetrathiafulvalenes: 5,16‐Bis(1,3‐benzodithiol‐2‐ylidene)‐5,16‐dihydrotetraepoxy‐ and 5,16‐Bis(1,3‐benzodithiol‐2‐ylidene)‐5,16‐dihydrotetraepithio[22]annulenes(2.1.2.1) The title compounds are among the first tetrathiafulvalenes with annulene spacers, here with tetraepoxy‐[22]annulene(2.1.2.1) (see 3a ), tetraepithio[22]annulene(2.1.2.1) (see 3b ), and diepithiodiepoxy[22]annulene(2.1.2.1) (see 23 ) units. The annulenoid tetrathiafulvalenes 3a and 3b are prepared by cyclizing McMurry coupling of the 5,5′‐(1,3‐benzodithiol‐2‐ylidenemethylene)bis[furan‐ or thiophene‐2‐carbaldehydes] ( 8a or 8b , resp.) or by Wittig reaction of (1,3‐benzodithiol‐2‐yl)tributylphosphonium tetrafluoroborate ( 13b ) with tetraepoxy[22]annulene(2.1.2.1)‐1,12‐dione 20 (formation of 3a ) or diepithiodiepoxy[22]annulene(2.1.2.1)‐1,12‐dione 22 (formation of 23 ). The annulenoide tetrathiafulvalene 3a is obtained as a mixture of the isomers (E,E)‐ and (Z,Z)‐ 3a . At 130°, (Z,Z)‐ 3a rearranges quantitatively into the (E,E)‐isomer. Isomer (E,E)‐ 3a is a dynamic molecule, where the (E)‐ethene‐1,2‐diyl bridges rotate around the adjacent σ‐bonds. The tetraepithioannulene derivative 3b as well as 23 only exist in the (Z,Z)‐configuration. The oxidation of (E,E/Z,Z)‐ 3a with Br₂ yields the annulene‐bridged tetrathiafulvalene dication (E,E)‐ 3a _Ox, while with 4,5‐dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile (DDQ) obviously only the radical cation 3a _Sem is formed, which belongs to the class of cyanine‐like violenes. The annulenoide tetrathiafulvalenes 3b and 23 , which exist only in the (Z,Z)‐configuration, obviously for steric reasons, cannot be oxidized by DDQ. Electrochemical studies are in agreement with these results.     

Synthesis and Photophysical Properties of Dimethoxybis(3,3,3‐trifluoropropen‐1‐yl)benzenes: Compact Chromophores Exhibiting Violet Fluorescence in the Solid State

Dimethoxybis(3,3,3‐trifluo‐ropropen‐1‐yl)benzenes were prepared through palladium‐catalyzed double cross‐coupling reactions of diiododimethoxybenzenes with CF₃C≡CZnCl, followed by reduction of CF₃C≡C groups with LiAlH₄ or H₂ in the presence of the Lindlar catalyst. The edges of the absorption spectra of 1,2‐(MeO)₂‐4,5‐(CF₃CHC=CH)₂benzenes 1 and 1,3‐(MeO)₂‐4,6‐(CF₃CH=CH)₂benzenes 2 in cyclohexane ranged from 348 to 360 nm, whereas the absorption spectra of 1,4‐(MeO)₂‐2,5‐[(E)‐CF₃CH=CH]₂ benzene ((E)‐ 3 ) ended at 406 nm. These findings indicate that the effective conjugation length of (E)‐ 3 was significantly larger than those of 1 and 2 . Consistently, 1 and 2 in cyclohexane exhibited fluorescence with emission maxima in the UV region, whereas (E)‐ 3 in cyclohexane emitted violet light with an emission maximum at 407 nm. All the fluorescence spectra of 1 – 3 in various solvents redshifted as the solvent polarity increased. The photoluminescence of 1 , E‐1 , Z‐1 , 2 , E‐2 , E‐2H , Z‐2 , E‐3 , E‐3H , Z‐3 in the solid states was also observed with emission maxima in the violet region. It is important to note that the quantum yields of (E)‐ 3 in a neat thin film and in a doped polymer film were 0.37 and 0.49, respectively. Density functional theory calculations suggested that the fluorine atoms contribute to a slight extension of both the HOMOs and the LUMOs, as well as narrowing of the HOMO–LUMO gaps when compared with the corresponding fluorine‐free analogues. In the case of (E)‐ 3 , it is suggested that the HOMO–LUMO transition includes charge transfer from the ethereal oxygen atoms to the C(sp²) CF₃ moieties.     

Synthesis and antiproliferative activity of (Z + E)‐1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐hydroxyphenyl)‐but‐1‐ene against breast cancer cells

This paper describes the synthesis of (Z + E)‐1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐hydroxyphenyl)‐but‐1‐ene. Two synthetic pathways were explored. The best pathway consisted of the alkylation of 1,2‐bis‐[4‐(tert‐butyl‐dimethylsilyloxy)phenyl]‐1‐(4‐hydroxyphenyl)but‐1‐ene with BrCH₂COOEt. The ester obtained was transformed into the Weinreb amide by reaction with HN(OMe)Me–HCl. The reaction of lithium manganese tricarbonylcyclopentadienide with the Weinreb amide produced 1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐tert‐butyldimethylsiloxyphenyl)‐but‐1‐ene. The deprotection of phenolic functions of the latter compound led to the formation of the final compound. The Z and E isomers could be separated but the isomerization of these isomers from one to another is an easy process. The Z + E compound 2 was tested against the hormone‐dependent MCF‐7 and hormone‐independent MDA‐MB‐231 breast cancer cell lines. The IC₅₀ values of compound 2 were 4.80 ± 2.00 µm and 4.79 ± 0.70 µm for MCF‐7 cells and MDA‐MB‐231 cells, respectively, which was three times better than the ferrocenyl analogue. Copyright © 2012 John Wiley & Sons, Ltd.     

Novel immonium type peptide coupling reagent: 5‐(1H‐benzotriazol‐1‐yloxy)‐3,4‐dihydro‐1‐methyl 2H‐pyrrolium hexachloroantimonate (BDMP® )

A novel immonium type coupling reagent, 5‐(1H‐benzotriazol‐1‐yloxy)‐3,4‐dihydro‐1‐methyl 2H‐pyrrolium hexachloroantimonate (BDMP) has been designed, synthesized and utilized to synthesize oligopeptides and biologically active peptide both in solution and solid phase with satisfactory yield, low racemization and fast reaction rate. The estimation of racemization and the influence of several reaction parameters were studied by HPLC method using the model reaction: Z‐Gly‐Phe‐OH + Val‐OMe·HCl·Z‐Gly‐D/L‐Phe‐Val‐OMe. It was shown that the reactivity of BDMP was much higher and the racemization was much lower than those of HOBt‐based ‘onium’ reagents, even though its analogues BOMI. To further verified me effectiveness of BDMP, Leu‐enkephalin was synthesized both in solution and solid phase using BDMP as coupling reagent. The proposed mechanism was also speculated.     

Synthesis and structural analysis of (E)‐2‐(2′‐nitrovinyl)indoles from the corresponding 2‐formylindole derivatives

Preparation of 2‐formylindoles was carried out from the appropriate methylindole by oxidation with selenium dioxide and by Vilsmeier formylation. The 2‐(2′‐nitrovinyl)indoles have been obtained by condensa tion of 2‐formylindoles with nitroalkanes in the presence of ammonium chloride in good yields. In this reac tion, only the (E)‐isomer of the 2‐(2′‐nitrovinyl)indoles was observed by ¹H nmr and NOE experiments. Evidence for an extended conjugation through the double bond and the nitro group can be evaluate by the deshielding effect on the olefinic protons. Moreover, the non‐Beer's law behaviour in the uv‐visible spectra suggest the existence of some sort of complex for these compounds.     

The ambident electrophilic behavior of 5‐nitro‐3‐X‐thiophenes in σ‐complexation processes

Kinetics of the reactions of 3,5‐dinitrothiophene 1 and 3‐cyano‐5‐nitrothiophene 2 with a series of parasubstituted phenoxide anions 3a–c have been investigated in aqueous solution at 20°C. Two unsubstituted electrophilic centers (C(2) and C(4)) of the two thiophenes have been identified. The Fukui functions correctly predict the C(2) and C(4) atoms as the most electrophilic centers of these electron‐deficient thiophenes 1 and 2 . Analysis of the experimental data in terms of Brønsted relationships reveals that the reaction mechanism likely involves a single‐electron transfer (SET) process. The excellent correlations upon plotting the rate constants versus the oxidation potentials E^o values is an additional evidence that reactions between thiophenes and phenoxide anions are proceeding through an initial electron transfer. It is of particular interest to note that the systems studied in this paper provide a rare example of a SET mechanism in σ‐complexation reactions. According to the free energy relationship log k = s(N + E) (Angew. Chem., Int. Ed. Engl., 1994, 33, 938–957), the electrophilicity parameters E of the C‐4 and C‐2 positions of the thiophenes have been determined and compared with the reactivities of other ambident electrophiles. On the other hand, the second‐order rate constants for the reactions of these thiophenes with the hydroxide ion has been measured in water and 50% water–50% acetonitrile and found to agree with those calculated theoretically using Mayr's equation from the E values determined in this work and from the previously published N and s parameters of OH⁻.