Electrophilic Substitution of Heteroaromatic Compounds with Six-Membered Rings

The limited amount of quantitative data available on the electrophilic substitution of heterocycles is surveyed. Initial objectives are first to determine the species undergoing substitution and then to find out the amount by which the heterocyclic atom or group activates or deactivates the ring by comparison with the corresponding benzenoid compound. When sufficient data are available it is hoped to correlate this by means of a Hammett-type treatment or by MO methods.     

Carbocations and Electrophilic Reactions

The general concept of carbocations encompasses all cations of carbon containing compounds which can be differentiated into two distinct classes: trivalent (“classical”) carbenium ions and pentacoordinated (“nonclassical”) carbonium ions. In this paper the preparation and structural study (by NMR, IR, Raman and ESCA spectroscopy) of stable carbenium ions and carbonium ions are discussed. As is well known, trivalent carbenium ions play an important role in electrophilic reactions of π- and n-donor systems. Similarly, pentacoordinated carbonium ions are the key to electrophilic reactions of σ-donor systems (single bonds). The ability of single bonds to act as σ-donor lies in their ability to form carbonium ions via triangular two electron, three-center bond formation. Consequently there seems to be no principle difference between the electrophilic reactions of π- and σ-bonds except that the former react more easily, even with weak electrophiles, whereas the latter necessitate more severe conditions. The role of carbocations in electrophilic reactions of π- and σ-donor systems is discussed.     

Studies on Electrophilic Substitution of Quasi-Aromatic Metal Ion Complexes

The electrophilic substitution reaction occurring to the chelate ring of the complexes could be regarded as an indication of quasi-aromaticity of the ring systems, no catalyst was used and only triethylamine was employed, implying that the aroylating agents with different p-substituents are polarized enough to be effective electrophiles to attack the methine carbon of the electron-rich substrate 1. This property is probably the clue to polarization of the ligand electrons by the nickel( Ⅱ ) ion and to the participation of the nickel( Ⅱ ) in the π-bond systems of the two coordinated conjugated rings. The linearity relationship between vd-d maxima, E1/2OX(1) and σp are obtained, respectively. The electronic environment of central metal ion as well as the aromaticity of the ring system are affected by the electronic properties of the p-substituents. A comparison of the electrochemical results with each other showed .that when the electronegativity of the substituent was higher, the oxidation(Ni2+/Ni3+)     

Displacement Reactions of Phosphorus(V) Compounds and Their Pentacoordinate Intermediates

Reactions of phosphorus(v) compounds involving the mutual interconversion of tetra- and pentacoordinate species are discussed in a critical review emphasizing stereochemical implications of the reaction mechanism. This discussion includes the formation and decomposition of the stable oxyphosphoranes, the Michaelis-Arbusov, Perkov, and Wittig reactions, interconversions of phosphines and their oxides, and the nucleophilic displacements on phosphonium compounds. Reactions of phosphate esters and related compounds receive particular attention. All chemical arguments are derived by considering the effect of factors determining the relative stabilities of phosphorane derivatives, their rates of formation, decomposition and rearrangement by bond deformation or rupture and recombination processes, considerations which are uniformly applied on the basis of concepts developed in a preceding communication^[2]. It is shown that a comprehensive mechanistic interpretation of the foregoing reactions requires substantial addition to available conceptual foundations such that, in many cases, present concepts and mechanisms must be revised.     

Electrophilic aromatic prenylation via cascade cyclization

To gain access to prenylated hexahydroxanthenes, tandem cascade cyclization–electrophilic aromatic substitution reactions have been studied on substrates bearing allylic and propargylic substituents. Both BF₃·OEt₂ and TMSOTf can be used to initiate this reaction sequence, resulting in different ratios of the C-2 and C-6 substitution products. Even though allylic transposition is observed in some cases, the results of a crossover experiment are consistent with an intramolecular reaction sequence. Taken together, these studies now allow preparation of either the C-2 or C-6 prenylated hexahydroxanthene products.     

Electrophilic fluorination: the aminopyridine dilemma

An unusually high yielding fluorination of aminopyralid (3) using F-TEDA (SELECTFLUOR™) in warm water, followed by kinetic resolution (via iterative esterification/saponification) of the crude fluorination product with dry HCl in methanol produced pure ring-fluorinated pyridine 2 in an overall yield of 31% for the two steps.     

Kinetic Studies on Ligand Substitution Reactions of Metallothioneins with DTPA and EDTA

Cd, Zn-thionelns were isolated from the rat liver by improved Winge method and purified further. The composition was determined. The mobilization of Cd ions from the Cd, Zn-metallothioneins was studied with spectrophotometric method. The results show that the reaction of DTP A or EDTA with Cd, Zn-thioneins occurs through three steps. The first step follows pseudo-first order reaction with association mechanism. The formation constants and the dissociation rate constants of the relevant intermediate ternary complexes and apparent rate constants, Kapp were determined. The properties and structure of Cd, Zn-thioneins and ligands with low molecular weights affect the values of Kapp.     

Ligand substitution reaction at a binuclear organoplatinum(II) complex

The ligand substitution reactions of the N-donor ligand in the binuclear dimethylplatinum(II) complex of formula cis,cis-[Me₂Pt(μ-NN)(μ-dppm)PtMe₂], 1, in which dppm = bis(diphenylphosphino)methane and NN = phthalazine, by different nucleophilic phosphorous-donors L, L = P(O-ⁱPr)₃ or PPh₃ and L₂ = dppm, to form the dinuclear complexes 2, cis,cis-[Me₂LPt(μ-dppm)PtLMe₂] and cis,cis-[Me₂Pt(μ-dppm)₂PtMe₂], respectively, are studied. Complex 1 has a MLCT band in the visible region which was used to easily follow the kinetics of its ligand substitution reactions. These reactions which involve diplatinum(II) complex 1 containing cis Pt-C bonds, proceeded by the normal associative mechanism. In associative reactions of the present work, as expected, the rate of the reactions was depended on the concentration and the nature of the entering group. The nucleophilicity of PPh₃ is stronger than P(O-ⁱPr)₃ on the basis of its stronger σ-donor ability and its lower solvation and is responsible for the observed 3-fold increase of its rate as compared to that of P(O-ⁱPr)₃. Also, the solvation energy involved is suggested to be responsible for the observation of higher rates in benzene than in acetone. The ΔH^‡/ΔS^‡ compensation plot gives a straight line which suggests the operation of the same mechanism for all entering nucleophiles.     

Nucleophilic Substitution at Phosphorus Centers (SN2@P)

We have studied the characteristics of archetypal model systems for bimolecular nucleophilic substitution at phosphorus (S_N2@P) and, for comparison, at carbon (S_N2@C) and silicon (S_N2@Si) centers. In our studies, we applied the generalized gradient approximation (GGA) of density functional theory (DFT) at the OLYP/TZ2P level. Our model systems cover nucleophilic substitution at carbon in X^?+CH₃Y (S_N2@C), at silicon in X^?+SiH₃Y (S_N2@Si), at tricoordinate phosphorus in X^?+PH₂Y (S_N2@P3), and at tetracoordinate phosphorus in X^?+POH₂Y (S_N2@P4). The main feature of going from S_N2@C to S_N2@P is the loss of the characteristic double‐well potential energy surface (PES) involving a transition state [X? CH₃? Y]^? and the occurrence of a single‐well PES with a stable transition complex, namely, [X? PH₂? Y]^? or [X? POH₂? Y]^?. The differences between S_N2@P3 and S_N2@P4 are relatively small. We explored both the symmetric and asymmetric (i.e. X, Y=Cl, OH) S_N2 reactions in our model systems, the competition between backside and frontside pathways, and the dependence of the reactions on the conformation of the reactants. Furthermore, we studied the effect, on the symmetric and asymmetric S_N2@P3 and S_N2@P4 reactions, of replacing hydrogen substituents at the phosphorus centers by chlorine and fluorine in the model systems X^?+PR₂Y and X^?+POR₂Y, with R=Cl, F. An interesting phenomenon is the occurrence of a triple‐well PES not only in the symmetric, but also in the asymmetric S_N2@P4 reactions of X^?+POCl₂? Y.     

N-Phenylselenosaccharin (NPSSac): a new electrophilic selenium-containing reagent

A new reagent N-phenylselenosaccharin (NPSSac) was simply prepared and used as a source of the electrophilic phenylselenyl group. This relatively stable new compound was able to react with a series of electron rich organic molecules like alkenes in the presence of external or internal nucleophiles, activated aromatic substrates, or enolizable carbonyl derivatives, under very mild experimental conditions.     

Substitution reactions involving cyclometalated platinum(II) complexes: Kinetic investigations

Substitution reaction of the labile SMe₂ ligand in the cyclometalated platinum(II) complexes of general formula [PtAr(ppy)(SMe₂)], 1, in which ppy = deprotonated 2-phenylpyridyl and Ar = p-MeC₆H₄ or p-MeOC₆H₄, by several N or P donor reagents were studied; the N-donors, N, are pyridine (Py) and substituted pyridines, N = 4-MePy, Py, Py-d₅, 2-MePy, 3-PhPy, 3,4-Me₂Py, 4-^tBuPy or 3-C(O)OMePy, and the P-donors, L, are phosphines or phosphites, L = P(OPh)₃, P(O-ⁱPr)₃, PPh₃, PPh₂Me and L₂ = Ph₂PCH₂PPh₂, bis(diphenylphosphino)methane (dppm). The products were identified by multinuclear NMR studies as [PtAr(ppy)(N)], 2, or [PtAr(ppy)(L)], 3, respectively. Complexes 1 have a MLCT band in the visible region which was used to easily follow the kinetics of the ligand substitution reactions by UV-vis spectroscopy. Although the complexes 1 contain two cis Pt-C bonds, the substitution reactions followed a normal associative mechanism. The rates of reactions were depended on the concentration and the nature of the entering group. The ΔH^‡/ΔS^‡ compensation plot gave a straight line suggesting the operation of the same mechanism for all entering nucleophiles.     

The reactivity of 1,1-diamino-2,2-dinitroethene (FOX-7)

The reactivity of 1,1-diamino-2,2-dinitroethene (DADNE) or FOX-7 was studied. Various reactions like cycloadditions, nitration, halogenation and acylation were performed in order to evaluate the reactivity of the C-C double bond and the amino moieties. Several products were isolated and two of them were characterised by X-ray analysis. Two reactive sites were identified. The chemical behaviour of DADNE is also discussed.     

Electrophilic carbon transfer in gold catalysis: synthesis of substituted chromones

Using easily accessible aromatic alkoxy-arylalkynones, we have investigated the gold-catalyzed intramolecular addition of ethers to alkynes, to give easy access to various substituted chromones. This reaction involves the transfer of the ether substituent via a carbodemetallation process. We also noticed a competing isomerization of several starting materials for which we propose a second gold catalyzed mechanism.     

Functionalization of 2,3,4,5-Tetrahydro-1,5-benzodiazepin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones by Electrophilic Aromatic Substitution

Summary. Highly substituted, novel, 8- and 9-nitro-2,3,4,5-tetrahydro-1,5-benzodiazepin-2(1H)-ones were obtained by direct nitration of the 7-bromo-5-trifluoroacetyl (or formyl)-substituted tetrahydrobenzodiazepinones. Alkaline and acidic hydrolysis of the novel mononitro derivatives was examined. Semiempirical AM1 calculations of aromatic substituents orientation in the nitration products are presented.     

Hexamethylenetetraamine-Bromine Catalyzed Rapid and Efficient Synthesis of Bis(indolyl)methanes

Summary. Highly rapid and convenient syntheses of bis(indolyl)methanes in excellent yields were carried out using the inexpensive and easily available catalyst, hexamethylenetetraamine-bromine (HMTAB). Mild reaction conditions, short reaction times, and excellent yields are important features of this method.     

Which Factors Determine the Reactivity and Regioselectivity of Free Radical Substitution and Addition Reactions?

The relative importance of bond strength, steric effects, and polarity in determining the rate and orientation of free radical subsitution and free radical addition reaction is considered. The factors which control substitution reaction (radical transfer reaction) are gathered together as five “rules”, and a similar five “rules” are proposed for addition rections. These “rules” are shown to be special cases of two “laws” which govern all free radical reactions.     

Electrophilic amination of enolates with oxaziridines: effects of oxaziridine structure and reaction conditions

A range of N-alkoxycarbonyl- and N-carboxamido-oxaziridines has been prepared to test the effects of oxaziridine structure on yields of enolate amination product. Side-products arising from reaction of aldehyde-derived oxaziridines with base were identified, while a ketone-derived oxaziridine afforded moderate yields of amination product with stabilised carbanions.