Electrophiles substituents

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Reactions that occur with the development of an electron deficiency, such as aromatic electrophilic substitutions, are best correlated by substituent constants based on a more appropriate defining reaction than the ionization of benzoic acids. Brown and Okamoto adopted the rates of solvolysis of substituted phenyldimeth-ylcarbinyl chlorides (r-cumyl chlorides) in 90% aqueous acetone at 25°C to define electrophilic substituent constants symbolized o-. Their procedure was to establish a conventional Hammett plot of log (.k/k°) against (t for 16 /wcra-substituted r-cumyl chlorides, because meta substituents cannot undergo significant direct resonance interaction with the reaction site. The resulting p value of —4.54 was then used in a modified Hammett equation. 

Monosubstituted benzene derivatives containing an electrophilic substituent. 

Disubstituted benzene derivatives containing electrophilic substituents C6H3... 

To sum up, the rate retardation attributed to steric effects of bulky alkyl groups can arise from substituent-electrophile, substituent-substituent and substituent-solvent interactions in the first ionization step of the reaction and also from substituent-nucleophile interactions in the product-forming step. It is therefore not surprising that the usual structure-reactivity correlations or even simpler log/log relationships cannot satisfactorily describe the kinetic effects of alkyl groups in the electrophilic bromination of alkenes. 

The influence of electronic factors on the regioselective cycloadditions of nitrones (551), and (583) to (585) to acrylates has been demonstrated by using dipolarophiles with electrophilic substituents at the P-carbon of the alkene in y-bromo a, 3-unsaturated esters and lactones (774) and in ethyl 2-hydroperfluoro-2-alkenoates (586) (775). The reactions of enoates (586) with nitrones are regio-specific and afford isoxazolidines with the CC>2Et and R/, groups in C-4 and C-5... 

The trilluoromethyl group behaves in a similar way , but it is now clear that deprotonation of sites ortho to such acidifying but non-coordinating and non-electrophilic substituents is best carried out with BuLi-KOBu-t superbases (see Section VI). A combination of BuLi metallation and superbase metallation of fluoroarenes has been used in the synthesis of components 163 and 164 for fluorinated liquid crystals (Scheme 82). ... 

The experimental data on the isomeric thienothiophenes 1—3 support these predictions. Electrophilic attack on thienothiophenes 1 and 2 results in 2-substituted compounds (see refs. 20, 21, 25, 28, 41, 218, 219). The second electrophilic substituent enters position 5. Tliieno-thiophene 3 is attacked at positions 6 and 4 to give, for example, 4- and 6-formylthieno[3,4-6]thiophenes on formylation. ... 

Figure 2.9. Electrophilic substitution of lithiated 1 IF (strategy S8). E stands for electrophilic substituent, (a) Generic reaction, (b) monosubstituted TTE with the electron withdrawing substituent COaEt and (c) monosubstituted TTE with the electron donor substituent CH3. E = Br, I, CO2H, COaEt, CH2OH, CH3, CONR2, CHNR2, CHO, etc.

The delocalization of the conduction electron onto the side chains would be expected if the pendant groups were replaced with more electrophilic substituents than the phenyl group. However, this is not the case. Figure 22 shows the absorption spectrum of poly-(methylnaphthylsilane) radical anion. The absorption spectrum is very similar to that of the naphthalene radical anion, which implies that the unpaired electron is localized on the pendant group. Increase of the electron affinity of pendant groups does not necessarily cause the delocalization. 

These results can be interpreted as the sum of the steric effects of the different substituents as depicted in 41. The effects of the two substituents R and phenyl more or less cancel each other out and what remains is the shielding effect of the alkoxycarbonyl group. Thus, a possible un-directing stereoelectronic effect by an electrophilic substituent which is perpendicular to the plane of the enolate (see COOCH3 in 41) has not been observed and instead substitution takes place from the less shielded side. 

Ideally, electrophilic substituents should never be incorporated into a substance, because such substances often cause serious toxic effects due to their ability to react... 

Introduction of thio substituents on to the pyrrole ring by electrophilic substitution has been demonstrated under several conditions for the parent molecule. Methanesulfenyl chloride gives 2-methylthiopyrrole (equation 212) (61JOC2615). Other electrophilic substitu-... 

The rate constants for OH radical addition to aromatic rings are calculated using the correlation between the OH radical addition rate constant and the sum of the electrophilic substituent constants Xo (Zetzsch, 1982 Atkinson, 1986). As Zetzsch (1982) discussed, Xo is calculated by assuming that steric hindrance can be neglected Xo+ is the sum of all of the... 

Electrophilic substituent factors for the -C6H5 XC1X and -OC6H5 XC1X groups, needed to calculate the OH radical addition rate constants for polychlorinated biphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs), and polychlorodibenzofurans (PCDFs), appear in Atkinson (1996), with discussion of an approach to calculating the rate constants for the PCDDs and PCDFs. The room temperature rate constants for the reactions of the OH radical with phenanthrene and anthracene, recently measured by Kwok et al. (1994,1997), are lower by factors of 2.5-8 than the previous recommendations and rate data (Biermann et al., 1985 Atkinson, 1989), casting doubt on the previously proposed correlation between the OH radical addition rate constant and ionization potential (Biermann et al., 1985). 

The electrophilic substituent constants for a -C(CH3)3 substituent group are o+0 p = -0.256 and o+m = -0.059, and for an -OH group o+G p = -0.92 (Brown and Okamoto, 1958). For 2,6-di-ferf-butylphenol, the most negative value of Xo+ = -1.038 is obtained for initial OH radical addition at the 4-position. Use of this value of Xo+ together with Equation (6) then leads to a calculated value of k(OH radical addition to the aromatic ring) = 4.8 x 10-11 cm3 molecule-1 s-1. The rate constant for H-atom abstraction from the two -C(CH3)3 groups is given by ... 

Enamines are highly valued intermediates in organic synthesis. Almost invariably they are prepared by reaction of a carbonyl compound with a secondary amine. In principle, another attractive route to enamines could be based on construction of the double bond by a Wittig- or Horner-Wittig reaction. The enamines J thus obtained could be easily converted into the corresponding homologous aldehydes, if desired fitted with an extra electrophilic substituent at the original carbonyl carbon atom. 

Zetzsch, C. (1982) Predicting the rate of OH-addition to aromatics using o+-electrophilic substituent constants for mono- and polysubstituted benzene. 15th Informal Conference on Photochemistry, June 27-July 1, 1982, Stanford, CA. 

With respect to a-substituents bearing p- or 7r-electrons which are directly attached to the C—Cl bond (Table 6, Z = CH2=CH to CH3CH20), these may delocalize their electrons through resonance or mesomeric effects with the positively charged carbon atom in the transition state. Because of this, they were not plotted in the Taft figure for a-substituted ethyl chlorides. Furthermore, the rates for these substituents also could not be correlated with the electrophilic substituent constants a+. The o+ parameters have been defined for substituents on the benzene ring which are far from the reaction site. Even though steric effects may interfere with the coplanarity and hence with delocalization, the effect of these substituents was believed to be polar in nature. 

Another important target for fluorescent sensors are highly toxic phosphates, found in various pesticides and chemical warfare agents, commonly known as nerve gases (Figure 16.16) [47]. There are two main families of these chemical warfare agents G and V family. Hie former contains electrophilic substituent at phosphorus atom... 

Atkinson77 and Kwok et al.95 have proposed and discussed methods for the estimation of OH radical reaction rate constants for the PCBs, PCDDs and PCDFs, based on the correlation of the rate constants for OH radical addition to aromatic rings, kOH, with the sum of the electrophilic substituent constants, Ecr+.77,100 Based on a review of the literature rate constants for OH radical addition to a wide range of aromatic compounds, Atkinson77 derived the correlation,... 

Similar a,a -annulations were achieved from reaction of oc,/ -unsaturated acid chlorides with cyclic ketone enamines which afforded bicyclo[3.3.1]nonane-2,9-diones41,60 65 or bicyclo[4.3.1]decanones66. In this reaction, 7V-acylation of the enamine 109 occurs as the first step giving 110, followed by a [3,3] sigmatropic rearrangement to a ketene intermediate (111). Ketene 111 subsequently cyclized via 112 to a bicyclic immonium salt (113) which after hydrolysis gave the corresponding dione 11463. If there is an axially oriented electrophilic substituent at C-4 of the enamine (for example, R = COPh) the enolate anion 115 may cyclize to an adamantane derivative 116 (equation 20). 

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