Electrophilic Process

The electrostatic potentials of the nucleic acid bases [adenine (9), guanine (10), cytosine (1), and thymine (11)] were first studied in the early 1970s. Each of these molecules has several likely sites for electrophilic attack V(r) 

Benzene (12) and fluorobenzene (13) were among the first nonhetero-cyclic aromatic molecules for which electrostatic potentials were computed. Benzene and other benzenoid hydrocarbons have extensive negative regions above and below their aromatic rings, which are attributed to the n electrons 

In the past electrophilic PEK and PEKEKK have been produced by Raychem and BASF, respectively. Currently the vast majority of the world s supply of PAEK is made by nucleophilic routes. However, recent commercial electrophilic products include PEKK and Gharda s Gatone PEEK technology - which is now owned by Solvay. PAEK produced by these processes do not have fluorine end groups. 

PEKK is produced from diphenylether and phthaloyl chlorides [19]. It is one of the few PAEK that would be difficult to make by nucleophilic routes because of the obvious complexity of the monomer required. The high melting point of linear, 100% para PEKK means that commercial PEKK is actually made from both terphthaloyl (T) and isophthaloyl chloride (I). Crystalline PEKK is typically 80 20 T/I whereas the amorphous grades used for thermoforming are 60 40 T/I. 

The isophthaloyl groups limit the size of crystals and hence reduce their melting point - together with crystallisation rate and overall crystallinity. If all three monomers are used together then the resulting backbone sequence is somewhat random. However it is possible to pre-react one of the acid chlorides and diphenylether and then use the other acid chloride in a second step to produce a more regular structure. PEKK chemistry is quite versatile. Polymics produces a series of PEKK resins with Tg in the range 167-172 °C, 310-360 

Dahl and V. Jansons in Polymers and Other Advanced Materials Emerging Technologies and Other Business Opportunities, Eds., P.N. Prasad, J.E. Mark and T.J. Fai, Plenum Press, New York, NY, USA, 1995, p.69. 

Shibata, R. Yosomiya, J. Wang, Y. Zheng, W. Zhang and Z. Wu, Macromolecules Rapid Communications, 1997,18, 

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Ring closures based upon electrophilic processes are uncommon. The cationic cyclization in Scheme 29a proceeds via transformation of the commencing oxime into a nitrilium ion (81CC568). Schemes 29b (82CB706) and 29c (82CB714) exemplify the application of intramolecular acylation. 

Similarly to the P-CHj group, secondary phosphine-boranes react smoothly in the presence of a base (BuLi, NaH) under mild conditions to afford other kinds of functionalized phosphine-boranes in good to high yields, without racemi-zation. Yet the success of deprotonation/treatment with an electrophile process to afford substituted phosphine derivatives without any loss in optical purity may depend on the deprotonation agents employed. Use of butyllithium usually provides the products with high enantiomeric excess in good to high yields [73]. 

The isothiocyanate (21) reacted with dienes to give the phosphoranes (22) more rapidly than did the corresponding fluoride and chloride, but less rapidly than did the bromide. The rates of reactions of (21) with various dienes were in the order isoprene > butadiene > piperylene > chloroprene. These data support the previous suggestion that attack on the diene is an electrophilic process. 

There have been a number of computational studies of the epoxidation reaction. These studies have generally found that the hydrogen-bonded peroxy acid is approximately perpendicular to the axis of the double bond, giving a spiro structure.75 Figure 12.8 shows TS structures and Ea values based on B3LYP/6-31G computations. The Ea trend is as expected for an electrophilic process OCH3 < CH3 CH = CH2 < H < CN. Similar trends were found in MP4/6-31G and QCISD/6-31G computations. 

The mechanistic conundrum presented by such a dichotomy between electron-transfer and electrophilic processes can only be rigorously resolved by the experimental proof of whether the cation radical (or the electrophilic adduct) is, or is not, the vital reactive intermediate. However, in a thermal (adiabatic) reaction between arene donors and the nitrosonium cation, such reactive intermediates cannot be formed in sufficient concentrations to be observed directly by conventional experimental methods since their rates of follow-up reactions must perforce always be faster than their rates of formation, except when they are formed in a reversible equilibrium like the... 

Thermal (electrophilic) and photochemical (charge-transfer) nitrations share in common the rapid, preequilibrium formation of the EDA complex [ArH, PyNO ]. Therefore let us consider how charge-transfer activation, as established by the kinetic behaviour of the reactive triad in Scheme 12, relates to a common mechanism for electrophilic nitration. Since the reactive intermediates pertinent to the thermal (electrophilic) process, unlike those in its photochemical counterpart, cannot be observed directly, we must rely initially on the unusual array of nonconventional nitration products (Hartshorn, 1974 Suzuki, 1977) and the unique isomeric distributions as follows. 

For many years, intramolecular reactions such as conformational changes, bond cleavage, bond formation, and valence isomerizations have been observed only when hydrocarbons were reduced with alkali metals in ethereal solvents. In most electrochemical experiments, these reactions were dominated by the electrophilic processes already described. However, progress in experimental techniques [8, 9, 27-29] has made these reactions accessible to electroanalytical investigations, providing new mechanistic insight. 

Indeed, it has recently been shown by Rozen [13] that tertiary carbon-hydrogen bonds can be selectively replaced by carbon-fluorine bonds when the reaction is carried out in a polar solvent at low temperature,but it was suggested that an electrophilic process involving a carbocationic transition state is occuring in these instances (see 3.1.1.1). 

Fluorination of toluene gives a mixture of ortho- and para- uorotoluene, as expected for an electrophilic process (B), but the partial rate factors (Table 4) [139] show a very high ortho para ratio indicating that radical processes (A) must also be involved. Furthermore, fluorination of the methyl group, giving benzyl fluoride, also occurs in increasing yield as the reaction temperature is raised. 

There have been only a few reports of direct hydroxylation362 by an electrophilic process (see, however, 2-26 and 4-5).363 In general, poor results are obtained, partly because the introduction of an OH group activates the ring to further attack. Quinone formation is common. However, alkyl-substituted benzenes such as mesitylene or durene can be hy-droxylated in good yield with trifluoroperacetic acid and boron trifluoride.364 In the case of mesitylene, the product is not subject to further attack ... 

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophilic process and only works well for electron-rich rings. 

The popular approach to tetrahydrofurans involves an electrophilic process and the commonly used electrophiles for the cyclization are acids, oxygen, halogen, mercury (see Section 3.11.2.2.9) and selenium. The ionic hydrogenation of furans with excess triethyl-silane in trifluoroacetic acid affords high yields, e.g. 2-methylfuran is reduced to 2-methyl-tetrahydrofuran and 2-ethylfuran to 2-ethyltetrahydrofuran (see Section 3.11.2.5). The synthesis of several dihydro and tetrahydrofurans containing natural products by chirality transfer from carbohydrates has been used successfully for total synthesis, e.g. (-)-nonactic acid. A reasonable yield of 2-alkyltetrahydrofuran was prepared from 4-alkylbut-l-en-4-ol by hydroboration followed by cyclization with p-toluenesulfonic acid. 

The addition of thiols to C—C multiple bonds may proceed via an electrophilic pathway involving ionic processes or a free radical chain pathway. The main emphasis in the literature has been on the free radical pathway, and little work exists on electrophilic processes.534-537 The normal mode of addition of the relatively weakly acidic thiols is by the electrophilic pathway in accordance with Markovnikov s rule (equation 299). However, it is established that even the smallest traces of peroxide impurities, oxygen or the presence of light will initiate the free radical mode of addition leading to anti-Markovnikov products. Fortunately, the electrophilic addition of thiols is catalyzed by protic acids, such as sulfuric acid538 and p-toluenesulfonic acid,539 and Lewis acids, such as aluminum chloride,540 boron trifluoride,536 titanium tetrachloride,540 tin(IV) chloride,536 540 zinc chloride536 and sulfur dioxide.541... 

The direct palladation procedure is limited to substitution with aryl and heterocyclic groups. The met-allation is an electrophilic process and therefore does not work well with deactivated aromatics. When possible, mixtures of isomers may be obtained. Since the palladium salts employed for the metallation are moderately strong oxidizing agents, the reaction cannot be used with easily oxidizable alkenes or aromatics. The only effective method for making this procedure catalytic is to reoxidize the palladium in situ with oxygen under pressure an inconvenient and potentially dangerous procedure. 

The features of the electronic structure of aryl-substituted pyrazolines influence their chemical properties. For example, in the case of 3-substituted 7V-phenyl-pyrazolines 100 reactions of formylation, acylation, nitration, sulfonation, azocoupling and other electrophilic processes involve the para position of the 7V-phenyl ring, with formation of compounds 101 [103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113]. On the other hand, some electrophilic reactions, including nitration, bromination, chlorination, formylation and azocoupling, for 3-unsubstituted pyrazolines 102 occur at position 3, yielding heterocycles 103 and in some cases as a mixture with 104 [108, 114, 115] (Scheme 2.26). This fact provides evidence for orbital control of these reactions. 

The Ziegler reaction is an important method for the synthesis of benzylic or allylic bromides. /V-bromosuccinimide (NBS) is the reagent used in this reaction, which proceeds via the mechanism outlined in Scheme 4.13. The role of NBS is to provide a low, steady-state concentration of Br2 in solution so as to avoid competing electrophilic processes. The choice of solvent is critical for this reaction. It is important to use a solvent in which NBS is insoluble in order to prevent Br abstraction from NBS, which results in formation of the succinimidyl radical. Previously, CC14 was the solvent of choice. However, this study found that the reaction could be conducted in sc C02 reaction yields and selectivities were identical to those found in CC14. 

The formation of significant amounts of polymeric material, with even a slight excess of TFE, along with formation of dimeric products in reaction with HFP bromine tris (fluorosulfate) is strong evidence in favor of the radical mechanism, which in this reaction may compete with the electrophilic process. 

An aggravating phenomenon associated with the (salen)Mn complexes is that the epoxidation of /ram-olefins proceeds typically with low ee s. Remarkably, however, the analogous chromium complexes (e.g., 14) catalyze such epoxidations with greater selectivity than for the corresponding d.v-olefins under the same conditions. Here the mechanism is presumed to involve an electrophilic process, which is supported by the fact that only electron-rich alkenes are effectively epoxidized. In the case of ram-l.l-methy 1-styrcnc (15), enantioselectivities of ca. 80% are observed [95TL7739],... 

The heteroaromatic substitution reflects the Friedel-Crafts reaction with the opposite reactivity and selectivity. The synthetic advantages and disadvantages are also opposite to those of concern for the selectivity of monosubstitution - whereas introduction of a carbonyl group deactivates the aromatic ring toward further substitution in the electrophilic process, in contrast it activates the heteroaromatic... 

Cabaleiro and Johnson (1967) report that the addition of chlorine to -methyl cinnamate in chloroform or acetic acid is syn-selective, SS 0-75, in chloroform and acetic acid acetoxychloro derivatives are produced as well. Again, Dewar and Fahey (1964) argue that the normal course of addition of hydrogen halides onto olefins is a polar electrophilic process involving classical carbonium ions as intermediates and leading mostly but not exclusively to cis-adducts. A syn-preference was found in the additions of deuterium bromide to acenaphthylene, indene, and cis- and fraws-phenylpropene. In the case of indene, phenylpropene and methyl cinnamate, which are styrene analogs, concerted syn addition is symmetry-allowed (see bottom of p. 273). 

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