Stable intermediates

A number of reactions proceed via intermediates which would be recognised as stable species outside the reaction system. Typical of these are the aldehydes and peroxides formed in the combustion of hydrocarbons. If during the course of the 

Direct on-line analytical techniques may also be used. Typical of these studies is that made by Bradley et al. of stabilised cool flames in the oxidation of acetaldehyde and propionaldehyde. A fine qu2utz probe was attached to an A.E.I. MS 10 mass spectrometer, and could be moved through the cool flame. In this way composition profiles were obtained for reactant aldehyde and oxygen and also for carbon dioxide, carbon monoxide, formaldehyde, methane and methanol. 

Rarefaction waves have been used in shock tubes to produce rapid quenching of a reaction. Fig. 2 shows the usual experimental arrangement. The rupture of diaphragm 1 forms the initial shock and leads to the ordinary temperature rise in the reaction chamber. The temperature is increased to the required value by the return of the reflected shock wave from the end-wall. Diaphragm 2 is then ruptured mechanically at about the time that the rarefaction wave arrives this rupture produces a stronger expansion wave which rapidly cools the reacting gases. 

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The picture of the process of substitution by the nitronium ion emerging from the facts discussed above is that of a two-stage process, the first step in which is rate-determining and which leads to a relatively stable intermediate. In the second step, which is relatively fast, the proton is lost. The transition state leading to the relatively stable intermediate is so constructed that in it the carbon-hydrogen bond which is finally broken is but little changed from its original condition. 

The cases of pentamethylbenzene and anthracene reacting with nitronium tetrafluoroborate in sulpholan were mentioned above. Each compound forms a stable intermediate very rapidly, and the intermediate then decomposes slowly. It seems that here we have cases where the first stage of the two-step process is very rapid (reaction may even be occurring upon encounter), but the second stages are slow either because of steric factors or because of the feeble basicity of the solvent. The course of the subsequent slow decomposition of the intermediate from pentamethylbenzene is not yet fully understood, but it gives only a poor yield of pentamethylnitrobenzene. The intermediate from anthracene decomposes at a measurable speed to 9-nitroanthracene and the observations are compatible with a two-step mechanism in which k i k E and i[N02" ] > / i. There is a kinetic isotope effect (table 6.1), its value for the reaction in acetonitrile being near to the... 

Attack at the meta position leads to a more stable intermediate than attack at either the ortho or the para position and so meta substitution predominates Even the inter mediate corresponding to meta attack however is very unstable and is formed with dif ficulty The trifluoromethyl group is only one bond farther removed from the positive charge here than it is m the ortho and para intermediates and so still exerts a significant although somewhat diminished destabilizing inductive effect... 

Positively polarized atoms not adjacent most stable intermediate... 

Factor VIII, immunoglobulin, and albumin are all held as protein precipitates, the first as cryoprecipitate and the others as the Cohn fractions FI + II + III (or FII + III) and FIV + V (or FV), respectively (Table 7, Fig. 2). Similarly, Fractions FIVj + FIV can provide an intermediate product for the preparation of antithrombin III and a-1-proteinase inhibitor. This abiUty to reduce plasma to a number of compact, stable, intermediate products, together with the bacteriacidal properties of cold-ethanol, are the principal reasons these methods are stiU used industrially. 

Total hafnium available worldwide from nuclear zirconium production is estimated to be 130 metric tons annually. The annual usage, in all forms, is about 85 t. The balance is held in inventory in stable intermediate form such as oxide by the producers Teledyne Wah. Chang (Albany, Oregon) and Western Zirconium in the United States Ce2us in France Prinieprovsky Chemical Plant in Ukraine and Chepetsky Mechanical Plant in Russia (crystal bar). 

Electrophilic Addition. In the following example, an a-olefin reacts with a Lewis acid to form the most stable intermediate carbocation. This species, in turn, reacts with the conjugate base to produce the final product. Thus electrophilic addition follows Markovnikov s rule. 

Free-Radical Addition. A different outcome is expected in free-radical addition. The reaction of an a-olefin with a typical free radical affords the most stable intermediate free radical. This species, in turn, reacts further to form the final product, resulting in the anti-Markownikov mode of addition. 

At pH 4—6, the cure is slower than it is at pH 8 and higher, and much slower than at pH 1—3. Reactions at pH 4—6 resemble those on the more alkaline side, but with a substantial increase in side-products. This is partly the result of the low rates of the main reactions and partly the result of stable intermediates at this pH range. 

A continuous process has been described (14) which can produce either the amide or the nitrile by adjusting the reaction conditions. Boric acid has been used as a catalyst in the amidation of fatty acid (15). Other catalysts employed include alumina (16), titanium, and 2inc alkoxides (17). The difficulty of complete reaction during synthesis has been explained by the formation of RCOOH NH RCOO , a stable intermediate acid ammonium salt (18). 

Stable intermediates are those where concentration and lifespan are comparable to those of stable reactants and products. An example is the reaction between methane and oxygen in the gas phase at 700 K and 1 atmosphere. The overall reaction is ... 

In these reactions, the stable intermediates are CHjO, CO, and H2O2. ACTIVE CENTERS... 

Figure 3-8 is a plot of Ca, Cb, Cq, and Cd for a hypothetical system of the Scheme X type. An interesting feature is the time delay after the start of the reaction before the final product, D, appears in significant concentrations. This delay in product appearance is called an induction period or lagtime. In order to observe an induction period it is only necessary that the system include several relatively stable intermediates, so that the bulk of the material balance is temporarily stored in these prior forms. An experimental measurement of the induction period requires an arbitrary definition of its length. 

The underlined configuration is the more probable intermediate (more stable intermediate) in most systems. 

The first stable intermediate, B4H10, is then formed followed by BsHn. ... 

Electrophilic nitration of a substituted benzene may lead to ortho, meta or para products, depending on the substituent. According to the Hammond Postulate, the kinetic product will be that which follows from the most stable intermediate benzenium ion, i.e. 

Branching occurs especially when free radical initiators are used due to chain transfer reactions (see following section, Free Radical Polymerizations ). For a substituted olefin (such as vinyl chloride), the addition primarily produces the most stable intermediate (I). Intermediate (II) does not form to any appreciable extent ... 

The head-to-tail addition mode produces the most stable intermediate. For example, styrene polymerization mainly produces the head-to-tail intermediate ... 

Although there is no simple quantitative relationship between the stability of a carbocation intermediate and the rate of its formation, there is an intuitive relationship. It s generally true when comparing two similar reactions that the more stable intermediate forms faster than the less stable one. The situation is shown graphically in Figure 6.13, where the reaction energy profile in part (a) represents the typical situation rather than the profile in part (b). That is, the curves for two similar reactions don t cross one another. 

Figure 6.13 Energy diagrams for two similar competing reactions. In (a), the faster reaction yields the more stable intermediate. In (b), the slower reaction yields the more stable intermediate. The curves shown in (a) represent the typical situation.

Ethers with a tertiary, benzylic, or allylic group cleave by an S l or FI mechanism because these substrates can produce stable intermediate carbocations. These reactions are often fast and take place at moderate temperatures. fcrf-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. We ll see in Section 26.7 that the reaction is often used in the laboratory synthesis of peptides. 

Electrophilic substitutions normally occur at C2, the position next to the nitrogen, because reaction at this position leads to a more stable intermediate cation having three resonance forms, whereas reaction at C3 gives a less stable cation with only two resonance forms (Figure 24.6). 

The P450 reaction cycle (Scheme 10.4) starts with four stable intermediates that have been characterized by spectroscopic methods. The resting state of the enzyme is a six-coordinate, low-spin ferric state (complex I) with water (or hydroxide) coordinated trans to the cysteinate ligand. The spin state of the iron changes to high-spin upon substrate binding and results in a five-coordinate ferric ion (com-... 

The deprotonated flavin in the complex is readily attacked by molecular oxygen at C4a, giving 4a-hydroperoxide of the flavin-luciferase complex (intermediate A). This complex is an unusually stable intermediate, with a lifetime of tens of seconds at 20°C and hours at subzero temperatures, allowing its isolation and characterization (Hastings et al., 1973 Tu, 1979 Balny and Hastings, 1975 Vervoort et al., 1986 Kurfuerst et al., 1987 Lee et al., 1988). 

Vervoort, J., et al. (1986). Identification of the true carbon-13 nuclear magnetic resonance spectrum of the stable intermediate II in bacterial luciferase. Biochemistry 25 8062-8067. 

Schultz and Ganguly, in 1925, noted that the surface of pulverized TNT became colored on exposure to sunlight. They concluded that tautomeric quinoximes were formed thru an unstable intermediate. In acetone, a stable intermediate formed (Ref 1). Gray, Bonomo and Denner (Ref 8) could not repeat their results Leighton and Lucy studied o-nitrobenzalde-... 

Pyridine Perchlorate is almost as powerful as TNT (Pb block expansion 95% TNT, 87% PA), but is much more sensitive to impact (FI 40% PA), being comparable to PETN in this respect (Refs 4 5). Kuhn (Ref 7) states that it can be detonated on impact, but is normally considered a stable intermediate, suitable for purification of pyridine. Occasionally explns have occurred when the salt was disturbed (Ref 11), which have been variously attributed to the presence of ethyl perchlorate, AP or chlorates. A safer preparative modification is described (Ref 8). It explds on heating to above 335°, or at a lower temp if AP is present (Ref 10). According to Mellor (Ref 9), the salt can expld violently in contact with metals, while Zacherl (Ref 6) describes a lab expln which occurred during the distn of pyridine liberated from its perchlorate... 

The condition K2>KX has far-reaching consequences. Consider the diazonium ion during neutralization one hydroxide ion is taken up but, unlike the oxalate ion, it cannot rest after the first stage. The diazohydroxide formed must lose a proton immediately to yield the diazoate, a second hydroxide ion acting as proton acceptor. In other words, the diazohydroxide is not a stable intermediate and is not present in aqueous solution in appreciable concentration. It follows that the diazohydroxide... 

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