The Reaction Sequence

Derive the steady-state rate law corresponding to the reaction sequence of Eqs. XVIII-40-XVIII-44, that is, without making the assumption that any one step is much slower than the others. See Ref 234. 

We have already explored this route (frame 184) and found that the reaction sequence actually is ... 

N. Trachtenberg, 1969). products or even as the major 1958). The reaction sequence with SeOj, except that the C—< the dehydrogenation of C—C other reagents have also been quinones. 

The reaction sequence is successful because reverse, ring-contraction reactions are unlikely and because only the final product contains a secondary lactam group, which is depro-tonated under the reaction conditions. 

Recognize too that the reaction sequence is one that is characteristic of p keto esters in general and not limited to just ethyl acetoacetate and its derivatives Thus... 

The acetoacetyl group is then transformed to a butanoyl group by the reaction sequence illustrated m steps 2 to 4... 

The net effect of this sequence is the destmction of 2 molecules of as the one is lost in NO2 formation and the O of equation 26 would have combined with O2 to form the other. In addition, the NO acts as a catalyst. It is not consumed, and therefore can participate in the reaction sequence many times. 

Metha.nol-to-Ga.soline, The most significant development in synthetic fuels technology since the discovery of the Fischer-Tropsch process is the Mobil methanol-to-gasoline (MTG) process (47—49). Methanol is efftcientiy transformed into C2—C q hydrocarbons in a reaction catalyzed by the synthetic zeoHte ZSM-5 (50—52). The MTG reaction path is presented in Figure 5 (47). The reaction sequence can be summarized as... 

AH components of the reaction mixture, whatever their source, are subject to the same kind of radical attacks as the starting substrate(s). Any free-radical oxidation is inevitably a cooxidation of substrate(s) and products. The yields of final products are deterrnined by two factors (/) how much is produced in the reaction sequence, and (2) how much product survives the reaction environment. By kinetic correlations and radiotracer techniques, it is... 

Catechol Derivatives. An elegant synthesis of trimethoxybenzaldehyde [86-81-7] (4) starting from quaiacol [90-05-1] (5) and formaldehyde (75) has been developed. The reaction sequence is as follows ... 

Ben2odioxane is reasonably stable at neutral pH, but may decompose when the resin is cured, serving as a source of labile formaldehyde. Ben2odioxanes are not found in sulfuric or sulfonic acid-cataly2ed resins, since the stronger acid readily cataly2es the second step in the reaction sequence. 

The in situ process is simpler because it requires less material handling (35) however, this process has been used only for resole resins. When phenol is used, the reaction system is initially one-phase alkylated phenols and bisphenol A present special problems. As the reaction with formaldehyde progresses at 80—100°C, the resin becomes water-insoluble and phase separation takes place. Catalysts such as hexa produce an early phase separation, whereas NaOH-based resins retain water solubiUty to a higher molecular weight. If the reaction medium contains a protective coUoid at phase separation, a resin-in-water dispersion forms. Alternatively, the protective coUoid can be added later in the reaction sequence, in which case the reaction mass may temporarily be a water-in-resin dispersion. The protective coUoid serves to assist particle formation and stabUizes the final particles against coalescence. Some examples of protective coUoids are poly(vinyl alcohol), gum arabic, and hydroxyethjlceUulose. 

The first syntheses of florfenicol (2), 3-fluorochloramphenicol, (6, R = NO2) and other fluoroanalogues were accompHshed beginning with thiamphenicol (1, R = SO2CH2) according to the reaction sequence... 

The dimsyl ion also adds to carbon—carbon double bonds, and if the mixture is heated for several hours, methanesulfenate is eliminated. The overall result is methylation, and for compounds such as quinoline or isoquinoline (eq. 20), yields ate neady quantitative (50). The reaction sequence for isoquinoline to 1-methyhsoquinoline is as follows ... 

Toluene Diisocyanate. Toluene diisocyanate is the basic raw material for production of flexible polyurethane foams. It is produced by the reaction sequence shown below, in which toluene is dinitrated, the dinitrotoluene is hydrogenated to yield 2,4-diaminotoluene, and this diamine in turn is treated with phosgene to yield toluene 2,4-diisocyanate. 

Methylcobalamin is involved in a critically important physiological transformation, namely the methylation of homocysteine (8) to methionine (9) (eq. 2) catalyzed by A/ -methyltetrahydrofolate homocysteine methyltransferase. The reaction sequence involves transfer of a methyl group first from... 

Monocarbams. The reaction sequence for monocarbam preparation is shown in Figure 7. Simple carboxyl N-1 substitution, representing one... 

Neopentanoic acid has also been produced commercially from diisobutylene [18923-87-0], in which the first step in the reaction sequence is a cracking or depolymeri2ation of the olefin to give isobutylene. 

Seb cic Acid. Sebacic acid [111-20-6] C QH gO, is an important intermediate in the manufacture of polyamide resins (see Polyamides). It has an estimated demand worldwide of approximately 20,000 t/yr. The alkaline hydrolysis of castor oil (qv), which historically has shown some wide fluctuations in price, is the conventional method of preparation. Because of these price fluctuations, there have been years of considerable interest in an electrochemical route to sebacic acid based on adipic acid [124-04-9] (qv) as the starting material. The electrochemical step involves the Kolbn-type or Brown-Walker reaction where anodic coupling of the monomethyl ester of adipic acid forms dimethyl sebacate [106-79-6]. The three steps in the reaction sequence from adipic acid to sebacic acid are as follows ... 

Benzimidazole 3-oxides, e.g. (189), react with phosphorus oxychloride or sulfuryl chloride to form the corresponding 2-chlorobenzimidazoles. The reaction sequence involves first formation of a nucleophilic complex (190), then attack of chloride ions on the complex, followed by rearomatization involving loss of the fV-oxide oxygen (191 -> 192). 

In terms of cost, the effectiveness of the catalytic cycle in the ring closure makes this process economical in palladium. The first three steps in the reaction sequence -- ring opening of an epoxide by a Grignard reagent, converison of an alcohol to an amine with inversion, and sulfonamide formation from the amine — are all standard synthetic processes. 

The relationship between a kinetic expression and a reaction mechanism can be appreciated by considering the several individual steps that constitute the overall reaction mechanism. The expression for the rate of any single step in a reaction mechanism will contain a concentration term for each reacting species. Thus, for the reaction sequence... 

Whenever a rate law contains non-integers orders, there are intermediates present in the reaction sequence. When a fractional order is observed in an empirical rate expression for a homogeneous reaction, it is often an indication tliat an important part of the mechanism is the splitting of a molecule into free radicals or ions. 

In many of the reaction sequences utilizing protecting groups, t4e overall yield of the final product is poor. This is frequently due to a poor yield obtained in the removal of the protecting group at the end of the sequence. 

The mechanism of oxidation with chromic acid has been the object of much study. The pioneering efforts of Westheimer and his group have resulted in the postulation of the mechanism shown in the reaction sequence below... 

For some fungi, the reaction sequence outlined rests on sound evidence ... 

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

Formation of five-membered ring systems (1,2-addition) can compete with formation of the seven-membered heterocycles (1,4-addition). If the first step of the reaction sequence, namely the nucleophilic attack of the terminal heteroatoin of the diene, is hindered by steric or electronic effects, the five-membered ring product is formed exclusively. 

In green plants, water serves as the ultimate electron donor for the photosynthetic generation of reducing equivalents. The reaction sequence... 

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

Methyl propiolate and pyridine give a rather unstable 2 1 molar adduct which is the 1,2-dihydropyridine (112). The reaction sequence proposed to account for its formation is identical in principle to a similar scheme proposed earlier in the acridine series (Section II,A,2) and is also supported by the observation that the 1-benzoyl-pyridinium cation with the phenylacetylide anion yields (113). ... 

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