Protonation, complete

In compounds with R=H, at equilibrium the proton completely exchanged to R = D. For 297 (R = Me) and 299 (R = Me) ring closures were slower and the equilibrium shifted more toward the monocyclic compounds (Equations 29 and 30) <20050BC1964>. 

Reduction of stilbene [18] or dipheny-lacetylene [214] in DME yields 1,2,3,4-tetraphenylbutane, whereas phenanthrene [214] provides 9,9, 10,10 -tetra-hydro-9.9 -biphenanthrene. Hydrodimerization was also observed with benzalfluo-rene [225]. If DME is replaced by acetonitrile, protonation completely dominates hydrodimerization [18]. In carefully dried ethers, using alkali or alkaline earth metals salts as supporting electrolyte, 1,1-diphenylethylene can be reduced ca-thodicaUy to give stable solutions of 1,1,4,4-tetraphenylbutane dianions [226]. These dianions can be cleaved by flash... 

Radicals can be obtained from reduction of molecules followed either by protonation or departure of a nucleophile as illustrated in Schemes 6 [10] and 7 [11], respectively. In the first example, a generally accepted mechanism involves a reduction of a double bond activated by an electron-withdrawing group to a radical anion followed by protonation and cyclization of the resulting radical. The addition of a second electron and proton completes the process. 

In this reaction, ionization results in migration of a methyl group with its bonding pair of electrons from the (3 to the a carbon, thereby transforming an unstable primary carbocation to a relatively stable tertiary carbocation. Elimination of a proton completes the reaction. 

The difference between the most kinetically favoured cyclisations is easily seen in the type of base needed to cyclise chloro-alcohols to three- and five-membered cyclic ethers (epoxides and THFs). Chloroethanol 19 cyclises only as the oxyanion specific base is needed, i.e. a strong enough base to remove the OH proton completely. By contrast, 4-chlorobutanol cyclises by general base catalysis the proton is removed during the cyclisation 22 and weak bases will do.1, 2... 

Hence, the greatest variation in rx is observed for pH values around pH = 14 — pKb. On silica-based RPLC columns the range of 2 < pH < 7 will correspond to bases with 7 very weak bases pH is a relevant parameter in RPLC. Much stronger bases (pKb<6) will be protonated completely, or almost completely in RPLC using silica-based CBPs. On these columns, their ionization cannot be suppressed, and they should be chromatographed as ions, either on ion-exchange or on ion-pairing systems (see section 3.3 below). 

The point is that the base used, ethoxide ion EtCT, is too weak (EtOH has a pKd of about 16) to remove the proton completely from ethyl acetate (pkTa about 25), but is strong enough to remove a proton from the acetoacetate product (p about 10), Under the conditions of the reaction, a small amount of the enolate of ethyl acetate is produced—just enough to let the reaction happen—but the product is completely converted into its enolate. The neutral product, ethyl acetoacetate itself, is formed on acidic work-up. 

In two independent studies three [(468)—(470)] of the four possible dia-stereoisomers have been synthesized and none of these has proved to be identical to the naturally occurring compound. This only leaves (471) as the final possibility with a cycloeudesmol structure. It may, however, be that this compound requires further investigation since the n.m.r. spectrum seems to have some anomalous features [e.g. the isopropylol methyl groups are reported at S 1.25 and 1.33 whereas the lowest-field methyl signal in (468)—(470) is at S 1.11 in addition, the cyclopropyl protons are reported as two doublets, / = 5 Hz, with no apparent coupling to the C-4 proton]. Complete details of the synthesis of the nor-sesquiterpenoid chamaecynone (472) have been published. A new route to... 

The proposed reaction pathway to 251 (Scheme 41) starts by nucleophilic attack of the dianion of the ethyl thioglycolate I on l,2-diimidoyl-l,2-dichloroethane 250, affording an intermediate II. Two possible routes, A and B, have been hypothesized for the formation of intermediate IV, which by proton migration leads to reactive species V. The cyclization step with simultaneous elimination of lithiated ethyl acetate, followed by protonation, complete the reaction cycle to give product 251. 

The normal primary deuterium isotope effect in the first part shows that an OH bond is being broken in tile rate-detertnining step. Imidazole is loo weak a base to remove the OH proton completely so its role must be as general base catalyst. Attack on the carbonyl is the slow step with (aster breakdown of the tetrahedral intermediate arid hydrolysis of the lactone. Lactones arc hydroly,sed faster than esters because they lack anomeric stabilization (p. 1134). [ he role ttf the OH group is intramolecular nucleophilic catalyst. 

Titrations of polyprotic acids will have more than one equivalence point and more than one half equivalence point. For the MCAT, assume that the first proton completely dissociates before the second proton begins to dissociate. (This assumption is only acceptable if the second proton is a much weaker add than the first, which is usually the case.) Thus we have a titration curve like the one shown below. 

The regioselectivity of Friedel-Crafts acylations of unsymmetrical alkenes can often be predicted simply by consideration of the alternative carbenium ions formed in an initial electrophilic attack. Pathways via tertiary carbocations are generally preferred over those involving secondary ions. It is the subsequent fate of the initially generated ion that determines the products formed. As has been indicated already, elimination of a proton completes a substitution, although there is a predominance of nonconjugated unsaturated ketone formed, and treatment with base is required to form the conjugated product."... 

FIGURE 5.1(a). The nC-NMR spectrum of diethyl phthalate with the protons completely coupled. The solvent used was CDC13 at 25.2 MHz. 

When an unactivated aryl halide (333) is treated with a very strong base, an elimination reaction is possible that generates an intermediate called a benzyne (336). Benzyne is electron deficient and will be attacked by nucleophiles in a reaction that opens the Jt bond not part of the aromatic cloud, and produces a new carbanion (337). Protonation completes the sequence to give the aromatic substitution product 338. 

We attribute the effect of the amine at C-6 as deriving from the extent of dissociation of the ammonium salt at C-6, and it is an equilibrium effect which depends on the relative concentrations of the protonated phenolate group and the dissociated salt form. Strongly basic amines remove the proton completely and form the ammonium salt. Weakly basic amines do not cause complete ionization of the C-6 phenol. This same effect has been observed for monomeric models in solution. (We can ignore free amine quenching because the concentration of the amine is very low.)... 

HBr—AlBrj benzene is protonated completely if the molar ratio AlBrjtHBr 2. 

V TABLE 4.2 lists the strong acids and bases we are most likely to encounter. You need to commit this information to memory in order to correctly identify strong electrolytes and write net ionic equations. The brevity of this list tells us that most acids are weak. (For H2SO4, as we noted earlier, only the first proton completely ionizes.) The only common strong bases are the common soluble metal hydroxides. Most other metal hydroxides are insoluble in water. The most common weak base is NH3, which reacts with water to form OH ions (Equation 4.11). 

Important information can be obtained from the electrophoretic mobility at different pH values regarding the acidic and basic groups present in the molecule. Thus, no change is observed in the mobility for acid amides between pH 6.5 and 2.0, weak acids as succinic acid will be protonated completely at pH 3.0 (loss of a negative charge as compared with pH 6.5) while a-keto glutaric acid will be protonated completely only at pH 2.0 (cf. Section 2.3) (refs. 18, 19). 

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