Conjugate base procedures

Procedures to compute acidities are essentially similar to those for the basicities discussed in the previous section. The acidities in the gas phase and in solution can be calculated as the free energy changes AG and AG" upon proton release of the isolated and solvated molecules, respectively. To discuss the relative strengths of acidity in the gas and aqueous solution phases, we only need the magnitude of —AG and — AG" for haloacetic acids relative to those for acetic acids. Thus the free energy calculations for acetic acid, haloacetic acids, and each conjugate base are carried out in the gas phase and in aqueous solution. 

The two-step procedure includes formation of a N-substituted phthalimide 3, and its subsequent cleavage to the primary amine 5. Phthalimide (which can be obtained from reaction of phthalic acid with ammonia) shows NH-acidity, since the negative charge of the phthalimide anion (the conjugated base) is stabilized... 

STRATEGY The CH3C02 ion is the conjugate base of a weak acid so the solution will be basic and we expect pH > 7. Use the procedure in Toolbox 10.2, taking the initial con-... 

Amides are very weak nucleophiles, far too weak to attack alkyl halides, so they must first be converted to their conjugate bases. By this method, unsubstituted amides can be converted to N-substituted, or N-substituted to N,N-disubstituted, amides. Esters of sulfuric or sulfonic acids can also be substrates. Tertiary substrates give elimination. O-Alkylation is at times a side reaction. Both amides and sulfonamides have been alkylated under phase-transfer conditions. Lactams can be alkylated using similar procedures. Ethyl pyroglutamate (5-carboethoxy 2-pyrrolidinone) and related lactams were converted to N-alkyl derivatives via treatment with NaH (short contact time) followed by addition of the halide. 2-Pyrrolidinone derivatives can be alkylated using a similar procedure. Lactams can be reductively alkylated using aldehydes under catalytic hydrogenation... 

In situ reaction of the resultant phosphine, converted to its conjugate base, with several types of electrophiles has been investigated for organophosphorus syntheses. While early reports of the use of white phosphorus in basic solution with haloalkanes did not in themselves provide procedures for the efficient preparation of organophosphorus compounds, they pointed the way for the development of more useful techniques. 

Three experimental methods that are capable of determining dissociation constants with a precision of the order of tenths of 1% have been most commonly used. Each of these methods—the cell potential method (2), the conductance method (3), and the optical method (4)—provides data that can be treated approximately, assuming that the solutions obey Henry s law, or more exactly on the basis of the methods developed in Chapter 19. We will apply the more exact procedures. As the optical method can be used only if the acid and conjugate base show substantial differences in absorption of visible or ultraviolet light, or differences in raman scattering or with the use of indicators, we shall limit our discussion to the two electrical methods. 

Procedure 3 We construct cell (V) using the HA type acid under study and its conjugate base and measure the emfs by varying the ratio Ca/Cs. The procedure to vary the ratio Cs/Ca can be replaced by the titration of the acid HA with a strong base (BiuNOH in MeOH, toluene-MeOH, or 2-PrOH), but the alcohol introduced with the base may have some influence on the results. Because the glass electrode has been calibrated in Procedure 2, the emf values can be converted to pH values. 

After incubation with primary and secondary antibody conjugates (see Basic Protocol or see Alternate Protocol), bound antigens are typically visualized with chromogenic substrates. The substrates 4CN, DAB/NiCl2, and TMB are commonly used with horseradish peroxidase (HRP)-based immunodetection procedures, whereas BCIP/NBT is recommended for alkaline phosphatase (AP)-based procedures (see Table B3.4.1). After incubation with primary and secondary antibodies, the membrane is placed in the appropriate substrate solution. Protein bands usually appear within a few minutes. 

While there are few examples of conjugate additions of either a-oxygen- or a-silyl-stabilized carbanions, Tamao and Posner have reported two hydroxymethyl synthons ["ClfcOH] (246 and 247) which show synthetic promise. Additions with the silicon-based synthon (246) is restricted to 2-cyclohexen-l-ones and work-up requires a successive acid and base procedure that is incompatible with sensitive molecules,188a-b while the tin-based synthon (247) is more versatile and the hydroxyl group is obtained under neutral conditions (Scheme 83).,88c... 

This procedure illustrates a recently published, simple, general method for the synthesis of conjugated dienes from olefins. The scope of the reaction is shown in Table I.5 In most of these examples hydrogen bromide. .elimination can be effected by stirring a solution of the olefin-bromo-methanesulfonyl bromide adduct in methylene chloride with one equivalent of triethylamine at room temperature. Only two equivalents of the more costly potassium tert-butoxide are then needed in the second elimination step the yields using the two-base procedure are generally superior to that obtained using only potassium tert-butoxide. 

Protonation by superacids of solutes such as these displaces the self-ionisation of the superacids causing enhancement of concentration of the base of the superacid system, F, S03F or CF3S03-. This may be a disadvantageous situation when acidity/basicity control is required for synthetic purposes. If controlled increase of basicity is required, the simplest procedure is by direct addition of the conjugate base of the parent acid, i.e. by addition of F, S03F- or CF3S03 as indicated in Sec. 11.2.3. 

A related reaction that yields the same types of products as does the Michaelis-Arbuzov reaction begins with either a phosphinous acid or a monoester of a phosphonous acid. (The corresponding reaction may also be performed with a diester of phosphorous acid.) By treatment with an appropriate base, the conjugate base of the phosphorus-containing acid is generated that serves as the nucleophihc reagent for direct formation of the phosphonate or phosphine oxide product (or phosphonate product from a phosphorous acid diester). This procedure is commonly referred to as the Michaehs Becker reaction. ... 

Control of pH is vital in synthetic and analytical chemistry, just as it is in living organisms. Procedures that work well at a pH of 5 may fail when the concentration of hydronium ion in the solution is raised tenfold to make the pH 4. Fortunately, it is possible to prepare buffer solutions that maintain the pH close to any desired value by the proper choice of a weak acid and the ratio of its concentration to that of its conjugate base. Let s see how to choose the best conjugate acid-base system and how to calculate the required acid-base ratio. 

Before the stoichiometric point is reached, the solution is a buffer with differing amounts of acid/conjugate base. To calculate the pH, follow the procedure outlined in Example 11.6 in the text. At the stoichiometric point, the analyte solution consists of the salt of a weak acid or of a weak base. To calculate the pH, fol low the procedure outlined in Example 11.5 in the text. 

Estimate p values for reaction of acetylketene with ArO (Scheme 20). Make use of ptg = -1-29 for the displacement of the phenolate ion from the conjugate base of the ester. You will need to estimate for the overall reaction and for the dissociation of proton on the C(2)-carbon. The Peq for dissociation of the ester can be calculated by inserting CO-C between H and O of ArO-H and assuming attenuation by two atoms (1.00 X 0.4 X 0.4). Calculate peq for the overall reaction from data in Scheme 1, Chapter 3. Consult Scheme 3 (Chapter 7) and Scheme 3 (Chapter 3) for models of the procedure. 

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