Reactions in Strongly Acidic Media

The reverse of glycoside hydrolysis (cf. 4.2.4.5) i.e. re-formation of glycosides, occurs in dilute mineral acids. All the possible disaccharides and higher oligosaccharides, but preferentially isoma- 

Such reversion-type reactions are observed, e. g., in the acidic hydrolysis of starch. 

In the formation of reversion products, it is assumed that in the presence of strong acids an oxonium cation is formed which, as an alkylating agent, reacts with the nucleophilic hydroxy groups with the cleavage of H+ (Formula 4.34). 

The reaction pathway in acid starts slowly with enolization to important intermediates called ene-diols. Glucose gives rise to 1,2-enediol, and fructose to 2,3-enediol as well (Formula 4.36). Starting with the enediols, the further course of the reaction is shown below. 

The steps in the formation of 5-hydroxymethyl furfural (HMF) from 1,2-enediol is shown in Formula 4.37. HMF is also used as an indicator for the heating of carbohydrate containing food, e. g., honey. The (retro-Michael addition) water elimination at C-3 and subsequently at C-4 leads to a 1,2-diulose (3,4-dideoxyosone), which after cyclization to a hemiacetal, a dihy-drofuran, releases another molecule of water, producing HMF. In the same way, e. g., furfural can be made from pentoses and 5-methylfurfural from the 6-methylpentose rhamnose. 2-Hydroxyacetylfuran, which is preferentially formed from fructose, can be obtained starting from the corresponding 2,3-enediol by water elimination at C-4, followed by C-5 (Formula 4.38). 

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Nitration. Because nitration frequentiy generates nitrogen oxides which can participate in oxidative transformations, the nitration of indole itself is a complex reaction. In strongly acidic media, the nitration of 2-substituted indoles can proceed through the conjugate acid (8). Because the aromatic system is thereby transformed to an a2astyrene, the 5-position is the primary site of reaction. 

This method can also be applied to reactions in strong acid media 155... 

The position of electrophilic substitution of quinolones and isoquinolones depends upon the pH of the reaction medium. Each type protonates on carbonyl oxygen, so reactions in strongly acidic media involve attack on this cation and therefore in the benzene ring the contrast is illustrated below by the nitration of... 

For these and several other reactions in strongly acidic media, protonation of the substrate is probably unimportant, e.g. solvolysis of benzenesulphonyl bromide (PhS02Br) even in 99.98% sulphuric acid132. Rates of SN2 reactions are probably more dependent on solvent nucleophilicity10. Also, electrophilic aromatic substitutions on protonated substrates are expected to be disfavoured, e.g. methanesulphonanilide (39) is half protonated in 84% sulphuric acid, but sulphonation reactions in 80-99.8% sulphuric acid are explained (see below) without postulating protonation of the substrate133. 

Electrophilic substitution occurs readily in Af-phenyl groups, e.g. 1-phenyI-pyrazoIes, -imidazoles and -pyrazolinones are all nitrated and halogenated at the para position. The aryl group is attacked preferentially when the reactions are carried out in strongly acidic media, where the azole ring is protonated. 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

We mention Williams work briefly here because it may also explain Blangey s observations strongly basic primary amines unequivocally form 7V-nitrosoanilinium ions in strongly acidic media. In contrast to the rate-limiting deprotonations of the less basic aromatic and heteroaromatic nitrosoamine cations discussed in this section, the TV-nitroso cation of a strongly basic amine deprotonates extremely slowly. Therefore, the nitroso rearrangement, the Fischer-Hepp reaction, competes effectively with the 7V-deprotonation. 

Kinetic studies of the oxidation of sulphoxides to sulphones by chromium(VI) species have been carried out131-133. The reaction has been found to be first order with respect to the chromium(VI) species and the sulphoxide and second order with respect to acid. At high sulphoxide concentrations the order with respect to sulphoxide is two. The proposed mechanism involves an electron transfer from the sulphoxide to the active chromium(VI) species (HCr03+ in strong acidic media) in the rate-determining step producing a sulphoxide radical cation which further reacts to give the sulphone. 

Carbonium ions are likewise known to be stabilized by solvation in strongly acidic media (Olah and Pittman, 1966), and consequently the reduction potential of carbonium ions, the ease of formation of a carbonium ion by the oxidation of a substrate and the products from these reactions would be expected to depend on the acidity of the electrolysis... 

The Aq dependence of the oxidation in strongly acidic media was taken by Rodek as implying that no water molecule is involved in the transition state and that consequently the ester mechanism as portrayed above cannot hold. However, the Zucker-Hammett hypothesis upon which this argument is based, i.e. that a reaction forming a transition state containing a water molecule will follow a [H30 ] dependence, but that otherwise an dependence will be followed, may not be valid, and in any case the ester can be depicted as breaking down as fol-lows - ... 

Many of the reactions that take place in strong acid media cannot really be defined as being simple Al, A-Se2 or A2 processes, and some of these will be described here. Space considerations preclude detailed discussion of all of the... 

N-nitro amines, RNHN02, decompose to alcohols and nitrous oxide in strong acid media. Rate constants obtained for R = methyl in sulfuric acid222 224 are illustrated as excess acidity plots in Fig. 12.119 This shows multiple curvature, but analysis according to equation (59) shows that one water molecule is involved in the reaction up to about 80 wt% H2S04, and one bisulfate ion above this point, see Fig. 13. The proposed mechanism is shown in Scheme 2. 19... 

The epoxidation of fatty acid methyl esters (FAME) is traditionally conducted in strong acidic media, e.g., with peracetic acid in sulfuric acid solutions. These reactions can be conducted by an environmentally benign route, however, in the... 

The behavior of chiral phenyl /-butyl sulfoxide 219 and a-phenyl-ethyl phenyl sulfoxide 220 is completely different in strongly acidic media and in the presence of halide ions. Two reactions were found (266) to occur in parallel. One results in the loss of optical activity, and the second leads to the decomposition of the sulfoxide. It was observed that the racemization process is not accompanied by [ 0] oxygen exchange. In the case of sulfoxide 220 the complete loss of optical activity at chiral sulfur is accompanied by partial racemization at the chiral carbon center. These results are consistent with a sulfenic acid-ion-pair mechanism formulated by Modena and co-workers (266) as follows (it is obvious that the formation of achiral sulfenic acid is responsible for racemization). 

Kinetic and thermodynamic parameters have been measured for the chlorination of simple aliphatic and aryl alkyl ketones in strong acid media by chloramine-B (sodium A-chlorobenzenesulfonamide). Catalysis of the monochlorination of acetaldehyde in anhydrous carbon tetrachloride by trichloroacetic acid, and by hydrogen chloride, are reported. IR and UV spectroscopy have been used to probe the reaction of acetaldehyde with trichloroacetic acid in carbon tetrachloride. " Two cyclic 1 1 intermediates have been identified, and are found to be in equilibrium. 

Reactions with secondary or tertiary alcohols in strongly acidic media yield amides (Ritter reaction) ... 

In another route, catechol is first reacted with methylene chloride and converted into 1,2-methylenedioxybenzene [177]. Reaction with glyoxylic acid in strongly acidic media yields 3,4-methylenedioxymandelic acid [178]. Subsequent oxidation and decarboxylation with nitric acid affords heliotropin. 

Substituted benzyl chlorides were carbonylated using a Pd/tppts catalyst in aqueous/organic two phase systems under basic reaction conditions to afford the sodium salts of the corresponding phenylacetic acids. After acidification the phenylacetic acid dissolved in the organic phase and could be readily separated from the Pd/tppts catalyst contained in the aqueous phase (Figure 12) 466-468 TOFs up to 21 h 1 (turnover number, TON=165) and phenylacetic acid yields up to 94% were obtained at 70°C, 1 bar CO, tppts/Pd=10, NaOH/substrate=3/2 in an aqueous/toluene (1/1) two phase system in a batchwise procedure.466 The TOFs were improved to a maximum of 135 h 1 (TON=1560) in a continuous operation mode. Palladium catalysts modified with binas (Table 2 25) exhibited low catalytic activity (TONs up to 140) in the carbonylation of benzyl chloride 466 In strongly acidic media (pH=l) the Pd/25 catalyst was active and remained stable during the reaction which contrasts with Pd/tppts where palladium black was observed. However, the catalyst was completely deactivated after three cycles.466... 

The electrochemical oxidation of aromatic aldehydes (1) must be studied in strongly alkaline media. Acidity functions for strongly alkaline aqueous solutions of alkali metal and quaternary ammonium hydroxides, corresponding to dissociation of proton (H ), are well established (2, 3). Substituted anilines and diphenylamines (4,5) and indoles (6) were used as acid-base indicators for establishment of such scales, but whether an acidity scale based on one type of indicator can be rigorously applied to acid-base equilibria involving structurally different acidic groups for reactions in strongly alkaline media remains questionable. For substituted anilines, behavior both parallel (7) and nonparallel (8) to the H scale based on indole derivatives has been reported. The limited solubility of anilines in aqueous solutions of alkali metal hydroxides, the reactions of the aniline derivative with more than one hydroxide ion, irreversible substitution reactions (9), and the possibility of hydroxide ion addition rather than... 

N-Oxidation proceeds on the free base form of heterocycles, in strongly acidic media the substrate exists mainly in the protonated form and this reaction does not occur. Under strongly alkaline conditions the oxidation is hampered because of conversion of the peracid into an unreactive anion. 

Hudson et a/.156 have shown that N,N-dialkylcarbamates decompose in strongly acidic media to carbon dioxide, olefin, alkyl halide and alcohol, the rate of reaction of the secondary esters closely following h0. This fact, together with the variation in the rate of hydrolysis of carbamates of cyclic alcohols with the ring size154, shows that these reactions involve the intermediate formation of carbonium ions. 

Bisulfite ions, HS03", condense with anthocyanins. This reversible reaction decreases the color by forming a colorless compound (12) (16). This effect is less evident in strongly acid media because the bisulfite ions are not as numerous since they are being converted to the undissociated acid. This property explains the decolorization of red wines following sulfite treatment but, since it is reversible, the color gradually reappears as the free S02 (bisulfite ions) disappears. The major role of tannins in the color of old wines explains their insensitivity to color change with SOo. 

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