Pseudoacids

In conclusion, it appears that in neutral or weakly acidic conditions only the methyl in the 2-position shows pseudoacidic behavior. The same conclusion can be drawn from the base-induced hydrogen-metal exchange reactions discussed in Section III.5.B. 

Chlorthalidone (49) is another thiazide-like diuretic agent that formally contains an isoindole ring. Transformation of the amine in benzophenone, 47, to a sulfonamide group by essentially the same process as was outlined for chlorexolone (46) affords Intermediate 43. This product cyclizes to the desired pseudoacid 1-ketoisoindole (49) on successive treatments with thionyl... 

A related sulfonamide is classed as an isoindolone by virtue of typical benzoyl-benzoic acid pseudoacid isomerism. The amino group in benzoylbenzoic acid... 

Primary amines react slowly with ammonia in a benzene medium, to form ammonium salts. Hence Hantzsch [11] assumed that primary nitramines (I), like primary and secondary nitroparaffins, are pseudoacids and react in a tautomeric aci-form (II)... 

Nitroaminoguonidine(NAGu) Salts. As mentioned under nitroaminoguanidine, this compd exists in two forms the normal and the pseudo-acid. The existence of a pseudoacid form explains the possibility of formation of metallic salts... 

The following heavy metal salts, which may be considered as derived from the pseudoacid form of nitroaminoguanidine are explosive ... 

Experimental evidence of the existence of aci-forms has soon been provided. In 1895 Holleman [51] found that m- nitrophenylnitromethane yielded a yellow salt, which under the influence of hydrochloric acid was converted initially into a yellow substance having a high electrical conductivity. After some time, the product changed into a colourless substance, showing no electrical conductivity. The aci-structure was assigned to the yellow substance, and that of a pseudoacid to the colourless one. 

Information regarding the physical and chemical properties of the selected dinitrocresols is located in Table 3-2. Like dinitrophenols, the dinitrocresols are pseudoacids and readily form water soluble sodium, potassium, ammonium, and calcium salts (HSDB 1994 Metcalf 1978). Of the theoretically possible 18 isomers of dinitrocresols (Harvey 1953), the isomer 4,6-dinitro-o-cresol is the most commercially important (HSDB 1994). At a pH of 4.4, 50% of the DNOC in water exists as the dissociated compound (see pKa value in Table 3-2). The concentration of the ionized form increases as the pH increases. Essentially, 100% of the DNOC at pH 7 or above will be in the ionized form. Thus, in a whole animal all of the DNOC exists in the ionized form or is associated with a macromolecule such as albumin (King and Harvey 1953b). 

Regiosehctive anthraquinone synthesis. The methoxy-substituted phthalic anhydride 1 reacts with the Grignard reagent 2 to give essentially only the pseudoacid 3. The product is cyclized (cone. H2SO4, 25°) and demethylated (HBr-HOAc) to digitopurpone (4) in 51% overall yield. 

On the other hand, treatment of 6,6-diphenyl-3-oxabicyclo[3.1.0]hexane-2,4-dione with phenylmagnesium bromide gave the pseudoacid 4-hydroxy-4,6,6-triphenyl-3-oxabi-cyclo[3.1,0]hexan-2-one in low yield (11 %). Replacing the Grignard reagent with diphenyl-... 

Dinitro-o-cresol or 4,5-di-nitro-2-methyl phenol is an yellow crystalline compound having m.p. of 87°C (pure grade). It is pseudoacid and readily forms water-soluble ammonium potassium or sodium salts. 

This book does not discuss the details of alkali-oil chemistry related to saponification. It assnmes a highly oil-solnble single pseudo-acid component (HA) in oil. The alkali-oil chemistry is described by partitioning of this pseudoacid component between the oleic and aqneons phases and snbseqnent hydrolysis in the presence of alkali to prodnce a solnble anionic snrfactant A (its component is conventionally denoted by RCOO ), as shown in Fignre 10.3. 

The first synthesis of a member of this class, verrucarin A (116) is a result of the efforts of Still and is outlined in Scheme 4.20. 2" Construction of the muconic acid fragment began with pseudoacid 107, available from the electrochemical oxidation of furfural. A one-carbon homologation with a stabilized ylide afforded solely the ( ,Z)-isomer of (3-trimethylsilylethyl ester 108 in 72% yield. 

Accordingly, treatment of 129 with potassium f-butoxide and pseudoacid 107 gave a 58% yield of the required ( ,Z)-muconic ester 130. Macrolactonization was then achieved via the mixed pivaloyl anhydride in the presence of 4-pyrrolidinopyridine to afford verrucarin (124) in 60% yield along with its ( , )-muconate isomer 131 (30%). The latter could be isomerized with 12 in benzene to provide additional 124 (61%) contaminated with another muconic ester isomer. 

In the case of pseudoacids, for example, C acids, the resulting ions are stabilized by changes in electronic structure, so that the reactions are generally not diffusion-controlled. A very good example of this phenomenon is the protolysis and hydrolysis of acetylacetone, which has been studied in detail by Eigen and Kruse [12]. This acid can exist in keto (85%) and enol forms (15%) the conjugate base can have two resonance structures (I). 

All the possible protolytic rate constants for this system have been obtained and are recorded in Table 8-3. Note that the protonation at the C atom is slower than protonation at the O atom by a factor of 10. A similar effect is exhibited by the deprotonation rates. In this case the enol form is stabilized by an internal H bond, so that its rate of reaction with OH" is slower than a diffusion-controlled reaction by a factor of 10. These relatively slow protonation and deprotonation rates are characteristic of pseudoacids in general. 

In practice, this ideal case is only approached (see Fig. 8-6). Instead, the transition from a = 1 to 0 occurs smoothly in the range pK pX. In terms of the mechanism in Eq. (8-37), this means that more intermediate states are kinetically significant. This transition becomes broader for resonance-stabilized donors, until finally in the case of pseudoacids the transition is extremely broad. As a case in point, an actual experimental curve obtained with acetylacetone is included in Fig. 8-6. 

Hieracin I, H-80087 Hirsutinolide, H-80089 4a-Hydroperoxydesoxyvulgarin, in V-80013 7 -Hydroxyabscisic acid, H-70098 8 -Hydroxyabscisic acid, H-70099 Psilostachyin, P-70131 Secoisoerivanin pseudoacid, S-70024... 

Two diphenylaminophthalides have been synthesized The 3,3-diphenyl-6-aminophthalide [24] was synthesized in 20% yield by the following sequence of reactions which was patterned after early work °. This series involved nitration of phthalimide, hydrolysis and dehydration to 4-nitrophthalic anhydride, Friedel-Crafts reaction with benzene to 2-benzoyl-5-nitrobenzoic acid, cyclization with thionyl chloride to the pseudoacid chloride, Friedel-Crafts reactions with benzene, and, finally reduction of the nitro group to the amino function with Adams catalyst. 

A mixture of 48 g (0.10 mol) of benzophenone-4,4 -dibenzoyl-3,3 -dicarboxylic acid and 140 mL of thionyl chloride was heated at reflux for 4 hrs. The excess thionyl chloride was removed by distillation, and the residue was dried under vacuum to give 51 g of the pseudoacid chloride. 

Dry benzene (260 mL) was added to the pseudoacid chloride followed by 56 g (0.42 mol) of aluminum chloride. The mixture was heated at reflux until the evolution of hydrogen chloride ceased. After being cooled, the aluminum chloride complex was destroyed with 6 N hydrochloric acid. The benzene layer was extracted with 5% sodium bicarbonate and dried over sodium sulfate. The benzene was removed under vacuum, and the residue was recrystallized from acetone/water to give 32 g (13% based on tetracarboxylic dianhydride) of bis(3,3-diphenyl-6-phthalidyl) ketone, m.p. 238-39 C. 

A sample of 4-nitrophthalic anhydride (64 g, 0.33 mol) was added to 500 mL of dry benzene, followed by the slow addition with stirring of 107 g (0.80 mol) of aluminum chloride. The mixture was then heated at reflux until the evolution of hydrogen chloride ceased, then cooled. The aluminum complex was destroyed by the addition of 500 g of ice and 200 mL of 12 M HCl. The benzene was extracted with water and with saturated NaCl and dried over sodium sulfate. The benzene was then removed, and the crude benzoylbenzoic acids were placed in a Soxhlet and extracted with methanol for 24 hrs. The extract was allowed to cool and after filtration gave 2-benzoyl-4-nitrobenzoic acid. Yield 10%, m.p. 158-160 C (lit. 163-5 C). The other isomer, 2-benzoyl-5-nitrobenzoic acid, was isolated by reducing the filtrate to one-third its volume and cooling. The yield was 50.0 g (55.6%) m.p. 207-211 C (lit. S 212 °C). A solution of 50.0 g (0.18 mol) of 2-benzoyl-5-nitrobenzoic acid and 50 mL of thionyl chloride was heated at reflux for 3 hrs. After the excess thionyl chloride was removed under vacuum, 500 mL of dry benzene was added to the pseudoacid chloride. Aluminum chloride (46.0 g, 0.40 mol) was slowly added and the mixture was heated at reflux until the evolution of hydrogen chloride ceased. After the aluminum chloride complex was destroyed... 

Just as NHO3 in a dry environment seems to have the constitution of a pseudoacid , 2 ... 

Pschorr ring closure 15, 561 Pseudoacids s. Hydroxylactones Pseudoaromatic rings s. Di-thiylium salts. Metal complex compounds, ar., Tropenium salts Pseudoazulenes 15, 468 N-Pseudoazulenes 14, 791 0-Pseudoazulenes 14, 338 Pseudobase adducts and their reactions 13, 584 —, dehydrogenation 14, 769 —, p-methylation of quinolines via — 14, 769 Pseudobases 11, 323 Pseudobases, N-heterocyclic (s. a. 0-Alkylpseudobases, N-heterocyclic) 15, 304... 

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