C under acidic conditions

The simple spectrophotometric thiobarbituric acid (TBA) test has been frequently used for many years as an indicator of the peroxidation of PUFAs present in biological matrices. This test involves the reaction of aldehydes in the sample with TBA at c. 100°C under acidic conditions (Equation 1.13) to produce a pink-coloured chromogen, which absorbs light strongly at a wavelength of 532 nm (Nair and Turner, 1984). 

Figure 10.2 Optimization of a purification protocol by LC-MS analysis. (1) LC-MS analysis of C-terminal fragment from reference molecule purified by cation-exchange chromatography (CEX) and hydroxyapatite chromatography (HA). (2) Incubation at 37°C under acidic conditions shows degradation of the purified molecule if CEX precedes HA. (3) The molecule is stabilized when the sequence of the two purification steps is swapped. 

Chemical/Physical. At temperatures greater than 189.5 °C, decomposes to carbon dioxide, carbon monoxide, formic acid, and water (Windholz et al, 1983). Ozonolysis of oxalic acid in distilled water at 25 °C under acidic conditions (pH 6.3) yielded carbon dioxide (Kuo et al., 1977). 

The reductive decyanation of cyanopyrazine using H2 and Pt/C under acidic conditions has been reported <2002TL6747>, that is, 2-amino-3-cyano-5-phenylpyrazine 1-oxide 73 is hydrogenated to 2-amino-5-phenylpyra-zine 74 in 90% yield (Equation 11). The double reduction has also been shown to be realized with sodium dithionite. 

Hydrogenation of o-nitrophenylglycine (32) as hydrochloride over 5% Pt-C under acidic conditions afforded 3-amino-l-hydroxy-2-indolinone (33), the cyclization product at the hydroxylamino compound, in good yield. On the other hand, hydrogenation of the free base of 32 over a palladium black under neutral conditions gave o-aminophenylglycine (34), which could be converted to 3-amino-2-indolinone (35) by spontaneous cyclization in acidic solution (Scheme 9.15).159... 

In all oxidations of sulfides to sulfoxides, yield loss because of overoxidation to form the sulfones is common unless temperatures are low. Another source of yield loss in aliphatic sulfoxides with a-hydrogens arises from the Pummerer reactions, which occur at temperatures greater than 80° C under acidic conditions or in the presence of acid anhydrides/halides. The Pummerer reactions are quite general, leading to products of the general formula RSCR2Z, with Z being acetate, chloride, hydroxide, etc. 

An initial search for the thioester-forming sequence indicated that a peptide 67 containing a Cys-Pro-Cys/Ser sequence appeared to be converted into the DKP thioester. An N-SIO acyl shift at the second Cys or Ser residue (path b) would produce a Cys-Pro (thio)ester structure 68b. Once the CPE structure is formed, the DKP thioester 52 would be obtained via an N-S acyl shift at the first Cys residue (path a) followed by DKP formation (path c). The order of reactions a and fe would not be critical for the overall reaction. As of this writing, DKP thioester formation from the CPC peptide was demonstrated only in model systems (Scheme 22). When the CPC peptide, H-Ala-Lys-Leu-Arg-Phe-Gly-Cys-Pro-Cys-NH2 (70), was treated at 110°C under acidic conditions, dilute hydrochloric acid or heptafluorobutyric acid (HFBA), the corresponding DKP thioester 71 was obtained. Although epimerization in the DKP moiety was observed, the reaction mixture was reacted with cysteinyl peptide, H-Cys-Tyr-NH2 (72), to produce 73 as a single isomer. 

Decarboxylation is even easier ( 30 °C) under acidic conditions because the reaction is catalyzed by an intramolecular transfer of a proton from the carboxyl group to the carbonyl oxygen. The enol that is formed immediately tautomerizes to... 

Alkylation can also be accomplished with electrophilic alkenes. There is a dichotomy between basic and acidic conditions. Under basic conditions, where the indole anion is the reactive nucleophile, A-alkylation occurs. Under acidic conditions C-alkylation is observed. The reaction of indole with 4-vinylpyri-dine is an interesting illustration. Good yields of the 3-alkylation product are obtained in refluxing acetic acid[18] whereas if the reaction is done in ethanol containing sodium ethoxide 1-alkylation occurs[19]. Table 11.2 gives some examples of 3-alkylation using electrophilic alkenes. 

A traditional method for such reductions involves the use of a reducing metal such as zinc or tin in acidic solution. Examples are the procedures for preparing l,2,3,4-tetrahydrocarbazole[l] or ethyl 2,3-dihydroindole-2-carbox-ylate[2] (Entry 3, Table 15.1), Reduction can also be carried out with acid-stable hydride donors such as acetoxyborane[4] or NaBHjCN in TFA[5] or HOAc[6]. Borane is an effective reductant of the indole ring when it can complex with a dialkylamino substituent in such a way that it can be delivered intramolecularly[7]. Both NaBH -HOAc and NaBHjCN-HOAc can lead to N-ethylation as well as reduction[8]. This reaction can be prevented by the use of NaBHjCN with temperature control. At 20"C only reduction occurs, but if the temperature is raised to 50°C N-ethylation occurs[9]. Silanes cun also be used as hydride donors under acidic conditions[10]. Even indoles with EW substituents, such as ethyl indole-2-carboxylate, can be reduced[ll,l2]. 

This procedure may result in a concentration of cumene hydroperoxide of 9—12% in the first reactor, 15—20% in the second, 24—29% in the third, and 32—39% in the fourth. Yields of cumene hydroperoxide may be in the range of 90—95% (18). The total residence time in each reactor is likely to be in the range of 3—6 h. The product is then concentrated by evaporation to 75—85% cumene hydroperoxide. The hydroperoxide is cleaved under acid conditions with agitation in a vessel at 60—100°C. A large number of nonoxidising inorganic acids are usehil for this reaction, eg, sulfur dioxide (19). 

TSPP is readily crystallised from water as the decahydrate between —0.4° and 79°C, and as the anhydrous salt above 79°C. The solubiUty of tetrasodium pyrophosphate is illustrated in Figure 8. The pH of a 1% solution is 10.2. TSPP is quite stable in alkaline medium but hydrolyses rapidly to orthophosphate under acid conditions. 

Refluxing linoleic acid and a primary or secondary alkyl amine with -toluenesulfonic acid in toluene for 8—18 h also yields the substituted amides (32—34). The reaction of methyl esters with primary or secondary amines to make substituted amides is catalyzed with sodium methoxide. Reactions are rapid at 30°C under anhydrous conditions (35). Acid chlorides can also be used. Ai,A/-dibutyloleamide [5831-80-17 has been prepared from oleoyl chloride and dibutyl amine (36). 

N,]S7-bis(methoxymethyl)uron was first isolated and described in 1936 (41), but was commercialized only in 1960. It is manufactured (42) by the reaction of 4 mol of formaldehyde with 1 mol of urea at 60°C under highly alkaline conditions to form tetramethylolurea [2787-01-1]. After concentration under reduced pressure to remove water, excess methanol is charged and the reaction continued under acidic conditions at ambient temperatures to close the ring and methylate the hydroxymethyl groups. After filtration to remove the precipitated salts, the methanolic solution is concentrated to recover excess methanol. The product (75—85% pure) is then mixed with a methylated melamine—formaldehyde resin to reduce fabric strength losses in the presence of chlorine, and diluted with water to 50—75% soHds. Uron resins do not find significant use today due to the greater amounts of formaldehyde released from fabric treated with these resins. 

Formaldehyde may react with the active hydrogens on both the urea and amine groups and therefore the polymer is probably highly branched. The amount of formaldehyde (2—4 mol per 1 mol urea), the amount and kind of polyamine (10—15%), and resin concentration are variable and hundreds of patents have been issued throughout the world. Generally, the urea, formaldehyde, polyamine, and water react at 80—100°C. The reaction may be carried out in two steps with an initial methylolation at alkaline pH, followed by condensation to the desired degree at acidic pH, or the entire reaction may be carried out under acidic conditions (63). The product is generally a symp with 25—35% soHds and is stable for up to three months. 

Wet chlorination is performed by sparging slimes slurried either in water or hydrochloric acid using chlorine gas, or other oxidants such as sodium chlorate or hydrogen peroxide which Hberate chlorine from hydrochloric acid, at about 100°C. Under these conditions, selenium and selenides rapidly oxidize and dissolve. 

Studies of reaction mechanisms ia O-enriched water show the foUowiag cleavage of dialkyl sulfates is primarily at the C—O bond under alkaline and acid conditions, and monoalkyl sulfates cleave at the C—O bond under alkaline conditions and at the S—O bond under acid conditions (45,54). An optically active half ester (j -butyl sulfate [3004-76-0]) hydroly2es at 100°C with iaversion under alkaline conditions and with retention plus some racemization under acid conditions (55). Effects of solvent and substituted stmcture have been studied, with moist dioxane giving marked rate enhancement (44,56,57). Hydrolysis of monophenyl sulfate [4074-56-0] has been similarly examined (58). 

Another successhil strategy for derivatization of erythromycin employed modification of functional groups involved in intramolecular cyclizations. The C-9 ketone, C-6 hydroxyl group, C-8 proton, and/or C-ll,12-diol of erythromycin were converted into functional groups which participate poorly, if at all, in intramolecular cyclizations. Some derivatives which have been extensively evaluated in preclinical and clinical trials exhibit such desirable properties as better stabiUty under acidic conditions, greater oral bioavadabihty, and higher and more prolonged concentrations of antibiotic in semm and tissues. 

Under acidic conditions, dehydration to an anhydrotetracycline [20154-34-1] (8), C22H22N20y, occurs under basic ones, ring C opens to an isotetracycline [3811-31-2] (9), C22H24N20g. The anhydrotetracyclines, such as (8), appear to exhibit a mode of antibacterial action, but it is unlike that of tetracycline (24). Epimerization (23,25,26) at C-4 occurs in a variety of solvents within the pH range 2—6, particularly in acetic acid (25). A number of anions (27) facihtate this reaction. The reverse process, from 4-epitetracycline [79-85-6] C22H24N20g, to tetracycline, is promoted by chelation with ions such as calcium and magnesium (28). 

Fig. 5. Direct red dyes, (a) Direct Red 81 described ia text (68) (b) Direct Red 2 (o-toLidiae coupled to two moles of naphthionic acid) (69) (c) Direct Red 23 (aniline coupled to 6,6 -ureylenebis-l-naplitliol-3-sulfonic acid with a second coupling with j aminoacetanilide) (70) and Direct Red 80 (2 mol 6-amino-3,4 -azobenzenedisulfonic acid coupled twice to 6,6 -ureylenebis-l-naphthol-3-sulfonic acid) (73). Direct Red 24 (4-aniino-y -toluenesulfonic acid coupled under acidic conditions to 6,6 -ureylenebis-l-naphthol-3-sulfonic acid followed by an alkaline coupling of o-anisidine) (71) (d) Direct Red 72 (Broenner s acid, ie, 6-artiino-2-naphthalenesulfonic acid coupled under acidic conditions to 6,6 -ureylenebis-l-naphthol-3-sulfonic acid followed by an...

Many of the metal chlorites are not particularly stable and will explode or detonate when stmck or heated. These include the salts of Hg", Tl", Pb ", Cu", and Ag". Extremely fast decomposition with high heat evolution has been noted for barium chlorite [14674-74-9] Ba(Cl02)2, at 190°C, silver chlorite [7783-91-7] AgC102, at 120°C, and lead chlorite [13453-57-17, at 103°C (109). Sodium chlorite can be oxidized by ozone to form chlorine dioxide under acidic conditions (110) ... 

Alkyl groups under nonacidic conditions sterically deflect nucleophiles from C, but under acidic conditions this steric effect is to some extent offset by an electronic one the protonated oxirane opens by transition states (Scheme 40) which are even more 5Nl-like than the borderline Sn2 one of the unprotonated oxirane. Thus electronic factors favor cleavage at the more substituted carbon, which can better support a partial positive charge the steric factor is still operative, however, and even under acidic conditions the major product usually results from Cp attack. 

Adenosine-3 -monophosphoric acid hydrate [3 -adenylic acid, 3 -AMP] [84-21-9] M 347.3, m 197°(dec, as 2H2O), 210°(dec), m 210°(dec), [a]s46 -50° (c 0.5, 0.5M Na2HP04), pK 3.65, pKz 6.05. It crystallises from large volumes of H2O in needles as the monohydrate, but is not very soluble in boiling H2O. Under acidic conditions it forms an equilibrium mixture of 2 and 3 adenylic acids via the 2, 3 -cyclic phosphate. When heated with 20% HCl it gives a quantitative yield of furfural after 3hours, unlike 5 -adenylic acid which only gives traces of furfural. The yellow monoacridine salt has m 175°(dec) and... 

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