Under Acidic Conditions

In the cyclization of 7V-(het)arylaminomethylenemalonates, a wide variety of acidic agents have been used. Under such circumstances, not only iV-mono but also N /V-disubstituted derivatives could readily be cyclized. 

When diethyl phenyl(phenylamino)methylenemalonate (4) was dissolved in concentrated sulfuric acid and the solution was kept at ambient temperature for a few days, 2-phenyl-4-hydroxyquinoline-3-carboxylic acid was obtained on the dilution of the reaction mixture with water (36JCS428). 

3-Indolylaminomethylenemalonates (681) were regioselectively cyclized on the action of acetic anhydride or trifluoroacetic anhydride in carbon tetrachloride at 10-20°C for 3 hr, to give 8-carbolines (682) in 22-75% yields (85ZOR432). 

Pyrido[l,2,3-t/e]-l,4-benzoxazine-6-carboxylate (683) was prepared in 96% yield by the cyclization of (l,4-benzoxazin-4-yl)methylenemalonate (272) on the action of a mixture of acetic anhydride and concentrated sulfuric acid at room temperature [84JAP(K)122493], or in 58-94% yields by heating in a mixture of acyl halides and concentrated sulfuric acid at 80-110°C for 1 hr [84JAP(K)216890], or in 75% yields by heating in 

Diethyl (arylamino)methylenemalonates (684) were cyclized with a 2 1 mixture of acetic anhydride and concentrated sulfuric acid at ambient temperature to give 4-hydroxyquinoline-3-carboxylates (685) in 15-80% yields (54JIC555, 54JIC711, 54JIC951). 

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The chromates of the alkali metals and of magnesium and calcium are soluble in water the other chromates are insoluble. The chromate ion is yellow, but some insoluble chromates are red (for example silver chromate, Ag2Cr04). Chromates are often isomorph-ous with sulphates, which suggests that the chromate ion, CrO has a tetrahedral structure similar to that of the sulphate ion, SO4 Chromates may be prepared by oxidising chromium(III) salts the oxidation can be carried out by fusion with sodium peroxide, or by adding sodium peroxide to a solution of the chromium(IIl) salt. The use of sodium peroxide ensures an alkaline solution otherwise, under acid conditions, the chromate ion is converted into the orange-coloured dichromate ion ... 

We chose benzyli dene acetone (4.39, Scheme 4.11) as a model dienophile for our studies. The uncatalysed Diels-Alder reaction of this compound with cyclopentadiene is slow, justifying a catalytic approach. Reaction of 4.39 with paraformaldehyde and dimethyl amine under acidic conditions in an aqueous ethanol solution, following a literature procedure, produced the HCl salt of 4.42 (Scheme 4.11). The dienophile was liberated in situ by adding one equivalent of base. 

Finally, in the last step, the chelating auxiliary had to be removed Ideally, one would like to convert 4.54 into ketone 4.55 via a retro Mannich reaction. Unfortunately, repeated attempts to accomplish this failed. These attempts included refluxing in aqueous ethanol under acidic and basic conditions and refluxing in a 1 1 acetone - water mixture in the presence of excess paraformaldehyde under acidic conditions, in order to trap any liberated diamine. Tliese procedures were repeated under neutral conditions in the presence of copper(II)nitrate, but without success. 

Nitration is almost always carried out under acidic conditions. If the compound being nitrated is basic, the problem arises of deciding whether the free base or its conjugate acid is being nitrated, or if both of these species are reacting. 

Indoles can also be alkylated by conjugate addition under alkaline conditions. Under acidic conditions, alkylation normally occurs at C3 (see Section 11.1). Table 9.1 includes examples of alkylation by ethyl acrylate, acrylonitrile, acrylamide and 4-vinylpyridine. 

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]. 

The nucleophUic reactivity in neutral medium has been used extensively to prepare various thioethers of thiazole (122). In acidic medium, alkylation may be performed with alcohols (123, 124). An unexpected reaction encountered was the decarboxylation of 2-mercapto-4-methyl-5-thiazolecarboxyhc acid (60) when treated with butyl alcohol under acidic conditions (Scheme 27) (123). Reaction between A-4-thiazoline-2-thione... 

With arylthioamides except for some nitrothiobenzamides (101), yields are usually higher than those obtained above, due to the increased stability of these amides under acidic conditions (3), Rj = Ph, yield 70 to 82% (264, 285, 336, 483, 578, 641). In this case, cyclizations are carried out several hours to reflux, in absolute alcohol, in the presence of melted sodium acetate and few drops of piperidine. 

Under acidic conditions, a thiosemicarbazone intermediate (145) has been isolated, this can be cyclized in alcohol either into the corresponding 2-hydrazinothiazole (142) in the presence of benzaldehyde or into 1,3,4-thiadiazine (146) in the absence of benzaldehyde (Scheme 71) (375, 397, 408). 

Not all of the hydrogens in phenol are equally reactive. Under acid conditions the quinoid structure... 

Under acidic conditions, furfuryl alcohol polymerizes to black polymers, which eventually become crosslinked and insoluble in the reaction medium. The reaction can be very violent and extreme care must be taken when furfuryl alcohol is mixed with any strong Lewis acid or Brn nstad acid. Copolymer resins are formed with phenoHc compounds, formaldehyde and/or other aldehydes. In dilute aqueous acid, the predominant reaction is a ring opening hydrolysis to form levulinic acid [123-76-2] (52). In acidic alcohoHc media, levulinic esters are formed. The mechanism for this unusual reaction in which the hydroxymethyl group of furfuryl alcohol is converted to the terminal methyl group of levulinic acid has recendy been elucidated (53). 

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). 

Reaction with Chlorine. Polyacrylamide reacts with chlorine under acid conditions to form reasonably stable A/-chloroamides. The polymers are water soluble and can provide good wet strength and wet web strength in paper (60). 

Combination Flame Retardant—Durable Press Performance. Systems using THPC, urea, and TMM can be formulated to give fabrics which combine both flame-retardant performance and increased wrinkle recovery values (80). Another system employs dimethylol cyanoguanidine with THPC under acidic conditions (115). Both of these systems lead to substantial losses in fabric tensile and tearing strength. 

Flame-Retardant Treatments For Wool. Although wool is regarded as a naturally flame-resistant fiber, for certain appHcations, such as use in aircraft, it is necessary to meet more stringent requirements. The Zirpro process, developed for this purpose (122,123), is based on the exhaustion of negatively charged zirconium and titanium complexes on wool fiber under acidic conditions. Specific agents used for this purpose are potassium hexafluoro zirconate [16923-95-8] [16923-95-8] K ZrF, and potassium hexafluoro titanate [16919-27-0], K TiF. Various modifications of this process have been... 

Formaldehyde condenses with itself in an aldol-type reaction to yield lower hydroxy aldehydes, hydroxy ketones, and other hydroxy compounds the reaction is autocatalytic and is favored by alkaline conditions. Condensation with various compounds gives methylol (—CH2OH) and methylene (=CH2) derivatives. The former are usually produced under alkaline or neutral conditions, the latter under acidic conditions or in the vapor phase. In the presence of alkahes, aldehydes and ketones containing a-hydrogen atoms undergo aldol reactions with formaldehyde to form mono- and polymethylol derivatives. Acetaldehyde and 4 moles of formaldehyde give pentaerythritol (PE) ... 

Methylamines are formed by heating formaldehyde with primary or secondary amines or their salts under acid conditions (61) ... 

Ketones and aldehydes react with ethylene glycol under acidic conditions to form 1,3-dioxolanes (cychc ketals and acetals) (eq. 7). 

Branched-chain alkenes react with hydrazine under acidic conditions to give the corresponding alkyl hydrazine. For example, isobutylene bubbled through an aqueous solution of hydrazine and HCl gives /-butyUiydrazine in reasonably good yields (64). 

The condensation of an aldehyde with resorcinol gives rise to calix (3) arene (114). Isoprene reacts with resorcinol under acidic conditions to give ben2odipyran (24) and monochroman (25) (115). 

The Fischer Indole Synthesis and Related Sigmatropic Syntheses. In the Fischer indole synthesis (26) an Ai-aryUiydra2one is cyclized, usually under acidic conditions, to an indole. The key step is a [3,3] sigmatropic rearrangement of an enehydra2one tautomer of the hydra2one. 

Under high pressures and temperatures, iodine reacts with oxygen to form iodine pentoxide [12029-98-0] (44). The reaction of iodine with carbon monoxide under acidic conditions is catalyzed by palladium salts (45). Phosphorous vapor and iodine react to form phosphoms trHodide [13455-01 -17, PI (46). 

Under acidic conditions, pH < 3.5, and in the presence of certain reducing agents, the permanganate ion can undergo a five-electron exchange resulting in the divalent manganese ion. 

Even though the mechanism of the reaction between oxalate and permanganate is extremely compHcated, titration under acidic conditions is extremely accurate. This is the recommended method for standardi2ation of permanganate solutions. 

An alternative method for the analysis of permanganate is the use of conventional iodometric methods (177) where excess potassium iodide is added to a solution of permanganate under acidic conditions. The Hberated iodide is then titrated with standard thiosulfate solution using starch as an indicator. 

Examples include acetaldehyde, CH CHO paraldehyde, (CH CHO) glyoxal, OCH—CHO and furfural. The reaction is usually kept on the acid side to minimize aldol formation. Furfural resins, however, are prepared with alkaline catalysts because furfural self-condenses under acid conditions to form a gel. 

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. 

Bisnitrophthalimides can be prepared in high yields and high purity from nitrophthaUc anhydrides and diamines under acidic conditions (93). 

Reactions with Aldehydes and Ketones. An important use for alkylphenols is ia phenol—formaldehyde resias. These resias are classified as resoles or aovolaks (see Phenolic resins). Resoles are produced whea oae or more moles of formaldehyde react with oae mole of pheaol uader basic catalysis. These resias are thermosets. Novolaks are thermoplastic resias formed whea an excess of phenol reacts with formaldehyde under acidic conditions. The acid protonates formaldehyde to generate the alkylating electrophile (17). 

The higher aUphatic amine oxides are commercially important because of their surfactant properties and are used extensively in detergents. Amine oxides that have surface-acting properties can be further categorized as nonionic surfactants however, because under acidic conditions they become protonated and show cationic properties, they have also been called cationic surfactants. Typical commercial amine oxides include the types shown in Table 1. 

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