Sulfuric acid, reaction with aromatic aldehydes

Further, isoxazole derivatives were subjected to two related reactions. 3,5-Dimethylisoxazole was found to react in the presence of dry hydrogen chloride with aromatic aldehydes (chlorobenzylation, 72- 71),and with formaldehyde in the presence of sulfuric acid it undergoes hydroxymethylation (72- 73). ... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

An acidic solution of 2,4-dinitrophenylhydrazine reacts with N-p-chlorophenyl-sulfonyl-3-ethoxy-l,2-thiazetidine 1-oxide to give (80%) the bis-2,4-dinitrophenyl-hydrazone of glyoxal. The adduct of A-sulfinyl-p-chlorophenylsulfonamide with dihydropyran is inert to catalytic hydrogenation and bromination. Treatment of two l,2-thiazetidine-3-one 1-oxides (e.g., 421) with hydriodic acid results in ring-cleavage and loss of sulfur. They are not oxidized to 1,1-dioxides by peracetic acid, ° but m-chloroperbenzoic acid accomplishes this oxidation. The unstable adducts with ketene decompose to amides with loss of hydrogen sulfide and sulfur dioxide or may be trapped by reaction with aromatic amines as shown for thiazetidine 1-oxide 422.An aldol-type condensation has been reported for A -cyclohexyl-1,2 thiazetidine-3-one 1-oxide and p-(A(A"-dimethylamino)benz-aldehyde. " Sulfur monoxide is lost in the flash-vacuum thermolysis of 422a. ... 

The reaction of nitriles with aromatic aldehydes is carried out at heating the reactants to 50-70°C with a 1 -h 10 (v/v) mixture of concentrated sulfuric acid and glacial acetic acid. The cycloaddition reaction is regiospecific. The oxazines 21 (equation 10) are formed as diastereoisomeric pairs which are free from their regioisomeric products in the limit of the NMR analysis. Precursors used were benzonitrile and acetonitrile as well as acetaldehyde, benzaldehyde and its substituted derivatives, and a number of the olefins having various structures. Until now, the reaction of aldehydes with nitriles was interpreted as an extension of the Ritter reaction. The initial O-protonation of aldehyde 22 is postulated to form in the presence of acid the hydroxycarbenium ion 23 which then reacts as a cationoid electrophile with the nitrile (equation 11) giving the nitrilium ion 24. 

Unsaturated and hydroxylated triterpenes and steroids give colored products with aromatic aldehydes in strong mineral acids, with acetic anhydride in sulfuric acid, and with inorganic salts (cerium(IV) sulfate and antimony(III) chloride, for example) in an acidic solution. These reactions have been used as the basis for determination of saponins. The analysis of Ginseng radix (Panax ginseng, Araliaceae) in Pharmacopoeia Helvetica VII, for example, relies on reaction with glacial acetic acid/sulfuric acid and spectrophotometric determination at 520 nm of the red product. The jS-aescine component of horse chestnut (Aesculus hippocastanum, Hippocastan-aceae) saponin can be determined spectrophoto-metrically after treatment with a mixture of iron(III) chloride, acetic acid, and sulfuric acid. 

In these cases it is usually possible to explain why the color is formed. The reactions can be further classified, on the basis of the type of colored compound formed, into reactions leading to the formation of azo dyes, di- or triphenylmethane dyes, xanthene dyes, polymethine dyes, indophenols, etc. Azo dyes are formed, for example, in the reaction of diazonium salts and phenols (p. 192) or amines (p. 324), azomethines in the reaction of primary aromatic amines with aromatic aldehydes (p. 215), di- and triphenylmethane dyes in the reaction of aromatic aldehydes with aromatic hydrocarbons in concentrated sulfuric acid (p. 213), triphenylmethane dyes in the reaction of phenols with aromatic aldehydes or oxalic acid (p. 196), xanthene dyes in the reaction of anhydrides of dicarboxylic acids with resorcinol (p. 196), polymethine dyes are formed after the cleavage of the pyridine ring in the reaction of the glutaconaldehyde formed and barbituric acid (p. 378), indophenols on reaction of phenols with Gibbs reagent (p. 195), or 4-aminoantipyrine according to Emerson (p. 194), or on the Liebermann reaction (p. 195). 

Dozens of applications of the color reaction of aliphatic alcohols with aromatic aldehydes in sulfuric acid can be found in the literature imder the name Komarowsky reaction. ... 

A variation involves the reaction of benzylamines with glyoxal hemiacetal (168). Cyclization of the intermediate (35) with sulfuric acid produces the same isoquinoline as that obtained from the Schiff base derived from an aromatic aldehyde and aminoacetal. This method has proved especially useful for the synthesis of 1-substituted isoquinolines. 

Aromatic aldehydes give 2-aryl-4-oxo derivatives (181) in the presence of concentrated sulfuric acid (70EGP73039), whilst pyrimidine derivatives (182) give octahydropyrido[4,3-with formaldehyde (e.g. 66M52). A similar reaction is observed with 6-methylpyrimidinones (e.g. 70M1415). 

The decarbonylation of aromatic aldehydes with sulfuric acid" is the reverse of the Gatterman-Koch reaction (11-16). It has been carried out with trialkyl- and trialkoxybenzaldehydes. The reaction takes place by the ordinary arenium ion mechanism the attacking species is H and the leaving group is HCO, which can lose a proton to give CO or combine with OH from the water solvent to give formic acid." Aromatic aldehydes have also been decarbonylated with basic catalysts." When basic catalysts are used, the mechanism is probably similar to the SeI process of 11-38. See also 14-39. 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

Diperoxyketals and Diperoxyacetals. Aromatic aldehydes react with alkyl hydroperoxides in the presence of strong acid catalysts such as sulfuric acid to form diperoxyacetals (1, X = OOR5 R1 = H, R2 = Ar. R3 = R3 = alkyl). Diperoxyketals (1, X = OCR5 R1, R2, R3. R3 = alkyl) are generally prepared by acid-catalyzed reaction of a ketone with two equivalents of an alkyl hydroperoxide. 

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