Fischer mineral acids

The only acid-resistant protective group for carbonyl functions is the dicyanomethy-lene group formed by Knoevenagel condensation with malononitrile. Friedel-Crafts acylation conditions, treatment with hot mineral acids, and chlorination with sulfuryl chloride do not affect this group. They have, however, to be cleaved by rather drastic treatment with concentrated alkaline solutions (J.B. Basttis, 1963 H. Fischer, 1932 R.B. Woodward, 1960, 1961). 

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

The question at once arose whether this a-pyrrolidine carboxylic acid, or a-proline as Fischer termed it in 1904, was a primary product or a secondary product formed by the action of mineral acids upon other products, but its formation by hydrolysis by alkali and by the action of pepsin followed by trypsin decided that it was a primary product and therefore one of the units of the protein molecule. Sorensen, in 1905, suggested that it might arise from an a-amino-S-oxyvalerianic acid which he synthesised, but the fact that this amino acid has not yet been obtained by hydrolysis of protein and the above facts seem to exclude this possibility. 

In the formation of glycosides by the Fischer process (equilibration in the presence of an acid catalyst), fucopyranosides are apparently formed more rapidly than galactopyranosides. In the presence of mineral acids, fucose attains equilibrium in boiling methanol within 6-8 h, whereas a reaction time of 20 h is customary for D-galactose. In reactions catalyzed by cation-exchange resins, maximum pyranoside formation is attained by 8 h for L-fucose,35a whereas D-galactose requires35612-24 h. 

Pyrrole was first isolated in pure form in 1857 from bone oil, although it had been observed in 1834 that coal tar and bone oil contained a substance which imparted a red color to pine splinters moistened with mineral acid. The structural formula was established in 1870. Pyrrole chemistry up to the early 1930s is reviewed in the comprehensive treatise of Fischer and Orth (B-34MI30400) and two modern (excellent) books by Gossauer, and Jones and Bean are available (B-74MI30400, B-77MI30400). 

Esters, RC02R, are named as salts are the R group is named first, followed by the name of the carboxylate group (for example, CH3CO2CH2CH3 is ethyl acetate). Esters can be prepared from an acid and an alcohol, with a mineral acid catalyst (Fischer esterification). The key step of the mechanism is nucleophilic attack by the alcohol on the protonated carbonyl group of the acid. Many esters are used as flavors and perfumes. 

The stability of an acetal or a ketal may depend on the catalyst employed in its synthesis. For this and other reasons, Fischer and Taube20 recommended the use of zinc chloride, rather than a mineral acid, as the catalyst in acetonation processes. Presumably the instability of the products prepared with the aid of strong acids is due to the difficulty of ensuring complete removal of the catalysts. 

Primary, secondary, and tertiary carboxylic amides, carboxylic esters, and carboxylic acids are protonated by mineral acids or sulfonic acids at the carboxyl oxygen to a small extent (Figure 6.9). This corresponds to an activation as discussed in Section 6.2.3. This activation is used in acid hydrolyses of amides and esters, in esterifications of carboxylic acids according to Fischer, and in Friedel-Crafts acylations of aromatic compounds with carboxylic acids. 

A side-chain methylenamino group reacts with a nitroso group (introduced in situ) when the compound is heated with mineral acid [2466]. An unusual reaction occurred when the nitro-t-amine (103.4) was refluxed with acetic anhydride and zinc chloride the course of this reaction may involve an A -oxide [2039]. When an o-nitroalkylamine is heated with ethoxide, the two functions are converted into a 1-hydroxyimidazole ring [3004]. Nitrosation of the pyrim-idinone (103.5) involves several steps including a Fischer-Hepp rearrangement of an iV-nitroso to a ring-C-nitroso the final product is a 6-(4 -nitrophenyl-amino)purin-2-one [2667]. In a weakly basic medium, the nitroamine (103.6) is cyclized to either the benzimidazole (when R == H), or the benzimidazolone (when R H). 

The Fischer glycosylation involves the use of acids mineral acids such as HCl, HF, and H2SO4 have been applied successfully [15-23]. p-Toluenesulfonic acid can also be used. The use of homogeneous acids results in the need for neutralization and washing steps, and the inconvenience of possible corrosions in the unit... 

Asymmetrically disubstituted hydrazines can be obtained by reduction of nitrosamines. Singly substituted hydrazines can be prepared, in principle, analogously through the intermediacy of alkylnitrosoureas. These reductions are usually carried out by zinc in acetic acid if mineral acid is used the nitroso group is split off. The method goes back to work by Emil Fischer.124... 

The mechanism of the Fischer indole synthesis is related to that of the benzidine rearrangement.91 This synthesis consists of the preparation of indole and substituted indoles by heating the phenylhydrazones or substituted phenylhydrazones of aldehydes, ketones, or oxo acids with reagents such as zinc chloride, or mineral acids that lead to elimination of ammonia, thus 92... 

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