Carboxylic acids rearrangement

Carboxylic acid azides give rise to three different reactions under different conditions. Azide coupling (equation 9) was the earliest method in peptide synthesis and is still one of the most important in fragment condensation and preparation of cyclic peptides due to its almost complete lack of racemization. At elevated temperatures a frequent side reaction is the Curtius rearrangement. Trapping of the intermediate isocyanate with amines (equation 10) gives urea derivatives and with carboxylic acids rearranged amides are obtained (equation 11). ... 

This reaction applies to many i,2 diketones, and is termed the Benzilic Acid Rearrangement. It provides a ready method for the preparation of disubstituted a4iydroxy-carboxylic acids. When applied to a cyclic 1,2-diketone, the ring system is necessarily reduced by one carbon atom for example, cyclohexan-i,2 ... 

The conversion of a carboxylic acid into an amine by treatment with hydrazoic acid in concentrated sulphuric acid is known as the Schmidt reaction or rearrangement ... 

The reaction of trivalent carbocations with carbon monoxide giving acyl cations is the key step in the well-known and industrially used Koch-Haaf reaction of preparing branched carboxylic acids from al-kenes or alcohols. For example, in this way, isobutylene or tert-hutyi alcohol is converted into pivalic acid. In contrast, based on the superacidic activation of electrophiles leading the superelectrophiles (see Chapter 12), we found it possible to formylate isoalkanes to aldehydes, which subsequently rearrange to their corresponding branched ketones. 

Another useful route to cyciopentanes is the ring contraction of 2-bromo-cydohexanones by a Favorskii rearrangement to give csrdopcntanecarboxylic acids. If a 0 dibromoketones are used, ring opening of the intermediate cydopropanone leads selectively to, y-unsaturated carboxylic acids (S.A, Achmad, 1963, 1965 J. Wolinsky, 1965). 

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Carboxylic acids react with butadiene as alkali metal carboxylates. A mixture of isomeric 1- and 3-acetoxyoctadienes (39 and 40) is formed by the reaction of acetic acid[13]. The reaction is very slow in acetic acid alone. It is accelerated by forming acetate by the addition of a base[40]. Addition of an equal amount of triethylamine achieved complete conversion at 80 C after 2 h. AcONa or AcOK also can be used as a base. Trimethylolpropane phosphite (TMPP) completely eliminates the formation of 1,3,7-octatriene, and the acetoxyocta-dienes 39 and 40 are obtained in 81% and 9% yields by using N.N.N M -tetramethyl-l,3-diaminobutane at 50 in a 2 h reaction. These two isomers undergo Pd-catalyzed allylic rearrangement with each other. 

Fig. 21. Representative nonionic photoacid generators. A variety of photochemical mechanisms for acid production ate represented. In each case a sulfonic acid derivative is produced (25,56,58—60). (a) PAG that generates acid via 0-nitrobenzyl rearrangement (b) PAG that generates acid via electron transfer with phenohc matrix (c) PAG that is active at long wavelengths via electron-transfer sensitization (d) PAG that generates both carboxylic acid and...

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

Imtdazo[4,5-c]pyridtne, 4,5,6,7-tetrahydro-synthesis, 5, 623, 640, 641 Imidazo[4,5-c]pyridine-6-carboxylic acid, 4,5,6,7-tetrahydro-synthesis, 5, 623, 641 Imidazopyridines as anthelmintic, 1, 202 synthesis, 5, 462 Imidazo[l,2-n]pyridines deuterium exchange, 5, 611 diazo coupling, 5, 614 Dimroth rearrangement, 5, 613 halogenation, 5, 611 hydrogenation, 5, 614 Mannich reaction, 5, 612 nitration, 5, 612 1-oxides... 

Isotubaic acid — see Benzofuran-5-carboxylic acid, 4-hydroxy-2-isopropyl-Isouramil occurrence, 3, 144 5-Isoxalones potentiometry, 6, 11 Isoxanthopterin, 6-acetonyl-structure, 3, 276 Isoxanthopterin, 3,8-dimethyl-rearrangements, 3, 309 Isoxanthopterin, 6-methoxy-3,8-dimethyl-synthesis, 3, 297 Isoxanthopterin, 6-methyl-bromination, 3, 301 Isoxanthopterin, 8-methyl-synthesis, 3, 319 Isoxanthopterin, 6-phenacyl-structure, 3, 276... 

Boekelheide rearrangement, 3, 303 Lumazine, 6,7,8-trimethyl-hydrogen exchange, 3, 303 Lumazine, 1,3,6-trimethyl-7-hydroxy-bromination, 3, 302 Lumazinecarboxylic acid occurence, 3, 324 Lumazine-6-carboxylic acid methylation, 3, 297... 

Pterin-6-cafboxylic acid, 3,8-dimethyl-rearrangements, 3, 309 Pterincarboxylic acids occurence, 3, 323 Pterin-6-carboxylic acids acidity, 3, 277 methylation, 3, 297 synthesis, 3, 295, 304 Pterin-7-carboxylic acids acidity, 3, 277 methylation, 3, 297 synthesis, 3, 295 Pterin coenzymes biochemical pathways, 1, 260-263 Pterin-6,7-dicarboxylic acid decarboxylation, 3, 304 reactions, 3, 304... 

Rearrangement of 0-acyi hydroxarrac acxl derivatives with base or heat to amines or urea derivatives (via isocyanates) or rearrangement of carboxylic acids via their hydroxamic acxis to amines... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

A formal Pictet-Spengler condensation to give 2,3-dihydro-lH-2-benzazepine-3-carboxylic acid 36 was achieved in quantitative yield via a sigmatropic rearrangement of ci5-2,3-methanophenylalanine 35 in the presence of paraformaldehyde and hydrochloric acid at room temperature. It is interesting to note that homophenylalanine 38 did not cyclize to give 37, even under vigorous reaction conditions. 

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