Protection of imidazoles

KOH, H2O, reflux, 12 h, 64-92% yield. This group is more stable to n-BuLi than is the benzyl group in the protection of imidazoles... 

Protection of imidazole NH, The imidazole NH group of the histidine derivative 2 is protected as the p-methoxysulfonamide 3 by reaction with 1 and EtsN. This sulfonamide derivative is stable to the acidic conditions required to remove the... 

Reagent for the Protection of Secondary Amines. SEM-Cl can be used to protect secondary aromatic amines (eq 13), and is an ideal reagent for the protection of imidazoles, indoles, and pyrroles (eqs 14-16). Many functional groups are compatible with the introduction and cleavage of SEM amines, and the SEM substituent is unusually stable to further functionahzation of the molecule. " Recently, a one-pot method for protection and alkylation of imidazoles employing w-butyllithium and SEM-Cl has been developed (eq 17). ... 

The phenolic hydroxyl group of tyrosine, the imidazole moiety of histidine, and the amide groups of asparagine and glutamine are often not protected in peptide synthesis, since it is usually unnecessary. The protection of the hydroxyl group in serine and threonine (O-acetylation or O-benzylation) is not needed in the azide condensation procedure but may become important when other activation methods are used. 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

The THP derivative of the imidazole nitrogen in purines has been prepared by treatment with dihydropyran (TsOH, 55°, 1.5 h, 50-85% yield). It is cleaved by acid hydrolysis. The THP group is useful for the protection of 1,2,4-triazoles. ... 

Hydroxy group of perhydropyrido[l,2-A][l,2]oxazin-8-one 23 (R = H) was protected with t-BuPh SiCl in the presence of imidazole in DMF (OOOL2955, 01JOC3338). 

In a one-to-one ratio the reaction of CDI with (CH3)3Si(CH2)20H gave the corresponding imidazole carboxylate (97% yield), which was used in a selective protection of verrucarol, the parent compound of mycotoxines, as follows 12403... 

Carbamates by Reaction of Imidazole- or Imidazolium-iV-carboxylates. Introduction of Amino Protecting Groups... 

The 2-adamantyloxycarbonyl group has been found suitable for protection of the imidazole function in histidine during peptide synthesis.[7a]... 

AM Kimbonguila, S Boucida, F Guibe, A Loffet. On the allyl protection of the imidazole ring of histidine. Tetrahedron 53, 12525, 1997. 

The parent 2(3/i/)-oxazolone moiety functions as a bifunctional leaving group when carboxyl groups are activated for acylations and condensations, similar to other five- and six-membered heterocycles such as imidazole, triazole, and 2-pyridinethiol. The excellent leaving ability of a 2(3//)-oxazolone moiety has led to the development of versatile reagents. Thus, 3-acyl- and 3-alkoxycarbonyl-2(3//)-oxazolones serve as ready-to-use -type agents for the regioselective and chemoselective N-protection of amino alcohols, amino phenols and polyamines. 

Protection of alcohols.1 Dimethylthexylsilyl ethers are prepared from primary or secondary alcohols by reaction with 1 and either imidazole or N(C2H5)3 in DMF. The ethers of tertiary alcohols are prepared by reaction with dimethylthexylsilyl trifluoromethanesulfonate in the presence of lutidine or N(C2H5)3. Silylation of amines, amides, mercaptans, and acids is conducted under similar conditions. 

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