Imidazole protecting groups

The trityl-, dimethylsulfamoyl- and the SEM-groups work best for NH protection in the C5 functionalisation of the imidazoles. Protective groups for the C2 position such as the... 

CHAPTER 8 STUDIES OE BIOMACROMOLECULAR STRUCTURES CHEMICAL SYNTHESIS TABLE 8.5 Imidazole protecting groups, Y in Y—Nim R... 

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 dinitrophenyl group has been used to protect the imidazole — NH group in histidines (45% yield)" by reaction with 2,4-dinitrofluorobenzene and potassium carbonate. Imidazole —NH groups, but not a-amino acid groups, are quantitatively regenerated by reaction with 2-mercaptoethanol (22°, pH 8, 1 h)." The 2,4-... 

Two new sections on the protection for indoles, imidazoles, and pyrroles, and protection for the amide — NH are included. They are separated from the regular amines because their chemical properties are sufficienth different to affect the chemistry of protection and deprotection. The Reactivity Charts in Chapter 8 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first discussed. 

An interesting synthesis of a nucleoside carbonic ester was conducted in excellent yield by reaction with 1 -methyl-3 - [2-(p-nitropheny l)ethoxycarbony 1]-imidazolium chloride (for an analogous introduction of the npeoc-protecting group, see also Section 3.10.1) [2393 as mentioned in Section 3.1.8, methylation of the imidazole unit increases significantly the reaction rate. 

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

The benzyloxycarbonyl protecting group for amines is introduced in high yield using benzyl imidazole-carboxylate with a catalytic amount (5%) of dimethylamino-pyridine.[1953... 

An AT-dimethylsulfamoyl-protected 4-iodoimidazole is joined with N-tert-butoxy-carbonyl-4-piperidone via a Grignard reaction to give, in good yield after dehydration and elimination of the two protecting groups with concentrated HC1, 4(5)-( 1,2,5,6-tetra-hydropyridin-4-yl)imidazole as dihydrochloride c 151... 

The hydroxyl group was usually protected, because cyanohydrins have tendency to racemization or even decomposition. Vinyl ethers or acetal and acid catalysts furnish acetals [62]. Trialkylsilyl chlorides and imidazole are used to give silyl ethers [63]. Commonly used protective groups are silyl ether, ester, methoxy isopropyl (MIP) ether, and tetrahydro-pyranyl ether. ( -Protected cyanohydrins are tolerant to a wider range of cyanide/nitrile transformations and are utilized widely in the synthesis of compounds of synthetic relevance in organic chemistry. 

Interestingly, with only slight difference in the imidazole N-protection, an anomalous Stille reaction occurred for the stannane 43 [29]. When the protecting group of the 5-stannylimidazole was changed from methyl into 1-ethoxymethyl, the reaction between 3-iodoindole 44 and 1-ethoxymethyl-5-bromo-2-methylthioimidazole (46) gave not only the normal ipso product 47 but also the cine product 48. 

Several methods are available to access glycosyl iodides (Scheme 2.50). Anomeric hemiacetals bearing diverse protecting groups (Bn, Bz, Ac, N3, CMe2) upon treatment with a polymer-bound triphenylphosphine-iodine complex and imidazole can be converted into a-glycosyl iodides [179]. The precipitated by-products,... 

Halotriazoles can act as halogenating agents and A-acyltriazoles can act as acyl transfer reagents. Triazole can be used for the synthesis of peptide bonds and is superior to imidazole in that less racemization is observed. It can also be used to transfer the t-butyloxycarbonyl (t-Boc) protecting group to the nitrogen of amino acids. For details see Polya <84CHEC-I(5)733, p. 786). 

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