Imidazole as a base

The amino acid histidine contains an imidazole ring. We have just seen that unsubstituted imidazole as a base has p/Ca 7.0. From the Henderson-Hasselbalch equation... 

Initial optimisation between crotonaldehyde and a PMP-protected imine gave a high ratio of ElZ enal (17 1) in excellent enantiomeric excess (98%) and good yield (71%) using 1.0 equivalent of imidazole as a base in only 2 h. 

The second pol5mierization method of EDOT is also possible by utilizing FelII(Ots)3, at elevated temperature, in combination with imidazole as a base, resulting in a black insoluble and infusible... 

The primary hydroxyls are better nucleophiles than the secondary ones so they can be selectively modified using a weak base. Using tert-butyldimethylsilyl chloride (TBSCl) in dimethylformamide (DMF) with imidazole as a base, or in pyridine, gives access to cyclodextrins 5a-c persilylated on their primary rim (Scheme 9.2) [13]. Once these positions are protected, the position 2 can be efficiently functionalized... 

General Considerations. Like other bulky trialkylsilyl groups, the triphenylsilyl group was introduced to serve as a hydrolytically stable protecting group for alcohols. The hydroxyl functionality can be easily derivatized using Ph3SiCl in the presence of a tertiary amine or imidazole as a base (eqs 1 and 2). ... 

An imidazole ring is a structural unit m the ammo acid histidine (Section 27 1) and is involved m a large number of biological processes as a base and as a nucleophile... 

One-pot multi-bond-forming reactions are one of the ways to address the ever growing demand for efficiency in organic synthesis. Rosini and coworkers have developed (tandem) processes for the synthesis of a highly functionalized tricyclic system. The reaction is simply performed by bringing together, at room temperature, a-bromo aldehydes, ethyl nitroacetate, and chlorodimethylvinylsilane in the presence of imidazole as the base (Eq. 8.83).134... 

Anodic oxidation of o-amino substituted aromatic Schilf bases (38 and 40) to imidazole derivatives 39 and 41 were carried out in CH3CN-O.I mol/1 Et4C104 solution with addition of pyridine as a base, using controlled potential electrolysis and a divided cell [72] (Scheme 22). 

This level of ionization is particularly relevant in some enzymic reactions where histidine residues play an important role (see Section 13.4.1). This means that the imidazole ring of a histidine residue can act as a base, assisting in the removal of protons, or, alternatively, that the imidazolium cation can act as an acid, donating protons as required. The terminology used for such donors and acceptors of protons is general acid catalyst and general base catalyst respectively. 

A typical role for the histidine imidazole ring is shown below, in the enzyme mechanism for a general base-catalysed hydrolysis of an ester. The imidazole nitrogen acts as a base to remove a proton from water, generating hydroxide that attacks the carbonyl. Subsequently, the alkoxide leaving group is reprotonated by the imidazolium... 

The stability of dialkylimidazolium cation-containing ionic liquids can be a problem even at moderate temperatures in the presence of some reagents or catalysts. For example, when CsF and KF were used in the ionic liquid [BMIM]PFg to perform a halogen exchange reaction in an attempt to replace Br from bromo-carbons with F , it was found that alkyl elimination from the [BMIM] cation took place, forming methyl imidazole, 1-butene, 1-fluorobutane, and other unidentified products at 150°C overnight 69). The fluoride ion acted as a base that promotes elimination or substitution processes. 

When pyridine is used as a base, a pyridinium salt C5H5NH+(CH30S03) is formed. Nowadays, pyridine is replaced by imidazole or diethanolamine, which yield more stable and less odorous commercial products. 

In an attempt to couple halobenzaldehydes with amines, A1203 was pre-absorbed with the substituted benzaldehydes and imidazole or piperidine as a base and irradiated with microwaves. However, the corresponding benzylic alcohols and benzoic acids were unexpectedly obtained by the Cannizzaro route (Scheme 4.20). The products of Cannizzaro reactions were also obtained as the main products, when microwave-assisted condensation reactions of benzaldehydes with vinyl acetate using barium hydroxide as the catalyst were attempted40. 

Regioselective phosphate hydrolysis of 41 and 42 was realized with bifunctional catalysts 43-45, in which one imidazole acts as a base, while the other protonated species acts as an acid (Scheme 13.10) [38]. Whereas all three catalysts were able to hydrolyze 41, only 44 and 45 could cleave 42, and in all cases the maximum... 

Another kinetically equivalent possibility must be considered the free imidazole in these catalysts may be acting as a nucleophile at phosphorus, not as a base. This is not yet excluded experimentally, but it seems unlikely. No intermediate phosphoimidazole is detectable, but of course it might be hydrolyzing rapidly. However, molecular models for such a reaction of VII with VIII are very strained, and essentially impossible with the naphthalene substrate to be described below. Only with the extra water molecule of the general-base mechanism do the models fit well. 

A similar reaction sequence starting with m-dimethoxy tellurium tetrafluoride, but using imidazole as the base, yielded cis-hydroxy methoxy tellurium tetrafluoride (b.p. 48°/8 torr)1,2. 

Much effort has been devoted to finding synthetically useful methods for the palladium-catalyzed aerobic oxidation of alcohols. For a detailed overview the reader is referred to several excellent reviews [163]. The first synthetically useful system was reported in 1998, when Peterson and Larock showed that simple Pd(OAc)2 in combination with NaHC03 as a base in DMSO as solvent catalyzed the aerobic oxidation of primary and secondary allylic and benzylic alcohols to the corresponding aldehydes and ketones, respectively, in fairly good yields [164, 165]. Recently, it was shown that replacing the non-green DMSO by an ionic liquid (imidazole-type) resulted in a three times higher activity of the Pd-catalyst [166]. 

We created a mimic of the cleavage of the cyclic phosphate by this enzyme by attaching two imidazole groups to a cyclodextrin molecule in well-defined positions (18). In water, the cyclodextrin bound a cyclic phosphate substrate—not, however, one derived from RNA—and performed the cleavage of the cyclic phosphate by using the two imidazoles as the enzyme does. That is, one functioned as a base, which delivered water... 

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