N of imidazole

In contrast, LFMM/LFMD is much faster and provides a uniform treatment over the whole molecule (i.e., there are no link atoms). Moreover, proteins behave like giant ligands. They may be exquisitely complex and varied but, at the end of the day, the intrinsic bonding interaction between, say, Cu(II) and the N of imidazole is essentially the same whether the imidazole is a free ligand or happens to be part of a histidine which is, in turn, connected to a peptide backbone. Hence, if an LFMM FF can be constructed for small coordination complexes containing biologically relevant donors, then it should work for whole proteins. 

Is such an open coordination on Cu(I) in BESOD, presumably occupied by a water molecule , entirely compatible with the mentioned similarity of the X-ray absorption edge of reduced (Cu, Zn )-BESOD and Cu (imidazole) A distinction between O of water and N of imidazole might not have been possible. 

In hemin and hematin there is no protein the fifth ligand is HjO in place of N of imidazole as in the hemoglobins. 

Ogiso (1967) obtained two kinds of crystals from the reaction of histidine and cupric ion. The ratio of histidine and Cu was found to be 1 1 and 2 1, and the structures of the Cu-histidine chelates were deduced from infrared data. In the 2 1 chelate, coordination from the a-amino N and the N of imidazole to Cu was presumed. The carbonyl-oxygen approaches the Cu closely enough to be considered as loosely bound. In the 1 1 chelate, coordination through the carbonyl group and the N of the imidazole ring was presumed to form a 7-membered ring. 

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

If this intermediate, in turn, is more n idly attacked by water or hydroxide ion than the original ester, the overall reaction will be faster in the presence of the nucleophile than in its absence. These are the requisite conditions for nucleophilic catalysis. Esters of relatively acidic alcohols (in particular, phenols) are hydrolyzed by the nucleophilic catalysis mechanism in the presence of imidazole ... 

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... 

Annular tautomerism of azoles and benzazoles [the nonaromatic tautomers of imidazole 17, 2H and 4(5)H have been calculated at the MP2/6-31G level to be about 15 kcal mol less stable than the IH tautomer (95JOC2865)]. We present here the case of 4(5)-substituted imidazoles, different from the histamine, histidine, and derivatives already discussed. By analogy with these histamines, 4-methylimidazole 17a is often named distal [N(t)H] and 5-methylimidazole 17b, proximal [N(7t)H] (Scheme 9). 

By far the most common starting material is l-methylimidazole. This is readily available at a reasonable cost, and provides access to the majority of cations likely to be of interest to most researchers. There is only a limited range of other N-substituted imidazoles commercially available, however, and many are relatively expensive. The synthesis of l-alkylimidazoles may be achieved without great difficulty, though, as indicated in Scheme 2.1-2. 

Rhodium(III) hydroxide is an ill-defined compound Rh(0H)3.nH20 (n 3) obtained as a yellow precipitate by careful addition of alkali to Na3RhCl6-Addition of imidazole solution to suitable aqua ions leads to the precipitation of active rhodium(III) hydroxides formulated as Rh(0H)3(H20)3, Rh2(/x-0H)2(0H)4(H20)4 and Rh3(/z-0H)4(0H)5(H20)5 [31]. Hydrated iridium(III) hydroxide is obtained as a yellow precipitate from Ir3+ (aq.) at pH 8. 

When the aromatic group of the sulfoxide is replaced by a heteroaromatic group (e.g., N-methylimidazole), the internal coordination between Li—N to form a five-membered metallocycle apparently predominates over Li—O coordination to form a four-membered metallocycle . Reaction of imidazole (S)-sulfoxide 16 with benzaldehyde produces aldol 17 as the major product in which the a-H and the sulfoxide lone pair are syn (equation 14) imidazole (R)-sulfoxide 18 reacts similarly (equation 15). The stereochemical outcome of these reactions is rationalized in terms of a-lithiosulfoxides in which the reactive diastereomer (i.e., 20 and 21) is that having one diastereotopic face of the five-membered Li—N metallocycle carrying both H and sulfoxide lone pair. 

Fig. 40 Microwave-assisted substitution of imidazole on C-2 in solid-phase. Reagents and conditions a benzaldehyde, N,N-diisopropylethylamine, CH2CI2, 24 h, rt b Nucleophile, TEA, Bp3Et20, THP, MW 120 °C, 5 min, closed vessel...

Scheme 14). The diversity of the collection of imidazoles prepared was relatively high, and yields ranged from 17 to 83%. It is interesting to observe that the intermediate N-hydroxyimidazole 46 was obtained when the reaction was carried out at temperature lower than 200 °C. 

The mechanism of the reaction has not been eiuddated. Presumably iodine eliminates the imidazole ring from N-substituted imidazole derivatives such as clotrimazole, and this then couples with diazotized sulfanilic acid to yield an azo dye. 

With sUght modifications of these conditions it is possible to prepare mono N-substituted imidazoles (Scheme 5), the reaction working well with aliphatic amines but not with many aromatic amines. The imsymmetrical... 

Burgess followed a similar strategy for the preparation of the salts 8 (Scheme 7). On that occasion several routes to mono-N-substituted imidazoles were explored yielding the desired compoimds in variable yields depending on the nature of the amines. The chirality was introduced via alkylating reagents 9 bearing chiral oxazolines [15]. 

Gade and Bellemin-Laponnaz have reported the synthesis, in good yields, of chiral oxazoline-imidazoliums salts 10a (Scheme 8) obtained by reaction of 2-bromo-4(S)-t-butyl oxazoline with several mono-N-substituted imidazoles [16]. Similaly an imidazolium salt 10b bearing a paracyclophane substituent was prepared by Bolm [17]. 

Because esters 745 a, b of imidazole-acetic acid are unstable when stored for long periods, owing to intramolecular catalysis by the imidazole moiety, the esters should be converted into their salts or free acids and stored as such. Only tert-butyl imidazole-(4,5)acetates derived from tert-butyl 4-chloroacetoacetate seem to be stable [232, 233]. N-alkyl-substituted amidines give rise to a mixture of alkyl N-alkylimidazole-4- and 5-acetates [232, 233]. 

On heating DMSO with 2 equivalents of imidazole and hexamethyldisilazane (HMDS) 2, or of N-trimethylsilylimidazole 1219 [32], to 140-160°C the intermediate S-ylide 1220 adds to the imidazole to give N-methylthiomethylimidazole 1221 in 40-60% yield and HMDSO 7 and NH3 or imidazole [33]. The analogous reac-... 

Treatment of the sulfoxide 1222 a with tert-butyldimethylsilyl chloride 85 a and excess imidazole in DMF at 25 °C furnishes the imidazole derivative 1223a in 70% yield, whereas the phenyl derivative 1222b affords, besides 47% of 1223b , the cyclized product 1224 in 24% yield and 94 a and imidazole hydrochloride [34] (Scheme 8.14). Reaction of 1225 with N-(trimethylsilyl)imidazole 1219 at 170°C affords 1226 in 50% yield [35]. 

We have also shown ( 8) that other bases stronger than CH-CX) (pK. 4.75) catalyse the decomposition of N -nitroso-2-pyrrolidone at o C. With the exception of imidazole, these reactions follow uncomplicated second order kinetics (Rate = kp[Substrate][Base]) and only products of deamination (hydrolysisT are obtained. Generally, values increase with the base strength of the catalyst and fit tne Br/e(nsted relationship withes 0.66. However, the absence of significant catalysis by sterically hindered bases 2,6-lutidine), the strong catalysis by imidazole relative to HPOi (k2(Imidazole)/k2(HP0J ) = 83) and by hydroxide ion relative to... 

Similarly, pyrrole, indole, and tetrahydrocarbazole [285] as well as diarylamines give the corresponding N-vinyl compounds [286]. Several improvements of yields and reaction rates were observed by conducting the reactions in the presence of additives [287, 288]. The vinylation of imidazole and benzimidazole was reported to be catalyzed by KOH in the presence of zinc or cadmium salts [289]. The above reactions were reviewed in 1965 [290]. 

Further improvements in activity of the ruthenium carbene complexes were achieved by incorporation of methyl groups in 3,4-position of imidazol-2-ylidene moiety. Introduction of sulfur in the trara-position to the N-heterocyclic carbene leads to increased stability of the resulting ruthenium complexes. The synthesis and the first applications of these new rathenium complexes are described herein. 

The use of AMximethylsilylimidazole has been suggested in the reaction with acid chlorides to form imidazolides.[3] In fact, the rate of conversion to imidazolides by reaction of iV-trimethylsilylimidazole with acid chlorides is remarkably rapid even at rather low temperatures. On the other hand, the preparation of the N-trimethylsilylimid-azole from imidazole requires the heating of imidazole with hexamethyldisilazane for several hours. 

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