N-methylimidazole

Here AX is the acetyl compound (acetyl chloride or acetic anhydride), N is N-methylimidazole, I is the intermediate (presumably A -acetyl-A -methylimidazo-lium ion), X is the counterion (chloride or acetate), and ROH is the acetyl acceptor (alcohol or water). A general treatment of Scheme XXIII requires specification of the detailed nature of and k[ and is probably too complicated to be of practical use. However, several important special cases may arise from the operation of the ratio kxlk x, the behavior of apparent rate constants k /. and k, the relative magnitudes of k / and k, the relative concentrations of the reactants, the method of observation, and the nature of ROH. These cases are outlined in Scheme XXIV. 

The rate constant /ct, determined by means of Eq. (6-47) or (6-48), may describe either general base or nucleophilic catalysis. To distinguish between these possibilities requires additional information. For example, in Section 3.3, we described a kinetic model for the N-methylimidazole-catalyzed acetylation of alcohols and experimental designs for the measurement of catalytic rate constants. These are summarized in Scheme XVIIl of Section 3.3, which we present here in slightly different form. 

Bu3Sn)20, toluene, reflux BnBr. N-methylimidazole, 95% yield. Equatorial alcohols are benzylated in preference to axial alcohols in diol-containing substrates. 

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. 

To a 50-mL polypropylene vial (Note 1) are added 0.839 g (2.67 mmol) of 2-[ethyl[4-[(lE)-(4-nitrophenyl)azo]phenyl]amino]ethanol (Disperse Red 1, Note 2), 0.985 g of (2.39 mmol) N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-aspartic acid,l-(l, 1-dimethylethyl) ester (Fmoc-L-Asp-OtBu, Note 3), 3.26 g (4.73 mmol) of polystyrylsulfonyl chloride resin (Note 4), and 30 mL anhydrous methylene chloride (Note 5). The vial is capped and the mixture is shaken for five min (Note 6). N-Methylimidazole (0.764 mL, 9.58 mmol) is then added to the deep red mixture (Note 7) and the resulting mixture is shaken for 2 hr (Note 8). 

N-Methylimidazole is then removed from the reaction mixture with Amberlyst 15 ion exchange resin (Note 9) using the following procedure. To a 2-cm diameter column equipped with a glass frit (Note 1) is added 7 g of Amberlyst 15, which is rinsed with 25 mL of methylene chloride. The reaction mixture is added and the resin mixture is rinsed with 50 mL of methylene chloride. The filtrate is collected in a 250-mL flask (Note 10) and the solvent is removed on a rotary evaporator to afford 1.63-1.66 g (96-98%) of the desired ester 1 as a deep red foam. HPLC analysis showed a purity of 98% (Notes 11, 12, 13, 14). 

In place of N-methylimidazole (Melm), only dimethylaminopyridine (DMAP) could be substituted. The solid-supported amines piperidinomethyl- or morpholinomethyl polystyrene resins, pyridine, and tertiary amines like triethylamine andN-methylmorpholine were not effective. 

The amino acid 58 was used in the solid-phase synthesis of sequence-specific DNA binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids <96JACS6141> and it was also reported that the imidazole-acridine conjugate 59 could effectively catalyze the cleavage of t-RNA <96TL4417>. 

THF, tetrahydrofuran DMF, dimethylformamide DMSO, dimethyl sulfoxide DPSO, diphenyl sulfoxide en, ethylenediamine py, pyridine pic, picoline lut, lutidine nic, nicotinamide IMD, imidazole MelMD, N-methylimidazole 1-Cl-nap, 1-chloronaph-thyl acac, acetylacetonyl anion, CH3COCHCOCH3 C4H9O3, acetoacetic ester anion, CH3COCHCOOC2HS C4H,oN2, piperazine C7HSN2, benzimidazole. 

This mechanistic interpretation is supported by the isolation of N-acetylimidazole as a major product and the observation of only first order catalysis by N-methylimidazole irrespective of the pH... 

Trinucleotides are formed by 5 -deprotection of the dinucleotide and subsequent conversion with the monotriazolide in the presence of N-methylimidazole. The fully protected di- and trideoxyribonucleotides of the following nucleotide sequences have been obtained in high yield T-T (82%), C-T (88%), C-C (84%), CM3 (81%), G-T (83%), A-G-T (65%), C-G-T (61%). The yields are similar to those obtained in a reaction involving l-(triisopropylbenzenesulfonyl)tetrazole as coupling agent(see also Section 12.7). 

Figure 10 Three views of the Co-02 adduct of (261), with a disordered N-methylimidazole as the sixth ligand (reproduced with permission of the American Chemical Society from Inorg. Chem., 1994, 33, 910-923).

NLO active molecules can be embedded in or chemically anchored to a sol-gel-matrix without changing the optical absorption spectrum. Disperse Red 1, a very efficient molecule for NLO applications, was embedded in a sol-gel-matrix, synthesized by hydrolysis and condensation of 3-glycidoxypropyltrimethoxysilane in the presence of N-methylimidazole. The dye-doped gel was applied to glass substrates and thermally cured to form a layer of perfect optical transparency. Currently, poling experiments and NLO measurements with these layers are being performed. 

A pyridyl bis-N-heterocydic carbene (NHC) ligand has been prepared by Steel and Teasdale based on nudeophilic aromatic substitution of dichloroisonicotinic amides with N-methylimidazole (Scheme 6.122) [250]. Microwave heating of the neat reagents at 140 °C for 10 min provided a 91% yield of the corresponding bis-... 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

Generally, the N,C-coupling reactions of compounds (475) with nucleophiles are performed at 20°C in dichloromethane in the presence of 5% triethylamine or N-methylimidazole. 

The reactions of most of known Nu (tertiary amines, N-alkylated azoles, etc.) with BENA proceed through the pathway (a). This interpretation is additionally confirmed by the fact that the reaction of N-methylimidazole with unsymmet-rical BENA (434a) produces exclusively trimethylsilyl salt (512"), whereas the pathway (b) would afford salt (512 ). 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

Ohta s group thoroughly studied the heteroaryl Heck reactions of chloropyrazines and jt-electron-rich heteroaryls [42-44], The substitution occurred at the electron-rich C(5) position of the imidazole ring for the heteroaryl Heck reaction of 2-chloro-3,6-dimethylpyrazine and N-methylimidazole. 

The similarity in the rate laws does not allow a clear choice to be made between mechanisms, but Mechanism A is required in H20 by the observation of general base catalysis. However, the relative stability of the (red) T° intermediate in Me2SO (this is dependent on the nature of the AA side chain, cf. Section III,C) in the absence of proton-ated amine makes us prefer Mechanism B for reaction in this solvent, since the solvent is unable to assist the departure of MeOH. The similar catalytic rate constants found for B = imidazole, Af-methylimidazole (26) suggest that transfer of the proton from T+ to the alcohol function remains stepwise (i.e., via T°) since N-methylimidazole cannot carry out a concerted transfer. Such general acid-catalyzed loss of MeOH from T° supports a suggestion made many years ago by Burnett and Davies relating to purely organic esters (62). 

Especially noteworthy is the following feature the oxygen donors, dimethyl-formamide, tetrahydrofuran, methanol, and ethanol seem to allow a stabilization of the CO ligand which is well comparable with that achieved by the much stronger a-donors, triethylamine or N-methylimidazole (Table 10, [50a-/]). It is suggested that these ligands also act as simultaneous a- and ir-donors, as do the imidazoles. With its low basicity, DMF seems to have a very favorable a/ff-donor balance for the trans fixation of rr-acceptor ligands, which are themselves weak o-donors, like CO, N2, NO , or 02, and indeed, the 7r-donor function of DMF is well documented (S). 

The authors reasoned that the aqueous succinic anhydride capping buffer (comprised of 96% NMP and 4% sodium borate) may have led to the redissolving of probe DNA fhaf was subsequently randomly redeposited over the entire slide, leading to elevated backgrormd. As a result, a reformulation of succinic anhydride info a nonaqueous medium of dichloroet-hane (DCE) solvenf confaining N-methylimidazol (acylation catalyst) was undertaken. Significant improvements in interspot backgrounds were evident. 

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