Imidazol 2, 3 Formamid

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

Ye et al. reported that the reduction of 2,4-dichlorophenyl-2-chloroethanone 1 with potassium borohydride in dimethylformamide to give 90% a-chloromethyl-2,4-dichlorobenzyl alcohol 2. Alkylation of imidazole with compound 2 in dimethyl formamide in the presence of sodium hydroxide and triethylbenzyl ammonium chloride, gave l-(2,4-dichlorophenyl-2-imidazolyl)ethanol 3 and etherification of 3 with 2,4-dichlorobenzyl chloride under the same condition, 62% yield of miconazole [9]. 

The protected 5-amino-l-ribofuranosyl-4-(5-methyl-l,2,4-oxadiazol-3-yl)imidazole 58 (Equation 4) undergoes MHR to afford the 3-acetamidoimidazopyrazole 59 in dimethyl formamide (DMF) or DMSO as solvent at... 

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). 

Dagegen laBt sich das bei der Synthese von 2-Methyl-imidazol durch Fragmentierung von Ethandial (Glyoxal) in Formamid und Formaldehyd in geringer Menge gebildete Imidazol durch Destination Oder Umkristallisation leicht abtrennen. 

Aryl-imidazole konnen direkt aus Alkyl-aryl-ketonen in einer Eintopfreaktion durch Bromierung in Formamid und anschlieBende Cyclisierung unter Durchleiten von Ammoniak hergestellt werden48. 

Wenn man die Umsetzung unter Zusatz von Ammoniak im Autoklaven durchfuhrt, ist die Cyclisierung bereits bei niedrigeren Reaktionstemperaturen moglich. So wird durch Umsetzung von 2-Oxo-propanol mit Formamid und Ammoniak unter Druck bereits bei 130° 4-Methyl-imidazol in 62% Ausbeute erhalten49. 

Auch Ammoniumformiat wird gelegentlich als Ammoniak-Quelle verwendet. Dadurch gelingt bei der Umsetzung von 2-Chlor-3-oxo-3-phenyl-propansaure-ethylester mit Formamid zu 5(4)-Ethoxycarbonyl-4(5)-phenyl-imidazol (37%) in einer drucklosen Reaktion ebenfalls eine Sen-kung der Reaktionstemperatur auf 135°50,... 

Statt der a-Halogen-ketone konnen auch a-Halogen-0,0-acetale eingesetzt werden. So erhalt man aus 2-Brom-l,l-dimethoxy-ethan mit Formamid unter Durchleiten von Ammoniak-Gas Imidazol in 50% Ausbeute51 ... 

Imidazole allgemeine Arbeitsvorschrift54 0,01 mol Bis-[trim.ethylsiloxyJ-a ken werden mit 5 ml Formamid bei 200" Badtemp. 6 h zum Sieden erhitzt. Dann wird die Disiloxan-Phase abgetrennt und der Rest de-stilliert. 

Die Umwandlung von (2-Oxo-alkyl)-l, 2,4-triazolium-Salzen mit Natriumhydrid in Dimethyl-formamid fiihrt zu 4-Acyl-5-amino-imidazolen. Diese Reaktion verlauft iiber offenkettige N-Cyan-formamidine, was in einem Beispiel durch Isolierung des N-Cyan-formamidins und dessen thermische Cyclisierung zum 4-Acyl-5-amino-imidazol nachgewiesen wurde. Die Ausbeuten liegen im allgemeinen um 30%. In einem Fall wurden 60% Ausbeute erzielt [5-Amino-l-(4-chlor-benzyl)-4-(2,4-dichlor-benzoyl)-imidazol Schmp. 220°]373 ... 

Oxo-l-propenylamino)-l,2,4-oxadiazole lagern sich mit Natriumethanolat in Dimethyl-formamid in Ausbeuten von 60-80% in 4(5)-Acyl-2-acylamino-imidazole um392 ... 

Since formamide is a weak nucleophile, the use of imidazole or 4-dimethylaminopyridine (DMAP) is necessary for acyl transfer to formamide via an activated amide (imidazolide) or acylpyridinium ion. As Scheme 22 illustrates, the reaction starts with the oxidative addition of aryl bromide 152 to Pd(0) species, followed by CO insertion to form acyl-Pd complex 154. Imidazole receives the aroyl group to form imidazolide 155 and liberates HPdBr species. Then, imidazolide 155 reacts with formamide to form imide 156. Finally, decarbonylation of imide 156 gives amide 157. In fact, the formations of imidazolide intermediate 155 and imide 156 as well as the subsequent slow transformation of imide 156 to amide 157 by releasing CO were observed. This mechanism can accommodate the CO pressure variations observed during the first few hours of aminocarbonylation. When the reaction temperature (120 °C) was reached, a fast drop of pressure occurred. This corresponds to the formation of the intermediary imide 156. Then, the increase of pressure after 3 h of reaction was observed. This phenomenon corresponds to the release of CO from imide 156 to form amide 157. ... 

An example of the use of DMF as CO source in the Pd-catalyzed aminocarbonylation with microwave irradiation is shown in Scheme 28. Thus, n-bromotoluene was reacted with benzylamine (4 equiv.) in the presence of Pd-dppf catalyst, imidazole, KOBu, and DMF (17equiv.) with microwave irradiation for 20min to give amide 196 in 94% yield (Scheme 28). A proposed mechanism (Scheme 28) has a close similarity to that of the aminocarbonylation of aryl bromide with formamide (see Scheme 22). However, in this process, a large excess (4 equiv.) of benzylamine was used to suppress a possible reaction involving dimethylamine generated in situ from DMF under reaction conditions. 

As mentioned earlier, the synthesis of primary amides is rather challenging due to technical difficulty in handling gaseous ammonia. Thus, the use of ammonia substitutes such as HMDS and formamide has been studied (see Schemes 21 and 22). With the use of microwave irradiation, however, it has been shown that it is possible to generate both CO and ammonia at the same time for the synthesis of primary amides from aryl bromides. This protocol is very useful for laboratory organic syntheses, especially combinatorial syntheses. As Scheme 29 illustrates, the Pd-catalyzed aminocarbonylation of aryl bromides 200 with formamide (33.5 equiv.) in the presence of KOBu (1.5 equiv.) and imidazole (1 equiv.) with microwave irradiation for 400 s (6.7 min) gave the corresponding benzamides... 

Bromo-6-hydroxynaphthalene (0.45 mol) and imidazole (1.10 mol) were dissolved in 300 ml of N, iV-di meth I formamide and then treated with /-butyl-dimethylsilyl chloride (0.53 mol) and stirred at ambient temperature overnight. The mixture was then poured into water and the precipitate isolated. After washing with water and cold ethanol, it was recrystallized from ethanol and 97.2 g of product isolated as off-white crystals, mp = 62-64°C. 

The oxazole (232) heated with formamide gave the imidazole (233) oxazolium cations undergo similar conversions. Primary amines convert oxazole-4-carboxylic acids (234) at 150°C into imidazoles (235) with accompanying decarboxylation (53CB88) (see CHEC 4.07 and 4.18). 

Anode solution contains an alcohol, a base, S02, I-, and possibly another oiganic solvent. Methanol and diethylene glycol monomethyl ether (CH3OCH2CH2OCH2CH2OH) are typical alcohols. Typical bases are imidazole and diethanolamine. The organic solvent may contain chloroform, formamide, or other solvents. The trend is to avoid chlorinated solvents because of their environmental hazards. When analyzing nonpolar substances such as transformer oil, sufficient solvent, such as chloroform, should be used to make the reaction homogeneous. Otherwise, moisture trapped in oily emulsions is inaccessible. (An emulsion is a fine suspension of liquid-phase droplets in another liquid.)... 

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