Imidazolines reaction with isocyanates

Good yields of imidazoline derivatives have been obtained in the cocyclooligomerization of phenylacetylene with isocyanates and carbodiimides (Scheme 100).166 It has been demonstrated166 by labeling studies in the isocyanate reaction that the hydrogen shift is intramolecular and a mechanism accommodating this feature is illustrated in Scheme 101.166 The final step (85 - 86) in the proposed166 mechanism (Scheme 101) probably occurs via a coordinated acetylene complex and it is notable that related complexes... 

A number of nitrogen- and sulfur-containing heterocyclic compounds are effective corrosion inhibitors (62MI11502), the imidazolines and the benzotriazoles being particularly important types. The imidazolines are derived from ethyleneamines by reaction with fatty acids the free bases (53), the fatty acid salts (54), and various derivatives obtained by reaction with anhydrides, isocyanates or alkyl halides (55) are effective inhibitors. 

The Lewis acid-catalysed 3 + 2-cycloaddition of aziridine-2-carboxylates with isocyanates proceeds regio- and stereo-specifically to produce enantiomerically pure 4-substituted imidazolin-2-ones in high yields.33 The reaction of ethyl 7-iodo-2-heptynoate (27), 2-arylaziridines (28), and K2C03 produces polysubstituted indolizidines (30) via an S /formal 3 + 2-cycloaddition (29) process (Scheme 8).34... 

Tetrakis(dimethylamino)titanium converts DMF to tris(dimethylamino)methane (529 equation 236). This compound is also formed in the reaction of V-tetramethyloxamide with the titanium reagent, whereas amides which have a-CH bonds are converted to ketene aminals. Cyclic and spitocyclic compounds, containing the substitution pattern of a trisamino compound, are formed in the reaction of IVA -dialkylformamides or A/ -aryl-(VJV-dialkylformamidines with aryl isocyanates. Similar compounds, e.g. (530 equation 237), are produced in the reaction of imidazolines or lactamid-ines with isocyanates. 

Regarding the importance of these compounds in various fields of biochemistry, many remarkable reactions have been outlined for the formation of other valuable derivatives. The synthesis of imidazolines begins with the addition of isocyanic acid or thiocyanic acid, as described by Huber and coworkers and Garcia Gonzalez and coworkers. Thiocyanic acid is especially well suited for a direct and easy characterization of the Amadori compounds. A reaction time of 2-3 hours results in a 60-70% yield. 

Because of their predictable behavior and reactivity, thioacyl isocyanates comprise the bulk of this work, and extensive studies of their [4 + 2] reactions with olefins,83 enamines,84 enol ethers,843 thioacyl isocyanates,85 imines,85 1 86 carbodiimides,84387 isocyanates,843 azirines,88 /3-enaminoke-tones,89 dianils,86d azines,90 hydrazones,91 imidazoline-4,5-diones,92 aryl cyanates,93 disubstituted cyanamides,93 aldehydes,94 ketones,94 ketenes,94 alkyl or aryl iminodithiocarbonates,95 and the carbon-carbon double bond of ketenimines96 have been detailed. In an extensive comparative study of the [4 + 2] cycloaddition reactions of thioacyl isocyanates, the heterocu-mulenes bearing strong electron-withdrawing substituents were found to be more stable and less prone to participate in cycloaddition reactions.84 Representative examples are summarized in Scheme 9-IV. 

The synthesis of carboxylate-substituted imidazoline derivatives has previously been accomplished by the condensation of presynthesized 1,2-diamines with amides, or through the transition metal catalyzed aldol-type reaction between isocyanates and imines (4,5). We have recently communicated an alternative palladium catalyzed route to synthesize a new class of imidazoline carboxylates, utilizing acid chloride, imines and carbon monoxide as starting materials (see Table 1)... 

Although acetonitrile is one of the more stable nitriles, it undergoes typical nitrile reactions and is used to produce many types of nitrogen-containing compounds, eg, amides (15), amines (16,17) higher molecular weight mono- and dinitriles (18,19) halogenated nitriles (20) ketones (21) isocyanates (22) heterocycles, eg, pyridines (23), and imidazolines (24). It can be trimerized to. f-trimethyltriazine (25) and has been telomerized with ethylene (26) and copolymerized with a-epoxides (27). 

Diazadienes have been shown by various groups to be suitable precursors of imidazoline derivatives by means of [4 + 1 ] cycloaddition reactions. In 1976 Matsuda and co-workers were able to cycloadd heterodienes 303, available from AMrimethylsilyl benzophenone imine and phenyl isocyanate, with cyclohexyl isocyanide to obtain 305 in 91% yield, after methanolysis of the initial adduct 304 [76JCS(P1)1523] (Scheme 67). 

The reactions of 3-amido-l-hydroxyazetidin-2-ones 327 with />-toluenesulfonyl chloride in the presence of triethyl-amine provided the ring-expanded 4-imidazolin-2-ones 328 (Equation 114) <1995TL1617>. The key step in the mechanism of this reaction involved the ring opening by cleavage of the C(2)-G(3) bond, which is followed by double bond migration and an intramolecular nucleophilic addition of the amide nitrogen to an intermediate isocyanate. 

It is a general rule that imidazoles and benzimidazoles are resistant to Friedel-Crafts reactions. This is not surprising since such basic compounds must be markedly deactivated in the presence of Lewis acids. Imidazolin-2-ones appear to be an exception and apparently possess sufficient activation to react. Reactions between imidazoles and Af-methylfor-manilide and phosphoryl chloride are also unproductive. With 4,5-diphenylimidazole, phenyl isocyanate at 80 °C gives products of both N- and C-substitution, but in boiling nitrobenzene only the latter (86) is formed. 2-Methyl-4-phenylimidazole gives (87) under the same conditions, and 1,3-diphenylimidazolium perchlorate is transformed by potassium t-butoxide into a ylide which reacts at C-2 with phenyl isothiocyanate. Sufficient activation is present in l-methyl-2-phenyl-4-phenylaminoimidazole for it to react by substitution at C-5 with acetic anhydride (71JOC3368). 

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