Imidazolines, formation

Fabric Softeners, Surfactants and Bleach Activators. Mono- and bisamidoamines and their imidazoline counterparts are formed by the condensation reaction of one or two moles of a monobasic fatty acid (typically stearic or oleic) or their methyl esters with one mole of a polyamine. Imidazoline formation requires that the ethyleneamine have at least one segment in which a secondary amine group Hes adjacent to a primary amine group. These amidoamines and imidazolines form the basis for a wide range of fabric softeners, surfactants, and emulsifiers. Commonly used amines are DETA, TETA, and DMAPA, although most of the polyethylene and polypropane polyamines can be used. 

As may be seen from the above structures, the dimer-based liquid polyamides and monomeric fatty amido amines contain free amine groups that are available for further reaction. One such reaction is imidazoline formation, which occurs intermolecularly (9), The structure of imidazoline can be indicated diagrammatically as follows. 

Apparently, cyclization involves the formation of open-chain intermediates 342, 343, further closing up to imidazolidines 344 and oxazolidines 345 which eliminate the secondary amine, thus leading to imidazolines 346 and oxazolines 347. The latter exist in the solution exclusively in the enolic forms 348, 349 which are stabilized by conjugation and intramolecular hydrogen bonds. 

In these reactions, the formation of imidazoline and oxazoline rings corresponds to the reagent orientation previously observed for ynamines (84ZOR1648) and alkenylynamines (83ZOR926), as well as in their reactions with mononucleophiles such as amines (79ZOR1824 81ZOR1807) and alcohols (80ZOR1141). 

As yet, a number of experiments have failed to convert ureas 205 such as N-phenylurea or imidazolin-2-one by silylation amination with excess amines R3NHR4 such as benzylamine or morpholine and excess HMDS 2 as well as equivalent amounts of NH4X (for X=C1, I) via the silylated intermediates 206 and 207 in one reaction step at 110-150°C into their corresponding guanidines 208 with formation of NH3 and HMDSO 7 [35] (Scheme 4.13). This failure is possibly due to the steric repulsion of the two neighbouring bulky trimethylsilyl groups in the assumed activated intermediate 207, which prevents the formation of 207 in the equilibrium with 206. Thus the two step Rathke-method, which demands the prior S-alkylation of 2-thioureas followed by amination with liberation of alkyl-mercaptans, will remain one of the standard syntheses of guanidines [21, 35a,b,c]. 

The high enantioselectivity again can be rationalized by enantioface-selective alkene coordination in 63 (Fig. 35). The olefin moiety is expected to bind trans to the upper imidazoline moiety [70,73] thereby releasing the catalyst strain. Coordination at this position may, in principal, afford four different isomers assuming the stereoelectronically preferred perpendicular orientation of the alkene and the Pt(II) square plane. In the coordination mode shown, steric repulsion between both olefin substituents and the ferrocene moiety is minimized. Outer-sphere attack of the indole core results in the formation of the product s stereocenter. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

Unsaturated five membered 2-chalcogenons with two heteroatoms at 1,3-positions (6) will show versatile reactivities with acceptors, since E in 6 must be very electron rich with the formation of a stable cyclic 671 electron system (6A).27,28 A saturated ring system 7 is expected to show similar trend due to the stabilization by the allylic X-C-Y framework with 471 electrons (7A). Arduengo reported the TBP formation of 1,3-dimethyl-4-imidazoline-2-thione (8), a typical example of 6 (X = Y = NMe and E = S), with bromine (8 Br2), together with the reactions.36... 

The TBP structures of 9 I2 and 11 2I2 are noteworthy, since iodine adducts of selenides are predicted to be MC based on the general rule (x(Se) (=2.48) > xCO (=2.21)). This must be the reflection of the high ability of the imidazoline ring to donate electrons to Se by the formation of the stable cyclic 6ji system. It will decrease xeff of Se in 9 and 11 to give TBP with iodine. Since the electronic conditions in 10 must not be so different from those in 9 and 11, they should not be responsible for the different structures of the adducts. This working hypothesis is supported by DFT calculations.38 Therefore, the crystal packing effect must play a crucial role in determining the structures of the iodine adducts of 9-11. The reactions are followed by spectroscopic and conductometric methods.37... 

Unlike the 4H- imidazoles (219), (223), (224) electrochemical oxidation of the nitrone group in 4-R-3-imidazoline-3-oxides (228), (230-232), as in a-PBN and DMPO is of irreversible nature. Therefore, the formation of radical cations... 

Owing to the existence of two centers for nucleophilic attack (at C2 and C5) in radical cations (220) obtained from the oxidation of 4-H -imidazole-1,3-dioxides (219), the formation of two products of methoxy group addition was observed, namely NNR (221) and NR of 3-imidazoline-3-oxide (222). The ratio of the products depends on the electronic nature of substitutes R1 and R2. Both, the donor character of R1 and acceptor character of R2 facilitate the formation of nitroxyl radicals (222) with the yield of (221) increasing with the inverted effect of the substituents. As was mentioned in Section 2.4, the results of preparative electrochemical oxidative methoxylation of 4H -imidazole-1,3-dioxides are similar to the results of chemical oxidation. 

Oxidative Fluorination of Nitrones to a-Fluorosubstituted Nitroxyl Radicals Formation of nitroxyl radicals by the radical cation route was observed in reactions of various nitrones with xenon difluoride in dry methylene chloride (520, 523). In this reaction, more than 40 nitrones, including 4H -imidazole N,N -dioxides (219), 4H -imidazole TV-oxides (223) and (224), 2H -imidazole N -oxides (225), 2H -imidazole TV,TV-dioxides (226), 3,3,5,5-tetramethylpyrroline N -oxide (TMPO), derivatives of 3-imidazoline-3-oxides (231) and (232), have been examined. ESR spectra of nitroxyl radicals containing one or two fluorine atoms at a-C have been registered (Scheme 2.108) (523). In the case of... 

The reaction of nitrones of the 3-imidazoline series (295) with bromine and amyl nitrite, in the presence of base, gives a-tribromomethyl-(296) and a-hydroxyaminomethyl derivatives (297) (538). Bromination of nitrones (295) with N -bromosuccinimide (NBS) in CCI4 or bromine in methanol leads to the formation of a-bromoalkyl (298 a,b, Hal = Br) and a-dibromomethyl (299) nitrones (539-541). The reaction with iodine in methanol gives the mono iodo derivative (300) (541). The reaction with A-chlorosuccinimide (NCS) in CCI4 leads to a-chloroethyl nitrones (298b, Hal = Cl) and a,a-dichloromethyl nitrones (301) (Scheme 2.118) (225). 

The formation of derivatives of 2,3,6,8-tetraazabicyclo-[3.2.1]3-octene (425) arises from an intramolecular nucleophilic addition to the nitrone group of hydra-zone (424). Compound (424) was prepared by reaction of 2-acyl-3-imidazoline-3-oxides (423) with hydrazine. From the cis- and frans-derivatives (424), exo- and enr/o-isomers (425) were obtained (Scheme 2.197). The reaction of intramolecular cyclization does not occur in cases with monosubstituted hydrazones (316). 

Onr resnlts strongly indicate that the antithyroid drugs PTU (2) and N-Methyl-2-mercapto-imidazoline (MMI) have a different way of action. Thns, (2) together with NMBZT (4) forming weak S-I c.t. complexes (Table 13.1) may interfere either by inhibiting TPO activity or by inhibiting Deiodinase (ID-1) enzyme which is responsible for the formation of T3 from T4 hormone. 

The fact that NHCs form stable compounds with beryllium, one of the hardest Lewis acids known and without p-electrons to back donate, shows the nu-cleophilicity of these ligands. Reaction of l,3-dimethylimidazolin-2-ylidene with polymeric BeCl2 results in the formation of the neutral 2 1 adduct 23 or the cationic 3 1 adduct 24. The first NHC-alkaline earth metal complex to be isolated was the 1 1 adduct 25 with MgEt2- Whereas l,3-dimesitylimidazolin-2-ylidene results in the formation of a dimeric compound, the application of sterically more demanding l,3-(l-adamantyl)imidazolin-2-ylidene gives a monomeric adduct. ... 

The elimination of an alcohol from a neutral 2-alkoxy-1,2-dihydro-1//-imidazole leads to the formation of NHCs [Eq. (18)]. Upon heating, the elimination of alcohol forms the NHC, which in the case of imidazolin-2-ylidenes dimerizes to... 

In cases where the free NHC cannot be synthesized the complex formation has to be accomplished in situ from a ligand precursor, e.g., the imidazolium salt in the case of imidazolin-2-ylidenes. By this method, it is often possible to prepare complexes which do not have the maximum number of NHC ligands attached to the metal center. 

Bioinorganic chemists have been attracted by the complex formations of NHC because the imidazolin-2-ylidene motif is encountered frequently in living organisms. The imidazole moiety is part of the purin bases in both DNA and RNA as well as the amino acid histidine which appears in proteins and enzymes and is in many cases considered to play a decisive role within the catalytically active center. The possible formation of NHC complexes under physiological conditions or in vivo has been addressed by investigation of A-confused caffeine 73 or purine 74 complexes. 

In 2003, we reported a multicomponent approach toward highly substituted 2H-2-imidazolines (65) [157]. This 3CR is based on the reactivity of isocyano esters (1) toward imines as was studied in detail by Schollkopf in the 1970s [76]. In our reaction, an amine and an aldehyde were stirred for 2 h in the presence of a drying agent (preformation of imine). Subsequent addition of the a-acidic isocyanide 64 resulted in the formation of the corresponding 2//-2-imidazolines (65) after 18 h in moderate to excellent yield. The mechanism for this MCR probably involves a Mannich-type addition of a-deprotonated isocyanide to (protonated) imine (66) followed by a ring closure and a 1,2-proton shift of intermediate 68 (Fig. 21). However, a concerted cycloaddition of 66 and deprotonated 64 to produce 65 cannot be excluded. 

Fig. 22 Possible reaction paths for the reaction between a-acidic isocyano amides (2 or 31), primary amines, and carbonyl components, including the Ag catalyzed formation of 2//-2-imidazolines (65)...

The MCR toward 2//-2-imidazolines (65) has found apphcation in the construction of A(-heterocyclic carbene (NHC) complexes (74). Alkylation of the sp Af-atom with an alkyl halide followed by abstraction of the proton at C2 with a strong base (NaH, KOtBu) resulted in the formation of the free carbene species, which could be trapped and isolated as the corresponding metal complexes (Ir or Rh) [160]. The corresponding Ru-complexes were shown to be active and selective catalysts for the transfer hydrogenaticm of furfural to furfurol using iPrOH as hydrogen source [161]. 

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