4.5- Dihydroimidazoles, alkylation

The saturated imidazolidinium salts can be obtained by alkylation of dihydroimidazole or by selected cyclization reactions [22]. A multicomponent reaction leading to unsymmetric derivatives of type 2 has also been reported (Fig. 3c) [30]. 

Synthesis oe Heterocyclic Compounds. In some cases, dehydroamino acids obtained from unsaturated 5(477)-oxazolones have been used as intermediates to prepare other heterocyclic compounds. For example, reaction of 2-benzoylamino-3-substituted-2-alkenoic acids 485 with alkyl or arylisothiocyanates affords 4-aryl-methylene-l,2-disubstituted-5-oxo-4,5-dihydroimidazoles 486 (Scheme 7.155). ... 

The methylation of l-methyl-2-thioxo-2,3-dihydroimidazole (125) with methyl iodide gives 55% yield of the S-alkylated product, whereas with unsubstituted 2-thioxo-2,3-dihydroimidazole (126) N,S-dialkylation is observed. 

The C-thioacylation of l-alkyl-2-methyltetrahydropyrimidines and 1,2-dimethyl-dihydroimidazole has been achieved by reaction with thiophene-2-carbaldehydes in the presence of sulfur (Scheme 115) (82T1673). The yield of product is better with thiophene-2-carbaldehydes (30-40%) than with benzaldehyde. 

A related intramolecular N-alkylation leading to saturated nitrogen heterocycles 99 can proceed via dehydration of intermediates 98 (Eq. 39) [96]. Unsaturated nitrogen heterocycles such as pyrroles [97], indoles [98], benzo-azoles [99], 2,3-dihydroimidazol-2-ones [100], and imidazo[l,2-a]pyridines [101] were obtained through similar cyclocondensation reactions. Interesting ruthenium-catalyzed syntheses of quinolines have been achieved by means of cyclocondensations of aniline derivatives with propanediols, aminoalcohols, or... 

Dihydroimidazoles 490 are readily N-alkylated or N-acylated to form 1-alkyl 491 or 1-acyl derivatives more efficient alkylations involve pregeneration of an N-anion. With excess alkyl halide, a quaternary salt 492 is formed, and suitable 2-substituents allow side-chain deprotonation to give enamines, 2-alkylideneimidazolidines, e.g., 493. 

Strong bases can deprotonate the 2-alkyl group of neutral l-alkyl-4,5-dihydroimidazoles, for example, leading to 496 by trapping with a nitrile, then tautomerism (Scheme 108) <1999T2695>. 

Except for 12 and 13 b-d, the isolation of the amidine tautomer has been reported only recently. Spectral data show that alkylated 1,1-enediamines such as 16 tautomerize predominantly to 4,5-dihydroimidazole derivatives 16 3 6 (equation 4). More interestingly, the adducts of enediamines and diethyl diazenedicarboxylate exist exclusively as the enediamine tautomer when R2 = H (17) and as the amidine tautomer when R2 = Et (17 )37 (equation 5). Since 17 and 17 differ only in an ethyl group, it appears that the steric effect plays an important role in determining the tautomeric equilibrium. 

Another way to form a-aminoketones from a-amino acids is via the Dakin-West reaction, in which amino acids are treated with aliphatic acid anhydrides to give ketone amides. Thus, reaction of ( )-phenylalanine with the appropriate aliphatic acid anhydrides followed by acidic hydrolysis afforded keto-amide 1271. Cyclization of 1272 with potassium cyanate gave 5-alkyl-4-benzyl-l,3-dihydroimidazol-2-ones 1273 (Scheme 322) <2002JHC375>. 

While 2-substituted-4,4,6-trimethyl-5,6-dihydro-1,3-oxazines 2-substituted-4,4-dimethyl-2-oxazo-lines and l-benzyl-2-alkyl-4,S-dihydroimidazoles are inert to organometallic addition, their corresponding methiodide salts ST)- S9) are reactive and have been utilized for the synthesis of ketones (60 ... 

A study has correlated the reactivities of different onium salts based on HOXt [66]. The nature of the different reagents, phosphonium versus aminium or uronium, iV-alkyl substituents (R), and OAt versus OBt influences were investigated. HXTU, HAPyU, PyXOP, XOP, the piperidino derivative, 0-(7-azabenzotriazol-1 -yl)-1,1,3,3-bis(pentamethylene)uronium hexafluorophosphate (32) (HAPipU), both dihydroimidazole derivatives, 0-(7-azabenzotriazol- 1-yl)-1,3-dimethyl-1,3-dimethyleneuronium hexaflu-... 

Stabilized Cu(I) in the form of its iV-heterocyclic carbene (NHC) complex, e.g., (SIMes)CuBr (SIMes = iV,7V -f>is(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene), and the eyclohexyl analog [(ICy)2Cu]PF6, catalyzes click reactions very well in aqueous /-butanol, and even better in water alone. Low conversions were noted in nonaqueous solvents such as tetrahydrofuran (THF), /-BuOH, and dichloromethane (DCM). Starting from an alkyl bromide, triazoles could be smoothly generated by m situ conversion to the corresponding azide (aqueous NaNs) followed by copper-catalyzed cycloaddition. This is but one example of the potential for combining several steps in a single flask that culminates with a click reaction vide infra). The... 

Much research has been geared to improve catalytic activity and stability by increasing the o donation via A-alkyl-substituted NHCs. However, many symmetrically A-alkyl-substituted complexes were either not formed or were unstable and displayed reduced activity compared to the parent complexes [55-57]. For example, complex 30 bearing l,3-di(l-adamantyl)-4,5-dihydroimidazol-2-ylidene could not be formed [55] and complex 31 reported by Louie and Grubbs failed to perform even the benchmark RCM of 17 [57]. The reduced stability of these complexes was attributed to the weak NHC-metal bond resulting from the sterically demanding alkyl substituents [56]. In contrast, the phosphine-free... 

The saturated imidazolinium salts of type 11 (Scheme 1.7) can be obtained by alkylation of dihydroimidazole or by the cyclization reactions between A,A -dialkyl-a,p-ethyldiamines with orthoesters (Scheme 1.7a). A multi-component reaction leading to unsymmetrical derivatives of type 11, which is particularly interesting for the synthesis of imidazolinium salts with substituents at the C4 and C5 positions of the heterocycle, was reported by Orru... 

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