Imidazolines, hydrolysis

Reaction of the spirocyclic imidazoline 316 with glyoxal and sodium hydrogen sulfite results in hydrolysis of the aminal and subsequent double condensation to give the tetrazolopyridopyrazine 317 (Equation 109) <1999JHC117>. The pyridopyridazinylhydrazine 318 can be cyclized to the fused triazole 319 by reaction with formic acid (Equation 110) <1998SC2871>. 

Initially, one molecule of fatty acid reacted with the secondary amine of BETA, followed by a second fatty acid molecule, reacting with one of the two primary amines. The product formed was the N-(2-aminoethyl) diamide, which will be referred to as the diamide. The diamides could be cyclized by heating under vacuum to form imidazolines, which were unstable to hydrolysis. In the presence of water, or upon exposure to atmospheric moisture, they revert back to the diamide. 

Imidazolines (245) have been prepared from (S)-alanine and (S)-proline. Upon hydrolysis (R)-alanine was obtained. This result can be explained in terms of epimeri-zation and stereoselective protonation with asymmetric induction by the chiral center originating from (S)-proline246). 

Unlike the 2-alkyl-2-imidazolines, this structure is stable and resistant to hydrolysis. After ring cleavage, reaction with sodium chloroacetate yields linear products ... 

Imidazoline-2,5-dione, 1 -methyl-4-phenyl-reduction, 5, 415 Imidazolines acylation, 5, 425-426 alkylation, 5, 425 corrosion inhibitors, 1, 408 as drugs, 5, 498 lH NMR, 5, 353 hydrolysis, 5, 426 N -oxides synthesis, 5, 463 polymers, 1, 280, 305 reactions... 

Most of the amphopropionate surfactants produced are of the amphodipropionate type, 2 mol of methyl acrylate or sodium acrylate added per mole of imidazoline. Depending on the reaction conditions, 1 mol of acrylate can add to the fatty R group at the alpha carbon. Upon hydrolysis of the imidazoline, the second reacts with the liberated secondary amine to produce the beta alanine derivative. If methyl acrylate is used, the methyl ester of the amphoteric surfactant is formed. An equimolar amount of sodium hydroxide is added to effect saponification to the sodium salt of the surfactant. Methanol is formed as a by-product and it is generally left in the final product as part of the solvent system. 

Like the amphoacetates and amphopropionates above, the amphohydroxypropylsulfonates are derived from hydrolyzed alkyl hydroxyethyl imidazolines. In this, amido-functional alkanolamine hydrolysis product is alkylated with sodium l-chloro-2-hydroxypropane sulfonic acid (see Figure 6.13). These products have good hard water tolerance and have applications including metal cleaning as well as personal cleansing. 

Imidazolines can exist as three possible structures 2-imidazolines (171), 3-imidazolines (172) or 4-imidazolines (173) (Scheme 83). The first-named can exist as a pair of tautomers, but any proton shift in (172) will give (173) by rearrangement. In fact the hydrolysis of Af-unsubstituted 3-imidazolines to a-aminoketones occurs presumably via the 4-imidazoline. 2-Imidazolines are cyclic amidines, and as such exhibit the characteristic resonance stabilization and strongly basic natures of these compounds. Protonation occurs on the unsubstituted nitrogen to give a resonance-stabilized imidazolinium ion. Examples of p/fa... 

A modification of this method, which produces 2-aminoimidazoles in up to 90% yield, utilizes benzoins and diguanylhydrazine. The 2,2 -azoimidazoles (123) can be catalytically hydrogenated to the 2-amino compounds (Scheme 66) (66RCR122). When the disubstituted guanidine (124) is treated with phenacyl bromide the first product formed is the expected 2-( l-pyrazolyl)imidazole (125), but subsequent hydrolysis of this occurs to give a 57% yield of l-isopropyl-4-phenylimidazolin-2-one (Scheme 66) (70AHC(12)103). Benzamidine hydrochloride reacts with monosubstituted glyoxals to form 2-imidazolin-4-ones. 

The two general methods for preparation of 4-imidazoline-2-thiones are the reaction of acyloins with thioureas and the acid hydrolysis of alkyl- or arylthiureidoacetals. The above reactions have been summarized in a review by Hofmann. Aren and Bite recently reported that the 2-phenyl-2-thiureido-l,3-indanediones (17) undergo rearrangement in strong acid to produce in high yield a series of 4-imidazoline-2-thiones (18). 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

Hydrolysis in aqueous ethanol of 2-methyl imidazolines 561, derived from C2-symmetric diamines and the Pinner salt, leads to mono-protected 1,2-diamines 562. The latter are readily converted into A, A -disubstituted 1,2-diamines (Scheme 131) <2000TL8431>. N-protected A -imidazolines are readily hydrolyzed under milder conditions. Thus peptidyl trifluoromethyl ketones 564 were prepared through hydrolysis of 563 <1996JA8485>. 

Imidazolines on acid hydrolysis have been shown to give pyrazines (306). Thus 2,2-diethyl4-methylimidazoline-A with dilute hydrochloric acid at 60 gave diethyl ketone (62% of the theoretical) and 2,5-dimethylpyrazine (7%) 2,2-diethyl-4,5-dimethylimidazoline-A gave diethyl ketone (70.2%) and tetramethylpyrazine (20.4%) and 2,2,4-triethyl-5 methylimidazoline-A (41) gave diethyl ketone (84%) and 2,5-diethyl-3,6-dimethyl-3,6-dihydropyrazine (81%) (43). The pyrazines were formed presumably by self-condensation of the amino ketones (42) produced. 

Anti ( )-a-aminooximes (25) can be cyclized with phosgene [as well as by hydrolysis of the corresponding urethanes (26)] to 2-oxo-3-imidazoline... 

The cyclization of anfi-( )-a-aminooximes (87) to 3-imidazolin-2-one 3-oxides (89 Scheme 51) can be induced by phosgene (or by the hydrolysis of the urethanes 88). In instances in which (87) has an a-hydrogen atom (R = H), then the product formed is the... 

Tetrahedral intermediates have been shown to be kinetically important in the S->N transfer reaction of S-acetylmercaptoamine (Martin and Hedrick, 1962) the O N transfer reaction of 0-acetylethanolamine (Hansen, 1963), intramolecular-aminolysis of ethyl y-aminobutyrate, ethyl 8-aminovalerate, and related reactions (Martin et al., 1964), hydrolysis of thiazolines (Martin et al., 1959 Martin and Parcell, 1961a Schmir, 1965), hydrolysis of oxazolines (Martin et al., 1964 Greenhalgh et al., 1963 Martin and Parcell, 1961b), hydrolysis of 2-imidazolines (Harnsberger and Riebsomer, 1964), and in the hydrolysis of acetyl-malonate diethyl ester (Lienhard and Jencks, 1965). 

RCOOH -4 RCHO. 2-Substituted imidazolines prepared from acids and ethylenediamine in hot toluene are reduced by Na in ethanol to the imidazolidines. Acid hydrolysis of the latter affords aldehydes. ... 

Imidazolines can exist as the 2-, 3-, or 4-isomers ((5)- 7)), and whereas (5) can exist as a pair of tautomers, any proton shift in (6) will give (7) by rearrangement. Hydrolysis of A(-unsubstituted 3-imidazolines (6) to a-aminoketones presumably occurs via (7). Nickel boride , prepared in situ, transforms 3-imidazolines into 2-imidazolines by double-bond migration <86H(24)287l>. 

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