4- imidazolin-2-thiones preparation

Cyclic thiourea derivatives like l,3,4,5-tetramethylimidazole-2(3H)-thione— prepared by condensation of substituted thioureas with a-hydroxyketones—can be converted into the corresponding imidazolin-2-ylidene by desulfurization with sodium or potassium [Eq. (23)]. This method was used to prepare and isolate l,3-bis-neo-pentylbenzimidazolin-2-ylidene with Na/K. With LDA as the base it is also possible to generate free benzimidazolin-2-ylidenes in solution. ... 

Chiral imidazoUdin-2-thione or 2-one were prepared from o-glucoseamine by reaction with o,o -disubstituted arylisothiocyanates to give 39 which can be cycHzed to 40 [76]. Thus, a variety of derivatives were prepared carrying different aryl groups and as a consequence of hindered rotation, some of them exist as stable rotamers (Fig. 7). Treatment of 39 with acetic anhydride in pyridine at low temperature gave the respective per-O-acetyl derivative imidazolidine thione, which upon elimination of acetic acid gave the imidazoline thion 41 as a mixture of atropisomers [76]. 

The 5-thione analogue of Step 3, l-(3-pyridinylamine-2-thiomethyl-4-methyl-4-phenyl-2-imidazolin-5-thione, (II), and derivatives were previously prepared by the author and are described (1). 

Resistance to reduction processes seems to be a general characteristic as most catalytic methods (as well as sodium in ethanol) reduce only the ring. However hydantoin can be reduced by diisobutylaluminum hydride to imidazolin-2-one (81TL2063), and imidazoline-2-thiones can be prepared from 2-thiohydantoins (70AHC(12)103). Oxidative procedures often result in ring opening (B-76MI4070i). 

The earliest method of this type, developed by Marckwald, employed the reaction of a-aminocarbonyl compounds (or their acetals) with cyanates, thiocyanates or isothiocyanates to give 3//-imidazoline-2-thiones. These compounds can be converted readily into imidazoles by oxidation or dehydrogenation. The major limitations of this synthetic procedure are the difficulty of synthesis of a wide variety of the a-aminocarbonyl compounds, and the limited range of 2-substituents which are introduced. The reduction of a-amino acids with aluminum amalgam provides one source of starting materials. The method has been applied to the preparation of 4,5-trimethyleneimidazole (83) from 2-bromocyclopentanone (70AHC(12)103), and to the synthesis of pilocarpine (84 Scheme 47) (80AHC(27)24l). If esters of a-amino acids react with cyanates or thiocyanates, the products are hydantoins and 2-thiohydantoins, respectively. 

When urea (or thiourea) reacts with a-hydroxy ketones or a-diketones the products are imidazolin-2-ones (or -thiones) (70AHC(12)103,66RCR122). The reaction is limited to the preparation of 4,5-alkyl(or aryl)- or l,4,5-trialkyl(or triaryl)-imidazoles since an oxygen or sulfur function appears at C-2. Benzoin condenses with iV-phenylthiourea in hexanol in the presence of catalytic quantities of HCl to give l,4,5-triphenylimidazoline-2-thione (131) in 50-60% yield (Scheme 69). While 1-methylurea can also take part in the reaction. 

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). 

In the uncondensed imidazoles the standard method reacts an a-aminocarbonyl compound with a thiocyanate (see Section 4.1 and Table 4.1.1). If a 2-alkylthioimidazole is required directly, one can combine an N-alkyT or A -arylcarbonimidodithioate in refluxing acetic acid with the aminocarbonyl substrate (see Section 4.1 and Scheme 4.1.3). Alternatively, reaction between thiourea and a two-carbon synthon (ot-hydroxy-, a-halogeno-, a-dicarbonyl) leads to imidazoline-2-thiones (see Section 4.3). In sulfuric acid, 3-butynylthiourea cyclizes to 4,5-dimethylimidazolin-2-thione (see Section 2.2.1). 1-Substituted 2-methylthioimidazoles can be made, albeit in rather poor yields, from appropriately substituted 2-azabutadienes (see Section 3.2 and Scheme 3.2.3), and 2-arylthioimidazoles are available in moderate yields from benzyl isocyanides and arylsulfenyl chlorides (see Section 4.2 and Scheme 4.2.12). Ring transformations of 5-amino-2-alkylaminothiazoles and 2-acylamino-5-aminothiazoles may have occasional applications (see Section 6.1.2.7). The ease with which a thiol group or imidazole or benzimidazole can be alkylated, in comparison with the annular nitrogens, usually makes it more convenient to prepare alkylthioimidazoles from the thiols (or thiones). 

NHCs have become popular ligands in coordination chemistry owing to the facile access to this type of ligands and to metal-NHC complexes. Most NHC ligands are prepared from azohum compounds such as imidazolium, triazolium, benzimidazo-lium, imidazolidinium, or thi azolium salts [1]. Alternatively, the reductive desulfurization of imidazolin-, benzimidazolin-, and imidazolidin-2-thiones to yield a variety of NHCs has been described. The preparation of suitable azolium salts and imidazolin-2-thiones is presented in Sect. 2.1. This is followed by the description of methods to liberate the free NHCs from these compounds. Today, stable singlet... 

The most common method for the preparation of thioureas is, however, based on the reaction of isothiocyanates with amines, and, not unexpectedly, the majority of papers deal with this particular reaction. 6-2 1 Among the N-substituent groups thus introduced into thiourea are 3-cyclo-pentenyl, 1-adamantyl, furfuryl, diphenylphosphinoyl, diphenyl-phosphinothioyl, AW-9,10-diacetyldihydro-2-phena2inyl, and variously substituted aryls. - If the isothiocyanate or the amine contains other reactive groups, cyclization to heterocyclic compounds containing the thiourea grouping may occur, either spontaneously or promoted by external influence, as recently demonstrated in the synthesis of thiones derived from imidazoline, pyrimidine, - and j-triazine. - ... 

Wanzlick and Schikora were the first to attempt the preparation of saturated imidazolin-2-ylidenes by an a-elimination of chloroform from imidazoline derivatives but could only obtain the electron-rich entetraamines (see Scheme 1.2). It was Arduengo et al. who presented the first stable crystalline imidazolin-2-ylidene 86 (Figure 1.8) obtained by deprotonation of the corresponding imidazolinium salt. " Shortly thereafter, Denk et al. used the reductive desulfurization of imidazolin-2-thiones to obtain the N,N -A tert-butyl) substituted stable carbene of type 86 and the entetraamine 86=86 with the sterically less demanding A,A -dimethyl substituents (Figure 1.8). Additional imidazolin-2-ylidenes with varying A,A -substituents were obtained by... 

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