Imidazole 4-alkylthio

Alkylthio groups are oxidized to sulfoxides by H2O2 and readily by various oxidizing reagents to sulfones, e.g. in the imidazole series. The SR group is replaced by hydrogen with Raney nickel, and dealkylation is possible, e.g. of 3-alkylthio-l,2-dithiolyliums to give... 

A different multicomponent route to imidazoles has been described by the group of O Shea, involving the diversity-tolerant three-component condensation of an aldehyde, a 2-oxo-thioacetamide, and an alkyl bromide (5 equivalents) in the presence of ammonium acetate (Scheme 6.201) [364]. This allowed the preparation of a 24-membered 4(5)-alkylthio-lH-imidazole demonstration library from 21 different aldehydes, 12 alkyl bromides, and two 2-oxo-thioacetamides. The library was synthesized in a parallel format using a custom-built reaction vessel. Alkylthioimidazoles... 

Treatment of 2-mercaptoimidazoles 33 with a-halo ketones gives 2-(acyl-alkylthio)-imidazoles 34, which can be cyclized to substituted imidazo[2,l-fejthiazoles 35 [86HC(46)77]. A one-step synthesis from 33 with a-halo ketones is also successful. 

Quinazoline alkylthio derivatives are frequently made by S-alkylation of the corresponding quinazolinethiones. The conditions required are very mild, and S-alkylation can be performed in the presence of other groups capable of undergoing alkylation. For example, 777-imidazo[4,5-, ]quinazoline-6(777)-thione 209 was converted to the 4-methylthio derivative 210 at room temperature, without any alkylation of the nitrogen atoms of the imidazole ring <1996JME918>. 

Statt Amidinen konnen auch Guanidine103-105, Amino-guanidine104-109 oder S-Alkyl-isothio-harnstoffe110,111 verwendet werden. In diesen Fallen erhalt man Imidazole mit Amino- oder Alkylthio-Gruppen in 2-Stellung ... 

Alkylthio-imidazole werden bereits durch verdunnte Salpetersaure zu 2-Alkylthio-4(5)-nitro-imidazolen nitriert611 613, wobei manchmal auch die Alkylthio-Gruppe zum Sulfoxid oxidiert wird613. 

Substituierte 2-Phenylthio- oder 2-Alkylthio-imidazole (hergestellt durch Metallierung in... 

Schwefel-Funktionen wie Mercapto, Arylthio oder Alkylthio, sind die bei weitem am haufigsten durch Oxidation umgewandelten Hetero-Atome in der Seitenkette. Als Produkte werden je nach Edukt und Reaktionsbedingungen Diimidazolyl-disulfane, Sulfo-, Chlorsulfo-nyl-, Sulfinyl- bzw. Sulfonyl-imidazole erhalten. 

Alkylthio-imidazole konnen auch mit Salpetersaurc zu 2-Alkylsulfonyl-imidazolen oxi-diert werden1064 Die Oxidation mit 3-Chlor-perbenzoesaure fiihrt zu den entsprechenden 2-A Iky lsul fin yl-imidazolen1064. 

Mit Thiolen als Nukleophilen wird sogar direkt die Hydroxy-Gruppe bzw. die Methoxy-Gruppe in Hydroxymethyl-1163,1164 bzw. Methoxymethyl-imidazolen1165 ausgetauscht [(Alkylthio-methyl)-imidazole], Der Phosphonium-Rest der (Triphenylphosphoniono-methyl)-Gruppe kann durch Thiolate oder Alkanolate substituiert werden1166. 

Diaryl-5-thiono-4,5-dihydro- oder 5-Alkylthio-4,4-diaryl-4,5-dihydro-imidazole lagern sich in Gegenwart von Lewissauren wie Aluminiumchlorid oder Galliumbromid unter Entschwe-felung in 4,5-Diaryl-imidazole um1220,1221 z.B. ... 

Trimethylsilylimidazole (751) is used, with trimethylsilyltriflate as catalyst (84CHE662, 90S104), to make 1-alkylthio- and 1-phenylthio-l-trimethylsilyloxy-alkanes and -cycloalkanes. The use of two equivalents of the thiol prevents the formation of imidazole adducts (Scheme 106a) (90S 104). 

Formation of imidazoles from thiourea derivatives has been limited largely to the 2-alkylthio or 2-aralkylthio-substituted rings (unsubstituted 2-mercaptoimidazoles will be classified as 4-imidazoline-2-thiones in this review). 

Arylthioimidazoles can be made in high yields when thiophenates react with At-(l-cyanoalkyl) alkylidene A -oxides. Alkyl and aralkyl thiolates, however, react much less readily (see Section 2.1.1 and Scheme 2.1.10). Imidazole-4-thioethers can be made in a general reaction between nitriles and a range of isocyanides which are susceptible to o -metallation (see Section 4.2, Scheme 4.2.2 and Table 4.2.1). Oxoketene acetals bearing alkylthio substituents react with nitrosoaromatics to give 5-acyl-4-alkylthio-l-arylimidazoles in moderate to good yields (see Section 3.2 and Scheme 3.2.5). 

When cyanoimidothiocarbamates react with or-halogenocarbonyl compounds, the products cyclize in base to form 1-substituted 2-alkylthio-5-amino-imidazoles (see Section 2.3, Scheme 2.3.1 and Table 2.3.1), while similar condensations of IV-cyanoiminodithiocarbamates with sarcosine nitrile salts, sarcosine ester salts or methylaminoacetophenone lead to analogous products, often in quite high yields (see Scheme 2.3.2). 

E. K. Beloglazkina, A. G. Majouga, R. B. Romashkina, N. V. Zyk, A novel catalyst for alkene epoxidation A polymer-supported Co°LCl2 L = 2-(alkylthio)-3-phenyl-5-(pyridine-2-ylmethy-lene)-3,5-dihydro-4H-imidazole-4-one] complex. Tetrahedron Lett. 47 (2006) 2957. 

Alkylthio groups are readily removed by the well-known, Raney niclml desulfurization procedure, which is particularly valuable in cases in which the initial presence of the alkylthio group is necessary in order to direct the entering glycosyl moiety to the desired imidazole nitrogen atom (N-9).i < i -> i- - ... 

The action of trifluorobutenyl bromide (CF2=CFCH2CH2Br) on 3-phenyl-5-mercapto-l,2,4-thiadiazole and numerous analogs produces 5-(3,4,4-trifluoro-3-butenyl)thio derivatives (435), which are useful nema-tocides.344 The 5-alkylthio compound (436) is the product of the S-alkylation using l-(/ -chloro-2,4-dichlorophenetyl)imidazole.345 The formation of the monosulfide (437) from 3-isopropyl-5-mercapto-1,2,4-thiadiazole occurs under standard conditions.346... 

Structural extensions to the essential toxophore concept include replacement of the 4-(halo)alkylthio group by imidazole [92] and other five-membered-heterocycles [93], by phenyl [94], by cyclopropyl and other cycloalkyls [95, 96], by alkyl, haloalkyl, alkenyl and alkinyl groups [75, 97] (22-25, Fig. 29.5.7). 

Aluminum chloride Imidazole ring rearrangements Imidazoles from 5-alkylthio-4H-imidazoles... 

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