SU552024A3 - Method for producing sulfoxides - Google Patents

Description

(54) METHOD FOR OBTAINING SULPHOXIDES

This invention relates to a process for the preparation of new derivatives of sulfonic sites, with valuable pharmacological properties, in particular, to a method for the preparation of compounds of the general formula I Xk "(CH,) L- (CH,)" that are not described in the literature, where A forms with the specified carbon atom imkdazolium, pyridine, thiazole, isothiazole, oxazole, isoxazole, pyrazole, triazole, thiadiazole, pyrimidine, pyrazine or pyridazhi core; Xi and Xj are the same or different and are hydrogen, lower alkyl with 1-4 carbon atoms, trifluoromethyl, hydroxyl, halogen, amino group; or Xi may, together with Xj and the two atoms that make up radical A, form a benzene core; k and m are integers 0-4 prc provided that the sum of the whale is 3 or 4; E - oxygen or sulfur; R is hydrogen, lower alkyl, acyl or daalkylaminoalknl. About & Vaccines, on known reactions of oxidation of sulfides to sulfoxmides and joining of -N C bond I1, the described method allows for compounds with better properties than the known analogs of similar action. A method for the preparation of compounds of the formula I is proposed to conclude that the compound Formula 11 x | d-lCE, ilKS (CHa) where A, X,, X, k and m have the indicated ziacheni, process the acid or acid with kicim with an organic peracid or periodate, and a compound of the formula HI xp- (i- (CK, lKS (5H2lni "H2 A

subjected to interaction with the compound of formula IV

R, E

where RI and E have the indicated meanings,

with the subsequent selection of the target product.

Group A forms with the indicated carbon atom predominantly imidazolium, thiazole or pyridine nucleus. Xt is preferably hydrogen, methyl, bromine, amino, or hydroxyl; Xj is predominantly hydrogen; K-1-2; m 2 or 3. Most preferred compounds are those in which jfc is 1 and 2 E is predominantly sulfur; RJ is methyl.

The amines of the formula And can be obtained by a known method, starting from the compound of formula V

Xi

(CH2) to A

where A, Xi, Xj, and / f have the indicated meanings ;; U is hydroxyl, halogen, or methoxyl. According to the method, a compound of formula V is reacted with an aminomercaptan of formula VI

HS ----- (CHj) mNHj where m has the indicated value. In the case when 6 is halogen, the reaction may proceed in highly alkaline media, for example in the presence of sodium ethoxide or sodium hydrate. Since the compound of formula V is a primary amine, it may be necessary to protect the amino group, for example, with the phthalimide group, which can then be removed by means of acid hydrolysis or hydrogenolysis. If Q is hydroxyl or halogen, the reaction will proceed in an acidic medium, for example in the presence of hydrohalic acids, such as 48% hydrobromic acid, or in the presence of glacial acetic acid. In the case where Q is methoxy, the reaction will also proceed in the presence of 48% hydrobromic acid.

Example. Obtaining (5-methylimidazol-4-yl) -methyl-2- (N-methylt oureido) - stilsulfonate.

a) A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30 g) and hexamethylenetetramine hydrochloride (23 g), in acetic acid (200 ml) is heated under reflux for 10 hours. After cooling the solution to 15-20 ° C, a solid product crystallizes out, which is removed and washed with isopropyl alcohol, resulting in 2- ((5-methylimidazol-4-yl) -methyl-thiostilamine dihydrochloride (45.5 g) with m.p. 189-192 ° C;

b) 2- ((5-methyl-imidazol-4-yl) -methyl-thioethylamine dihydrochloride (14.5 rJ5.06 ml) is added in two portions to the transferred solution of catri metaperiodate (13.5 g, 0.063 mol) in water (126 ml), the temperature of which is maintained at 2-5 ° C, is stirred at this temperature for 3 hours and then left overnight at 0 ° C. The solid precipitate is filtered and washed with methanol, and the filtrates and the

washing (from which the precipitated. solid product that was again filtered) is basified until a value of 9-10 is obtained by adding potassium carbonate (15 g) and evaporated to dryness under reduced pressure at

70 ° C with the formation of an azeotropic mixture with n-ProP4NOLOM. Extraction of the residual product with isopropanol and extracting 1 filtered extracts gives crude (5-methylimidazol-4-yl) methyl-2-aminoethyl

sulfoxide in the form of an oily product. The study using and K - spectrum shows the presence of the line absorbed by SO at 1020 and 1040 cm M.

c) this oily product is dissolved in

ethanol (250 ml) containing three drops of water, and methyl isocyanate (5.1 g, 0.07 mol) is added to the solution. The solution is kept at room temperature during the night and is subjected to chromatographic separation on a thin-film chromatograph with isole of silica gel plate, with a solution of ethyl acetate (methanol) ammonium hydroxide in a ratio of 5: 1: 1. The treatment is carried out using

UV-1 and potassium iodoplatnat, with the complete disappearance of ammonia and the formation of a product (a white spot originally lusovial). As a result of chromatographic purification using silnagel and recrystallization

from acetoshtrile and after final recrystallization of ethanol from methanol / ether, (5-methyl "1dazol-4-yl) -methyl-2- (N-methylthioureido) ethyl sulfoxide (7.1 g) with m.p. 135-137 ° C. Analytical. sample given

product after further recrystallization has square 139-140C.

Found,%: C 41.39; H6.35; N21.39.

C, H, "N4057

Calculated,%: C 41.51; H6.19; N21.52.

Example 2. As a result of processing (5-methyl 1-imyl) -4-yl) - methyl 2-aminoethyl sulfoxide in accordance with the alumina described in example 1c, ethyl isothiocyanate, 2- (dimethylamino) - ethyl isothiocyanate, S-methyl isothiocyanate, S-methyl-2 - iitroisothiourea, benzoyl isothiocyanate, the following compounds are obtained: (5-methylimidazol-4-yl), methyl 2- (N-ethylthioureido) ethyl sulfoxide;

(5-methylimidazol-4-yl) -methyl-2-IN -2 (dimethylamino) ethylure)) ethyl sulfoxyl;

(5-methylimidazole-Phil) - methyl-2- | ya D1p ethyl sulfoxide;

(5-methylimidazol-4-yl) -metal-2- (m-nitroguanidino) -ethyl sulfonoxd;

(5-methylimidazol-4-yl) -methyl-2- (N-benzoylthoureido) ethyl sulfoxide.

Alkaline hydrolysis with an aqueous solution of a hydrate (potassium of the last sulfoxide leads to the formation of (5-methylimidazol-4-yl) methyl 2-thiourendoethylsulfox da.

Froze As a result of the flow of the 101 Chemical reactions described in Example 1, 6 hours, of the following compounds:

2-1 (nmidazol-4-yl) -methyl) -thioet alosh;

2- (5-ethylimidazol-4-yl) -methyl) thiostilamine;

2- {{5-isopropyl midazol-4-yl) methyl thiostilamine;

2 - (5 - benzitmidazole - 4 - yl) - methyl) - this ztilamine;

2- (5-bromindazol-4-yl) -methyl-thioazlnam n; 2- 1 (2-methylnmidazol-4-yl) -methyl-) -thioethylamine:

2- ((imidazol-2-yl). Metal - taoethylamine; 2-1 (1.5 - dimethylimidazol - yl) - metal - taostilamine;

2 - 1 (1-methyl - 5 - chlorimidazole - 2 - yl) - methyl) g -thioethylamine;

,}, 2,4-triazol-3-yl) Methyl-gaethylamino;

2- (pyrazole-2-nd l) -methyl) -thioagalamin; 2- (pyrid-2-yl) methyl -thioethylamine;

2- (3-6 xiga1rid-2-yl) -metal) -tao-thylamine;

2- (pyridasium-3-yl) -metal) -thiostalamine;

2-1 (5-amine, 3,4-thiadiazol-2-yl) -methyl-taoepotmin;

2- (5-trifluoromethylimidazol-4-yl) methylb-thioethylamine;

2-1 (pyrimidin-2-yl) -methyl-taostilamine;

2- (pyrazin-2-yl) -metal-taostalamin;

2- (2-aminotazol-3-yl) - methyl) - taoethylamine;

2- (isothiazol-3-yl) metal-taoethylamine;

2- (4-bromoisothiazol-3-yl) -metal-toethyl;

2- (3-aminopyrid-2-yl) -methyl) -thiostilamine;

3- (imidazol-4-yl) -methyl) -thioproshamine;

2- (2- (imidazop-4-yl) -ztal-taostalamin;

2- (benzimndazol-2-yl) - metal-tatilamineL

The following sulfoxides can be prepared:

(imidazol-4-yl) -meta-2- (N-metaltaurei .do) -isyl sulfoxide;

(5-ztalimidazol-4-yl) -metal-2- (N-methyltheoureido) - zthalsulfoxide;

(5-Isopropylimidazol-4-yl) methyl-2- (N-methylthioureido) methyl sulfoxide;

(5-benzylimidazole-4-sh1) -methyl-2- (N - (methylthioureido) methylsulfoxide;

(5-bromimidazol-4-yl) -metal- - (N.-methyltaoureido) - ethyl sulfoxide;

(2-metalimidazol-4-yl) -meta-2- (N mstmttaoureido) -ethklsulfoxide;

(imidazol-2-yl) -methyl-2- (O.-MWTC, - tauoureido) ethyl sulfoxide;

(1,5-Dimethyl imidazol-2-yl) -metn -2 (M-mstyylthioureido) ethyl sulfoxide;

(l-metal-5-hlori and azol-2-yl) (N | meta / tauoureido) ethyl sulfoxide;

(3,1,2,4-triazol-3-yl) metal-2- (N-methylthioureido) -ztal sulfoxide;

(pyrazol-3-yl) -metal-2- (N-methyltaoureido) -stal sulfonic seed; (pyrid-2-yl) -metal-2- (m-metaltaoureido) ethyl sulfoxide;

(3-oxch1-Irid-2-yl) metal-2- (N-methylthioureido) -sulfosulfoxide;

(pyridazin-3-yl) -methyl-2- (N-metaltaoureido) methyl sulfoxide;

(5-amino-1,3,4-taadiazol-2-yl) -metal-2- (N-metal-taureido) -ztal sulfoxide;

(5-Trifluorometalimidazol-4-yl) -metal-2- (Ni methyl-tauoureido) -ztal sulfoxide; (pyrimidin-2-yl) -methyl-2- (N.-metaltaoureido) -stal sulfoxide;

(pyrazin-2-yl) -methyl-2- (N-metaltaourekmo) -stilsulfoxide;

(2-amyothiazol-3-yl) -methyl-2- (N-methyltaoureido) -3-sulfoxide;

(isotazol-3-yl) methyl 2- (N-methylthioureido) methyl sulfoxide;

(4-bromoisothiazol-3-sh1) -metal-2- (N-methyl taourido) - zthal sulfoxide;

(3-aminopyrid-2-yl) -methyl-2- (N-metalthioureido) -stilcrythoxide;

(imidazol-4-yl) -methyl-3- (N-metal-taoureido) propyl sulfoxide;

2- (imidazol-4-yl) -ztal-2- (M-metaltaoureido) - zthalsulfoxide;

(Benzimidazol-2-yl) -metal-2- (N-methylthioureido) - zthalsulfoxide.

ft. and measure 4. Peracetic acid (100%) in an acetic acid solution is added to a persimpeous suspension of 2- (5-methylimidazol-4-yl) -metal) t -thiosisalamine dihydrochloride (1.2 g) in acetic acid ( 12ml. After 5 minutes, the stirred suspension is heated to 95 ° C for 5 minutes to form a solution, which is then left to stand at 20 ° C for three days. The solid is precipitated, isolated and recrystallized from ethanol to form (5-metalimidazol-4-yl) -metal-2-aminostilsulfoxide with m.p. 178-179 ° C.

The reaction of this product with metal etiocyanate, as described in Example 1c, led to the formation of (5-metalimidazol-4-yl) -metal-2- (N-methylto-ureido) -ethal sulfoxide.

Claims (7)

1. Method for obtaining general sulfoxides X9S - uiv xf- c (6H2) s ((iH,) iiH (; . where A forms with the specified carbon atom kszzholozenshndindovre, thiazole, ioothiaol Q, oxazrone, eoxazolyl, pyrazole, triazole, thia-azole, hafimidine, pyrazhnoe or shfidazinovo schfo; Xi Xa are identical or different and represent hydrogen, hydrogen or hydrogen with 1–4, j atoms of fatter, trifluoromethyl, hydrox, halogen, amino, or Xi with X, and two atoms that make up the radical A, regenerate benzol soup; the whale is the goal of the number 0-4, provided that the sum of JQ k and m Zili4; E - oxygen or sulfur; R is hydrogen, alkyl, acyl or daalkyl shnoalkyl, Is it a matter of how composites are 2S formulas ) mliHi | where A, Xj, and m have the indicated values, treat with an oxidizing reagent — organic peroxide with periodate, and the resulting formula is one Xi.o XJr-jSCCH l S dH lm "H" Agde A, Xi, and m have the indicated meanings, are treated with a compound of the formula where RI and B have the indicated meanings, followed by release of the target product. 2. A method according to claim 1, characterized in that A is such that the heteroduster nucleus formed is an imdazolium, thiazole or pyridine nucleus. 3. Ousob prow. 1 and 2, characterized by JM, that Xi is hydrogen, methyl, bromine, amino or ltsyuksil and Xj is hydrogen. 4. Method POSH1. 1 and 3, characterized in that K I or 2 and pg 2 or 3. 5. The method according to p. 4, about tl and h a and y and u with 8 so that 1 and 2, 6. Method according to paragraphs. 1-5, characterized in that E is sulfur. 7. Method according to paragraphs. 1-6, characterized in that RJ is methyl. Iskhochikki and formashga, sewn in attested by the examination: 1. Karvulova E. R Higa sulfides of oil. Above Science, M. 1970, p. 206.