CS266981B1 - 2,5,6,8,11,12-hexasubstituted 4,1/-di-(n,(-disubstituted n-thioureido)-1,3,7,9-tetraoxacyclododecanes and method of their preparation - Google Patents

Abstract

New 2,5,6,8,11,12-hexasubstituted are described 4,10-di (N, N-disubstituted Ν'-thioureido) -1,3,7,9-tetraoxacyklododekány of formula I wherein R 1 is methyl or ethyl, R 2 represents a hydrogen atom or methyl, ethyl, resp. R 5 is R 4 is morpholino and R 6 is ethyl n-butyl, phenyl, benzyl, 4-totyl. The essence of their preparation is that general isothiocyanates of formula III wherein R 1 and R 2 are the same as in Formula I, they react with primary or secondary amines to form thioureas of formula (II) wherein R 1, R 2, r 3 and R 6 means the same as in formula I, wherein at temperatures from 10 ° C to the boiling point solvents to form I.

Description

The present invention relates to novel substituted 1,3,7,9-tetraoxacyclododecanes

2-3 where R is methyl or ethyl, R is hydrogen or methyl, R is hydrogen,

4 4 methyl, ethyl, resp. R s R is morpholino and R represents ethyl, n-butyl, phenyl, benzyl or 4-totyl and a process for their preparation.

The substances according to the invention have not yet been described in the literature.

The essence of the method of their preparation lies in the fact that isothiocyanate

R ¹ of the general formula

III where r! and general general

R is the same as in 3 4 3 4 of formula NR R, where R and R are of formula II,

R ^{2 of} formula I,

R

NCS react with primary (III) or secondary amines] 2 * 3 4 where R ^x RR and R ⁴ are the same R ¹

R

R ² as in formula I, to give thioureas nh-cs-nr ³ r ⁴ (II) means the same as in formula I, the thioureas of formula II undergoing spontaneous dimerization in solution at temperatures from 10 ° C up to the boiling point of the solvent. to give compounds of formula I.

The dimerization can be performed by dissolving the substance in a suitable solvent such as e.g. chloroform, dichloromethane, acetone, acetonitrile, methanol and the like. at temperatures up to 10 ° C up to the boiling point of the respective solvent. The reaction time depends on the solvent and temperature used and can be advantageously determined by thin layer chromatography.

The advantage of the process for the preparation of substituted 1,3,7,9-tetraoxacyclododecanes of the formula I according to the invention is the easy availability of the starting materials, the simple procedure and the spontaneous dimerization of the compounds of the formula II in solution, which proceeds without by-products and in high yields. .

The use of the compounds of general formula I prepared according to the invention: is that they form - + + 2+ complexes with metal cations, e.g. with Li, Ag, Cu.

The following examples illustrate but do not limit the scope of the invention.

Example 1

Preparations of 4- (N-phenyl-N'-thioureido) -2,6-dimethyl-1,3-dioxane-1, R 2 = CH 2, R 2 = H,

R ⁴ = Ph).

To a solution of 1.73 g (0.01 mol) of 4-isothiocyanato-2,6-dimethyl-1,3-dioxane in 25 ml of ether was added dropwise at -10 ° C an ethereal solution of 0.93 g (0.01 mol) of aniline and the reaction mixture was stirred at room temperature for 5 h. The precipitated substance was filtered off, and after crystallization from chloroform-ether, 2.04 g (77%) of product m.p. t. 142-144 ° C.

CS 266 981 Bl

Example 2

Preparation of 4,1O-di- (N-phenyl-N'-thioureido (-2,6,8,12-tetramethyl-1,3,7,9-tetraoxacyclododecane (1, R ² = CH ₃ , R ² = R ³ = H, R ⁴ = Ph)

0.798 g (0.003 mol) of 4- (N-phenyl-N'-thioureido (-2,6-dimethyl-1,3-dioxane) are dissolved in 25 ml of acetone, the reaction mixture is heated at 50 DEG C. for 12 h, then the acetone was evaporated and the residue after crystallization from nitromethane-petroleum ether gave 0.59 g (74%) of product, mp 155-157 ° C.

The physicochemical properties of the compounds of formula I prepared as described above are given in Table 1. Ph in the example and table is phenyl.

Table 1

I

Physicochemical properties of substituted 1,3 / 7,9-tetraoxacyclododecanes I

Compound Yield <%) T. t. (° C) Molecular peak in the mass spectrum a Chemical shifts from the ¹³ C NMR spectrum ^b c = s c ₂ , c ₈ ^C 4 ' ^C 10 ^C 6 ' ^C 12 ^C 5 ' ^C U R ¹ R ² R ³ R ⁴ CH 2 H H nC ₄ H ₉ '70 96-97 492 182.7 97.4 81.5 72.1 37.4 ^CH 3 H H Ph-CH ₂ - 60 135-137 560 182.8 97.3 81.4 71.9 37.3 ch ₃ H H Ph- 74 155-157 532 180.4 97.6 81.7 71.5 37.9 ch ₃ H H 4-CH ₃ Ph- - 65 141-143 560 180.6 97.6 81.9 71.6 38.0 ch ₃ H CH- Ph- 60 135-136 560 181.3 97.6 82.2 71.6 38.1 CH ₃ H morpholino 69 138-140 520 181.9 97.7 83.1 72.1 37.7 ^C 2 ^H 5 ^ch ₃ H PhCH ₂ 60 154-156 644 184.0 100.7 85.9 82.0 39.3

^and measured by chemical ionization k expressed in units of δ, measured in CDCl 3

Claims (2)

Example 2 Preparation of 4,10-di- (N-phenyl-N'-thioureido (-2,6,8,12-tetramethyl-1,3,7,9-tetraoxacyclododecane (1,2) = CH 3, R 2 = R 3 = H, R 4 = Ph} 0.798 g (0.003 mol) of 4- (N-phenyl-N'-thioureido (-2,6-dimethyl-1,3-dioxane is dissolved in 25 acetone, reaction the mixture is heated at 50 ° C for 12 h, the acetone is evaporated off and the residue after crystallization from nitromethane-petroleum ether gives 0.59 g (74%) of the product with a melting point of 155-157 ° C. Table 1 I Physicochemical Properties of Substituted 1,3 / 7,9-Tetraoxacyclododecanes I Compound Yield T. m. Molecular Chemical Shifts from NMR Spectrum (%) <° C) nostnomspektre and C = S C2 'C8 C4' C10 C6 'C12 C5' C11 R1 R2 R3 R4 gh3 HH n-C4Hg 70 96-97 492 182,7 97,4 81,5 72,1 37,4 ch3 HH Ph-CH2- 60 135-137 560 182.8 97.3 81.4 71.9 37.3 CH3 HH Ph- 74 155-157 532 180.4 97.6 81.7 71 , 5 37.9 CH3 HH 4-CH3Ph- 65 141-143 560 180.6 97.6 81.9 71.6 38.0 ch3 H CH- Ph- 60 135-136 560 181.3 97.6 82, 2 71,6 38,1 CH, H morpholino 69 138-140 520 181,9 97,7 83,1 72,1 37,7 C2H5 ch3 H PhCH2 60 154-156 644 184,0 100,7 85,9 82 , 0 39.3 and measured by chemical ionization to δ in units of δ measured in CDCl 3. SUBJECT OF THE INVENTION 1. 2,5,6,8,11,12-Hexasubstituted 4,10-di- (Ν, Ν-disubstituted N ") -thioureido) -1,3,7,9-tetraoxacyclododecanes of formula I, R1 Wherein R is methyl or ethyl, R is hydrogen, or methyl, R is hydrogen, 4, 4 methyl, ethyl or ethyl; R 5 is R is morpholino and R is ethyl, n-butyl, phenyl, benzyl or 4-tolyl. 2. Process for the preparation of the compounds according to claim 1, characterized in that the isothiocyanates of the formula III, in which R and R are the same as in the formula I, are reacted with the primary or secondary general formula. NR 1 R 4, wherein R 1 and R 4 are the same as in formula I, to give the thiourea of formula II, R * 1 2 3 4 n 2 NH-cs-NR 3n 4 wherein R, R, R and R are the same as in formula 1, wherein thioureas are subjected in solution, preferably in acetone, to spontaneous dimerization at temperatures of from 10 ° C to the solvent of the solvent to form compounds of formula I. Severografia, np, MOST Price $ 2.40