CS268590B1 - Process for preparing 5-nitro-2-furen and 5-nitro-2-phenylene enantiols - Google Patents

Abstract

A new method for preparing enals of the 5-nitro-2-furan and 5-nitro-2-thiphenyl series of the general formula I is described, characterized in that 3-(5-nitro-2-furyl)propenoic or 3-(5-nitro-2-thiphenyl)propenoic acid of the formula II is reacted with bromine to form 2,3-dibro-3-(5-nitro-2-furyl)propionic, or 2,3-dibro-3-(5-nitro- -2-thiphenyl)propionic acid of the formula III, which, after isolation, are reacted with the appropriate secondary or primary alkane in an organic solvent.

Description

The invention relates to a process for the preparation of enanines of the 5-nitro-2-furan and 5-nitro-2-thiophene series of the general formula I 'o ₂ n

H-CH-NR R 1 2 (I) wherein Z is O or 8 and NR R 2 is N (CH 2).

^z * n <chch ₃ ) ₂

N ¢ 2 / ^NH '

CH NH, »5

CH 2 CH 2 H, (CH 2 CHNH, CH ₃ O-η 2> - ΝΗ,

Enamins are widely used in organic synthesis (Cook A.G., Enamines, Synthesis, Structures and Reactions, Dekker, New York-London 1969). The enanins of the 5-nitro-2-furin and 5-nitro-2-thiophene series show significant antibacterial activity and are the subject of intensive research / Végh D., Šejnkman AK, Nivorožkin LE, Kováč J., Dandárová M., Ivančo L .: Coll. Czech. Chem. Commun., £ 5, 155 (1980); Végh D., Šejnkman A.K., Kovií J., Kondratenko G.P., Geonja N.I .: USSR A0 671 254 /. Their preparations are based on highly reactive 5-nitro-2-furyl- resp. 5-nitro-2-thienylvinyl halides by reaction with amines, in particular secondary ones (Végh 0., Kováč J., Dandárová K .: Tetrahedron letters Jj, 969 (1980)); Végh D., Kováč J., Dandárová K., Ivančo L. Coll. Czech. Chem. Commun. 155/1980 //.

These disadvantages are substantially eliminated by the process according to the invention, which consists in that 3- (5-nitro-2-furyl) propenoic acid or 3- (5-nitro-2-thienyl) propenoic acid of the formula II.

_{0 N} — 2 - CH-CH-COOH ( ¹¹ ) __________ ² 'of ^J ______ ______ ____ where Z is the same as in formula I, is reacted with bromine to give 2,3-dibromo / 5-nitro-2 furyl / propionic acid), or Z, 3-dibromo-3- / 5-nitro-2-thienyl / .propiónovej of formula 111 rr ~ tti λ s 1 ₀ N -___ / '\ _- CHBr CHBr-COOH ~' Z wherein Z is indicated above, which optionally, after isolation, is reacted with a secondary amine selected from the group consisting of compounds of the formula

ΗΝ (0Η _{3) 2,} ΗΝ ₍₂ 0Η 0Η _{3) 2,} H N [CH _{(CH3) 2] 2} » '* QNH ^(2/41" ™ ° H or a primary amine selected from the group zahrňujáce) zláčeniny formula

CH ₃ NH ₂ , CH ₃ CH ₂ NH _{2 /} (CH ₃ ) ₂ CHNH ₂ , Q-NH ₂ , ^CH 3 ^{0 _- <} ^ - ' ^NH 2' - ' ^NH 2 ^# in the environment of organic solvents as in liquid aromatic hydrocarbons as ....... in benzene, toluene, xylene in ethers as in diethyl ether, tetrahydrofuran, dfoxane, 1,2-dimethoxyethane, polyethylene glycol with an average molecular weight of 200 to 600, further in ethyl acetate, acetonitrile, carbon disulfide, acetone and 2-butanone or mixtures thereof with each other or with water at temperatures of 20 to 160 ° C.

CS 268 590 B1

The reactions proceed according to the following scheme:

H-CH-C00H + Br ₂ ° ₂ n —K /--CHBr-CHBr-COOH+HNR.R -4 'Z ⁷ 12

ON - N-CH-CH-NR.R ¹ 2

The compounds of the invention can also be prepared by treating the low base amines pK_6 as B

They are primary amines / aromatic amines.

The present process utilizes substituent fragmentation reactions in contrast to the previously used $ _N in the reaction. Since the substitutions take place on saturated carbon and precede the fragmentation reaction, they have a wider application and I present! new type of reaction.

Example 1

19/3 g (0.1 mol) of 3- (5-nitro-2-furyl) propenoic acid were suspended in 250 ml of C18 and 16 g of bromine were added at the boiling point of the solvent over a period of 3 hours. After decolorization of the solution, 30 g of piperidine were added to the vigorously stirred solution, and after stirring for 5 hours, the solvent was removed in vacuo. 17 g of 1- (N-piperidyl) -2- (5-nitro-2-furyl) ethene were obtained, m.p. 77-79 ° C.

Example 2

19/3 g (0.1 mol) of 3- (5-nitro-2-furyl) propenoic acid in 300 ml of dioxane were mixed at 40 DEG C. with 216 g of bromine and, after heating for 1 hour to the boiling point of the solvent, 30 g of dimethylamine were added all at once. After stirring at room temperature for 1 h, the reaction mixture was heated at 100-110 ° C for 2 h. After cooling, it was filtered through 100 g of silica gel, eluent benzene-ethyl acetate. 17 g of 1-N, N-dimethylamino-2- (5-nitro-2-furyl) ethylene of m.p. 65-67 ° C.

Example 3

3.53 g of 2,3-dibromo-3- (5-nitro-2-furyl) propionic acid obtained by halogenation of 3- (5-nitro-2-furyl) propenoic acid with bromine were dissolved in 50 ml of acetonitrile and 50 ml of acetone and 4 g of anisidine were added with vigorous stirring. After heating at 60-70 ° C for 3 h, the mixture was purified by filtration through silica gel. 1.1 g of 1- (4-ethoxyphenyl) amino-2- (5-nitrofuryl) ethene of m.p. 123-127 ° C.

Example 4

20.9 g / 0.1 mot / 3- / 5-nitro-2-thienyl / propenoic acid in 250 ml of C $ ₂ at the boiling point of the solvent were mixed with 16 g of bromine. After decolorization of the solution, 14 g of dimethylamine were added and, after stirring for 10 minutes at 20 [deg.] C., the mixture was heated to reflux for 1 hour. Then 50 ml of polyethylene glycol with an average molecular weight of 300 were added and the carbon disulfide was distilled off. The temperature was gradually raised to 100 ° C over 2 h. After pouring into water, 11 g of 1-N (N-dimethylamino-2- (5-nitro-2-thienyl) ethane were obtained, m.p. 126-127 ° C.

Example 5

20.9 g (0.1 mol) of 3- (5-nitro-2-thienyl) propenoic acid and 16 g of bromine were mixed in 100 ml of 1,2-dimethoxyethane and, after stirring and heating at 60 DEG C. for 10 minutes, were added all at once.

CS 268 590 B1 g of morpholine in 200 ml of acetone. After heating to reflux for 3 h, the ammonium salt was filtered off and the filter was concentrated to crystallize from Acc to give 12 g of 1-N-morpholino-2- (5-nitro-2-thienyl) ethane, mp 167-168. ° C.

Example 6

35.3 g of 2,3-dibromo-3 (5-nitro-2-phenyl) propionic acid obtained by halogenation of 3- (5-nitro-2-phenyl) propanoic acid with bromine were dissolved in 500 ml of benzene and stirred vigorously with vigorous stirring. 0.22 mol of amine was added. After heating to reflux for 3 h, the final product was purified by filtration through silica gel. The anamines were obtained in a yield of 70 to 95 Xi

HN ^ Rg m.p. (° C) HN (ca ₃ ) ₂ 65 until 67 HN (CH ₂ CH ₃ ) ₂ 64 until 65 nh [ch (ch) J 53 until 57 H <> 129 until 130 hnO 77 until 79 HnQ ' 86 until 88 HN ^ ^ NH ^r 160 until 165 nh ₂ ch ₃ oil oil

metal violet oil νμ ₂ - ° ^η ₂ ° η ₃ nh ₂ -ch (ch ₃ ) ₂ metal violet oil

^ΝΗ 2 ~~ Ο ^ -och ₃ 123 to 127 ^NH 2 -O 115 to 117 nh ₂ —-θ- —CH 3 120 to 122 nh ₂ —O —Br 137 to 140

, · A

The compounds according to the invention can also be prepared by the process described in Example 6 using aromatic liquid hydrocarbons other than toluene, xylene and mixtures thereof.

Claims (1)

4 CS 268 590 B1 OBJECT OF THE INVENTION Process for preparing 5-nitro-2-furan and 5-nitro-2-thiophine enamels of the general formula I ° 2N-O- »HhCH-NR 4 (I) wherein Z is O or S and NR 4 R, Je ΝζΟΗ ^, ,, N (CH 2 CH 3) 2, N (CHCH 1 3 2 2) 2, nQ O 0, Νθ / nQ / N _ / NH 'CH-, NH CH CH 3 CH 2 NH H (CH 3) 2 CHNH Characterized by the fact that 3- (5-nitro-2-furyl / propyne and / or 3) -NH 1 CH 3 -? -? -? - (5-Nitro-2-tertienyl) propene acid of formula (II) N - (--CH - CH - COOH (II) 2 'zz) where Z is as defined in formula (I), is reacted with bromine to form 2.3. -dibromo-3- (5-nitro-2-furyl / propionic acid) or 2,3-dibromo-3- (5-nitro-2-tertienyl) propionic acid of formula (III) n-CHBr-CHBr-COOH (III) wherein Z is as defined above, which, optionally after Isolation, is allowed to react with a secondary seal selected from the group consisting of compounds of formula HN (CH 3) 2 r> <N (CH 2 CH 3) 2, Ην [οΗ (ΟΗ3) 2] 2 * ΗνΌ / ° »'ΗΝ ^' ^ ΗΝ, or with a primary amine selected from the group comprising compounds of formula CH 3 NH 2, CH 3 CH 2 NH 2, (CH 3) 2 CHNH 2, θ-ΝΗ 2, CH 3 ^N-NH 2 'CH 3 "O" -NH 2' Br- Q Q- in an organic solvent such as liquid aromatic hydrocarbon hydrocarbons, toluene, xyline in ethers such as methylethyl, tetrahydrofuran, daloxane, 1,2-dimethoxyethane, polyethylene glycol of average molecular weight 200-600, further in ethyl acetate, acetonitrile, carbon disulphide, acetone and 2-butanone or 1h mixtures of each other with water at 20 ° C to 160 ° C.