CS217376B1 - Aralkylidene malondialdehydes and method of preparing same - Google Patents

Description

wherein R is phenyl, p-chlorophenyl, p-nitrophenyl, p-dimethylaminophenyl, p-methoxyphenyl, p-hydroxyphenyl, p-aoethoxyphenyl, o-hydroxyphenyl, p-ethoxycarbonylphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, and the like C 1 H 4 -CH 2 CH-, 2-furyl-5-methyl-2-furyl and 2-thienyl.

The process for preparing these substances is based on the fact that the aldehyde of the formula II,

R-CHO (II) wherein R is as hereinbefore defined, does not react with the trimethinium salt of the general formula III, R ₂ n-ch = ch + c ₄ '(III) wherein R is C 1 -C 4 alkyl , in the presence of an acid catalyst in an acetic anhydride medium, a mixture of acetic anhydride and oleic acid, pivaloyl chloride or polyphosphoric acid at room temperature, and then the resulting intermediate of formula IV is converted to the final product by hydrolysis.

As the compound of formula (III), 1,3 bisdimethylaminotrimethinium perchlorate can advantageously be used in the medium of acetic anhydride, or a mixture of the acetic anhydride and oic acid, polyphosphoric acid or pivaloyl chloride, under acid catalysis conditions. The catalysts used were perchloric acid, sulfuric acid, zinc chloride, boron trifluoride etherate or titanium tetrachloride.

The reaction is usually carried out by adding an acid catalyst followed by the appropriate aromatic or heterooyllique aldehyde to a solution of the trimethinium salt in the acetic anhydride or the acetic anhydride-acetic acid mixture with ice-cooling. The reaction is carried out for a longer time, preferably at room temperature, usually 24 hours. A longer reaction time as well as an increase in temperature leads to a decrease in the reacoe yield. During the reaction, the intermediate of formula (IV) is formed, which is usually eliminated from the reaction mixture as a crystalline substance:

CH »NR.

2+

R-CH = Cl ·

CH = NR,

CIO.

(IV) in formula IV, R and R * are as defined above

Complete precipitation of the intermediate was accomplished with ether after the optimum reaction time, and the solid was washed 3 times with dry ether to remove residual o-acetic anhydride. The desired product, aralkylldenal malondlaldehyde, is obtained by hydrolysis. Usually, the crystalline intermediate is overlaid with distilled water, stirred with a meohanlocene or magnetic stirrer for 1 hour, then benzene is added and again stirred for 1 hour. Aralkylldenmalondlaldehyde is transferred to the organlocal phase. Extrakoe is usually repeated 2 times. In some cases, it is necessary to carry out the hydrolysis in a mildly alkaline medium and extract the product into a benzene-methylene chloride mixture. Very pure products were obtained by subsequent vacuum distillation or sublimation.

The process of the present invention is useful for the preparation of a wide variety of substituted benzylidene malonialdehydes (preferably substituted benzaldehyde and 1,3-bisdimethylaminotrimethinium perohorate), as well as a variety of heteroaralkylidene malondialdehydes (substituted heterooyl aldehydes and 1,3-bisdimethylamine dimethylamine). A great advantage of the process according to the invention is that, in a simple experimental setup with inexpensive raw materials, the unwritten aralkylidene malondialdehydes as yet very pure products are obtained in high yields. These can further be used in organic synthesis to prepare a wide variety of heterooyl compounds.

The invention is illustrated by the following non-limiting examples.

Example 1

Benzylidenmalondialdehyde

To a mixture of 5 ml of acetic anhydride and 5 ml of acetic acid was added 1 ml of 70% perchloric acid, followed by 2.26 g (10 mM) of 1,3-hisdimethylaminotrimethinium perorate and 1.07 g (11 mM) of henzaldehyde under ice-cooling. The reaction mixture was stirred at room temperature for 12 hours, then not allowed to stand overnight. The product was completely precipitated with dry ether (100 ml), then washed twice more with ether (2 x 50 ml). Hydrolysis with water with stirring, extraction into benzene (3 x 100 mL, stirred for 1 hour). The organic phase was washed with dilute sodium bicarbonate solution and water. Dry over magnesium sulphate over noo, evaporate solvent on rotary evaporator at 40 ° C.

Vacuum distillation (100 ° C / 25 Pa) yielded 1.06 g of benzylidene malonialdehyde (66%). For C ₁₀ H ₉ O ₂ (160.2) calculated: 74.99% C, 5.03% H; found: 74.59 56 C, 5.00 56 H.

1 H-NMR spectrum (CDCl 3): 10.16 (s, 1H, CHO), 10.05 (s, 1H, CHO), 6.17 (s, 1H, CH), 7.58 ( m, 5H, C ₆ H _5).

IC spectrum (CHCl 3, ν ¹ ): -9 (CH) CHO 2741 m, 2 (00) 1680 s, 1692 s, sh, 1754 m;

(C = C) 1633m; ý (ring) 1601 meters, 1575 meters, 1696 meters.

Mass Spectrum: HR 160.05265; theory: 160.0524.

Example 2 p-Chlorobenzylidene malonialdehyde

0.25 ml of 70% perchloric acid, followed by 0.452 g (2 mM) of trimethinium salt and 0.309 g (2.2 mM) of p-chlorobenzaldehyde were added to 3 ml of acetic anhydride under ice-cooling. Stir at room temperature for 24 hours. Processed according to the procedure of Example 1. The product was purified by sublimation (60 ° C / 25 Pa).

Yield 0.32 g (82%) of p-chlorobenzylidenemalondialdehyde, m.p. Mp 71-72 ° C. For

C ₇ H _1O C1O ₂ (194.6) calculated 61, 72% C, 3.63% H, 18.22 56 Cl; found: 61.51% C,

3.60 56 H, 18.07 56 Cl.

@ 1 H-NMR Spectrum (CDCl3, .delta.): 10.18 (d, 1H, CHO), .delta. 10.02 (s, 1 H, CHO),

8.03 (bs, 1H, CH), 7.63 (m, 2H, arom.), 7.45 (m, 2H, arom.).

Example 3 p-Nitro-benzylidene malendialdehyde

0.452 g (2 mM) of 1,3-bisdimethylaminetrimethinium perchlerate was dissolved in 3 * 1 acetic anhydride, added 0.5 g of zinc chloride and 0 (/ 333 g (2.2 mM) of p-nitrebenzaldehyde). and then treated as usual in Example 1, with extraction being carried out with a 5: 1 mixture of benzene methylenechleride to give 0.21 g (51%) by sublimation (100 ° C / 25 Pa). Product, bt 126-127 * C. Pr * Ο ^ ΗγΝΟ ^ (205,2)

% C, 58.54;% H, 3.44;% N, 6.83; found: 58.44% C, 3.42% H, 6.76% M. ¹ H-NMR spectrum (CDCl 3 (Λ): 10.18 (d, 1H, CHO), J _{CH> CHO} = O, 5 Hz, 10.07 (β, ΙΗ, ΟΗΟ), 8.12 (bs, 1H, CH), 8.37 (m, 2H, arem.), 7.77 (m, 2H, arem.).

Example. 4 p-Dimethylaminebenzylidemnalenedialdehyde

Following the procedure of Example 3, using 0.315 g (2.1 mM) of p-dimethylamine benzaldehyde.

Reaction time 24 h, the product precipitated and washed with ether (3 x 50 mL). Science (50 ml) and 5 ml of saturated potassium carbonate residue were added. Extraction with benzene-methylene chloride (5: 1). The product was sublimevan (100 ° C / 25 Pa). Crystallization from benzene-cyclehexane.

Yield 0.31 g (76%) of p-dimethylaminebenzylidene-maledialdehyde, mp 119-112 ° C. For ^C 12 ^H 13 ^NO 2 '( ² ° 3> ² > calculated: 70.92% C, 6.45% H, 6.89% W; found · 70.86% C, 6.32% H,

6.92% N ^I H-NMR (CDCl-j <T): 10.20 (d, IH, CHO), 9.90 (s, 1H, CHO), _{CHQ QH} J = 0.9 Hz 7.78 (bs, 1H, CH), 3.12 (s, 6H, (CH3 N, 7.88 (m, 2H, arem)), 6.70 (m, 2H, arem).

Example 5 p-Methexybenzylidene malendialdehyde

Passing Example 3, using 0.299 g (2.2 mM) of p-methexybenzaldehyde. The product was distilled at 110 ° C / 25 Pa, yield 0.36 g (94%). For θιχΗΗΟ (190.2) calculated: 69.46% C, 5.30% H; Found:% C, 69.21;% H, 5.21.

Example 6 p-Hydroxybenzylidene malendialdehyde

Passing Example 3, using 0.268 g (2.2 mM) of p-hydroxybenzaldehyde, reaction reaction 24 hedin. · Treated similarly as in Example l _r Yield: 0.28 g (64.2%) of p-acetexybenzylidenmalendialdehydu, mp 59-61 ° C. For (218.2) calculated: 66.05 ° C, 4.62% H-; found: 66.01% C, 4.57% H. The desired hydroxy derivative was obtained by hydrelysis from the prepared acetexyl derivative. 0.218 g (1 mM) of p-Acetexybenzylidene malendialdehyde was suspended in 20 ml of Ο, ΙχΜ hydroxide solution and stirred, dissolved and dissolved, then acidified with 5% chlorine acid to pH 2-3. Extraction of the product de with benezene-methylene chloride (3: 1). The yield after sublimation (100 * 0/25 Pa) was 0.167 g (95%) of p-hydroxybenzylidene-maledialdehyde, mp 176-177 [deg.] C.

For C 10 (8 ° 3, 76.2) calculated: 68.18% C, 4.58% H; Found:% C, 68.22;% H, 4.40.

Example 7 • -Hyirexybenzylidene malendieldehyde

Using the paddle procedure of Example 3, using 0.268 g (2.2 mM) of ε-hydroxybenzaldehyde, reaction time 24 hedin. Working up in the usual manner as in Example 1. After sublimation (110 * 0/25 Pa), 0.26 g (74%) of the product was obtained, mp 159-160 * C. After ^c xq ^H 8 ⁰ 3 ^ 76.2) cured. % H, 5.58; found: 68.21% C, 4.53% H.

Example 8 p-Ethylcarbenylbenzylidene-malealdialdehyde

To prepare a diluent as described in Example 2, 0.356 g (2 mM) of p-ethoxycarbenylbenzaldehyde was weighed. Working up in the same manner as in Example 1. The product was ehremategrafevan in a mixture of benzene-ethyl acetate and sublimevane (60 * 0/25 Pa). Yield of p-ethoxycarbenylbenzylidene-maledialdehyde 0.25 g (60%). 64-66 * C. For C ₁₃ H ^ ₂ 0 ₄ (232.2) calculated:

% C, 67.23;% H, 5.21; found: 67.09% C, 5.28% H. 0.232 g (1 mM) of p-ethoxycarbenylbenzylidene malonialdehyde was suspended # in 20 ml of 0.1W sodium hydroxide and stirred to dissolve (1 wt.). After acidification with 5% chloric acid, the product was extracted with ether-methylene chloride (2: 1). The yield of pe by crystallization from acetone with cooling is 0.190 g (93%) of p-carbexybenzylidene malenialdehyde, m.p. 184-185 * C. For C - ^^^ΗΗ 204 204 (204.2) calculated: 64.71% C, 3.95% H; found:

64.80% C, 3.98% H.

Example 9 (e, m, p) -Fluerbenzylidene malonialdehydes

For all the isemters, the same way of preparation was used. To 3 ml of acetic anhydride was added 0.25 ml of 70% chloric acid under ice-cooling, then 0.497 g (2.2 mM) with stirring.

1,3-bisdimethylaminetrimethiniuaperchlorate and 0.248 g of the corresponding fluorobenzaldehyde.

Reaction with stirring 24 hed. It was then treated in the same manner as in Example 1.

p-Fluorobenzylidene malendialdehyde was obtained in a yield of 0.30 g (84%), mp 77-79 ° C. For C ₇ H ₁₀ F0 ₂ (178.2) vypečtene: 67.41% C, 3.96% H, 10.66% F; found: 67.20% C, 3.85% H. m-Fuerbenzyliuenmalenedialdehyde was obtained in a yield of 0.21 g (59%), bp 95/0/25 Pa.

For C q H ₇ FO ₂ Found: 67.15% C 3.80% H E Fluerbenzylidenmalendialdehyd was obtained in a yield of 0.28 g (79%), mp 58-59,5 ° C. For C ₁₀ H ₇ FO ₂ found: 67.30% C, 3.87% H.

Example 10

Cinnamylidenmalendialdehyde

To prepare a diluent as in Example 3, weighing 0.291 g (2.2 mM) of cinnamon aldehyde. Reaction 20 hed, then treated as in Example 1. After sublimation (65 ° C / 25 Pa), 0.32 g (86%) of cinnamylidene malendialdehyde, mp 79-80 ° C, was obtained. ^C 12 ^H 10 ° 2 ( ¹⁸ 6 → 2) calculated: 77.40% C, 5.41% H; found: 77.33% C, 5.45% H. ¹ H-NMR spectrum (CDCl ₃ ,? / 5: 10.30 (d, 1H, CHO), 9.83 (β, ΙΗ, ΟΗΟ), 8 24 (dd, 1H, CH), 7.36 (d, 1H, CH), 7.42 (m, 1H, CH) Mass spectrum: HR 186.0680, theory: 186.0681.

Example 11

2-Furylmothylenemalondialdehyde

To a mixture of 3 ml of acetic anhydride and 3 ml of acetic acid was added 1.25 ml of boron trifluoride tetrahydrate and 1.13 g of 1,3-bisdimethylaminotrimethinium perchlorate and 0.5 ml of fural. Stir at room temperature for 8 hours, then allow to stand overnight. The working up of the reaction mixture was similar to that in the previous cases (Example 1). Yield: 0.68 g (91%) of 2-furylmethylenemaline-4-dialdehyde, m.p. 50-54 * C. For C 8 H 14 O 3 (150.1) calculated; % C, 64.00;% K, 4.03; aalezen ·:

63.67% C, 4.01% H. 1 H-NMR spectrum (CDCl 3): 10.08 (s, 1H, CHO), 10.70 (s, 1H, CHO),

7.66 (s, 1H, CH), 7.50 (d, 1H, furan C ₍₃₎ H), 6.68 (dd, 1H, C ₍₄₎ H), 7.80 (d, 1H, C ₍₅₎ H). Example 12

2-Thienylmethylenemalondialdehyde

To a mixture of 6 ml acetic anhydride and 6 ml acetic acid was added · 2.26 g (10 mM)

1,3-bisdimethylaminotrimethinium perchlorate, 2.5 ml boron trifluoride etherate and 1.12 g (10 mM) of 2-thiophenecarbaldehyde. Stir at room temperature for 24 hours. It was then treated in the same manner as in Example 1. Obtained 1.43 g (86%) of 2-thienylmethyl malondialdehyde, m.p. after sublimation (80 * 0/25 Pa) 96-97.5 * C. For C 8 H 8 O 3 S (166.2) calculated: 57.82% C, 3.64% H, 19.29% C; Found:% C, 57.67;% H, 3.52;% S, 19.38.

Claims (3)

1. Aralkylidene malonialdehydes of formula I, CHO R = CH = C CHO (I) wherein R is phenyl, p-chlorophenyl, p-nitrophenyl, p-dimethylaminephenyl, p-methexyphenyl, p-hydroxyphenyl, p-acetoxyphenyl, o-hydroxyphenyl, p-ethoxycarbonylphenyl, o-fluorophenyl, m-fluorophenyl, p -fluorophenyl; and further C 1 H 4 -CH 2 CH-, 2-furyl-5-methyl-2-furyl and 2-thienyl. 2. A process for the preparation of aralkylidene malondialdehydes of formula (I), characterized in that the aldehyde of formula (II): R-CHO (II) wherein R is as defined above, is reacted with the trimethinium salt of the Formula III, N-CH 2 CH-CH 3 NR 8 J + C 10 _(III) wherein R 1 is alkyl and 1 to 4 carbon atoms, in the presence of an acid catalyst in acetic anhydride, acetic anhydride / acetic acid, pivaloyl chloride or polyphosphoric acid at room temperature, and then the resulting intermediate of formula IV, R-CH = C _x ch = wr ₂ 2+ CH = NR _n 2 cio: (IV), wherein R and R 'have the above meaning, are converted to the final product by hydrolysis. 3. A process according to claim 2, wherein the acid catalysts are perchloric acid, sulfuric acid, zinc chloride, boron trifluorothorate and titanium tetrachloride.