Condensation of antipyrine with some aldehydes and ketones of the saturated and aromatic series
Abstract Generated abstract
This study examines acid-catalyzed condensation reactions of antipyrine with selected saturated and aromatic aldehydes and ketones, motivated by the analytical utility of diantipyryl methane derivatives. The work describes preparations, isolation procedures, solubilities, melting points, acid-base titration data, and Kjeldahl nitrogen analyses for products formed from anisaldehyde, vanillin, furfural, m-iodobenzaldehyde, isovaleraldehyde, heptanal, acetone, butanone, and acetophenone, and tests benzophenone and m-iodobenzophenone under similar conditions. The results indicate formation of monohydrochlorides with several aromatic aldehydes bearing methoxy, iodine, or furan functionality, while aliphatic aldehydes and certain ketones gave dihydrochlorides of 4,4-diantipyryl-R-methane derivatives. Benzophenone and m-iodobenzophenone did not undergo condensation, which the author attributes to reduced ketone reactivity in the presence of phenyl groups.
Full Text
Condensation of Antipyrine with Some Aldehydes and Ketones of the Saturated and Aromatic Series
F. Z. Gorfinkel
(Presented by Prof. B. V. Tronov, Doctor of Chemical Sciences)
Among pyrazole derivatives, a whole series of substances valuable for practical use is known—analytical reagents, dyes, and medicinal substances. Antipyrine and dimethylaminoantipyrine are good analytical reagents for Cd, Bi, Pb, Zn, Co, and other elements. But the most effective action is possessed by condensed derivatives of antipyrine, such as diantipyryl methane, the product of the condensation of antipyrine with formaldehyde; diantipyryl phenyl methane, a condensed derivative of antipyrine with benzaldehyde; and other derivatives. They are widely used in analytical chemistry [3].
Diantipyryl methane is used for the colorimetric determination of Co [2], the potentiometric determination of cadmium [6], and the quantitative determination of bismuth [5]. The use of diantipyryl methane in analytical chemistry made it possible to develop a special method for purifying Ni and Mn salts from impurities [4]. Diantipyryl phenyl methane is a good reagent for the determination of vanadium [1] and other elements. Proceeding from this, it should be considered of interest to synthesize a series of derivatives—products of the condensation of antipyrine with certain aldehydes and ketones of the saturated and aromatic series—and also to elucidate the influence of aliphatic and aromatic radicals and the influence of various functional groups on the nature of the condensation, which was the aim of the present investigation.
Experimental Part
We studied the following products of the condensation of antipyrine with aldehydes and ketones.
1) Condensed derivative of antipyrine with anisaldehyde,
2) condensed derivative of antipyrine with vanillin,
3) condensed derivative of antipyrine with furfural,
4) condensed derivative of antipyrine with meta-iodobenzaldehyde,
5) condensed derivative of antipyrine with isovaleraldehyde,
6) condensed derivative of antipyrine with heptanal,
7) condensed derivative of antipyrine with acetone,
8) condensed derivative of antipyrine with butanone,
9) condensed derivative of antipyrine with acetophenone,
10) condensed derivative of antipyrine with benzophenone,
11) condensed derivative of antipyrine with m-iodobenzophenone.
Condensation of Antipyrine with Anisaldehyde
3 g of finely powdered antipyrine (m.p. 112°) was mixed with the theoretically calculated amount of anisaldehyde, 1.08 g, purified by distillation (boiling point 244–246°), based on 2 moles of antipyrine per 1 mole of anisaldehyde. The mixture was thoroughly stirred in a porcelain dish and heated on a water bath at a temperature of 75–80°. When the mixture had completely melted, 6 ml of HCl of specific gravity 1.17 was added. The melt acquired a bright orange color. After heating the mixture with HCl for 1–2 minutes, 25 ml of distilled water was poured into the solution. The solution became decolorized, and from it a layer of oil gradually separated, from which a loose white precipitate then fell out.
The obtained precipitate was washed several times on the filter with water, dried in air, and recrystallized from ether. Yield: 2.7 g—63%.
The obtained condensed derivative dissolved in water on heating; in benzene, toluene, and ether it did not dissolve even on heating. For the titration of 0.1 g of the obtained condensed derivative in an alcohol–water medium with NaOH in the presence of phenolphthalein indicator, 2 ml of NaOH, titer 0.00351, was consumed, in all—0.00702 g NaOH. The theoretically calculated amount is 0.0141 g NaOH. That is, the NaOH consumed for titration of 0.1 g of the condensed derivative—antipyrine-anisaldehyde—is half the theoretically calculated amount. Thus, we may assume that what we obtained was not the dihydrochloride of 4,4-diantipyryl-para-methoxyphenylmethane, but the monohydrochloride of 4,4-diantipyryl-para-methoxyphenylmethane.
\[ \mathrm{C}_{30}\mathrm{H}_{31}\mathrm{O}_{3}\mathrm{N}_{4}\mathrm{Cl} \qquad \begin{array}{ll} \text{Found (by Kjeldahl)} & \%\,\mathrm{N}\ 11.10 \\ \text{Calculated} & \%\,\mathrm{N}\ 10.85 \end{array} \]
Preparation of the Free Base of 4,4-Diantipyryl-para-methoxyphenylmethane
0.8600 g of the monohydrochloride of 4,4-diantipyryl-para-methoxyphenylmethane was treated in a beaker with hot water; then the solution was brought to a neutral reaction. The white powder was filtered off in air. The obtained free base, 4,4-diantipyryl-para-methoxyphenylmethane, dissolved well at a temperature of 16–18° in alcohol and benzene, and somewhat less readily in toluene and dioxane. Melting point 175–176°.
\[ \begin{array}{ll} \text{Found (by Kjeldahl)} & \%: 11.00 \\ \mathrm{C}_{30}\mathrm{H}_{30}\mathrm{O}_{3}\mathrm{N}_{4}\ \text{Calculated} & \%: 11.33 \end{array} \]
We assume that we have isolated the free base of 4,4-diantipyryl-para-methoxyphenylmethane.
[structural reaction scheme]
Displayed structural formula of the condensation product of antipyrine with an aromatic aldehyde.
The condensation of antipyrine with vanillin, furfural, and m-iodobenzoic aldehyde was carried out by us according to the procedure described above.
The results of the syntheses are summarized in Tables 1 and 2.
Preparation of the condensed derivative of antipyrine—isovaleric aldehyde
2 g of antipyrine were mixed with the theoretically calculated amount of isovaleric aldehyde (b.p. 92°, 0.45 g). The mixture was heated on a water bath until complete melting; then 4–5 ml of HCl of specific gravity 1.17 was added to the melt, whereupon the solution turned pink. No precipitate was observed, even after the addition of 30 ml of distilled water. The precipitate separated after prolonged evaporation of the solution at 30–40° and was recrystallized from ether. The condensed derivative obtained dissolved well at 16–18° in water and alcohol; in benzene it dissolved on heating, and it did not dissolve in ether. Melting point 153–154°. For the titration of 0.1 g of the condensed derivative obtained in an alcoholic-aqueous medium with NaOH in the presence of phenolphthalein indicator, the following was consumed: 3.7 ml of NaOH, titer 0.00421; total NaOH—0.0155 g.
Theoretically calculated—0.0154 g NaOH.
\[ \mathrm{C}_{27}\mathrm{N}_{4}\mathrm{H}_{34}\mathrm{O}_{2}\mathrm{Cl}_{2} \qquad \begin{array}{ll} \text{Calculated} & \%:\ \mathrm{N}\ 10.8 \\ \text{Found (by Kjeldahl)} & \%:\ \mathrm{N}\ 11.0 \end{array} \]
We believe that we synthesized a compound of the following structure:
Displayed structural scheme of the antipyrine–isovaleric aldehyde condensation product and its hydrochloride, with addition of HCl.
The condensation products obtained in the case of aliphatic aldehydes [7] possess good solubility in a weakly acidic medium, as a result of which the procedure for their isolation changes.
In addition, by the method for obtaining the antipyrine–isovaleric aldehyde condensation product, condensed derivatives of antipyrine with heptanal, acetone, butanone, and acetophenone were obtained.
The results of the syntheses are summarized in Tables 3 and 4.
Table 1
Syntheses of condensed derivatives of antipyrine with vanillin; furfural; m-iodobenzoic aldehyde
| Amount of antipyrine taken in g | Amount of aldehyde taken | Molecular ratio of the substances taken | Experimental conditions | Amount of concentrated HCl added in ml, sp. gr. 1.17 | Color of the melt | Amount of water added to isolate the reaction product, in ml | Yield, % | Note |
|---|---|---|---|---|---|---|---|---|
| 1 | 0.4 g vanillin | 2 : 1 | On a water bath at temp. 80–85° | 2 | Bright orange | 20 | 72 | On standing, some additional precipitate separates from the filtrate (the reaction proceeds at ordinary temperature) |
| 1 | 0.4 g furfural, b.p. 160° | 2 : 1 | On a water bath at temp. 50–55° | 0.8–1 | Greenish | 10 | 65 | — |
| 2 | 1.24 g m-iodobenzaldehyde, m.p. 55–56° | 2 : 1 | At temperature 110–120° | 4–5 | Light yellow | 25 | 50.7 | — |
Table 2
Composition and properties of condensed derivatives of antipyrine with vanillin, furfural, and m-iodobenzaldehyde
| No. | Name of condensation product | Solubility: water | Solubility: ethyl alcohol | Solubility: benzene | Solubility: ether | Solubility: toluene | Quantitative determination of nitrogen by Kjeldahl: calculated, % | Quantitative determination of nitrogen by Kjeldahl: found, % | Composition of the condensed derivative: spent on 0.1 N NaOH | Composition of the condensed derivative: calculated with NaOH | Composition of the condensed derivative: compound obtained |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Antipyrine-vanillin | + | + | − | − | − | 10.25 | 10.01 | 0.0069 | 0.0137 | Monohydrochloride of 4,4′-diantipyril-4-methoxy-3-oxyphenylmethane |
| 2 | Antipyrine-furfural | + | + | − | − | − | 11.4 | 10.97 | 0.0073 | 0.0152 | Monohydrochloride of 4,4′-diantipyrilfurfurylmethane |
| 3 | Antipyrine m-iodobenzaldehyde | − | + | − | − | 8.9 | 8.58 | 0.0063 | 0.0120 | Monohydrochloride of 4,4′-diantipyril-m-iodophenylmethane |
Table 3
Syntheses of condensed antipyrine derivatives with heptanal, acetone, butanone, acetophenone, etc.
| No. | Amount of antipyrine taken, g | Amount of aldehyde or ketone taken, g | Molecular ratio of the substances taken | Reaction temperature (degrees) | Amount of hydrochloric acid taken, ml | Color of the melt | Yield, % |
|---|---|---|---|---|---|---|---|
| 1 | 2 | Heptanal 0.55 b.p. 152° |
2 : 1 | 75–80 | 4 | Brownish-pink | 60 |
| 2 | 3 | Acetone 0.46 b.p. 56° |
2 : 1 | 75–85 | 4 | Pale pink | 64 |
| 3 | 2 | Butanone 0.76 b.p. 77–78° |
2 : 1 | 80–85 | 6 | Yellow | 80.1 |
| 4 | 4 | Acetophenone 1.28 b.p. 198° |
2 : 1 | 85 | 14 | Pale pink | 71.4 |
| 5 | 2 | Benzophenone 0.96 m.p. 47° |
2 : 1 | 90 | 4 | Pale pink | 25 |
| 6 | 2 | m-Iodobenzophenone m.p. 52° |
2 : 1 | 90 | 9 | — | — |
Table 4
Composition and properties of condensed antipyrine derivatives with heptanal, acetone, etc.
| No. | Name of condensed derivative | Solubility in water | Solubility in ethyl alcohol | Solubility in benzene | Solubility in ether | Solubility in toluene | Amount of nitrogen by Kjeldahl, calculated, % | Amount of nitrogen by Kjeldahl, found, % | Determination of the composition of the condensation product: calculated NaOH per 0.1 g of substance | Determination of the composition of the condensation product: found | Determination of the composition of the condensation product: compound obtained | Melting point, °C (in degrees) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Antipyrine–heptanal | + | + | + | − | 10,0 | 9,80 | 0,0146 | 0,0143 | Dihydrochloride of 4,4-diantipyrine-heptane | 149—150 | |
| 2 | Antipyrine–acetone | + | + upon heating | − | 11,40 | 11,33 | 0,0163 | 0,0164 | Dihydrochloride of 4,4-diantipyrine-dimethylmethane | 154—155 | ||
| 3 | Antipyrine–butanone | + upon heating | + upon heating | − | − | 11,13 | 11,64 | 0,0158 | 0,0159 | Dihydrochloride of 4,4-diantipyrine-methyl-ethylmethane | 153—154 | |
| 4 | Antipyrine–acetophenone | + | + | + | − | + | 10,12 | 10,00 | 0,0145 | 0,0146 | Dihydrochloride of 4,4-diantipyrine-methyl-phenylmethane | — |
| 5 | Antipyrine–acetophenone (free base) | + | − | 11,71 | 11,81 | — | — | Free base of 4,4-diantipyrine-methyl-phenylmethane | 98—99 | |||
| 6 | Antipyrine–benzophenone | − | 9,10 | 1 | 0,0130 | — | Condensation product was not formed | — | ||||
| 7 | Antipyrine–m-iodobenzophenone | 7,55 | 0,1 | 0,0108 | — | ” |
From the data obtained it follows that, in the interaction of antipyrine with heptanal, acetone, butanone, and acetophenone, in all cases the dihydrochlorides of 4,4-diantipyril-\(R\)-methane were obtained; whereas interaction between benzophenone, \(m\)-iodobenzophenone, and antipyrine was not observed, and condensed derivatives were not formed. Apparently, phenyl groups sharply reduce the activity of the ketone group, and condensation with antipyrine does not occur.
Conclusions
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Eight condensed derivatives of antipyrine with aldehydes and ketones of the saturated and aromatic series were obtained.
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It was shown that the presence in the molecule of an aromatic aldehyde of the group \(-\mathrm{OCH}_3\), an iodine atom in the \(m\)-position, or ether oxygen in the ring (furan) lowers the basicity of the condensed derivatives obtained and leads to the formation not of the dihydrochlorides of 4,4-diantipyril-\(R\)-methane, but of the monohydrochlorides of 4,4-diantipyril-\(R\)-methane.
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The influence of aromatic and aliphatic radicals on the condensation reaction of antipyrine with aldehydes and ketones was clarified. The nature of the condensation of antipyrine with aromatic aldehydes and ketones of the saturated series is the same, but the condensation products obtained possess different physical properties, for example solubility, as a result of which the method for isolating the obtained condensation products changes.
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Some aromatic ketones and their derivatives, such as benzophenone and \(m\)-iodobenzophenone, do not give condensation products with antipyrine, which is apparently explained by a decrease in the activity of the oxygen of the ketone group in the presence of phenyl radicals.
Literature
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