INVESTIGATION OF THE COMPLEXATION REACTION OF AMIDES WITH PHENOLS AND CARBOXYLIC ACIDS

N. D. STRELNIKOVA

The present work is part of an investigation being carried out by the staff of the Department of Organic Chemistry of the Tomsk Polytechnic Institute, whose aim is to determine the type of reactivity of organic compounds of various classes and to clarify the influence exerted on the reactivity of a molecule by different atoms and atomic groups.

The principal task of the work was to elucidate the electronic type of the chemical activity (reactivity) of the amide group in various complexation reactions.

As is known, electronic chemistry distinguishes three types of reactivity of functional groups: atom-radical, electron-donor, and electron-acceptor. The type of chemical activity of the substance under investigation may be determined by both physical and chemical methods [1].

The type of reactivity of the amide group was investigated by a chemical method, namely by studying the complex-forming reactions of compounds containing an amide group with phenols, carboxylic acids, and certain other organic compounds.

The choice of the second component for the binary systems under investigation was made with allowance for the reactivity of the substance required in the given case. Various carboxylic acids were taken as standard electron acceptors, amines served as electron donors, and phenols or nitro compounds were used by us as substances with a mixed function.

In the literature there are numerous references to the formation by acetamide of molecular compounds with hydrogen halides [2], with carboxylic acids [3], with mineral halides [3], and with phenols [2]. Benzamide also forms complex compounds with the substances listed above. Acetanilide behaves similarly in complexation reactions [3]. Urea combines with acids and phenols; especially many complexes of urea with mineral salts are known, and it is interesting that the urea molecule, despite the presence of two \(NH_2\) groups, occupies one coordination position in these compounds.

Reviewing the literature material, we noted the one-sided character of all the available data. Complexes of amides are known with electron-acceptor reagents (acids, mineral halides, and other metal salts) or with reagents of mixed type, which often also exhibit electron-acceptor properties (phenols). From this it might be thought that, in any case, electron-donor reactivity must strongly predominate in amides, i.e., that they must be chiefly bases. On the other hand, we know that the carbonyl strongly weakens the basic properties of the amino group and increases the mobility of the hydrogen atoms attached to nitrogen, i.e., strengthens the acidic properties.

It was therefore of great interest to study complex-formation reactions of amides with more varied compounds, including substances exhibiting an electron-donor function.

Experimental Part

In the experimental part of the present work, binary systems were investigated that included the amides: acetamide, acetanilide, benzamide, and urea.

The second components were phenol, resorcinol, $\alpha$-naphthol, $\beta$-naphthol, or carboxylic acids, most often benzoic acid and, less often, cinnamic, isovaleric, and stearic acids.

Benzamide was prepared from benzoyl chloride and ammonium carbonate, washed repeatedly with cold water under strong cooling, and recrystallized from alcoholic solutions until a product with a constant melting point of $128^\circ$ was obtained.

Acetamide was obtained from ammonium acetate (glacial acetic acid and ammonium carbonate). Recrystallization was carried out from a mixture of benzene and ethyl ether $(10:3)$; cooling with ice, rapid suction filtration of the crystals, and repeated washing with pure ether were used. After the third crystallization, the acetamide had a melting point of $-82^\circ$.

Acetanilide,

\[ \mathrm{CH_3C(=O)NHC_6H_5}, \]

was obtained from freshly distilled aniline and glacial acetic acid; according to the usual procedure it was treated with a small amount of animal charcoal. The acetanilide crystals were washed with cold water and dried in a desiccator over calcium chloride. White, lustrous, odorless plates of acetanilide had a melting point of $114^\circ$. Tests of the acetanilide for purity gave the following results: the aqueous solution had a neutral reaction; the test for organic substances, in particular for aceto-toluidide, was negative.

Urea was taken in ready-made form. After twofold recrystallization from amyl alcohol, white prisms of urea with a melting point of $132^\circ$ were obtained.

Phenol was purified by distillation. The purity of phenol was checked not only by the standard constant melting point, but also by the value of the e.m.f. in volts obtained in the apparatus of B. V. Tronov and L. P. Kulev [5] when testing a benzene solution of phenol with platinum and sodium electrodes.

Purification of the other substances was carried out mainly by repeated recrystallization from various selected solvents. The purity of the products was checked by melting point or boiling point. For example, for isovaleric acid the criterion of purity was a boiling point of $177^\circ$; for benzoic acid, twice recrystallized from alcohol, a melting point of $121^\circ$ and a boiling point of $248$–$249^\circ$.

The greasy, lustrous white leaflets of stearic acid were sufficiently chemically pure, had a sharp melting point, and did not require purification.

The investigation was carried out by methods of physicochemical analysis, since most of the molecular compounds found in this section do not possess the degree of stability that would allow these compounds to be isolated in pure form.

Physicochemical analysis indicates the presence of complex formation, the composition of the molecular compounds obtained, and also the ste—

their strength and, consequently, the possibility of obtaining and isolating them in pure form.

Physicochemical analysis “makes it possible to detect qualitative changes in the properties occurring in a given system, as a function of quantitative changes in the composition of the system” [6]. Of the numerous methods of physicochemical analysis, two were used in the present work: measurement, by the method of B. V. Tronov and L. P. Kulev, of the electromotive force arising in the reaction of organic complex compounds with metals, and the classical melting method (thermal analysis).

Results of thermal analysis

1) Acetamide — α-naphthol. Fig. 1. Eutectic at 3°C.
2) Acetamide — benzoic acid. Fig. 2. Eutectic 28.8°.
3) Acetamide — stearic acid. Fig. 2. Absence of chemical interaction between the components.

4) Acetanilide — resorcinol. Fig. 3. Eutectic.
5) Acetanilide — benzoic acid. Fig. 4. Eutectic 73.0°.
6) Acetanilide — diphenylamine. Fig. 5. Eutectic 47.8°.
7) Acetanilide — p-nitrotoluene. Fig. 6. Eutectic.
8) Acetanilide — α-nitronaphthalene. Fig. 6. Eutectic 38.4°.
9) Benzamide — phenol. Fig. 7. Eutectic 8.2°.
10) Benzamide — resorcinol. Fig. 8. Maximum at a component ratio of 1:1, with a sharp melting temperature of 86.4° and two eutectics at 80.8° and 71.0°.

11) Benzamide — α-naphthol. Fig. 9. Eutectic 57.5°.
12) Benzamide — β-naphthol. Fig. 9. Eutectic deeper than with α-naphthol, despite the higher melting temperatures of the constituent components.

13) Benzamide — benzoic acid. Fig. 10. Eutectic 79.8°.
14) Benzamide — cinnamic acid. Fig. 10. Eutectic 71.0°.
15) Benzamide — α-naphthylamine. Fig. 11. Shallow eutectic at 41.6°.
16) Benzamide — diphenylamine. Fig. 11. Eutectic 49.4°.
17) Benzamide — p-nitrotoluene. Fig. 11. Eutectic 45.0°.
18) Urea — phenol. Fig. 12. Weakly expressed maximum and eutectics. Maximum at the component ratio
\((\mathrm{NH}_2)_2\mathrm{CO}\cdot 2\mathrm{C}_6\mathrm{H}_5\mathrm{OH}\).

19) Urea — resorcinol. Fig. 13. The maximum is well expressed; it has a component ratio at 50% composition. Formula of the molecular compound: \((\mathrm{NH}_2)_2\mathrm{CO}\cdot \mathrm{C}_6\mathrm{H}_4(\mathrm{OH})_2\) meta. The temperature of the maximum is 103.2°, that of the first eutectic 91.2°, and of the second 87.0°.

20) Urea — α-naphthol. Fig. 14. Eutectic shifted toward α-naphthol.

21) Urea — β-naphthol. Fig. 14. Low maximum with a temperature of 104.4°.

22—24) Urea with naphthylamine, diphenylamine, and p-nitrotoluene, in tests, gave two mutually immiscible liquids, each freezing and melting at its own characteristic temperature; for example, urea at 133°.

Fig. 1

System: acetamide—α-naphthol

Labels in the figure:
\( \mathrm{CH_3C(=O)NH_2} \); \( \alpha\text{-}\mathrm{C_{10}H_7OH} \); \(3.0^\circ\); \(96.0^\circ\).

Fig. 2

1) Acetamide—benzoic acid

2) Acetamide—stearic acid

Labels in the figure:
\( \mathrm{CH_3C(=O)NH_2} \); \( \mathrm{C_6H_5COOH} \); \(N1\); \(N2\); \(84.4^\circ\); \(28.80^\circ\); \(121^\circ\).

Fig. 3

Acetanilide—resorcinol

Labels in the figure:
\( \mathrm{CH_3C(=O)NHC_6H_5} \); \( m\text{-}\mathrm{C_6H_4(OH)_2} \); \(115^\circ\).

![Fig. 4]

Labels in the figure:
$CH_3C(=O)NHC_6H_5$; $C_6H_5COOH$; “Acetanilide—benzoic acid”; $73.0^\circ$.

Fig. 4

![Fig. 5]

Labels in the figure:
$CH_3C(=O)NHC_6H_5$; $(C_6H_5)_2NH$; “Acetanilide—diphenylamine”; $115^\circ$; $105.8^\circ$; $92.0^\circ$; $47.8^\circ$.

Fig. 5

![Fig. 6]

Labels in the figure:
$CH_3C(=O)NHC_6H_5$;
1) $oCH_3C_6H_4NO_2$;
2) $d\,C_{10}H_7NO_2$;
1) “Acetanilide—p-nitrotoluene”;
2) “Acetanilide—$\alpha$-nitronaphthalene”;
$115^\circ$; $52.4^\circ$.

Fig. 6

Fig. 7. System \( \mathrm{C_6H_5C(=O)NH_2} \)—\( \mathrm{C_6H_5OH} \) (“benzamide–phenol”).

Visible annotations on the diagram: \(114.8^\circ\), \(91.0^\circ\), \(33.0^\circ\), \(50\%\), \(14.5^\circ\), \(8.2^\circ\), \(41.8^\circ\).

Fig. 8. System \( \mathrm{C_6H_5C(=O)NH_2} \)—\(m\text{-}\mathrm{C_6H_4(OH)_2}\) (“benzamide–resorcinol”).

Visible annotations on the diagram: \(128^\circ\), \(115.8^\circ\), \(80.8^\circ\), \(85.4^\circ\), \(71.0^\circ\), \(74.0^\circ\), \(100.8^\circ\).

Fig. 9. Systems \( \mathrm{C_6H_5C(=O)NH_2} \)—\(\alpha\text{-}\mathrm{C_{10}H_7OH}\) and \( \mathrm{C_6H_5C(=O)NH_2} \)—\(\beta\text{-}\mathrm{C_{10}H_7OH}\).

1) “Benzamide–\(\alpha\)-naphthol”
2) “Benzamide–\(\beta\)-naphthol”

Visible annotations on the diagram: \(120^\circ\), \(93.1^\circ\), \(57.5^\circ\), \(93.2^\circ\), \(96^\circ\), \(122^\circ\).

Fig. 10

Text in the figure:

• \( \mathrm{C_6H_5C(=O)NH_2} \)
• \( \mathrm{C_6H_5CH{=}CHCOOH} \)
• 1) Benzamide—cinnamic acid
• 2) Benzamide—benzoic acid
• \(128^\circ\), \(96.4^\circ\), \(71.0^\circ\), \(80^\circ\), \(107.0^\circ\), \(112^\circ\), \(120^\circ\), \(130^\circ\), \(135^\circ\)
• No. 1
• No. 2

Fig. 11

Text in the figure:

• \( \mathrm{C_6H_5C(=O)NH_2} \)
• \((\mathrm{C_6H_5})_2\mathrm{NH}\)
• 1) Benzamide—diphenylamine, cpd. No. 1
• 2) Benzamide—\(\alpha\)-naphthylamine, cpd. No. 2
• 3) Benzamide—para-nitroaniline, cpd. No. 2
• \(128^\circ\), \(90^\circ\), \(70^\circ\), \(53^\circ\), \(50^\circ\), \(49.4^\circ\), \(41.0^\circ\)
• No. 1
• No. 2

Fig. 12

Text in the figure:

• \((\mathrm{NH_2})_2\mathrm{CO}\)
• \(\mathrm{C_6H_5OH}\)
• “Carbamide—phenol”
• \(133^\circ\), \(61.2^\circ\), \(60.8^\circ\), \(55^\circ\), \(45.2^\circ\), \(41.8^\circ\)
• 50%

Fig. 12

Results of measuring the emf by the method of B. V. Tronov and L. P. Kulev

1) Benzamide—benzoic acid. Maximum at 900 mV with the component ratio:

\[ 2\mathrm{C}_6\mathrm{H}_5\mathrm{C}(=O)\mathrm{NH}_2 \cdot \mathrm{C}_6\mathrm{H}_5\mathrm{COOH} \]

with the emf of the initial substances close to zero.

Fig. 13

2) Benzamide—isoamyl alcohol. Maximum at 1340 mV with the molecular ratio of the components

\[ \mathrm{C}_6\mathrm{H}_5\mathrm{C}(=O)\mathrm{NH}_2 : \mathrm{C}_5\mathrm{H}_{11}\mathrm{OH}. \]

3) Benzamide—benzonitrile. Maximum in the region of the molecular compound

\[ \mathrm{C}_6\mathrm{H}_5\mathrm{C}(=O)\mathrm{NH}_2 \cdot \mathrm{C}_6\mathrm{H}_5\mathrm{CN} \]

with a small emf value of 2.84 mV,

Fig. 14

less than that of one of the components of the benzonitrile system, equal to 4.698 mV.

4) Benzamide—pyridine. The maximum has the composition

\[ \mathrm{C_6H_5C(=O)NH_2 \cdot C_5H_5N}. \]

5) Benzamide—o-nitrotoluene. The maximum corresponding to the composition

\[ \mathrm{C_6H_5C(=O)NH_2 \cdot 2\,CH_3C_6H_4NO_2}. \]

Discussion of the Results

Let us offer several assumptions concerning the electronic type of the chemical activity of the amide group in various complex-formation reactions. Theoretically, for amides one may expect a mixed type of complex formation. On the one hand, they contain trivalent nitrogen, which should exhibit, although to a weak degree, electron-donor properties.

It is known that amides form salts with strong acids, for example

\[ \mathrm{CH_3C(=O)NH_2 + HCl \longrightarrow (CH_3C(=O)NH_3)\cdot Cl'} \]

These salts are unstable; they readily undergo hydrolysis. On the other hand, amides form metallic derivatives at the expense of the hydrogens of the amide group, i.e., they exhibit a weakly acidic character.

It is possible that in some cases their acidic properties are enhanced as a result of tautomerism:

\[ \mathrm{CH_3C(=O)NH_2 \rightleftarrows CH_3C(OH)=NH} \]

The results of our experiments confirm what has been said. In thermal analysis, acetamide with benzoic acid (Fig. 2) gave a weak inflection of the melting curve, indicating weak chemical interaction. With the still weaker stearic acid there is no chemism at all (Fig. 2, curve).

Simple eutectics with benzoic acid were given by acetanilide (Fig. 4, curve) and benzamide (Fig. 10), which should also have a weaker basic character. A eutectic was likewise obtained in the system benzamide—cinnamic acid (Fig. 10).

Experiments with amines—α-naphthylamine and diphenylamine—gave no indication of chemical interaction, but this fact does not indicate a complete absence of acidic properties in amides, since the amines taken are weak bases (Fig. 11).

Among the systems containing amides and phenols, the following combinations gave a positive result:

benzamide—resorcinol—a sharp maximum at the composition 1 : 1 (Fig. 8); carbamide—resorcinol (Fig. 13)—a compound of the same composition, \(\mathrm{(NH_2)_2CO \cdot C_6H_4(OH)_2}\); carbamide—β-naphthol with a composition corresponding to \(\mathrm{(NH_2)_2CO \cdot 2\,C_{10}H_7OH}\) (Fig. 14); carbamide—phenol (Fig. 12)—a bend of the curve at the same ratio of the components.

Phenols are complex-formers of a mixed type, but with some predominance of acidic properties. In addition, the more acidic amide, acetanilide, gives a eutectic with resorcinol (Fig. 3), whereas the more basic carbamide forms a definite chemical compound; in experiments with carbamide (Fig. 12), phenol gives only a bend in the melting curve, and with

more acidic in resorcinol’s properties, a noticeable maximum appeared on the melting diagram (Fig. 13). The facts enumerated indicate that, in complex compounds of amides with phenols, the amides exhibit an electron-donor function, and the phenols an electron-acceptor function, owing to the formation of a hydrogen bond

\[ \mathrm{R{-}O{-}H\ldots NH_2{-}C{-}R_1} \]
\[ \mathrm{\phantom{R{-}O{-}H\ldots NH_2{-}} \| \phantom{{-}R_1}} \]
\[ \mathrm{\phantom{R{-}O{-}H\ldots NH_2{-}} O} \]

Eutectics were also obtained with nitro compounds—nitronaphthalene and p-nitrotoluene. Evidently, in these cases complex formation is expressed only very weakly.

The electrochemical method of B. V. Tronov and L. P. Kulev, distinguished by great sensitivity, gave positive results for all the organic systems studied by this method.

Benzamide with benzoic acid gave a sharp maximum of electromotive force at the component composition

\[ \mathrm{C_6H_5COOH \cdot 2C_6H_5C(=O)NH_2}. \]

A high, stable maximum of e.m.f. was also obtained with pyridine in the ratio 1 : 1. Benzamide also exhibited chemical interaction with isoamyl alcohol, benzonitrile, and o-nitrotoluene, but nothing can yet be said about the mechanism of complex formation with these compounds or about the strength and stability of the compounds obtained, since in complex-forming reactions of organic chemistry all of them may be both electron donors and electron acceptors.

Conclusions

1. Binary systems were studied whose composition included acetamide, acetanilide, benzamide, and urea with phenols or carboxylic acids. For comparison, other complex-forming agents were sometimes also taken.

2. The systems considered were investigated by two methods of physicochemical analysis: thermal analysis and the electrochemical method of B. V. Tronov and L. P. Kulev. The electrochemical method, as had been observed earlier, showed significantly greater sensitivity.

3. In a number of systems, chemical interaction was found. Comparison of the results obtained shows that amides have a mixed type of reactivity. In complex formation with phenols and carboxylic acids they exhibit electron-donor properties, but with respect to amines they should behave as electron acceptors.

Literature

1. Tronov B. V. and Strelnikova N. D. Complexes of nitro compounds with other organic substances. Izv. Tomskogo politekhn. in-ta, vol. 71, pp. 63—99, 1952.

2. Menshutkin B. N. Index of binary organic systems investigated by thermal analysis. Izv. IFKhA, issue 2, 473, 1921.

3. Pfeiffer P. Organische Molekülverbindungen. Stuttgart, 1922.

4. Pfeiffer. Introduction to the chemistry of complex compounds. Goskhimizdat, 1951.

5. Tronov B. V. and Kulev L. P. A new electrochemical method for the study of organic compounds and their mixtures. Izv. Tomskogo politekhn. in-ta, vol. 64, pp. 3—87, 1948.

6. Kurnakov N. S., Acad. Introduction to physicochemical analysis, 1936.