- This article is about acid amides. For inorganic substances containing an NH 2 - ion, see the article Metal Amides .
Amides are derivatives of oxygen-containing acids ( carboxylic or mineral ) in which the hydroxyl group of the acid residue is replaced by an amino group (unsubstituted or substituted). Amides can also be considered as acyl derivatives of amines . Compounds with one, two, or three acyl substituents on the nitrogen atom are called primary, secondary, and tertiary amides, respectively. Secondary amides are also called imides [1] .
Carboxylic acid amides β RCO β NR 1 R 2 carboxamides (where R 1 and R 2 are hydrogen or another residue) βare usually referred to simply as amides. In the case of other acids, in accordance with the IUPAC recommendations, the name of the amide is indicated as the prefix with the name of the acid class, for example, RSO 2 NH 2 sulfide amides are called sulfamides . Amide analogs, which are formally products of the substitution of oxygen for chalcogen , are called thioamides , selenoamides, and telluroamides [1] .
Content
Nomenclature
The name of the class of amides comes from the name of ammonia . The IUPAC Golden Book divides amides into primary, secondary and tertiary depending on the number of acyl residues at the nitrogen atom. However, the same classification is also applied in those cases where the residues are not acyl, but any organic:
- RCONH 2 - primary amides;
- RCONHR '- secondary amides;
- RCONR'R '' - tertiary amides [1] [2] .
If the nitrogen atom contains two or three acyl groups, such compounds are also called imides and triacylamines, respectively. Cyclic amides are called lactams [2] .
The names of primary amides are formed from the names of the corresponding carboxylic acids , adding to them "-amide":
- CH 3 CONH 2 - acetamide ;
- C 5 H 11 CONH 2 - hexanamide ;
- PhCONH 2 - benzamide [2] .
- C 5 H 11 CONH 2 - hexanamide ;
If the nitrogen atom is additionally substituted, its substituents are listed at the beginning of the name with the prefix βNβ instead of the locant ( N, N-dimethylformamide ) [2] . Monoamides of dicarboxylic acids are called β-amic acidβ with the ending, for example phthalic acid monoamide can be called phthalamic acid [3] .
Structure and physical properties
Physical Properties of Amides
Primary and secondary amides are crystalline substances (with the exception of liquid formamide and N-methylformamide ); tertiary amides are liquids. Only lower aliphatic amides are well soluble in water [2] .
The structure of the amide group
The structure of the amide group was studied by x-ray diffraction analysis . It was shown that in crystalline amides it is approximately the same. The amide group is flat, the atoms C ', C, O, N lie in the same plane, but the hydrogen atoms at the nitrogen atom do not lie in this plane. The angles around the carbonyl carbon atom have the following meanings: Ξ± (C'-C = O) = 124 Β°, Ξ± (C'-CN) = 115 Β°, Ξ± (NC = O) = 121 Β°. The bond lengths are: l (C'-C) = 1.52 Γ , l (C = O) = 1.24 Γ , l (CN) = 1.34 Γ . The angle Ξ± (HNR) for secondary amides was also determined: it is 115 Β°. The bond lengths at the nitrogen atom are: l (NH) = 0.95 Γ , l (NR) = 1.44 Γ . In the gas phase, the amides slightly shortened the C = O bond (from 1.24 to 1.19-1.21 Γ ) and the CN bond (from 1.34 to 1.36-1.37 Γ ) was extended; angles remain approximately the same [4] .
The study of a number of amides both in the solid and in the gas phase showed that there is an inverse relationship between the bond lengths C = O and Π‘-N: with an increase in one, the second one is shortened. This is due to the fact that the nitrogen atom in the amide group is conjugated to the carbonyl group and two resonant structures A and B contribute to the real structure. With an increase in the contribution of the polar structure B, the C = O bond length increases and the CN bond length decreases [5 ] .
Amide Isomerism
Due to the conjugation system, the CN bond is partially doubly connected, so rotation around it is difficult and amides can exist as cis / trans isomers . Secondary amides are strongly dominated by trans isomers: a small fraction of cis isomers was found only if the group R at the carbonyl carbon atom is hydrogen. Even such a bulky R 'substituent like tert -butyl preferred to be near oxygen than with less bulky hydrogen. In tertiary amides, the predominant configuration is more obviously associated with spatial difficulties [6] .
Spectroscopic characteristics
In the NMR spectra, the protons of the amide group give a signal in the region of 5β8 ppm [2] . Since rotation around the amide bond is difficult, two hydrogen atoms at a nitrogen atom in amides of the RCONH 2 type give two separate signals, not averaging even at temperatures above room temperature. For example, in formamide HCONH 2, the proton located in the cis position to the oxygen atom of the C = O group is more screened. In N, N-dialkylamides, two alkyl groups also have different magnetic environments and give separate signals. For example, in dimethylformamide HCONMe 2, a methyl group closer to the oxygen atom is also more screened. The chemical shift of these substituents is highly dependent on the solvent; in aromatic solvents, their position may vary [8] .
In the IR spectra, amides are characterized by two types of vibrations: NH bond vibrations above 3000 cm β1 and C = O bond vibrations in the region of 1700β1600 cm β1 [2] .
| Compound | NH swing | Oscillation C = O |
|---|---|---|
| primary amides | two bands at 3500-3400 cm β1 | two bands: at 1690β1630 cm β1 (amide band I) and at 1620β1590 cm β1 (amide band II) |
| secondary amides | one strip at 3460-3420 cm β1 | two bands: at 1690-1630 cm β1 (amide band I) and at 1550-1510 cm β1 (amide band II) |
| tertiary amides | - | one band at 1670β1630 cm β1 (amide band I) |
Getting
From carboxylic acids and amines
Amides are formed by heating carboxylic acids with ammonia or primary and secondary amines . This process is possible due to the fact that ammonia and amines are stronger nucleophiles than water and alcohols. Spatially hindered carboxylic carboxylic acids do not enter into this reaction, although some industrially important amides, such as succinimide and phthalimide , are obtained in this way [9] .
The most probable mechanism of this transformation is the attachment - cleavage mechanism, since the reverse reaction of the hydrolysis of amides proceeds via this mechanism. In the case of dicarboxylic acids , their anhydrides are intermediate formed. Amides cannot be acylated by simple heating with carboxylic acid, since a re-acylation reaction takes place [10] . For amino acids, this reaction is carried out intramolecularly: in this case, they turn into cyclic amides - lactams . For example, when heated to 180 Β° C, gamma-aminobutyric acid gives gamma-butyrolactam [9] .
Acylation Reactions
A universal method for producing amides is the acylation of ammonia, primary and secondary amines with carboxylic acid chlorides and anhydrides , ketenes and esters [9] .
Most of these reactions proceed by the mechanism of attachment - cleavage. According to this mechanism, the higher the partial positive charge on the carbonyl carbon atom, the higher the reaction rate. Accordingly, acylating reagents can be arranged in a series of activities: RCOR <RCONR 2 <RCOOR <(RCO) 2 O <RCOHal <RCOBF 4 . Also, the reaction rate depends on the nucleophilicity of the amine, which can conditionally be associated with the basicity of the amine: alkylamines> arylamines> amides. Intramolecular acylation is easier than intermolecular [11] .
In the reaction with acid chlorides , hydrogen chloride is released, so a double amount of the amine must be taken in the reaction, so that the second equivalent bound this hydrogen chloride. The resulting ammonium salt precipitates and is filtered. As a result, the maximum amide yield from the amine is 50%. Alternatively, other organic and inorganic bases may be used to increase yield. For example, the Schotten-Bauman reaction uses sodium hydroxide or potassium hydroxide . From organic bases, pyridine , dimethylaniline , triethylamine , etc. are used [12]
Nitrile
Nitriles can be hydrolyzed under controlled conditions to amides. Hydrolysis proceeds in both acidic and alkaline environments. For example, aromatic amides and amides of hindered carboxylic acids are obtained by hydrolysis with sulfuric acid , since for them the stage of hydrolysis to carboxylic acid proceeds slowly. For many uncomplicated nitriles, this method is not suitable, because the amide is easily hydrolyzed further. Hydrochloric acid , phosphoric acid, and boron trifluoride are also used as acid catalysts [13] .
The main catalysis for these reactions was used less frequently due to the further hydrolysis of the amide. A reliable method from this group is the use of an alkaline solution of hydrogen peroxide [13] .
Nitriles can also be converted to secondary amides by the Ritter reaction . In this case, nitriles are alkylated at the nitrogen atom with carbocations obtained from alkenes and concentrated sulfuric acid, giving a secondary amide [9] . This reaction can be carried out by replacing alkenes with the corresponding alcohols [14] .
Alkenes and alcohols, which give secondary carbocations in an acidic environment, enter the Ritter reaction more slowly than those that give tertiary carbocations. Primary alcohols can be introduced into this reaction only under very harsh conditions. Branched alkanes and cycloalkanes , alkyl halides and carboxylic acids were also used to generate carbocations [14] .
Regrouping
The industry uses a method for producing amides through Beckman rearrangement . In this reaction, oximes are reacted with mineral acids , Lewis acids, or polyphosphoric acid . In laboratory conditions, this method is not used, but in practice it is useful for rearrangement of aromatic fatty ketones available due to the Friedel β Crafts acylation reaction , as well as for the production of lactams [9] [15] .
There are a number of other rearrangements that also lead to amides. Among them, the Schmidt rearrangement , the reaction of Wilgerodt and others. [15]
Chemical Properties
Hydrolysis
Under the influence of hot water or water vapor, amides are hydrolyzed . The reaction proceeds slowly, since water has a low reactivity with respect to amides: some amides even recrystallize from it. Hydrolysis is facilitated by an alkaline or acidic medium: in the first case, the more amidophilic hydroxide ion OH - attacks the amide, and in the second case, the amide is protonated by the oxygen atom, which makes the amide group more susceptible to attack [16] .
Almost all amides are hydrolyzed in an alkaline environment. The reaction is accelerated if electron- withdrawing groups are present in the amide, and slows down if there are spatial difficulties. Catalysis may not necessarily be carried out by a proton or hydroxide ion : general acid-base catalysis is also possible [17] [18] .
Recovery
Amides are resistant to reduction, and only strong reducing agents ( hydrides , sodium in liquid ammonia, and electrolysis ) react with them. When primary amides are treated with lithium aluminum hydride in diethyl ether or tetrahydrofuran, they are reduced to primary amines. Similarly, secondary amides give secondary amines, and tertiary amides give tertiary amines. Lactams under these conditions give cyclic amines. Diborane and electrolysis can also be used in these reactions [19] [20] .
N, N-dialkylamides can be reduced to aldehydes in a controlled manner: in this case, instead of lithium aluminum hydride, it is more convenient to use a weaker lithium triethoxy aluminum hydride reducing agent LiAlH (OEt) 3 , obtained from LiAlH 4 and ethanol . Also, such a reduction can be carried out under the action of diisobutylaluminum hydride and sodium in liquid ammonia [19] [20] .
Dehydration
Primary amides split off water to give nitriles under the action of thionyl chloride , oxalyl chloride and phosphorus oxychloride . The best option is the use of thionyl chloride in DMF . Trifluoroacetic anhydride is also used for this purpose in the presence of pyridine [21] .
Nitrosation
Primary amides are easily decomposed in the cold with a solution of nitrous acid , while nitrogen is released and the corresponding carboxylic acid is formed . In practical terms, RONO alkyl nitrites and nitrosonium tetrafluoroborate NO + BF 4 - have an advantage. Secondary amides, by analogy with amines, give N-nitrosoamides [22] [23] .
Hoffmann Halogenation and Rearrangement
Primary and secondary amides react with NaOCl , NaOBr to give the corresponding N-chloramides or N-bromamides. These compounds themselves are selective halogenating reagents (a typical example is N-bromosuccinimide ). Also, N-halides in excess of alkali enter the Hoffmann rearrangement , splitting off the CO 2 molecule and giving an amine having one carbon atom less than the starting amide [24] .
Reactions with Organometallic Reagents
Organometallic compounds, such as Grignard reagents and alkyl lithium reagents, can be attached to the carbonyl group of the amide. Such reactions with primary and secondary amides are useless, since the reagent interacts with an acidic proton at the nitrogen atom and turns into the corresponding alkane . Tertiary amides give strong addition products with Grignard reagents, which, when treated with aqueous acid, give ketones . Dimethylformamide gives the corresponding aldehyde [25] .
When using an excess of Grignard reagent, a formal substitution of the carbonyl oxygen atom by two alkyl groups occurs [25] .
ΠΠΈΡΠ»ΠΎΡΠ½ΠΎ-ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°
ΠΠΌΠΈΠ΄Ρ ΠΎΠ±Π»Π°Π΄Π°ΡΡ ΠΎΡΠ΅Π½Ρ ΡΠ»Π°Π±ΠΎ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌΠΈ ΠΊΠΈΡΠ»ΠΎΡΠ½ΡΠΌΠΈ ΠΈ ΠΎΡΠ½ΠΎΠ²Π½ΡΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ. Π Π΅Π°Π³ΠΈΡΡΡ ΡΠΎ ΡΠ΅Π»ΠΎΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠ°Π»Π»Π°ΠΌΠΈ , ΠΎΠ½ΠΈ Π΄Π°ΡΡ ΡΠΎΠ»ΠΈ , Π»Π΅Π³ΠΊΠΎ ΡΠ°Π·Π»Π°Π³Π°Π΅ΠΌΡΠ΅ Π²ΠΎΠ΄ΠΎΠΉ. ΠΠ΅ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠΎΠ»ΠΈ ΡΠ΅ΠΌ Π½Π΅ ΠΌΠ΅Π½Π΅Π΅ ΡΡΡΠΎΠΉΡΠΈΠ²Ρ (ΡΡΡΡΠ½Π°Ρ ΡΠΎΠ»Ρ Π°ΡΠ΅ΡΠ°ΠΌΠΈΠ΄Π° ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΡΡΡ ΠΏΡΠΈ ΠΏΡΠΎΡΡΠ°Π²ΠΊΠ΅ Π·Π΅ΡΠ½Π° ). ΠΠΌΠΈΠ΄Ρ ΡΠΏΠΎΡΠΎΠ±Π½Ρ ΠΏΡΠΈΡΠΎΠ΅Π΄ΠΈΠ½ΡΡΡ ΠΏΡΠΎΡΠΎΠ½ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΡΠΈΠ»ΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ, ΠΎΠ±ΡΠ°Π·ΡΡ ΡΠΎΠ»ΠΈ.
Application
Π ΠΏΡΠΎΠΌΡΡΠ»Π΅Π½Π½ΠΎΡΡΠΈ Π°ΠΌΠΈΠ΄Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡΡΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΎΡΠΎΠ² Π±ΡΠΌΠ°Π³ΠΈ ΠΈ ΠΈΡΠΊΡΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΊΠΎΠΆΠΈ , Π΄Π»Ρ ΡΠΊΡΡΡΠ°ΠΊΡΠΈΠΈ ΡΠ°Π΄ΠΈΠΎΠ°ΠΊΡΠΈΠ²Π½ΡΡ ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠ², Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΈΡΡ ΠΎΠ΄Π½ΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π΄Π»Ρ ΡΠΈΠ½ΡΠ΅Π·Π° ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΎΠ² , ΠΊΠ°ΠΊ ΠΏΡΠΎΠΌΠ΅ΠΆΡΡΠΎΡΠ½ΡΠ΅ ΠΏΡΠΎΠ΄ΡΠΊΡΡ Π² ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π΅ ΠΊΡΠ°ΡΠΈΡΠ΅Π»Π΅ΠΉ ΠΈ ΡΡΠ»ΡΡΠ°ΠΌΠΈΠ΄Π½ΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² [2] .
Notes
- β 1 2 3 IUPAC Gold Book β amides . Date of treatment April 2, 2019.
- β 1 2 3 4 5 6 7 8 9 Π₯ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ½ΡΠΈΠΊΠ»ΠΎΠΏΠ΅Π΄ΠΈΡ, 1988 , Ρ. 127.
- β ΠΠ°Π½ Π ., ΠΠ΅ΡΠΌΠ΅Ρ Π. ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ Π² Ρ ΠΈΠΌΠΈΡΠ΅ΡΠΊΡΡ Π½ΠΎΠΌΠ΅Π½ΠΊΠ»Π°ΡΡΡΡ / ΠΠ΅Ρ. Ρ Π°Π½Π³Π». Π. Π. Π©Π΅ΡΠ±ΠΈΠ½ΠΎΠ²ΡΠΊΠΎΠΉ, ΠΏΠΎΠ΄ ΡΠ΅Π΄. Π. Π. ΠΠΎΡΠ°ΠΏΠΎΠ²Π° ΠΈ Π . Π. ΠΠΈΠ΄ΠΈΠ½Π°. β Π. : Π₯ΠΈΠΌΠΈΡ, 1983. β Π‘. 136.
- β 1 2 Zabitsky, 1970 , p. 2β3.
- β Zabitsky, 1970 , p. 6.
- β Zabitsky, 1970 , p. 19β20.
- β Spectral Database for Organic Compounds, SDBS . Date of treatment April 3, 2019.
- β Zabitsky, 1970 , p. 14β18.
- β 1 2 3 4 5 Π Π΅ΡΡΠΎΠ², 2004 , Ρ. 237β239.
- β Zabitsky, 1970 , p. 106β108.
- β Zabitsky, 1970 , p. 74β77.
- β Zabitsky, 1970 , p. 77β81.
- β 1 2 Zabitsky, 1970 , p. 119β122.
- β 1 2 Zabitsky, 1970 , p. 125β129.
- β 1 2 Zabitsky, 1970 , p. 131β132.
- β Zabitsky, 1970 , p. 816.
- β Π Π΅ΡΡΠΎΠ², 2004 , Ρ. 240β242.
- β Zabitsky, 1970 , p. 824.
- β 1 2 Π Π΅ΡΡΠΎΠ², 2004 , Ρ. 242β244.
- β 1 2 Zabitsky, 1970 , Ρ. 795β801.
- β Π Π΅ΡΡΠΎΠ², 2004 , Ρ. 244β245.
- β Π Π΅ΡΡΠΎΠ², 2004 , Ρ. 245.
- β Zabitsky, 1970 , Ρ. 780β784.
- β Π Π΅ΡΡΠΎΠ², 2004 , Ρ. 246β247.
- β 1 2 Zabitsky, 1970 , p. 847.
Literature
- Π‘Π°Π΄ΠΎΠ²Π°Ρ Π. Π. ΠΠΌΠΈΠ΄Ρ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΎΠ²ΡΡ ΠΊΠΈΡΠ»ΠΎΡ // Π₯ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ½ΡΠΈΠΊΠ»ΠΎΠΏΠ΅Π΄ΠΈΡ: Π² 5 Ρ / ΠΠ½ΡΠ½ΡΠ½Ρ Π. Π. (Π³Π». ΡΠ΅Π΄.). β Π. : Π‘ΠΎΠ²Π΅ΡΡΠΊΠ°Ρ ΡΠ½ΡΠΈΠΊΠ»ΠΎΠΏΠ΅Π΄ΠΈΡ , 1988. β Π’. 1: ΠβΠΠ°ΡΠ·Π°Π½Π°. β Π‘. 127β128. β 623 Ρ. - 100,000 copies. β ISBN 5-85270-008-8 .
- Π Π΅ΡΡΠΎΠ² Π. Π., ΠΡΡΡ Π. Π., ΠΡΡΠΈΠ½ Π. Π. ΠΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠ°Ρ Ρ ΠΈΠΌΠΈΡ : Π² 4 Ρ. . - 4th ed. β Π. : ΠΠΠΠΠ. ΠΠ°Π±ΠΎΡΠ°ΡΠΎΡΠΈΡ Π·Π½Π°Π½ΠΈΠΉ, 2004. β Π’. 3, 18.9 ΠΠΌΠΈΠ΄Ρ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΎΠ²ΡΡ ΠΊΠΈΡΠ»ΠΎΡ. β Π‘. 237β252. β 750 ΡΠΊΠ·. β ISBN 978-5-9963-1335-8 .
- The Chemistry of Amides : [ eng. ] / Ed. Jacob Zabitsky. β Interscience Publishers, 1970. β ISBN 0471980498 .
Links
- ΠΠΌΠΈΠ΄Ρ // ΠΠ½ΡΠΈΠΊΠ»ΠΎΠΏΠ΅Π΄ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠ»ΠΎΠ²Π°ΡΡ ΠΡΠΎΠΊΠ³Π°ΡΠ·Π° ΠΈ ΠΡΡΠΎΠ½Π° : Π² 86 Ρ. (82 Ρ. ΠΈ 4 Π΄ΠΎΠΏ.). - SPb. , 1890-1907.