We also acknowledge previous National Science Foundation support under grant numbers 1246120, 1525057, and 1413739. An organic compound that is comprised of an amino group and other atoms is referred to as an amine. The reaction mixture was stirred at 90 C for 12 h, after which time the mixture was partitioned between EtOAc (100 mL) and H2O (50 mL). Naming amines can be quite confusing because there are so many variations on the names. Thus, although isopropylamine looks similar to isopropyl alcohol, the former is a primary amine, while the latter is a secondary alcohol. The nitrosonium cation is not sufficiently electrophilic to react with benzene itself, or even toluene, but highly activated aromatic rings such as amines and phenols are capable of substitution. 21.9: Mannich Reaction: Alkylation of Enols by Iminium Ions, 22: Chemistry of the Benzene Substituents: Alkylbenzenes, Phenols, and Benzenamines, 1°-Amines + HONO (cold acidic solution) $$\rightarrow$$ Nitrogen Gas Evolution from a Clear Solution, 2°-Amines + HONO (cold acidic solution) $$\rightarrow$$ An Insoluble Oil (N-Nitrosamine), 3°-Amines + HONO (cold acidic solution) $$\rightarrow$$ A Clear Solution (Ammonium Salt Formation). In chemistry, a functional group is a group of atoms which are responsible for certain reactions that the molecule may undergo, as well as specific properties of that molecule. Missed the LibreFest? For example, the simplest amine, CH 3 NH 2, can be called methylamine, methanamine or aminomethane. The mixture was concentrated in vacuo. Aromatic amines have the nitrogen atom connected to an aromatic ring. The SN1 product mixtures from 1º-amines are difficult to control, and rearrangement is common when branched primary alkyl groups are involved. For example: 1. Figure 1: Methylamine, Aniline and Alanine Because it is unstable, it is prepared immediately before use in the following manner: Under the acidic conditions of this reaction, all amines undergo reversible salt formation: This happens with 3º-amines, and the salts are usually soluble in water. Amines can be classified according to the nature and number of substituents on nitrogen. The org layer was dried (Na2SO4) and concentrated in vacuo. Diazonium cations may be described by resonance contributors, as in the bracketed formulas shown below. Secondary Amines. 2º-Aryl amines give N-nitrosamine derivatives on reaction with nitrous acid, and thus behave identically to their aliphatic counterparts. [Patent Reference: WO2010016005, page 85, (11.3 MB)], A mixture of the amine (B) (200 mg, 1 mmol), the aryl chloride (A) (149 mg, 1 mmol), and TEA (129 mg 1 mmol), in NMP (2 mL) was heated to 80 C. The reaction mixture was concentrated in vacuo and the crude material was purified by silica gel flash chromatography (30 -100% EtOAc/hexane) to provide the product as a clear oil. The org layer was dried (Na2SO4) and concentrated in vacuo to provide the product as a white solid. The resulting residue was diluted with H2O, treated with saturated aq NaHCO3, and extracted with EtOAc. A primary (1º) amine is an amine that has the following general structural formula.. R= alkyl, aryl. Loss of nitrogen is slower than in aliphatic 1º-amines because the C-N bond is stronger, and aryl carbocations are comparatively unstable. The org layer was washed with brine and dried (Na2SO4). The S N 1 product mixtures from 1º-amines are difficult to control, and rearrangement is common when branched primary alkyl groups are involved. A mixture of the aryl chloride (A) (1 Kg, 7.72 mol), the amine (B) (1.5 Kg, 10.03 mol), TEA (3.23 L, 23.2 mol), and n-BuOH (8 L) were stirred at reflux for 36 h. Upon completion, the reaction mixture was cooled to RT, diluted with H2O (8 L), and extracted with EtOAc (2 x 10 L). [582 mg], [Patent Reference: WO2010038081, page 259, (33.8 MB)], A solution of the SM (0.55 g, 1.799 mmol) in methylamine (33% in EtOH, 10 mL, 1.799 mmol) was heated via microwave at 120 C for 12 h. Additional methylamine (33% in EtOH, 2 mL) was added and the mixture was heated via microwave at 120 C for 12 h. Additional methylamine (33% in EtOH, 2 mL) was again added and the mixture was heated via microwave at 120 C for 15 h. The mixture was diluted with EtOAc, washed with sat aq NaHCO3 (2x), dried, and concentrated to provide the product. [180 mg, 70%], [Patent Reference: WO2014149164, page 290, (23.7 MB)], A suspension of the aryl chloride (A) (0.5 g, 2.00 mmol) and the amine (B) (0.390 mL, 2.99 mmol) in EtOH (3 mL) was heated in a microwave reactor at 140 C for 45 min. [1.3 g, 87%], [Patent Reference: WO2014149164, page 296, (23.7 MB)], A mixture of the aryl chloride (A) (16 g, 73.1 mmol), the amine (B) (10 g, 73.1 mmol), and TEA (15.2 g, 146 mmol) in DMSO (150 mL) was stirred at RT overnight. For more information contact us at [email protected] or check out our status page at https://status.libretexts.org. The org layer was washed with brine, dried (Na2SO4), concentrated onto silica, and purified by silica gel column chromatography (0-16% MeOH/DCM) to provide the product. Nitrous acid ($$HNO_2$$ or $$HONO$$) reacts with aliphatic amines in a fashion that provides a useful test for distinguishing primary, secondary and tertiary amines. The commonest name at this level is methylamine and, similarly, the second compound drawn above is usually called ethylamine. Nitrous acid is a Brønsted acid of moderate strength (pKa = 3.3). The N-nitrosamines formed from 2º-amines are carcinogenic, and are not generally useful as intermediates for subsequent reactions. The crude was purified by column chromatography (2% MeOH/CHCl3) to provide the product. alkylamine. The LibreTexts libraries are Powered by MindTouch® and are supported by the Department of Education Open Textbook Pilot Project, the UC Davis Office of the Provost, the UC Davis Library, the California State University Affordable Learning Solutions Program, and Merlot. In the common naming system, we name aliphatic amines by prefixing an alkyl group to a mine, i.e. (Systematic names are often used by some chemists.) Watch the recordings here on Youtube! The reactions of nitrous acid with 1°- and 2°- aliphatic amines may be explained by considering their behavior with the nitrosonium cation, NO(+), an electrophilic species present in acidic nitrous acid solutions. Legal. Primary Amines. The combined organics were dried (Na2SO4) and concentrated to provide the product. 1. Aliphatic amines contain only H and alkyl substituents. The mixture was diluted with EtOAc and washed with H2O (2x), then brine (1x), dried (MgSO4), and concentrated to provide the product. The combined organics were dried and concentrated to provide the product. Primary amines can be considered as compounds derived from ammonia by the substitution of one hydrogen atom with an organic radical alkyl or aryl, or as compounds resulting from the substitution of a hydrogen atom from an organic molecule with the group NH2. The reaction was stirred at 90 C for 30 min. Secondary and tertiary amines, having two or more similar groups are named by adding prefix ‘di’ or ‘tri’ before the name of the alkyl group. To a 15 C solution of the aryl chloride (A) (220 g, 860.37 mmol) and the amine (B) (137.7 g, 1.03 mol) in NMP (3.6 L) was added DIEA (450 mL, 2.58 mol). The common names for simple aliphatic amines consist of an alphabetic list of alkyl groups attached to the nitrogen atom, followed by the suffix - amine. Functional groups which contain a nitrogen atom linked by single bonds to alkyl groups, aryl groups, hydrogen groups, or some combination of these groups are called amino groups. The left-hand contributor is dominant because it has greater bonding. After completion, the reaction mixture was quenched with H2O and extracted with EtOAc. [160 mg, 26%], [Patent Reference: WO2010038081, page 89, (33.8 MB)]. The resulting mixture was stirred at 80 C for 16 h, after which time it was cooled to 30 C and transferred into H2O (5 L) at RT. Amines are derived from ammonia, chemical formula NH3. The resulting material was triturated in n-pentane to provide the product as an off-white solid. For example: The crude product was filtered and purified by HPLC (H2O/ACN with AcOH). [226 g, 75%], [Patent Reference: WO2014110000, page 19, (2.6 MB)], A mixture of the aryl chloride (A) (1 Kg, 7.72 mol), the amine (B) (1.5 Kg, 10.03 mol), TEA (3.23 L, 23.2 mol), and n-BuOH (8 L) were stirred at reflux for 36 h. Upon completion, the reaction mixture was cooled to RT, diluted with H2O (8 L), and extracted with EtOAc (2 x 10 L). The reaction mixture was stirred at 80 C for 10 h. After completion, the reaction mixture was concentrated in vacuo and partitioned between EtOAc (100 mL) and H2O (50 mL).