An Insight of the Reactions of Amines with Trichloroisocyanuric Acid

Abstract

The reaction between amines or α-aminoacids with trichloroisocyanuric acid is studied under various conditions: N,N-dichloroamines, nitriles and ketones can be obtained from primary amines, while free aminoacids undergo oxidative decarboxylation to the corresponding nitrile of one less carbon atom.

dichloroamines - trichloroisocyanuric acid - nitriles - aminoacids

References

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10

These results are obviously inconsistent with those published (ref.⁹). We have repeated the experiments with other substrates, such as those reported in Table 1, following the reported procedure and always no traces of nitriles were detected. We have no explanation for this disagreement: in our opinion, this might perhaps depend on the distillation procedure adopted from the above-cited authors that should have caused hydrochloride elimination from the substrate.

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12

The reaction is not chemoselective: a mixture of primary and secondary amines yielded a mixture of chloroamines when reacted with 1 equiv of TCCA.

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Probably owing to the formation of insoluble salts formed by TEA and the formed trihydroxytriazine.

16

The presence of the compounds in the reaction mixture was evidenced by ¹H NMR analysis.

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21

All solvents and reagents were used as obtained from commercial source. Standard ¹H NMR and ¹³C NMR were recorded from CDCl₃ solutions at 300 MHz and 75.4 MHz. Mass spectra were recorded at 70 eV with a direct probe for sample introduction. When possible, compounds were identified by comparison with authentic samples. All runs were conducted at least in duplicate. General Preparation of N , N -Dichloroamines. The procedure for the chlorination of benzylamine (Table 1, run 3) is representative for all cases. Benzylamine (2.00 g, 19 mmol) was dissolved in CH₂Cl₂ (80 mL) and treated with TCCA (4.64 g, 19 mmol) at 0 °C. After the addition, the mixture was warmed to r.t. and stirred for the required time until completion. After 1 h, TLC analysis showed the complete absence of the amine, the reaction mixture was filtered on Celite and the solvent evaporated to yield N,N-dichlorobenzylamine(3) that was isolated without further purification (oil, 3.2 g, 98%). ¹H NMR: δ = 7.39 (s, 5 H), 4.68 (s, 2 H). ¹³C NMR: δ = 135.1, 130.3, 129.5, 128.8, 79.1. MS: m/e (relative intensity): 179 (1), 177 (3), 176 (1), 175 (4), 112 (2), 106 (3), 105 (14), 104 (23), 103 (4), 92 (91), 91 (100), 79 (1), 78 (4), 77 (15), 76 (3), 65 (9), 63 (2), 51 (9). General Procedure for the Preparation of Nitriles and N -Chloroimines from N , N -Dichloroamine. The reported procedure is representative: N,N-dichlorocyclohexanamine (2, 1.00 g, 6 mmol) was dissolved in CH₂Cl₂ (20 mL) and treated with TEA (2.56 mL, 18 mmol) at 25 °C. After 2 h, TLC analysis showed the complete absence of the N,N-dichloroamine. Then the reaction mixture was washed with H₂O (15 mL), with HCl 0.5 N (10 mL), dried on Na₂SO₄, filtered on Celite and concentrated in vacuo to yield N-chlorocyclohexanimine (18, oil, 0.61 g, 77%). ¹H NMR: δ = 2.60-0.95 (br m, 10 H). ¹³C NMR: δ = 182.8, 36.9, 32.7, 26.9, 25.9, 25.1.
General One-Pot Procedure. The reported procedure is representative: Benzylamine (1.00 g, 9.5 mmol) was dissolved in DMF (10 mL) and treated with TEA (4 mL, 28.5 mmol), and with TCCA (2.32 g, 9.5 mmol) at 25 °C. After 4 h, the reaction mixture was quenched with H₂O (20 mL), and then it was extracted twice with Et₂O (15 mL). The organic layers were washed with H₂O (10 mL), then with HCl 0.5 N (10 mL), were dried (Na₂SO₄), and the solvent was evaporated to yield benzonitrile (19, 1.1 g, 95%). General One-Pot Procedure for the Preparation of Nitriles from α-Aminoacids. The reported procedure is representative: l-Phenylalanine (1.20 g, 7.6 mmol) was dissolved in an aq solution of 2 N NaOH (3.8 mL) and treated with TCCA (1.17 g, 5.1 mmol) at 25 °C. After 10 min, when TLC analysis showed the complete absence of the l-phenylalanine, the reaction mixture was treated with HCl (15 mL), followed by an aq solution of 3 N HCl (2.5 mL). After 10 min the mixture was extracted twice with Et₂O (15 mL). The organic layers were washed with H₂O (10 mL), dried on Na₂SO₄, filtered and concentrated in vacuo to yield 2-phenylacetonitrile (20, 0.87 g, 98%). ¹H NMR: δ = 7.38 (m, 5 H), 3.75 (s, 2 H). ¹³C NMR: δ = 142.1, 129.1, 127.9, 127.8, 117.8, 23.5.
Some other examples: N -Chlorodiphenylmethanimine (23): ¹H NMR: δ = 7.76 (m, 4 H), 7.39 (m, 6 H). ¹³C NMR: δ = 165.6, 132.9, 131.5, 129.2, 127.8. Anal. Calcd for C₁₃H₁₀ClN (215.68): C, 72.39; H, 4.67; Cl, 16.44; N, 6.49. Found: C, 72.40; H, 4.66; Cl, 16.44; N, 6.50. The compound was dissolved in THF (10 mL) and treated with 10 mL of aq HCl (1 N) to yield 1.0 g of benzophenone, identified by comparison with an authentic sample.
Methyl-2-chloroimino-3-phenylpropanoate (24): ¹H NMR: δ = 7.30 (m, 5 H), 4.26 (s, 2 H), 3.83 (s, 2 H). ¹³C NMR: δ = 172.3, 172.1, 137.5, 130.3, 129.1, 128.9, 128.7, 53.5, 38.5. Anal. Calcd for C₁₀H₁₀ClNO₂ (211.64): C, 56.75; H, 4.76; Cl, 16.75; N, 6.62. Found: C, 56.74; H, 4.76; Cl, 16.75; N, 6.60. The compound was then dissolved in THF (10 mL) and treated with 10 mL of aq HCl (1 N) to yield 1.0 g of methyl phenylpyruvate. ¹H NMR: δ = 8.15 (br s, 1 H), 7.30-7.14 (m, 5 H), 6.53 (s, 1 H), 3.93 (s, 3 H). ¹³C NMR:
δ = 162.4, 152.3, 137.5, 129.1, 128.9, 128.7, 104.5, 53.5.
( S )-2-Methylbutanenitrile (28): [α]_D ²⁵ +39 (c 1.5, CHCl₃). ¹H NMR: δ = 2.56 (d, J = 7 Hz, 1 H), 1.62 (m, 2 H), 1.31 (d, J = 7 Hz, 3 H), 1.08 (t, J = 7 Hz, 3 H). ¹³C NMR: δ = 124.8, 27.1, 26.9, 17.4, 11.1.