2-Amino-5-cyanopyridine CAS 4214-73-7

2-Amino-5-chloropyridine is prepared by chlorinating 2-aminopyridine in a strongly acidic medium. 2-Amino-5-chloropyridine is a useful intermediate in the preparation of chloro-substituted-imidazo-pyridine herbicides.

It has been discovered that reacting 2-aminopyridine with a chlorinating agent in a strongly acidic medium having a Hammett acidity function, Ho, of less than about -3.5 results in the production of 2-amino-5-chloropyridine with only minimal formation of the 2-amino-3,5-dichloropyridine overchlorination by-product.

While there is no wish to be bound to any theory of reaction mechanism, it is believed that in such a strongly acidic medium having an acidity function of less than -3.5, the chlorination process of the invention takes place through the formation of a reactive protonated species of 2-aminopyridine which thereafter undergoes selective mono-chlorination according to the following generalized reaction scheme.

In the above reaction scheme, the rate of chlorination of protonated 2-aminopyridine, k1, is much greater than the rate of chlorination of protonated 2-amino-5-chloropyridine, k2. Thus, the selective monochlorination reaction predominates in strongly acidic medium and competitive over-chlorination reactions are minimized.

In a weakly acidic medium, e.g. 20% sulfuric acid, however, the 2-aminopyridine reactants are present largely in unprotonated form. The rates of chlorination of unprotonated 2-aminopyridine and unprotonated 2-amino-5-chloropyridine are comparable. Therefore, the subsequent over-chlorination reaction resulting in the formation of substantial amounts of 2-amino-3,5-dichloropyridine is competitive with the desired monochlorination reaction.

The presence of over-chlorination products in the reaction mixture makes recovery of the desired pure 2-amino-5-chloropyridine product difficult. In addition, the further chlorination of 2-amino-5-chloropyridine to form 2-amino-3,5-dichloropyridine reduces the yield of the desired product.

Conveniently, the 2-aminopyridine starting material is added to the strongly acidic medium with external cooling to maintain the reaction mixture at about room temperature during the addition. At least one equivalent of a chlorinating agent is then added to the reaction mixture with stirring. The use of less than one equivalent of the chlorinating agent results in incomplete chlorination of starting material and consequently reduces the yield of the desired product. Preferably, between about one and about two equivalents of the chlorinating agent per equivalent of 2-aminopyridine starting material are employed. More than two equivalents of the chlorinating agent may be employed, but the use of a large excess of chlorinating agent tends to increase the formation of over-chlorination by-products without further promoting the desired complete reaction of the starting material.

Slow addition of the chlorinating agent to the reaction mixture is preferred. Most preferably, the chlorinating agent is added at about the rate at which it is consumed. Such slow addition prevents the buildup of large excesses of chlorinating agent in the reaction mixture and thus minimizes the production of over-chlorination by-products. While the temperature of the reaction mixture may be controlled if desired, external control of the reaction mixture temperature during addition of the chlorinating agent is not necessary.

After addition of the chlorinating agent is completed, the reaction mixture is stirred at ambient temperature for about 30 minutes to about 90 minutes. Longer reaction times are conducive to the formation of 2-amino-3,5-dichloropyridine and preferably are avoided.

Yes, pyridine is soluble in water. It dissolves in water due to the strong hydrogen bonds. Also, there are dipole-dipole intermolecular interactions that exist between lone pairs and hence pyridine dissolves in water. In simple words, pyridine is polar and is soluble at any concentration of the solution. Moreover during this process pyridine goes through hydrophilic hydration at the nitrogen atom. Pyridine is considered highly subjective to dispersion in atmospheres because of properties such as its volatility and water solubility.