Checked by Melvin S. Newman and John Eberwein.
1. Procedure
To a solution of
20.8 g. (0.3 mole) of hydroxylamine hydrochloride and
20.6 g. (0.5 mole) of sodium hydroxide (98%) in 100 ml. of water is added
22.26 g. (0.25 mole) of ethyl carbamate. After 3 days at room temperature the solution is cooled in an
ice bath and carefully neutralized with concentrated
hydrochloric acid (Note
1). If necessary (Note
2), the solution is filtered and then extracted with
ether; the aqueous phase is evaporated on a
water bath under reduced pressure as rapidly as possible at a temperature not above 50–60°.
The dry residue is extracted by boiling with
100 ml. of absolute ethanol, and the solution is filtered through a heated funnel. On cooling, a first crop (
6–8 g.) of
hydroxyurea crystallizes.
The saline residue on the filter is extracted once again with
50 ml. of boiling absolute ethanol. On concentrating the filtrate from the second extraction and the mother liquor from the first crystallizate to a small volume, a second crop (
4–6 g.) of product is obtained. The yield of the
hydroxyurea is
10–14 g. (
53–73%) of white crystals, m.p.
137–141° (dec.).
The product may be purified by recrystallization of
10 g. from
150 ml. of absolute ethanol. The rate of solution is slow (15–30 minutes is required), and the yield of
hydroxyurea, m.p.
139–141° (dec.), is about
8 g. (Note
3).
2. Notes
1. Neutralization to
phenolphthalein is satisfactory, but a glass electrode might give better results.
Hydroxyurea is decomposed very rapidly in aqueous acidic medium, whereas its metallic salts (sodium or the copper complex salts) are stable.
2. Insoluble matter is sometimes present if a commercial grade of reactants is employed.
3. It is preferable to store the crystals in a cool, dry place. Some decomposition may occur after a few weeks.
3. Discussion
The improved method herein described is adapted from the procedure of Runti and Deghenghi.
2 Hydroxyurea has been prepared from
potassium cyanate and
hydroxylamine hydrochloride.
3,4,5 A lower melting isomeric substance, m.p.
71°, has been described.
4,5,6 The structure NH
2CO
2NH
2 has been proposed
5,6 for this low-melting substance.
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