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IX,4. Bromural (α-Bromo-Isovalerylurea)

Iso-Valeric acid is converted by phosphorus and bromine into α-bromo-isovaleryl bromide; the latter upon heating with urea gives bromural.

Bromural

Equip a 1 litre bolt-head flask with dropping funnel and a double surface reflux condenser; to the top of the latter attach a device for the absorption of the hydrogen bromide evolved.

Place 100 g. (108 ml.) of dry iso-valeric acid and 12 g of purified red phosphorus in the flask. Add 255 g (82 ml) of dry bromine slowly through the dropping funnel at such a rate that little or no bromine is lost with the hydrogen bromide evolved; the addition occupies 2-3 hours. Warm the reaction mixture on a water bath until the evolution of hydrogen bromide is complete and the colour of the bromine has disappeared. Pour off the liquid reaction product into a Claisen flask and distil under the reduced pressure of a water pump. Collect the α-bromo-iso-valeryl bromide at 117-122°C/25-30 mm. The yield is 150g.

In a 500 ml. bolt-head flask provided with a thermometer (reaching almost to the bottom) and a calcium chloride (or cotton wool) guard tube, place 100g of α-bromo-iso-valeryl bromide and 50g of dry, finely divided urea. Start the reaction by warming the flask on a water bath; the temperature soon rises to about 80°C. Maintain this temperature for about 3 hours; the mass will liquefy and then resolidify. Transfer the sticky reaction product to a large beaker containing saturated sodium bicarbonate solution, stir mechanically and add more saturated sodium bicarbonate solution in small quantities until effervescence ceases. Filter at the pump, suck as dry as possible and dry the crude bromural upon filter paper in the air. Recrystallise the dry product from toluene. Alternatively, recrystallise the moist product from hot water (ca. 700 ml). The yield of pure bromural, m.p. 154-155°C, is 28 g.

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Bonus - Forensic article on a sedative Ureide:

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Sensitive and selective determination of bromisovalum by HPLC/particle beam mass spectrometry
T. Nagata, K. Kudo, T. Imamura & N. Jitsufuchi, Forensic Sci. Int. 74(3), 205-211 (1995)



Abstract
A specific procedure using high-performance liquid chromatography/particle beam mass spectrometry (HPLC/PBMS) has facilitated determination of bromisovalum in human plasma and whole blood. Bromisovalum, a sedative and hypnotic, was effectively extracted with SepPak C₁₈ cartridges and selectively determined by HPLC/PBMS of EI mode. An originally synthesized 2-bromohexanoylurea served as the internal standard (IS). The calibration curve was linear over the concentration range 0.5-5.0 µg/g and the lower limit of detection was 0.1 µg/g (10 ng at the time of direct injection). This method could be practically applied to detect bromisovalum in the whole blood of an autopsied individual.

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