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Org. Synth. 1951, 31, 8
DOI: 10.15227/orgsyn.031.0008
ARYLUREAS
I. CYANATE METHOD
p-BROMOPHENYLUREA
[Urea, (p-bromophenyl)-]
Submitted by Frederick Kurzer1
Checked by Richard T. Arnold and Lester C. Krogh.
1. Procedure
In a 2-l. beaker, 86 g. (0.5 mole) of p-bromoaniline is dissolved in 240 ml. of glacial acetic acid and 480 ml. of water at 35°. This solution is treated with a solution of 65 g. (1 mole) of sodium cyanate (Note 1) in 450 ml. of water at 35° (Note 2). About 50 ml. of the sodium cyanate solution is added slowly with stirring until a white crystalline precipitate of the product appears. The rest is then added quickly with vigorous agitation (Note 3). The very rapid separation of the product is accompanied by a rise in the temperature to 50–55°. The thick, paste-like suspension is stirred for another 10 minutes, allowed to stand at room temperature for 2–3 hours, and diluted with 200 ml. of water. After cooling to 0°, the material is filtered with suction, washed with water, drained thoroughly, and dried. The yield of crude p-bromophenylurea, a white crystalline powder, is 95–100 g. (88–93%). The product is sufficiently pure for further synthetic work, but it can be recrystallized from aqueous ethanol (12 ml. of ethanol and 3 ml. of water per gram of crude material) to give a 65% recovery of lustrous white prisms of p-bromophenylurea, m.p. 225–227° (Note 4). This method is suitable for the preparation in excellent yields of a large number of arylureas (Note 5).
2. Notes
1. Comparable results are obtained with an equivalent quantity (81 g.) of potassium cyanate.
2. Instead of the solution, a well-stirred suspension of the cyanate in 150 ml. of water may be used with equal success.
3. Considerable frothing occurs with loss of some isocyanic acid (faint smell resembling that of sulfur dioxide). The foam collapses readily on stirring.
4. Melting points varying between 220° and 278° have been reported for p-bromophenylurea (see Methods of Preparation). It has been shown2 that the thermal conversion of arylureas to the corresponding diarylureas takes place extremely rapidly, even below the melting point. This is particularly true of arylureas containing certain substituents in the para position to the ureido grouping. Melting points of such compounds are therefore liable to be indefinite and correspond to mixtures of the mono and sym disubstituted urea, especially if the temperature is raised slowly.
Reproducible values for the melting points of such compounds, including p-bromophenylurea, have now been determined by the following simple procedure: After the approximate softening temperature or melting range of the urea derivative has been found, the bath temperature of the apparatus is raised a further 10–20° above that point and samples are inserted into the slowly cooling bath until a temperature is reached at which a specimen just fails to liquefy. Insertion of a further specimen at a temperature 1° higher causes instantaneous fusion and can be taken as the "melting point" of the urea derivative under examination. Under these conditions practically no conversion to a diarylurea occurs, and samples withdrawn immediately after fusion show nitrogen contents corresponding to the original arylurea. This method gives reproducible physical constants for urea derivatives whose properties preclude slow heating.
5. A list of substituted arylureas prepared by the method above is given in the accompanying table, which records slight variations in the quantities of starting materials employed and in the yields obtained.
The quantities of water recorded in column III are used for preparing the arylamine acetate solutions. The sodium cyanate is dissolved or suspended in the appropriate volume of water as detailed in the synthesis of p-bromophenylurea. The yields refer to the quantity of crude product. The substituted ureas thus obtained are usually sufficiently pure for further syntheses but can be recrystallized from ethanol.
SUBSTITUTED ARYLUREAS

I

II

III

IV

V

VI

VII

Arylurea

Arylamine, moles

Water, ml.

Acetic Acid, ml.,

Sodium Cyanate moles,

Initial Temperature, °C

Yield, %


p-Tolylurea

0.5

500

50

1.0

25

96

m-Tolylurea

0.5

400

75

1.0

30

86

o-Tolylurea

0.5

400

75

1.0

30

94

1-(4-Biphenylyl)urea

0.3

500

350

0.6

40

80

1-(2-Biphenylyl)urea

0.25

400

400

0.5

30

75

p-Methoxyphenylurea

0.3

150

30

0.6

40

94

p-Ethoxyphenylurea

0.5

500

75

1.0

25

95

m-Ethoxyphenylurea

0.3

500

120

0.6

20

54

o-Ethoxyphenylurea

0.5

500

170

1.0

20

88

m-Bromophenylurea

0.5

300

150

1.0

20

90

o-Bromophenylurea

0.5

100

250

1.0

25

92

o-Chlorophenylurea

0.5

100

200

1.0

25

92


3. Discussion
p-Bromophenylurea has been prepared by the bromination of phenylurea, using glacial acetic acid,3,4 ethanol,4 or chloroform5 as solvents; by the action of potassium cyanate on p-bromoaniline hydrochloride;4,6 and by the interaction of p-bromoaniline and ethyl allophanate.7

References and Notes
  1. University of London, London, England.
  2. Kurzer, J. Chem. Soc., 1949, 2292.
  3. Pinnow, Ber., 24, 4172 (1891).
  4. Wheeler, J. Am. Chem. Soc., 51, 3653 (1929).
  5. Desai, Hunter, and Khalidi, J. Chem. Soc., 1934, 1186.
  6. Scott and Cohen, J. Chem. Soc., 121, 2034 (1922).
  7. Dains and Wertheim, J. Am. Chem. Soc., 42, 2303 (1920).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

ethanol (64-17-5)

acetic acid (64-19-7)

chloroform (67-66-3)

sulfur dioxide (7446-09-5)

nitrogen (7727-37-9)

Phenylurea (64-10-8)

potassium cyanate (590-28-3)

isocyanic acid (75-13-8)

sodium cyanate (917-61-3)

1-(4-Biphenylyl)urea

1-(2-Biphenylyl)urea

ethyl allophanate (626-36-8)

p-bromoaniline (106-40-1)

p-bromoaniline hydrochloride

p-Bromophenylurea,
Urea, (p-bromophenyl)- (1967-25-5)

p-Tolylurea (622-51-5)

m-Tolylurea (63-99-0)

o-Tolylurea (614-77-7)

p-Methoxyphenylurea (1566-42-3)

p-Ethoxyphenylurea (150-69-6)

m-Ethoxyphenylurea (13142-86-4)

o-Ethoxyphenylurea

m-Bromophenylurea (2989-98-2)

o-Bromophenylurea (13114-90-4)

o-Chlorophenylurea (114-38-5)