[420-04-2]  · CH2N2  · Cyanamide  · (MW 42.04)

(ammonia equivalent, urea equivalent, guanidine equivalent; sulfur bioequivalent)

Alternate Names: cyanoamine; carbodiimide.

Physical Data: mp 45-46 °C; bp 83 °C/380 mmHg; moist white crystals.1

Solubility: sol 100 g/100 g H2O at 43 °C; also sol alcohols, amines, ethers, ketones, ethyl acetate; sparingly sol benzene and halogenated hydrocarbons; insol cyclohexane.

Form Supplied in: pure hygroscopic solid; 50% aq. solution; salts: sodium, calcium, lead, etc.

Preparative Method: widely available. A checked literature preparation is available.2 Calcium salt is prepared from calcium carbide and nitrogen.

Handling, Storage, and Precautions: hygroscopic, caustic, highly toxic (LD50 rats 125 mg/kg), readily absorbed through the skin, produces dermatitis; polymerizes violently above melting point; should be stored in a cool, dry place. Incompatibilities are: various metals, acids, bases, strong oxidizing and reducing agents1. Use in a fume hood.

Because of its amphoteric nature, cyanamide displays both nucleophilic and electrophilic characteristics. This property makes it a useful reagent for the preparation of a variety of heterocycles.

Condensation Reactions.

Cyanamide will undergo cyclization reactions with ketols, thioketones, amino ketones, and related functionalities to yield the respective amino azoles (eqs 1-4).3-6

Nucleophilic Additions.

Cyanamide efficiently adds to a variety of electrophilic functionalities. Thiocyanates react with silver cyanamide to give unusual cyanocarbodiimides, albeit in low yield (eq 5).7

Xanthates and thiono esters undergo addition displacement reactions with potassium cyanamide (eqs 6 and 7).8

Thioureas react with lead cyanamide to give the N-cyanoguanidines. This technique was utilized in the preparation of the first H2 blocker, cimetidine (eq 8).9

Carbodiimides bearing electron-withdrawing aryl groups can be converted to the respective cyanoguanidines with cyanamide (eq 9).10

Orthoesters add cyanamide in the presence of acetic anhydride to give N-cyanoimino esters (eq 10).11

N-Cyanoimino esters and related thioesters are useful intermediates for the preparation of a variety of heterocycles, as shown in (eq 11).12

Cyanamide and the respective sodium salts have been found to add to b-keto esters and 4-pyranones (eqs 12 and 13).13-15

Disubstituted cyanamides are synthesized by direct alkylation of sodium cyanamide (eqs 14-16)14,15 (also see von Braun reaction as an alternative).15c

These cyanamides can be readily hydrolyzed to the respective amines (eq 17).14,15

Calcium cyanamide can be acylated with Benzoyl Chloride to give the N-cyanoamide (eq 18).16

Cyanamide readily adds to alkenes in the presence of N-Bromosuccinimide to give the 1,2-trans-bromocyanamides.17 These bromocyanamides can be converted to 1,2-cis-diamines in one of two similar three-step procedures, or the bromide may be reductively removed to yield the amines (eqs 19 and 20).17 The above reactions are reported for a number of alkenes with yields ranging from 35-70%.

Electrophilic Additions.

Amines, hydrazines, thiols, and alcohols add to cyanamide to give guanidines and pseudourea ethers (eqs 21-23).18-20

Cyanamide can also undergo bis addition with diamines to yield amino heterocycles (eqs 24 and 25).21,22

Related Reagents.

Aminoiminomethanesulfonic Acid; Cyanogen Bromide; Guanidine; O-Methylisourea; S-Methylisothiourea; 1H-Pyrazole-1-carboxamidine Hydrochloride.

1. Merck Index, 11th ed.; 1989; p 2691; Aldrich Material Safety Data Sheet for Product #18736-4.
2. Pinck, L.; Salisbury, J. Inorg Synth. 1950, 3, 39.
3. Wolf, V.; Hauschildt, P.; Loop, W. CB 1962, 95, 2419.
4. Soma, N.; Nakazawa, J.; Watanabe, T.; Sato, Y.; Sunagawa, G. CPB 1965, 13, 819.
5. Gewald, K.; Spies, H.; Mayer, R. JPR 1970, 312, 776.
6. Battegay, M. U.S. Patent 2 112 724, 1938.
7. Kämpf, A. CB 1904, 37, 1681.
8. Hartke, K.; Seib, B. TL 1968, 5523.
9. Durant, G.; Emmett, J.; Ganellin, C.; Miles, P.; Parsons, M.; Prain, H.; While, G. JMC 1977, 20, 901.
10. Kiyoi, T.; Seko, N.; Yoshino, K.; Ito, Y. JOC 1993, 58, 5118.
11. Huffman, K. R.; Schaefer, F. C. JOC 1963, 28, 1816.
12. Brigl, P. CB 1912, 45, 1557.
13. Woods, L. Cl(L) 1960, 51, 1567.
14. Vliet, E. B. OSC 1941, 1, 203.
15. (a) Jónczyk, A.; Ochal, Z.; Makosza, M. S 1978, 882. (b) Donetti, A.; Omodei-Sale, A.; Mantegani, A. TL 1969, 3327. (c) Hageman, H. A. OR 1953, 7, 198.
16. Crowther, A.; Curd, F.; Rose, F. JCS 1948, 586.
17. (a) Jung, S-H.; Kohn, H. TL 1984, 25, 399. (b) Kohn, H.; Jung, S-H. JACS 1983, 105, 4106.
18. Julia, M.; Gombert, R. BSF 1968, 369.
19. Pellizzari, G.; Cuneo, G. G 1894, 24, 453.
20. (a) Kurzer, F.; Lawson, A. OSC 1963, 4, 645. (b) Cox, E. H.; Raymond, Jr., S. M. JACS 1941, 63, 300. (c) McKee, R. Am. Chem. J. 1901, 26, 209.
21. Weiss, S.; Michaud, H.; Prietzel, H.; Krommer, H. AG(E) 1973, 12, 841.
22. King, H.; Wright, E. JCS 1939, 253.

Steven Schow

American Cyanamid, Pearl River, NY, USA

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