Guanidine Nitrate

[506-93-4]  · CH6N4O3  · (MW 122.08)

(reagent used for selective deacetylation and heterocyclic synthesis)

Alternate Name: guanidinium nitrate.

Physical Data: mp 213-215 °C.

Solubility: reported solubility in water, methanol, ethanol, and acetone.

Form Supplied in: granular white powder; commercially available.

Preparative Methods: there are several reported methods for preparation of the title compound, however, it should be noted that the explosive properties of guanidine nitrate and the reagents used in its preparation are akin to commercial explosives.1,2 It is therefore recommended that this product be purchased from one of several commercial suppliers. Guanidine nitrate has been prepared by heating carbamoylnitrile sodium salt or calcium salt in the presence of ammonium nitrate.3 Heating cyanoguanidine with aqueous ammonia and ammonium nitrate has also been reported.1

Purification: recrystallization from water or ethanol (500 g L-1).1 The commercial reagent can also be used as received.

Handling, Storage, and Precautions: strong oxidizing agent. Heating may cause explosion. Contact with combustible material may cause fire. Harmful if swallowed. Irritating to eyes, respiratory system, and skin. Should be used only in a well-ventilated fume hood to avoid dust inhalation. Toxicity (oral) rat LD50: 730 mg kg-1.4

Heterocyclic Synthesis

Guanidine nitrate and other salts of guanidine (see Related Reagents) offer a convenient source of guanidine when treated with a base in an appropriate solvent. Thus, it is not surprising that other salts of guanidine have been used interchangeably for such reactions. Guanidine nitrate has been used in preparation of five- and six-membered heterocycles.5 For example, the synthesis of the guanidine-containing natural product (+)-ptilocaulin (2) involves treatment of bicylic enone 1 with guanidine, generated from guanidine nitrate and potassium hydroxide in methanol (1).6

Likewise, the reaction of guanidine with substituted hydroxy ester (3) led to imidazolinone (4) in a total synthesis of hymenialdisine (5) (2).7

Guanidine nitrate is a useful reagent for the synthesis of substituted pyrimidines. Classically, the condensation of guanidine with 1,3-dicarbonyl compounds leads directly to substituted pyrimidines.6 The scope of this reaction has been expanded over the years to include other 1,3-dicarbonyl equivalents such as enaminones,8 acylketene dithioacetals,9 acylketene S,N-acetals10 (3) and bromo acrylonitriles (4).11

Selective Deacetylating Reagent

Kunesch et al. first reported the use of guanidine as a selective O-deacetylating reagent for carbohydrates and phenols in 1987.12 Recently, Ellervik and Magnusson reported the mild and selective deacetylation with guanidine/guanidine nitrate.13 This new protocol allows for selective acetyl group cleavage in the presence of the N-Troc group. For example guanidine/guanidine nitrate solution is prepared by treatment of guanidine nitrate (5 mmol) in methanol/methylene chloride (9:1) with sodium methoxide (1 mmol). Treating 10 with this solution cleanly affords the deacetylated product in high yield after just 15 min (5).


Other references involving guanidine nitrate include sulfonylation,14 triazene formation,15 N-arylation16, and epoxide ring-opening reactions.17

Related Reagents.

Guanidine [113-00-8], and other salts including guanidine acetate [593-87-3]; guanidine carbonate [593-85-1]; guanidine hydrochloride [50-01-1]; guanidine sulfate [1184-68-5]; and guanidine thiocyanate [593-84-0].

1. Davis, T. L., Org. Synth., Coll. Vol. 1941, 1, 302.
2. Baumgarten, H. E., Org. Synth., Coll. Vol. 1973, 5, 589.
3. (a) Imperial Chemical Industries Ltd.; US 2230827; 1938, CA35:3267c. (b) Patent; Farbenind IG; Fortsch. Teerfarbenfabr. Verw. Industriezweige; DE 490876; CA24:2149a.
4. Material Safety Data Sheet, Sigma-Aldrich Chemical Company.
5. (a) Brown, D. J., In The Chemistry of Heterocyclic Compounds: The Pyrimidines; Weissberg, A.; Taylor, E. C., Eds; Wiley-Intersciences: New York, 1970, pp 31-110. (b) Brown, D. J., In The Chemistry of Heterocyclic Compounds, Vol. 16: The Pyrimidines, Suppl. 2; Weissberg, A.; Taylor, E. C., Eds; Wiley-Intersciences: New York, 1985, pp 21-108.
6. (a) Snider, B. B.; Faith, W. C., Tetrahedron Lett. 1983, 24, 861. (b) Snider, B. B.; Faith, W. C., J. Am. Chem. Soc. 1984, 106, 1443. (c) Schellhaas, K.; Schmalz, H.-G.; Bats, J. W., Chem. Eur. J. 1998, 4, 57.
7. Annoura, H.; Tatsuoka, T., Tetrahedron Lett. 1995, 36, 413.
8. (a) Bredereck, H.; Effenberger, F.; Botsch, H., Chem. Ber. 1964, 97, 3397. (b) Bejan, E.; Haddou, H. A.; Daran, J. C.; Balavoine, G. G. A., Synthesis 1996, 1012.
9. (a) Kumar, A.; Aggarwal, V.; Ila, H.; Junjappa, H., Synthesis 1980, 748. (b) Apparao, S.; Rahman, A.; Ila, H.; Junjappa, H., Synthesis 1982, 792.
10. Takahata, H.; Nakajima, T.; Yamazaki, T., Synthesis 1983, 226.
11. Pochat, F., Synthesis 1980, 379.
12. Kunesch, N.; Miet, C.; Poisson, J., Tetrahedron Lett. 1987, 28, 3569.
13. Ellervik, U.; Magnusson, G., Tetrahedron Lett. 1997, 38, 1627.
14. Kelly, W.; Robson, T. D.; Short, W. F., J. Chem. Soc. 1945, 87, 240.
15. Kelarev, V. I.; Karakhanov, R. A.; Kokosova, A. S.; Gankin, G. D., Chem. Heterocycl. Compd. (Engl. Transl.) 1992, 28, 1060.
16. Lipinski, C. A.; Craig, R. H.; Wright, R. B., J. Heterocyclic Chem. 1985, 22, 1723.
17. Fitsche-Lang, W.; Wilharm, P.; Hädicke, E.; Fritz, H.; Prinzbach, H., Chem. Ber. 1985, 118, 2044.

Scott A. May

Eli Lilly and Company, Indianapolis, USA

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