Di-2-pyridyl Carbonate1

[1659-31-0]  · C11H8N2O3  · Di-2-pyridyl Carbonate  · (MW 216.21)

(dehydration agent; preparation of esters,3 amides,4 nitriles;5 alkoxycarbonylation6 or protection7 of amines; carbonyl transfer8)

Alternate Name: 2-DPC.

Physical Data: mp 76-78 °C.

Solubility: sol CH2Cl2.

Form Supplied in: white solid.

Preparative Methods: from Phosgene and 2-Hydroxypyridine in the presence of Pyridine in THF9 or Triethylamine in CH2Cl2 (eq 1).3,7 Phosgene can also be replaced with triphosgene (Bis(trichloromethyl) Carbonate).2 The usual yield is about 80%.

Handling, Storage, and Precautions: quite stable and can be stored under nitrogen at rt for several months without any noticeable decomposition.

Introduction.

The advantages of using 2-DPC are the following: 2-hydroxypyridine is a neutral compound and can be removed completely from the reaction mixture by the usual aqueous workup. The 2-pyridyl esters are also highly reactive.10

As a Dehydrating Agent.

2-DPC can be used for the direct esterification of carboxylic acids in good yield and under mild conditions.1,3 The reaction can be carried out with equimolar amounts of acids, alcohols, and 2-DPC in the presence of 0.1 equiv 4-Dimethylaminopyridine (DMAP) in CH2Cl2 at rt. The reaction of diphenylacetic acid and benzyl alcohol gave the corresponding ester in 90% yield (eq 2).

Typical yields are as follows: methyl diphenylacetate, 95%; benzyl octanoate, 94%; isopropyl phenylacetate, 90%. With aromatic acids and hindered carboxylic acids the esterification is not very satisfactory. The yields drop to 68% for ethyl benzoate or 42% for benzyl pivalate. In these cases the corresponding 2-pyridyl benzoate and pivalate are isolated.

For the preparation of amides a stepwise procedure must be used.4,11 Formation of activated pyridyl esters and subsequent treatment with amines provide the carboxylic amides. This reaction gave benzyloctanamide in 80% and cyclohexylbenzamide in 85% yield.1

2-DPC can also be used to form nitriles via dehydration of the corresponding aldoximes. The reaction was carried out in refluxing toluene or in presence of 0.1 equiv of 1,8-Diazabicyclo[5.4.0]undec-7-ene in CH2Cl2 at rt.5 The last procedure gave benzonitrile in 83% yield.

Alkoxycarbonylation of Amines.

2-DPC is useful for the N-protection of amino acids via an activated carbonate.7 The mixed carbonate is obtained by the reaction of 2-DPC with an equimolar amount of t-butyl alcohol in the presence of 0.1 equiv DMAP in CH2Cl2. The isolated carbonate obtained in 80% yield was added to a solution of L-proline and Triethylamine in DMF-water (eq 3). After crystallization the yield of N-Boc-proline was 98%. Some other typical yields were as follows: N-Boc-Ala, 84%; N-Boc-Leu, 95%.

The same strategy was used to synthesize functionalized carbamates.2 The reaction between (+)-menthol and 2-DPC in the presence of triethylamine (CH2Cl2) gave the mixed carbonate which was used directly, after classical workup. The reaction of this carbonate and the amine gave the carbamate in 81% yield (eq 4). Amines produced in situ by reduction of the azide can also be transformed into the corresponding carbamate.6

Carbonyl Transfer Reaction.

2-DPC is useful for the preparation of cyclic carbonates or 2-oxazolidones.1,8 The reaction with diols is carried out in refluxing toluene. The reaction of ethylene glycol gave an 85% yield of the corresponding carbonate. In the presence of DMAP in CH2Cl2 at rt, 1,3-butanediol gave the cyclic carbonate in 85% yield. The reaction of 2-DPC with b-amino alcohols in CH2Cl2 at rt gave good yields of the corresponding 2-oxazolidone: 1-aminopropan-2-ol, 87%; 1-phenyl-2-aminoethanol, 93%; 2-amino-4-nitrophenol, 96% (eq 5).

Related Reagents.

1-(t-Butoxycarbonyl)imidazole; 1-N-(t-Butoxycarbonyl)-1H-benzotriazole 3-N-Oxide; 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile; t-Butyl Chloroformate; Di-t-butyl Dicarbonate.


1. Kim, S. OPP 1988, 20, 145.
2. Ghosh, A. K.; Duong, T. T.; McKee, S. P. TL 1991, 32, 4251.
3. Kim, S.; Lee, J. I.; Ko, Y. K. TL 1984, 25, 4943.
4. Kim, S.; Ko, Y. K. CC 1985, 473.
5. Kim, S.; Ko, Y. K. Bull. Korean Chem. Soc. 1987, 8, 50.
6. Ghosh, A. K.; McKee, S. P.; Duong, T. T.; Thomson, W. J. CC 1992, 1308.
7. Kim, S.; Lee, J. I.; Yi, K. Y. BCJ 1985, 58, 3570.
8. Kim, S.; Ko, Y. K. H 1986, 24, 1625.
9. Kampe, W. AG(E) 1963, 2, 479.
10. Dutta, A. S.; Morley, J. S. JCS(C) 1971, 2896.
11. Kim, S.; Ko, Y. K. Bull. Korean Chem. Soc. 1985, 6, 175.

Joseph Schoepfer

University of Neuchâtel, Switzerland



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