Abstract
A solution of tert.butanol (74.1 g = 94 ml, 1 mol) and quinoline (130 g = 119 ml, 1 mol) in dichloromethane (150 ml) is stirred while phenyl chlorocarbonate [2] (157 g = 126 ml, 1 mol) is added dropwise. The rate of addition is regulated to maintain the temperature of the reaction mixture between 38 and 41 °C. After overnight storage at room temperature enough water is added to dissolve the precipitated quinoline hydrochloride. The organic layer is separated and washed twice with water (60 ml each time) and with 5% hydrochloric acid (3 to 4 times, 60 ml each time). The solution is dried over MgSO4, the solvent removed by distillation and the crude tert.butyl phenyl carbonate distilled from a Claisen flask. At 0.5 mm it boils at 74–78 °C [3]. The yield is about 143 g (73%).
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References
Carpino, L. A.: J. Amer. Chem. Soc. 79, 98, 4427 (1957)
Haas, W. L., Krumkalns, E. V., Gerzon, K.: J. Amer. Chem. Soc. 88, 1988 (1966)
Stetter, H., Schwarz, M., Hirschhorn, A.: Chem. Ber. 92, 1629 (1959); Commercially available.
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This reagent, although an oil, gives somewhat better coupling results than the originally proposed l-ethyloxycarbonyl-2-ethyloxy-1,2-dihydroquinoline (EEDQ) (Belleau, B., Malek, G.: J. Amer. Chem. Soc. 90, 1651 (1968)). Both EEDQ and IIDQ can be stored at room temperature for prolonged periods of time.
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Diphenyl phosphorazidate converts carboxylic acids into the corresponding acid azides. It can be applied for the activation of the C-terminal carboxyl group in partially protected peptides, and can also be used as coupling reagent if added to a mixture of the carboxyl- and amino-components. Cf. also Yokoyama, Y., Shiori, T., Yamada, S.: Chem. Pharm. Bull. 25, 2423 (1977).
As an example for the use of diphenylphosphoroazidate the execution of the Young test (cf. p. 227) is described here. A stirred solution of benzoyl-L-leucine (2.35 g, 10 mmol) arid glycine ethyl ester hydrochloride (1.53 g, 11 mmol) in dimethylformamide (25 ml) is cooled in an ice-water bath and treated with the reagent (DPPA, 3.03 g = 2.40 ml, 11 mmol). A solution of triethylamine (2.12 = 2.90 ml, 21 mmol) in dimethylformamide (25 ml) is added dropwise in the course of about 10 minutes. Stirring and cooling with ice-water are continued for about 6 hours. The mixture is diluted with benzene (250 ml) and ethyl acetate (500 ml) and the solution washed with 50 ml portions of N HCl (twice), water, a saturated solution of NaCl in water (twice). The solution is dried over anhydrous Na2SO4 and evaporated to dryness in vacuo. The crude product is chromato-graphed on a column of silica gel (about 500 g). The purified material is eluted with a 10:1 mixture of chloroform and ethyl acetate. Benzoyl-leucyl-glycine ethyl ester thus obtained (2.05 g, 87%) melts at 145–158 °C. The specific rotation of this material, [α]D 20 — 30.9° (c 3, ethanol) indicates that it contains 91% of the L-isomer (excluding the amount present as the racemate). For an isomeric mixture with the same composition Williams and Young (J. Chem. Soc. 1963, 882) report a m.p. of 148–152 °C.
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This compound is an efficient catalyst in acylation with active esters; cf. König, W., Geiger, R.: Chem. Ber. 106, 3626 (1973)
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1-Guanyl-3,5-dimethyl-pyrazole reacts with primary amines to form guanidine derivatives (and 3,5-dimethyl-pyrazole). It has been recommended for the guanylation of the side chain amino groups of lysine residues in proteins (Habeeb, A. F. S. A.: Canad. J. Biochem. Physiol. 38, 493 (1960)) and is also suitable for the conversion of ornithine residues to arginine residues in synthetic peptides (Bodanszky, M., Ondetti, M. A., Birkhimer, C. A., Thomas, P. L.: J. Amer. Chem. Soc. 86, 4452(1964)).
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Bodanszky, M., Bodanszky, A. (1984). Reagents for Peptide Synthesis. In: The Practice of Peptide Synthesis. Reactivity and Structure Concepts in Organic Chemistry, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-96835-8_7
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DOI: https://doi.org/10.1007/978-3-642-96835-8_7
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