2,3,4,5,6-pentachlorophenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Tritylthiopropionic acid [1.0 g, 2.87 mmoles, described by R. C. Hiskey and M. A. Harpold, J. Org. Chem., 33, 559 (1968)] is dissolved in dry tetrahydrofuran (25 ml) and pentachlorophenol (0.765 g, 2.87 mmoles) is added. The mixture is cooled to 0° C, dicyclohexylcarbodiimide (0.596 g, 2.87 mmoles) is added and the reaction is stirred for 1 hr at 0° C and 1 hr at 25° C. The reaction mixture is then cooled to 0° C, filtered and the filtrate is evaporated under reduced pressure. The residue is crystallized from ethyl acetate to give the title compound, mp 154°-156° C. The reaction mixture is then cooled to 0° C filtered the filtrate is evaporated under reduced pressure The residue is crystallized from ethyl acetate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a preferred embodiment of the preparation of the above first tetrapeptide hydrazide, the activated ester of 3-tritylthiopropionic acid, preferably the pentachlorophenyl ester, is prepared by combining substantially equimolar amounts of 3-tritylthiopropionic acid, pentachlorophenol and dicyclohexylcarbodiimide in an inert organic solvent, preferably tetrahydrofuran, at about 0° to 10° C. The mixture is stirred at about 0° to 10° C for about 1 hour and then at about 20° to 30° C for about 1 hour. The mixture is cooled to about 0° C, filtered and the filtrate evaporated. The residue is crystallized to obtain 3-tritylthiopropionic acid pentachlorophenyl ester. A solution of said last-named compound and a substantially equimolar amount of the tetrapeptide of formula H-Lys(Boc)-Asn-Phe-Phe-OMe acetate, prepared as described by H. U. Immer et al., cited above, in an inert organic solvent, preferably dimethylformamide or tetrahydrofuran, is treated with a substantially equimolar amount of an organic base, preferably triethylamine, at about 20° to 30° C. The mixture is stirred for 2 to 3 days at about 20° to 30° C and the solvent evaporated under reduced pressure. The residue is triturated with cold dilute aqueous citric acid and water, dried, and crystallized to give the tetrapeptide of formula Trt--SCH2CH2CO--Lys(Boc)--Asn--Phe--Phe--OMe. Said last-named compound is dissolved in an inert organic solvent, for example, methanol, ethanol, or preferably dimethylformamide. The solution is treated with an excess of hydrazine hydrate, for example 15 to 30 molar equivalents. The reaction mixture is kept at about 20° to 30° C for about 20 to 30 hours and evaporated under reduced pressure. The residue is triturated with cold water and dried to give said tetrapeptide hydrazide of formula (2, R = H) Trt--SCH2CH2CO--Lys(Boc)--Asn--Phe--Phe--NHNH2. at about 0° to 10° C at about 20° to 30° C for about 1 hour filtered the filtrate evaporated The residue is crystallized

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In run A two principal product fractions are obtained: (1) 60.3 g, bp 91°-97° /31 mm, mp 30°; (2) 18.6 g, semisolid residue. Fraction (1) was identified as 1,1,4,4-tetrafluorotetrachloro-2,5-cyclohexadiene by comparison of its IR and MS data with those of a known sample of the compound (Hasek et al., Jour. Am. Chem. Soc., vol. 82, p. 543, 1960) Fraction (2) was indicated by fluorine NMR, IR, VPC and EA analyses to be a mixture of isomeric 1,1,4-trifluoropentachloro-2,5-cyclohexadiene and 1,5,6-trifluoropentachloro-1,3-cyclohexadiene. In run A two principal product fractions are obtained

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: