Notizen 1359

1 F . A. S c h r ö d e r , Z. Naturforsch. 32b, 361 [1977]; 5 W . H . B a u r , Acta Crystallogr. B28, 1456 [1972]. in this paper the positional parameters of H2II should read 0.1, 0.65, 0.6 and not 0.1, 0.65, 0.82 6 The 0(w)-H(w) distances assumed by Schröder (private communication from F. A. S c h r ö d e r ) . range from 1.3 to 1.9 A, the angles (Hw(-O(w)-H(w) vary from 57 to 93°. None of these values are real­ 2 F . A. S c h r ö d e r and A. N 0Rlund Christensen, Z. Anorg. Allg. Chem. 392, 107 [1972]. istic. 3 H . S c h u l z and F. A. S c h r ö d e r , Acta Crystallogr. 7 W . H . B a u r , Inorg. Chem. 4, 1840 [1965]. A 29, 322 [1973]. 4 W . H. B a u r , Acta Crystallogr. 19, 909 [1965]; pro­ 8 Z. M. E l S a f f a r and G. M. B r o w n , Acta Crystallo­ gram for calculating electrostatic energies, MANIOC. gr. B 27, 6 6 [1971].

Effect of Ortho Substitution on the Aminolysis of several active in two aprotic solvents. For of Active Esters in Aprotic Solvents this study active esters of were used3 because a) aminolysis of esters (including aminoacyl derivatives) proceeds through T. K Ö m iv es , A. F. MÁrton , F. D u t Ka a common mechanism4, and b) intramolecular Central Research Institute for Chemistry interactions between the leaving group and the acyl of the Hungarian Academy of Sciences, portion (as it may occur when using esters of amino- H-1525 Budapest, Hungary acids5) are absent. Under the pseudo first order conditions of excess M. LÖw, and L. K i s f a l u d y all the reactions followed the general rate Chemical Works of Gedeon Richter Ltd., equation for aminolyses in aprotic solvents6: H-1103 Budapest, Hungary d [ester] (Z. Naturforsch. 32b, 1359-1360 [1977]; received August 8, 1977) ------^ ----= (k2 [amine] + k 3 [amine]2) [ester]. Kinetics, Aminolysis, Active Ester, Our second and third order rate constants together Aprotic Solvent, Ortho Effect with literature pKa values for the leaving phenoxy groups are summarized in the Table. Kinetics of the piperidinolysis of active In accord with the early observation that esters of acetic acid in acetonitrile and chloro- aminolytic reactivity of active esters strongly benzene was investigated. The rate data show depends on the basicity of their leaving group8, with the exeption of 2,6-disubstituted compounds which intramolecular catalysis for the aminolysis of exhibit negative deviations, logarithms of k 2AN and 2 -nitro- and 2 -cyanophenyl esters, while k3CB values in the Table can be correlated linearly reactions of 2 ,6 -disubstituted compounds are with the p K a’s of the leaving groups (not shown). hindered by steric inhibition. Since the extent of the lag behind the expected rates for the aminolyses of 2,6-disubstituted re­ The active ester procedure of bond forma­ actants is related to the steric requirements for the tion plays an important role in peptide syntheses. o,o'-substituents (H < F

Table. Second and third order rate constants for the reactions of esters with piperidine in acetonitrile (k 2AN and ks^N) and chlorobenzene (k 2CB and k 3CB) at 25 °C; pKa values for the leaving phenoxy groups in water at 25 °C.

Ester pK a k 2AN k 3AN k 2CB k 3CB M -is-1 M -2s - 1 M -iS-i M-2 s-i

PhOAc I 0 .0 0 a 3.9 10- 5 5.6 1 0 - 5 _ _ 4-Cl-PhOAc 9.42a 8.5 10 - 4 1.5 1 0 - 3 1.0 io-4 8.3 I0 - 4 4-CH3OCOPhOAc 8.47b 2.70 IO " 2 3.2 1 0 - 2 1 . 2 1 0 - 3 1.6 IO- 2 4-CH3COPhOAc 8.05b 4.37 IO - 2 c 1.05 10- 3 2.40 10- 2 4 -N 0 2P h 0A cd 7.15e 2.19 c 3.50 10- 2 8 .2 10-i 2-F-PhO Ac 8.70* 1.51 10- 2 2.52 10-2 1.0 10-3 1.26 1 0 - 2 2-Cl-PhOAc 8.53a 1.15 10 - 2 2.07 io-2 7.5 10 - 4 1.42 10- 2 2 -N 0 2-Ph0Ac 7.23e 2.26 c 5.30 10-1 1.53 2-CN-PhOAc 7.18f 2.67 c 6.08 1 0 - 1 2.07 2,6-Cl2-PhOAc 6.79f 2 .8 8 1 0 - 1 c 2.58 10 - 2 7.6 IO - 3 2,6-(CH 3)2 -4-N 0 2-Ph0Acd 7.078 2.44 10- 3 c 1 . 2 1 0 - 4 1.5 10- 4 2,6-Cl2-4-N 0 2-Ph0Ac 3.55e 64.2 c 1 1 . 0 c 2 ,6 -Br2-4 -N 0 2 -P h 0 Ac 3.38e 13.4 c 4.49 c F s P h O A c d 5.53h 73.0 c 4.70 c Cl5PhOAcd 4.821 15.7 c 2.29 c

a A . I. Biggs and R. A. Robinson, J. Chem. Soc. 1961, 390; b P. M. G. Bavin and W. J. Canady, Can. J. C h e m . 35, 1555 [1957]; c undetectable third order rate constants; d rate data taken from ref. 7 ; e J. Juillard, C. R. Acad. Sei. Ser. C. 262, 241 [1966]; f J.-C. H alle, R. H arivel, and R. Gaboriaud, Can. J. Chem. 52, 1774 [1974]; s A. Fischer, G. J. L eary, R. D. Topsom, and J. V aughan, J. Chem. Soc. B,1966, 782; h J. M. B irchall and R. N. H aszeldine, J. Chem. Soc. 1959, 3653; 1 R. A. R obinson and R. G. B ates, J. Res. Nat. Bur. Stand. A 70, 553 [1966].

1 M. Bodanszky, Y . S. K l a u s n e r , and M . A. K o n d o , C. Y . L i n , and A. Bodanszky, J. Am. O n d e t t i , Peptide Synthesis, Wiley, New York 1976. Chem. Soc. 96, 2234 [1974]. 2 H . R. K ircheldorf, E. S t e n g e l e , and W . R e g e l , 6 D . P. N. S a t c h e l l and 1.1. S e c e m s k i , J. Chem. Soc. Liebigs Ann. Chem. 1975, 1379. B 1969, 130. 7 L. K isfaludy, M. Low, Gy. Argay, M. Czugler, 3 Kinetic arrangements followed previous lines, T. T. K ö m i v e s ,P. S o h ä r , and F. D a r v a s , in “Peptides K ö m i v e s , A. F. M a r t o n , and F. D u t k a , Z. N atur - 1976”, p. 55, Proc. XIVth Peptide Symposium, forsch. 31b, 1714 [1976]. Wepion, Belgium 1976. 4 H . J . J o n e s ,Chem. Ind. (London) 1974, 723. 8 J.P l e s s and R . A. Boissonas, Helv. Chim. Acta 46, 5 M. Bodanszky, M. L. F i n k , K . W . F u n k , M . 1609 [1963].

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