We therefore propose an essentially planar binding site, whose stereospecifity is presumably caused by the arrange- ment of six dipoles.

The binding energy between Con A and a glycoprotein is known to be 23 kJ mol-'.['lThis energy can be attributed to the dipole-dipole interactions of these six dipole pairs at an average distance of 0.45 nm.[lol Such a distance leaves ample room for the proposed acetyl groups (Fig. 2). There is even

0 0

o-Glu

Fig. 2. Model of the stereoselective binding of o-glucose with and without acetyl groups at a smooth surface of Con A with a planar binding site distribu- tion (hatched surface is tilted through 90").

enough space for an additional hydration sphere between both surfaces, which would explain the observed similarities of binding constants and rates. The carbonyl dipoles of the acetyl groups obviously do not play an important role in the binding process. Formal attempts to bind the wrong enan- tiomers or diastereomers in the model yield at least two dis- tances which are 20 % larger. This is in agreement with the observed decrease of binding energies and equilibrium con- stants.

Received: November 24, 1989 [Z 3650 IE] German version: Angew. Ckem. 102 (1990) 699

CAS Registry numbers: l a , 101009-69-2: 1 b, 127062-38-8; Ic, 127062-39-9; Id , 127062-40-2; l e , 101009-70-5; 1 f, 126979-69-9; 1 g, 126979-70-2; l b , 126979-71-3; Con A, 11028-71-0.

[l] L. Bhattacharyya, C. F. Brewer, Biochem. Biopkys. Res. Commun. 137

[2] H. Bader, K Dorn, B. Hupfer, H. Ringsdorf. Adv. Polym. Sci. 64 (1985) (1986) 670-674.

I .

[3] J. P. Carver. A. E. Mackenzie, K. D. Hardman, Btopolymers 24 (1985)

[4] J. W. Becker, G. N. Reeke, B. A. Cunningham, G. M. Edelman, Nature

[5] I. J. Goldstein, C. E. Hayers, Adv. Carbohydr. Ckem. 35 (1978) 128-316. [6] 2. Derewenda, J. Yariv, J. R Helliwell, A. J. Kalb, E. J. Dodson, M. 2.

Papiz, T. Wan, J. Campbell, EMBO J. 8 (1989) 2189-2193. [7] J. H. Fuhrhop, H. H. David, J. Mathieu, U. Liman, H. J. Wmter, E.

Boekema, J. Am. Chem. SOC. 108 (1986) 1785-1791. [S] Con A, Grade IV, Sigma, salt free; exact conditions are given in R. D.

Brown 111. C. F. Brewer. S. H. Koenig, Biochemistry 16(1977) 3883-3896. 1 mg of Con A per mL gave total stereoselectivity; with 25 mg Con A per mL nonselective precipitations of all vesicles were observed.

[9] T. G. I. Ling, B. Mattiason in T. C. Bsg-Hansen, E. van Driessche (Eds): Leftins. Voi. 2, de Gruyter. Berlin 1982, p. 563-571.

49-63.

(London) 259 (1976) 406-409.

[lo] Derived from the point dipole model:

Synergic Destabilization by Geminal Ester Groups** By Sergej Verevkin, Barbara Dogan, Hans-Dieter Beckhaus and Christoph Riichardt * Dedicated to Professor Roy Huisgen on the occasion of his 70th birthday

Stabilization by synergic interaction of geminal donor substituents on a saturated carbon atom, e.g. alkoxy groups in acetals, and its consequences, have long been known qual- itatively as the "anomeric effect"."' This anomeric stabiliza- tion and its dependence on structure was recently determined quantitatively by us.['] In contrast, geminal nitro groups on a saturated C atom lead to de~tabilization.[~"' Results of ab-initio calculations and other theoretical ~ t u d i e s , f ~ ~ - " point to analogous effects in the case of other acceptor groups. We have now examined the synthetically important malonates 1 a-c and the methanetricarboxylates 2 in order to establish whether geminal ester groups are also synergical- ly destabilizing.

Despite the universal use of malonates, to our knowledge no measurements of their standard enthalpies of formation have thus far been reported.[4] In the case of 1 a-c, 2, and the reference compounds ethyl 2-methylbutyrate 3 and ethyl pi-

H, ,CO,Et H, ,CO,Et Me, ,CO,Et

EtO,C/'\CO,Et Me/"Et Me /'\Me

2 3 4

valate 4 they were now obtained from their combustion enthalpies AH:( 1) and vaporization enthalpies (Table 1.).

Table 1 . Combustion enthalpies AH,O(l), vaporization enthalpies AH", and standard enthalpies of formation AH: of'la-c and 2-4 [kcal mol-l] [a].

~

l a - 552.38 f 0.15 14.78 f 0.19 -191.13 t 0.15 -176.35 f 0.24 l b - 708.38 f 0.13 13.81 i 0.17 -197.50 f 0.13 -183-69 i 0.21 I C - 863.08 ? 0.10 13.31 k 0.19 -205.17 f 0.10 -191.86 f 0.19 2 -1187.73 f 0.20 18.93k 0.17 -299.30 f 0.20 -280.37 k 0.26 3 -1002.62 0.33 10.59 f 0.07 -133.94 f 0.33 -123.35 & 0.34[b] 4 - 1001.08 f 0.25 9.86 0.03 [4] - 135.48 ? 0.25 - 125.62 0.26 [c]

[a] Standard deviation of the mean value from 5-8 measurements in each case. [b] Literature value [4]: - 124 86 f 2.02. [c] Literature value [4]: - 128.10 f 2.00.

For the determination of the extra stabilization or destabi- lization the method based on group increments, as developed for anomerically stabilized acetalsJZ1 was used, and not that

['I Prof. Dr. C. Ruchardt, Dr. B. Dogan, Dr. H.-D. Beckhaus Institut fur Organische Chemie und Biochemie der Universitat Albertstrasse 21, D-7800 Freiburg (FRG) Dr. S. Verevkin Kuibyshew Politechnisches Institut, Kuibyshew (UdSSR)

[**I Geminal Snbstitution Effects, Part 3. This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Indus- trie, S . V thanks Prof. Alexandr M . Roznov (Kuibyschew) for special sup- port and the DAAD (Deutscher Akademischer Austauschdienst) for an exchange grant.-Part 2: [2].

674 0 VCH Verlagsgeselisckafr mbH, 0-6940 Wetnhezm, 1990 0510-0833190j0606-0674 $03 50+.25/0 Angew Chem. Int Ed Engl 29 (1990) No. 6

of the isodesmic reactions which is otherwise frequently used. A possible influence of different alkyl branching on the central C atom can be tested, on the basis of the variously substituted malonic diesters 1 a-c.

Increments for the carboxy group, AHP(g) C02[2C], and the 0-bound carbon, AHP(g) CH;[CO,], CHi[CO,,C], as well as for the ester-bearing alkyl groups, AH,,,,, CHJCO,], CH,[CO,.C], CH[CO,,2C], C[C02,3C] could be calculated from the known AHP(g) values of monocarboxylates[61 with the help of already known increments for alkanes, AHalkylrS1 (Table 2). The increments for alkyl groups with two ester

mine the extent of geminal effects and their dependence on the structure of some other substituents.

When discussing the CH-acidity of malonic esters and other geminally substituted compounds one must not only consider the stabilization of the anion but also the destabi- lization of the ground state as contributing to the acidity.

Received: January 18. 1990 [Z 3745 IE] German version: Angew. Chem. 102 (1990) 693

CAS Registry numbers: la , 108-59-8; l b , 609-02-9; l c , 6065-54-9; 2,6279-86-3; 3. 7452-79-1; 4. 3938- 95-2.

Table 2. Increments in enthalpy of formation [kcal mol-'1 for pure alkyl groups (AH,, , , , ) and alkyl groups substituted by one (AHcs,e,), two (AH,,,,,.,). or three (AH,,,,,,,,) [a] ester groups.

AH,,,,, 151 AH,,,,, [bl AH,,,,,,, [CI AH,,,,,,., [dl

CH, [Cl- 10.05 [COJE - 10.05 - -

CH, [2C]-5.13 [C02.C] - 4.74 [2COJ - 1.57 - CH [3C]-2.16 [C02.2C] - 1.92 [2C02.C] + 1.14 [3CO,] f7.74 C [4C]-0 30 [C02,3C] + 0.40 [2C02, 2C] + 3.02 [3CO,,C] -

[a] Neighboring atoms in square brackets [b] From monocarboxylates [6] with CO,[2C] - 77 34, CH$[CO,] - 10.05 and CH:[CO,,C] - 8.80. [c] From the malonic diesters 1 a-c (Table 1) . [d] From tricarboxylates 2 (Table 1).

groups as neighbors, AHdiesler, were determined from the new thermochemical data for the malonic diesters la-c (see Table I ) , while the increments for CH with three ester groups as neighbors, AHlriesler were determined from the data for 2 (Table 2). On introducing an ester substituent instead of an alkyl group the increments hardly change; the destabiliza- tion energy AHesler-AHalLy, lies between 0.2 and 0.7 kcal mol- ' (Table 3). A second ester group, however, gives rise to

Table 3. Destabilization of geminal di- and tricarboxylates from the difference in group increments in Table 2 [kcal rnol-']

a significant destabilization: the destabilization energy AHdi,,,,,-AH,,,,, is 2.6 to 3.2 kcal mol-'. The corresponding destabilization by the third ester group (AHtTieSleT-AHdieSlei)r with a value of 6.6 kcal mol-', is substantial. The extra destabilization AAHsem = AHdiesler-2AHesle, + AH,,,,, and AAHpem,grm = AHlries,er-2AHdie,,er + AH,,,,, , i.e. the energy in excess of the additive destabilization energy is 1.9 to 2.8 kcal mol-' in the case of malonic diesters and 3.5 kcal mol-' in the case of tricarboxylates.

The classical anomeric effect is enhanced by alkyl groups on the central carbon atom.[21 The analogous dependence of the "inverse anomeric effect" on the degree of substitution is only slight in the case of the malonates.

The confirmation of the presumed inverse anomeric desta- bilization in the case of 1 and 2 indicates that the concept under discussion is a generally valid one. We shall next deter-

[l] A. J. Kirby: The Anomeric Effect and Related Stereoeleclronic Effecls at Oxygen, Springer, Berlin 1983. and references cited therein.

[2] H.-D. Beckhaus, B. Dogan, S. Verevkm, J. Hiidrich, C. Riichardt. Angrw. Chem. 102 (1990) 313; Angeu,. Chem. In l . Ed. Engl. 29 (1990) 320.

[3] a) K. Fritzsche, B. Dogan, H.-D. Beckhaus, C. Riichardt, Th'hrrmochim. Acta. in press; b) W. J. Hebre, L. Radom, P. von R. Schleyer, J. A. Pople: Ah initio molecular orbital theory, Wiley, New York 1986, p. 356; c) G. Leroy, Adv. Quantum Chem. 17 (1985) 6393; d) N. S. Zefirov, N. M. Sergeev, D 1. Makhon'kov, L. Ya. D'yacbkova, J Org. Chem. USSR (Engl. Transl.) 13 (1977) 1; e) N. D. Epiotis, New J Chem. I2 (1988) 231.

[4] a) J. B. Pedley, R. D. Naylor, S. P. Kirby: Thermochemical Data o/ Organrc. Compounds, Chapman and Hall, London 1986; b) J. D. Cox, G. Pilcher: Thermorhemistry o j Organir und Orgunome~allic Compounds, Academic Press, London 1970.

[5] P. von R. Schleyer. J. E. Williams, K. P. Blanchard, J Am. Chem. Soc. 92 (1970) 2377.

[6] The AHP(g) values of the following monocarboxylates were used in the calculation of the group increments AH,,,., (Table 2): methyl acetate, ethyl acetate, butyl acetate, ethyl propionate, methyl n-pentenoate, ethyl n-pen- tenoate, propyl n-pentenoate, ethyl a-methylbutyrate (Table 1). methyl pi- valate, ethyl pivalate (Table l), methyl hexanoate, methyl heptdnoate. methyl octanoate, methyl nonanoate, methyl decanoate ([4a] and own mea- surements).

Some Valenes of Benzannelated Five-Membered Heteroarenes - Synthesis and NMR Spectra ** By Manfred Christ!,* Stefan Krimm and Arno Krr@

Dedicated to Professor Rolf Huisgen on the occasion of his 70th birthday

The chemical shifts of the C-atoms common to both three-membered rings of endo,endo'-bridged bicyclobutanes stretch over the unusually large range of A6 x 90 (6 =

- 13.4 to 75.5).['] In the valenes of naphthalene, 1,4-disub- stituted phthalazines,""] and quinoxaline-2,3-dicarboni- trile121 recently investigated by us the corresponding &values lie between 42.4 and 48.6. We now present the first valenes of benzannelated five-membered heteroarenes and their NMR spectra.

The majority of the conventional methods for the synthe- sis of five-membered heteroarenes are unsuitable in the case of benzvalene-annelated derivatives. Thus, we were unable to dehydrogenate the benzvalene adducts of benzonitrile ox- ide and diphenyl nitrile imine.[3.4a1 We therefore carried out 1,3-dipolar cycl~additions[~] with benzvalenyl phenyl sul- fone 1.[61 This reacts with even more 1,3-dipolar compounds than does b e n ~ v a l e n e . [ ~ * ~ ~ Moreover, the phenylsulfonyl

[*I Prof. Dr. M. Christl. DipLChem. S . Krimm, Dr. A. Kraft Institut fur Organische Chemie der Universitat Am Hubland, D-8700 Wiirzburg (FRG)

the Deutsche Forschungsgemeinschaft [**I This work was supported by the Fonds der Chemischen Industrie and by

Angm (%em. In!. Ed. Engl. 29 (1990J No. 6 c> YCH Yerlagsgesrllsrhafi mbH. 0.6940 Wernheim. 1990 oS70-0H33j90]0n06-0675 $03.SO+ .25/0 675