- Email: [email protected]
Crystal structure of 1-hydroxy-1,2,3-benzotriazolium diphenyl phosphate reveals strong NHO and OHO hydrogen bonds
J o u r n a l of
MOLECULAR STRUCTURE ELSEVIER
Joumal of Molecular Structure 440 (1998) 113-119
Crystal structure of 1-hydroxy-l,2,3-benzotriazolium diphenyl phosphate reveals strong NHO and OHO hydrogen bonds 1 Frank Hoffmann, Carola Griehl* Department of Chemistry, Martin-Luther-University, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany Received 2 May 1997; revised 14 May 1997; accepted 14 May 1997
Abstract The structure of l-hydroxy-1,2,3-benzotriazolium diphenyl phosphate (HOBt/DPP) has been investigated by X-ray analysis. The compound crystallizes in the monoclinic space group P2 l/n with Z = 4 and the following lattice parameters: a = 11.711 (2), b = 12.727(2) and c = 12.794(3) ,~,/~ = 105.12(2) °, V= 1840.9(6) .~3. The structure was solved by direct methods and refined on F 2 to R values of wR2 = 0.084 and R 1 = 0.034 for 1985 observed reflections. HOBt/DPP has an ionic structure with very short OHO and NHO hydrogen bonds linking the different ions. Owing to these hydrogen bonds, infinite screw-shaped chains which are twisted parallel to the y-axis are formed. © 1998 Elsevier Science B.V. Keywords: X-ray crystallography; 1-hydroxy-1,2,3-benzotriazolium diphenyl phosphate; Hydrogen bonding
1. Introduction The most c o m m o n peptide coupling additive 1-hydroxy-benzotriazole (HOBt) [1] has routinely been used either in combination with carbodiimide derivatives or another coupling reagent. The wide application of this additive ensues from its ability to inhibit side reactions and to reduce epimerization. The best explanation which can be offered for the favourable effect of HOBt is the intermediate formation of an O-benzotriazolium (OBt) ester. Alternatively, the OBt ester is generated by phosphonium and uronium salts incorporating HOBt such as benzotriazole-l-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) * Corresponding author. Dedicated to Prof. Alfred Kolbe on the occasion of his 65th birthday.
[2] or O - ( b e n z o t r i a z o l e - l - y l ) - N , N , N ' , N ' - t e t r a m e t h y l uronium hexafluorophosphate (HBTU) [3]. Other additives, usually derivatives of hydroxylamine like N-hydroxy-succinimide or 2-hydroxy-iminocyanoacetic acid ethyl ester, are also incorporated in a coupling reagent. Recently [4] we reported analogue additive releasing reagents based on phosphates, sulfonates and onium salts. Comparing these coupling reagents with the same additive residue the diphenyl phosphates have been found to be more effective than the uronium salts and sulfonates regarding epimerization in dichloromethane and acetonitrile. A m o n g them, the benzotriazolyl diphenyl phosphate (BDPP) is very efficient. In this connection the knowledge of the structure of 1-hydroxy-l,2,3-benzotriazolium diphenyl phosphate (HOBt/DPP) containing HOBt and diphenyl phosphate (DPP) moieties like BDPP are of eminent importance to understand the coupling mechanism.
0022-2860/98/$19.00 © 1998 Elsevier Science B.V. All rights reserved PH S0022-2860(97)00230-5
114
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
This paper describes the molecular and crystal structure of HOBt/DPP.
2. Experimental 2.1. Synthesis
Diphenyl chlorophosphate, triethylamine and 1-hydroxy-l,2,3-benzotriazole hydrate were dissolved in tetrahydrofurane in an equimolar ratio. The solution was stirred at room temperature for 1 h. The solution was filtered and the solvent was removed under reduced pressure. The product was recrystallized from dichloromethane/n-pentane (nearly quantitative yield; m.p.: 88°C; calc. C 56.1, H 4.2, N 10.9%; found C 55.0 H 5.0 N 10.3%; 31p-NMR (CDCI3): 6 (ppm) - 11.53 (s); 13C-NMR (CDC13): t5 (ppm) 151.50/151.34 (C-Ar), 129.41 (CH-Ar), 135.46 (C-Ar), 128.48 (C-Ar), 127.96 (CH-Ar), 124.40 (CH-Ar), 120.23/120.14 (CH-Ar), 114.53 (CH-Ar), 112.45 (CH-Ar); IH-NMR (CDC13): 6 (ppm) 14.37 (s, 2H, OH, NH), 7.76 (t, IH, Ar-H), 7.58 (t, 1H, Ar-H), 7.46 (m, 2H, Ar-H), 7.16 (m, 8H, Ar-H), 7.02 (m, 2H, Ar-H)). 2.2. Crystal structure determination
Crystals suitable for X-ray analysis were obtained by slow evaporation of solvent from a chloroform/ n-pentane-solution. The crystals were mounted on a Stoe STADI4 four-circle diffractometer and investigated using graphite-monochromatized MoKa radiation at room temperature. Lattice parameters were derived by a least-squares treatment of the setting angles for 54 reflections in the 0 range of 7.7-13.2 °. Intensity data were measured by w/0-scanning mode. Data reduction was carried out applying Lorentz and polarization correction but neglecting absorption and extinction effects. The structure was solved by direct methods in SHELXS-86 [5]. Full-matrix leastsquares refinement on F 2 for all data was performed in SHELXL-93 [6] with anisotropic displacement parameters for the non-hydrogen atoms. The positions of the carbon-bonded hydrogen atoms were calculated geometrically and refined isotropically using the riding model. The positions of the two hydrogens participating in hydrogen bonds were located in a
difference map and refined freely with individual isotropic displacement parameters. Figures of molecular structure and packing were plotted using the program SIEMENS XP/PC [7]. Relevant crystal data and details of X-ray analysis for HOBt/DPP are summarized in Table 1, final atomic parameters are given in Table 2. Further details of the crystal structure determination are available on request from the Cambridge Crystallographic Data Centre CCDC. 2
3. Results and discussions 3.1. Molecular structure
The molecular structure and labelling scheme of HOBt/DPP is shown in Fig. 1. Parameters of the molecular geometry are summarized in Table 3 and Table 4. The structure consists of the negative diphenyl phosphate [CI2H10PO4] and the positive benzotriazolium ion [C6H6N30+]. Between both ions hydrogen bonds are formed. 3.1.1. Diphenyl phosphate anion
The stereochemistry of the phosphate group depends primarily on its charge and the ester substituents and less on the nonbonding environment and weak bonds such as hydrogen bonds. Recently, a systematic examination of geometries of the phosphate group in crystals was given and discussed in detail [8]. According to this survey, the geometric parameters found for the diphenyl phosphate group of HOBt/DPP agrees well with the reference values (within three-fold E.S.D.s, see Table 3) given in Ref. [8]. The phosphate group forms a deformed tetrahedron. As usually, the O - P - O angle is smaller and the O = P = O angle larger than 109.5 °. However the sum of the six O - P - O angles (655.3 °) differs only slightly from the sum of the angles of a regular tetrahedron (656.8°). Another cumulative measure of the phosphate geometry is that regarding the
2 12 Union Road, GB-CambridgeCB2 IEZ, Telefax: Int. + 12 23/3 36 033, E-mail: [email protected] by quoting the supplementary publication number CCDC-100413, the names of the authors, and the journal citation.
115
F. Hoffmann, C. Griehl/Journal o f Molecular Structure 440 (1998) 113-119
Table 1 Crystal data and details of X-ray structure analysis of HOBt/DPP Compound
HOBt/DPP
Empirical formula Molecular weight (g tool -I) Crystal system Space group Lattice parameters (with E.S.D.s)
C 18H16N3OsP 385.31 Monoclinic P2 iIn 11.711(2) 12.727(2) 12.794(3) 105.12(2) 1840.9(6) 4 1.390 0.184 0.53 x 0.46 x 0.42 0.71073 3, 11.3% 0/w-scan 2 -- 0 --< 22.5 21,31,31/12, 13, 13
a (~,) b (,~) c (X) /3 (°) V (~d)
Z Dcalc (g cm -]) ~t(Mo Kc0 (mm -I) Crystal size (mm) Wavelength (,~) Check reflections, intensity variation Scan method Range of measurement (°) Min. h,k,l/max, h,k,l
0.022 4968 1985 2389 252 a = 0.0399, b = 0.6272 0.001 - 0.276/0.245 0.034/0.084/1.076 0.046/0.093/1.083
R int
Measured reflections Observed reflections, 1 > 2a(/) Reflections used in refinement Refined parameters Weighting scheme: w = 1/[a2(F2o) + (a.P) 2 + b.P], P = (F2o + 2F~)/3 Max. shift/a (last least squares cycle) Min./max. heights in the final Ap map (e.m -3) R i/wR 2/S (observed data) a R =/wR 2/S (all data) a aValuesofRi,wR2andSaredefinedasR
t = ~,llFol_lFcll/~,lFol, wR2={ 3~[w(Fo-Fc) 2 2 2]/~[w(Fo) 2 2]} in , S = {~,[w(F2o-F2c)2]l(n-p)} ,/2,where
n is the number of reflections and p is the total number of parameters refined.
individual P - O bond lengths in any phosphate group [9]. A c c o r d i n g to Ref. [9] they can range b e t w e e n 1.40 and 1.69 A, but their sum is a p p r o x i m a t e l y constant with a m e a n v a l u e o f 6 . 1 8 ( 3 ) A . In H O B t / D P P the sum is 6.11 ,~. B o n d lengths and angles o f the phenyl rings correspond l i k e w i s e to standard values. T h e y are planar and inclined against each o t h e r by an angle o f 72 ° . O n e phenyl ring ( C 7 . . . C 1 2 ) and the b e n z o t r i a z o l i u m ring system are oriented nearly parallel (angle b e t w e e n least squares planes o f n o n - h y d r o g e n atoms is 4 °) with respect to each other. 3.1.2. Benzotriazolium
1-oxide (-O-+BtH). W h e r e a s the first f o r m crystallizes preferably f r o m anhydrous solvents the second t a u t o m e r does f r o m aqueous solutions. H I N I
I
OH
Oe "O.÷BtH
H-OBt
H I
cation
H O B t exists in two t a u t o m e r i c forms [10,11]: h y d r o x y - b e n z o t r i a z o l e ( H - O B t ) and b e n z o t r i a z o l e
I
OH HvOBt ÷
116
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
Table 2 Final atomic coordinatesand equivalentdisplacementparameters (,~2) of HOBt/DPP (E.S.D.s in parentheses): Ueq= 1/3 ~i ~j Uija~a]aiaj Atom
x/a
Pl Ol 02 03 04 05 N1 N2 N3 C1 C2 C3 C4 C5 C6 C7 C8 C9 C 10 C 11 C 12 C 13 C 14 CI5 C 16 C 17 C 18 Atom H(O5) H(N3)
0.1881(1) 0.1821(1) o. 1488(1) 0.3196(1) o. 1160(2) 0.0487( 1) 0.1361(2) 0.1513(2) 0.2384(2) 0.1958(2) 0.3076(2) 0.3490(3) 0.2803(3) 0.1689(4) 0.1250(2) 0.3957(2) 0.4563(2) 0.5357(3) 0.5533(3) 0.4927(3) 0.4124(3) 0.2105(2) 0.2259(2) 0.3111(3) 0.3785(3) 0.3636(2) 0.2774(2) x/a 0.085(3) 0.263(3)
v/b 0.1735(1) 0.0775(1) o. 1560(1) 0.2119(2) 0.2644(1 ) 0.2626(2) 0.2949(2) 0.3950(2) 0.3990(2) 0.0758(2) 0.0850(2) 0.0096(3) - 0.0741(3) - 0.0820(2) - 0.0069(2) 0.2352(2) 0.1578(3) 0.1838(4) 0.2856(5) 0.3637(4) 0.3380(2) 0.2326(2) 0.1245(2) 0.0921(3) 0.1628(3) 0.2677(3) 0.3023(2) y/b 0.263(3) 0.462(3)
Comparing the bond lengths and angles of both tautomers of HOBt [10] with those of the OBt core of the H2OBt ÷ cation (atoms C13...C18, N1...N3 and O5), it seems that the cation has an analogue constitution like the more polar N-oxide tautomer -O-+BtH. The double bond character of the bond N 1 - N 2 increases from H-OBt (distance: 1.319,~) and -O-+BtH (1.313 A) to HzOBt + (1.304(3) ,~) and decreases for N 2 - N 3 from H-OBt (1.321 A) to HzOBt + (1.327(3),~) and -O-+BtH (1.337 ,~). Like the HOBt-tautomers HzOBt + is planar. The angle between the least-squares planes through the non-hydrogen atoms of both sub-rings (C13...C18 and C13, C18, N1, N2, N3) is close to zero (0.6°).
z/c
Ueq
0.4805(1) 0.4168(1) 0.5883(1) 0.5301(I) 0.4264(I) 0.2309(2) 0.1891 (2) 0.1755(2) 0.1269(2) 0.6625(2) 0.7289(2) 0.8056(2) 0.8159(3) 0.7505(3) 0.6716(2) 0.4654(2) 0.4312(2) 0.3735(3) 0.3515(3) 0.3866(3) 0.4450(3) 0.1503(2) 0.1482(2) 0.1005(3) 0.0574(3) 0.0602(2) 0.1088(2) Jc 0.323(4) 0.111(2)
0.049(I) 0.064(1) 0.057(1) 0.068(1) 0.066(1) 0.070( 1) 0.055(1) 0.065(1) 0.067( 1) 0.051(1) 0.065(1) 0.083(1) 0.094(1) 0.096(2) 0.074(1) 0.054(1) 0.078(1) 0.106(2) 0.119(2) 0.120(2) 0.084( 1) 0.052(1) 0.070( 1) 0.088(1) 0.087(1 ) 0.074(1) 0.056(1) Ui~o 0.050(5) 0.035(4)
3.2. Crystal packing 3.2.1. Hydrogen bonds As can be seen in Fig. 1, the most striking features of the crystal structure of HOBt/DPP are the hydrogen bonds between 0 4 . . . 0 5 and O1...N3a (symmetry code for N3a: 0.5 - x, - 0.5 + y, 0.5 - z) and/or N 3 . . . O l a (symmetry code for Ola: 0.5 - x, 0.5 + y, 0.5 - z). They are almost linear (angles O . . . H - O : 174(4) °, O . . . H - N : 177(3) °) and very short (distances O...O: 2.418(3) ,~, N...O: 2.572(3) A). Phosphates with similar strong O . . . N hydrogen bonds were reported for pyridinium 2-hydroxyphenyl phenylphosphonate-catechol [12] (N...O: 2.600(5) A, O... H - N : 172(5) °) or 1,2,3-benzotriazolium
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
117
Table 3 Selected bond lengths and angles in HOBt/DPP (E.S.D.s in parentheses) Atoms
Distance (,~)
Atoms
HOBt/DPP
Standard b
Phosphate group P 1- O 1 P 1-04 P 1-02 P1-O3 O2-C1 O3-C7
1.460(2) 1.492(2) 1.580(2) 1.582(2) 1.405(3) 1.398(3)
1.494(10) 1.494(10) 1.607(14) 1.607(14) 1.394(9) 1.394(9)
Benzotriazolium ion O5-N1 N l-N2 N2-N3 N 1-C 13 N3-C 18 C13-C18
1.338(2) 1.304(3) 1.327(3) 1.364(3) 1.353(3) 1.378(3)
Hydrogen bonds O5-H(O5) 05...04 H(O5)...04 N3-H(N3) N3...OlaC/N3a d...O1 H(N3)...O 1aC/H(N3a)...O 1
1.15(4) 2.418(3) 1.27(4) 0.89(3) 2.572(3) 1.68(3)
Angle (o) HOBt/DPP
Standard b
116.8(1) 112.8(1)
116.9(1.4) 110.8(1.2)
O 1- P 1 - 0 4 O 1- P 1-02 O 1- P 1-03 04-PI-O2 O4-P1-O3 O2-P1-O3 CI -O2-P1 C7-O3-P1
112.5(1)
110.8(1.2)
104.8(9) 108.7(1) 99.7(1) 122.7(1) 122.2(1)
105.8(2.1 ) 105.8(2.1) 102.6(2.3) 124.0(2.1) 124.0(2.1)
O5-N l - N 2 O5-N 1-C 13 N 2 - N 1 - C 13 N I-N2-N3 N 2 - N 3 - C 18 N1-C13-C18 N3-C18-C13
119.9(2) 126.5(2) 113.4(2) 104.3(2) 112.4(2) 104.3(2) 105.5(2)
O5-H(O5)...04
174(4)
N3-H(N3)...Ola c and N3aO-H(N3a)... O 1
177(3)
b According to values given for phosphates with charge - 1 in Ref. [14]. c Symmetry code relating Ola to O1:0.5 - x, 0.5 + y, 0.5 - za Symmetry code relating N3a to N3:0.5 - x, - 0.5 + y, 0.5 - z. d i h y d r o g e n p h o s p h a t e [131 ( N . . . O : 2.611 ,~, n o a n g l e given). A review with comments of hydrogen bonded p h o s p h a t e esters is g i v e n in Ref. [14]. In H O B t / D P P , e a c h p h o s p h a t e i o n is c o n n e c t e d b y hydrogen bonds with two neighbouring benzotriazolium
ions a n d vice versa. In this m a n n e r , h y d r o g e n - b o n d e d infinite s c r e w - s h a p e d c h a i n s are f o r m e d . A u s e f u l tool to d i a g n o s e h y d r o g e n - b o n d p a t t e r n s is a n a n a l y s i s b a s e d o n g r a p h t h e o r y [15]. A c c o r d i n g to this t h e o r y t h e u n i t a r y set o f g r a p h s f o r t h e h y d r o g e n
Table 4 Selected torsion angles in HOBt/DPP (E.S.D.s in parentheses) Atoms Phosphate group O1-PI-O2-C1 O4-P1-O2-C1 P1-O2-CI-C2 PI-O3-C7-C8 Benzotriazolium ion O5-N1-N2-N3 O5-N 1- C 13-C 14 CI3-NI-N2-N3 N1-C13-C18-C17 NI-C13-C14-C15
Angle (o)
Atoms
52.2(2) 179.2(2) 74.9(3) - 83.3(3)
OI-P1 - O 3 - C 7 O4-P1-O3-C7 P 1 - O 2 - C 1-C6 P1-O3-C7-C12
58.3(2 - 72.6(2 - 109.5(2 101.3(3
O5-N1-C13-C18 N 1- N 2 - N 3 - C 18 N1-C13-C18-N3 N3-C18-C13-C14 N3-C18-C17-C16
175.3(2 0.6(3 0.4(2 - 179.1(2 179.6(3
- 176.0(2) - 5.3(4) - 0.3(3) - 179.2(2) 179.6(2)
Angle (~)
118
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119 QC3
".
CS
O
J
N2
NI
Fig. 1. Molecularstructure, labellingschemeand sectionof a screwshaped hydrogen-bonded molecular chain of HOBt/DPP. The dotted lines represent directionsof hydrogen-bondinteraction.
bond O 5 - H ( O 5 ) . . . O 4 (a) has to be designated as N~ = D owing to the lack of any symmetry relation between both molecules. The same result is found for N 3 - H ( N 3 ) . . . O l a . However, more information can be received from the binary set of graphs N2(ab) with the designation C~(9) implying hydrogen bonded chains with two different donors and acceptors, respectively, and nine atoms in the repetitive unit (see Fig. 1; N 3 a - H - O I - P 1 - O 4 - H - O 5 - N 1 N 2 ( - N 3 ) or O l a - H - N 3 - N 2 - N 1 - O 5 - H - O 4 - P 1 (O1) etc.). These chains are screw-shaped and the set of graphs C2(9) leads here to a half screw period. Consequently, the designation N2(ab) = C~(9) reveals the characteristics of the screw-shaped chains of HOBt/DPP in terms of graph theory. Discussing these results in terms of space group symmetry the twofold screw axis creates this arrangement. It should be mentioned here that all molecules related by a
Fig. 2. Crystal packingof HOBt/DPPin a projectionalongthe crystallographicy-axis.Hydrogenatoms have been omittedfor clarity. Hydrogen bonds are depicted by dotted lines. Hydrogen-bondedchains pass perpendicularto the drawingplane.
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
mirror plane or an inversion centre belong to neighboured chains (not depicted in Fig. 1) and hence no R-motif (hydrogen bonded rings) can be found in this structure.
3.2.2. Packing Crystal packing is illustrated in Fig. 2. The hydrogen-bonded chains are twisted parallel to the crystallographic y-axis. Abstracting from the molecular structure and considering the chains as infinite rods or trunks we observe sheets of parallel arranged rods in the bc-plane. Stacking up those sheets in a-direction the sheets are shifted in such a way that the rods of one sheet fit into the hollows between the rods of the neighbour sheet. In this manner the condition of a high economy of space [16] is fulfilled.
References [1] W. Krnig, R. Geiger, Chemische Berichte 103 (1970) 788. [2] B. Castro, J.R. Domroy, G. Evin, C. Selve, Tetrahedron Letters 31 (1972) 1219. [3] V. Dourtoglou, B. Gross, V. Lambropoulou, C. Zioudrou, Synthesis (1984) 572.
119
[4] C. Griehl, L. Jfiger, M. Plass, A. Kolbe, Peptides 1996, 24th EPS, Edinburgh, in press. [5] G.M. Sheldrick, SHELXS-86, Program for the Solution of Crystal Structures, University of Grttingen, Germany, 1986. [6] G.M. Sheldrick, SHELXL-93, Program for the Refinement of Crystal Structures, University of Grttingen, Germany, 1993. [7] SIEMENS XP/PC, Molecular Graphics Program Package for Display and Analysis of Stereochemical Data. V. 4.2. for MS-DOS, Siemens Analytical X-ray Instruments (1990). [8] B. Schneider, M. Kabel~c, P. Hobza, Journal of the American Chemical Society 118 (1996) 12207. [9] D.W.J. Cruickshank, Journal of the Chemical Society (1961) 5486. [10] R. Bosch, G. Jung, W. Winter, Acta Crystallographica Section C 39 (1983) 1089. [11] W. Schilf, L. Stefaniak, M. Witanowski, G.A. Webb, Magnetic Resonance in Chemistry 23 (1985) 181. [12] C.A. Poutasse, R.O. Day, R.R. Holmes, Journal of the American Chemical Society 106 (1984) 3814. [13] J. Emsley, N.M. Reza, H.M. Dawes, M.B. Hursthouse, Journal of the Chemical Society Section D: Chemical Communications (1985) 1458. [14] R.R. Holmes, R.O. Day, Y. Yoshida, J.M. Holmes, Journal of the American Chemical Society 114 (1992) 1771. [15] J. Berustein, R.E. Davis, L. Shimoni, N.-L. Chang, Angewandfe Chemie 107 (1995) 1689. [16] A.I. Kitaigorodski. Molekiilkristalle, Akademie Verlag, Berlin, 1979.
MOLECULAR STRUCTURE ELSEVIER
Joumal of Molecular Structure 440 (1998) 113-119
Crystal structure of 1-hydroxy-l,2,3-benzotriazolium diphenyl phosphate reveals strong NHO and OHO hydrogen bonds 1 Frank Hoffmann, Carola Griehl* Department of Chemistry, Martin-Luther-University, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany Received 2 May 1997; revised 14 May 1997; accepted 14 May 1997
Abstract The structure of l-hydroxy-1,2,3-benzotriazolium diphenyl phosphate (HOBt/DPP) has been investigated by X-ray analysis. The compound crystallizes in the monoclinic space group P2 l/n with Z = 4 and the following lattice parameters: a = 11.711 (2), b = 12.727(2) and c = 12.794(3) ,~,/~ = 105.12(2) °, V= 1840.9(6) .~3. The structure was solved by direct methods and refined on F 2 to R values of wR2 = 0.084 and R 1 = 0.034 for 1985 observed reflections. HOBt/DPP has an ionic structure with very short OHO and NHO hydrogen bonds linking the different ions. Owing to these hydrogen bonds, infinite screw-shaped chains which are twisted parallel to the y-axis are formed. © 1998 Elsevier Science B.V. Keywords: X-ray crystallography; 1-hydroxy-1,2,3-benzotriazolium diphenyl phosphate; Hydrogen bonding
1. Introduction The most c o m m o n peptide coupling additive 1-hydroxy-benzotriazole (HOBt) [1] has routinely been used either in combination with carbodiimide derivatives or another coupling reagent. The wide application of this additive ensues from its ability to inhibit side reactions and to reduce epimerization. The best explanation which can be offered for the favourable effect of HOBt is the intermediate formation of an O-benzotriazolium (OBt) ester. Alternatively, the OBt ester is generated by phosphonium and uronium salts incorporating HOBt such as benzotriazole-l-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) * Corresponding author. Dedicated to Prof. Alfred Kolbe on the occasion of his 65th birthday.
[2] or O - ( b e n z o t r i a z o l e - l - y l ) - N , N , N ' , N ' - t e t r a m e t h y l uronium hexafluorophosphate (HBTU) [3]. Other additives, usually derivatives of hydroxylamine like N-hydroxy-succinimide or 2-hydroxy-iminocyanoacetic acid ethyl ester, are also incorporated in a coupling reagent. Recently [4] we reported analogue additive releasing reagents based on phosphates, sulfonates and onium salts. Comparing these coupling reagents with the same additive residue the diphenyl phosphates have been found to be more effective than the uronium salts and sulfonates regarding epimerization in dichloromethane and acetonitrile. A m o n g them, the benzotriazolyl diphenyl phosphate (BDPP) is very efficient. In this connection the knowledge of the structure of 1-hydroxy-l,2,3-benzotriazolium diphenyl phosphate (HOBt/DPP) containing HOBt and diphenyl phosphate (DPP) moieties like BDPP are of eminent importance to understand the coupling mechanism.
0022-2860/98/$19.00 © 1998 Elsevier Science B.V. All rights reserved PH S0022-2860(97)00230-5
114
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
This paper describes the molecular and crystal structure of HOBt/DPP.
2. Experimental 2.1. Synthesis
Diphenyl chlorophosphate, triethylamine and 1-hydroxy-l,2,3-benzotriazole hydrate were dissolved in tetrahydrofurane in an equimolar ratio. The solution was stirred at room temperature for 1 h. The solution was filtered and the solvent was removed under reduced pressure. The product was recrystallized from dichloromethane/n-pentane (nearly quantitative yield; m.p.: 88°C; calc. C 56.1, H 4.2, N 10.9%; found C 55.0 H 5.0 N 10.3%; 31p-NMR (CDCI3): 6 (ppm) - 11.53 (s); 13C-NMR (CDC13): t5 (ppm) 151.50/151.34 (C-Ar), 129.41 (CH-Ar), 135.46 (C-Ar), 128.48 (C-Ar), 127.96 (CH-Ar), 124.40 (CH-Ar), 120.23/120.14 (CH-Ar), 114.53 (CH-Ar), 112.45 (CH-Ar); IH-NMR (CDC13): 6 (ppm) 14.37 (s, 2H, OH, NH), 7.76 (t, IH, Ar-H), 7.58 (t, 1H, Ar-H), 7.46 (m, 2H, Ar-H), 7.16 (m, 8H, Ar-H), 7.02 (m, 2H, Ar-H)). 2.2. Crystal structure determination
Crystals suitable for X-ray analysis were obtained by slow evaporation of solvent from a chloroform/ n-pentane-solution. The crystals were mounted on a Stoe STADI4 four-circle diffractometer and investigated using graphite-monochromatized MoKa radiation at room temperature. Lattice parameters were derived by a least-squares treatment of the setting angles for 54 reflections in the 0 range of 7.7-13.2 °. Intensity data were measured by w/0-scanning mode. Data reduction was carried out applying Lorentz and polarization correction but neglecting absorption and extinction effects. The structure was solved by direct methods in SHELXS-86 [5]. Full-matrix leastsquares refinement on F 2 for all data was performed in SHELXL-93 [6] with anisotropic displacement parameters for the non-hydrogen atoms. The positions of the carbon-bonded hydrogen atoms were calculated geometrically and refined isotropically using the riding model. The positions of the two hydrogens participating in hydrogen bonds were located in a
difference map and refined freely with individual isotropic displacement parameters. Figures of molecular structure and packing were plotted using the program SIEMENS XP/PC [7]. Relevant crystal data and details of X-ray analysis for HOBt/DPP are summarized in Table 1, final atomic parameters are given in Table 2. Further details of the crystal structure determination are available on request from the Cambridge Crystallographic Data Centre CCDC. 2
3. Results and discussions 3.1. Molecular structure
The molecular structure and labelling scheme of HOBt/DPP is shown in Fig. 1. Parameters of the molecular geometry are summarized in Table 3 and Table 4. The structure consists of the negative diphenyl phosphate [CI2H10PO4] and the positive benzotriazolium ion [C6H6N30+]. Between both ions hydrogen bonds are formed. 3.1.1. Diphenyl phosphate anion
The stereochemistry of the phosphate group depends primarily on its charge and the ester substituents and less on the nonbonding environment and weak bonds such as hydrogen bonds. Recently, a systematic examination of geometries of the phosphate group in crystals was given and discussed in detail [8]. According to this survey, the geometric parameters found for the diphenyl phosphate group of HOBt/DPP agrees well with the reference values (within three-fold E.S.D.s, see Table 3) given in Ref. [8]. The phosphate group forms a deformed tetrahedron. As usually, the O - P - O angle is smaller and the O = P = O angle larger than 109.5 °. However the sum of the six O - P - O angles (655.3 °) differs only slightly from the sum of the angles of a regular tetrahedron (656.8°). Another cumulative measure of the phosphate geometry is that regarding the
2 12 Union Road, GB-CambridgeCB2 IEZ, Telefax: Int. + 12 23/3 36 033, E-mail: [email protected] by quoting the supplementary publication number CCDC-100413, the names of the authors, and the journal citation.
115
F. Hoffmann, C. Griehl/Journal o f Molecular Structure 440 (1998) 113-119
Table 1 Crystal data and details of X-ray structure analysis of HOBt/DPP Compound
HOBt/DPP
Empirical formula Molecular weight (g tool -I) Crystal system Space group Lattice parameters (with E.S.D.s)
C 18H16N3OsP 385.31 Monoclinic P2 iIn 11.711(2) 12.727(2) 12.794(3) 105.12(2) 1840.9(6) 4 1.390 0.184 0.53 x 0.46 x 0.42 0.71073 3, 11.3% 0/w-scan 2 -- 0 --< 22.5 21,31,31/12, 13, 13
a (~,) b (,~) c (X) /3 (°) V (~d)
Z Dcalc (g cm -]) ~t(Mo Kc0 (mm -I) Crystal size (mm) Wavelength (,~) Check reflections, intensity variation Scan method Range of measurement (°) Min. h,k,l/max, h,k,l
0.022 4968 1985 2389 252 a = 0.0399, b = 0.6272 0.001 - 0.276/0.245 0.034/0.084/1.076 0.046/0.093/1.083
R int
Measured reflections Observed reflections, 1 > 2a(/) Reflections used in refinement Refined parameters Weighting scheme: w = 1/[a2(F2o) + (a.P) 2 + b.P], P = (F2o + 2F~)/3 Max. shift/a (last least squares cycle) Min./max. heights in the final Ap map (e.m -3) R i/wR 2/S (observed data) a R =/wR 2/S (all data) a aValuesofRi,wR2andSaredefinedasR
t = ~,llFol_lFcll/~,lFol, wR2={ 3~[w(Fo-Fc) 2 2 2]/~[w(Fo) 2 2]} in , S = {~,[w(F2o-F2c)2]l(n-p)} ,/2,where
n is the number of reflections and p is the total number of parameters refined.
individual P - O bond lengths in any phosphate group [9]. A c c o r d i n g to Ref. [9] they can range b e t w e e n 1.40 and 1.69 A, but their sum is a p p r o x i m a t e l y constant with a m e a n v a l u e o f 6 . 1 8 ( 3 ) A . In H O B t / D P P the sum is 6.11 ,~. B o n d lengths and angles o f the phenyl rings correspond l i k e w i s e to standard values. T h e y are planar and inclined against each o t h e r by an angle o f 72 ° . O n e phenyl ring ( C 7 . . . C 1 2 ) and the b e n z o t r i a z o l i u m ring system are oriented nearly parallel (angle b e t w e e n least squares planes o f n o n - h y d r o g e n atoms is 4 °) with respect to each other. 3.1.2. Benzotriazolium
1-oxide (-O-+BtH). W h e r e a s the first f o r m crystallizes preferably f r o m anhydrous solvents the second t a u t o m e r does f r o m aqueous solutions. H I N I
I
OH
Oe "O.÷BtH
H-OBt
H I
cation
H O B t exists in two t a u t o m e r i c forms [10,11]: h y d r o x y - b e n z o t r i a z o l e ( H - O B t ) and b e n z o t r i a z o l e
I
OH HvOBt ÷
116
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
Table 2 Final atomic coordinatesand equivalentdisplacementparameters (,~2) of HOBt/DPP (E.S.D.s in parentheses): Ueq= 1/3 ~i ~j Uija~a]aiaj Atom
x/a
Pl Ol 02 03 04 05 N1 N2 N3 C1 C2 C3 C4 C5 C6 C7 C8 C9 C 10 C 11 C 12 C 13 C 14 CI5 C 16 C 17 C 18 Atom H(O5) H(N3)
0.1881(1) 0.1821(1) o. 1488(1) 0.3196(1) o. 1160(2) 0.0487( 1) 0.1361(2) 0.1513(2) 0.2384(2) 0.1958(2) 0.3076(2) 0.3490(3) 0.2803(3) 0.1689(4) 0.1250(2) 0.3957(2) 0.4563(2) 0.5357(3) 0.5533(3) 0.4927(3) 0.4124(3) 0.2105(2) 0.2259(2) 0.3111(3) 0.3785(3) 0.3636(2) 0.2774(2) x/a 0.085(3) 0.263(3)
v/b 0.1735(1) 0.0775(1) o. 1560(1) 0.2119(2) 0.2644(1 ) 0.2626(2) 0.2949(2) 0.3950(2) 0.3990(2) 0.0758(2) 0.0850(2) 0.0096(3) - 0.0741(3) - 0.0820(2) - 0.0069(2) 0.2352(2) 0.1578(3) 0.1838(4) 0.2856(5) 0.3637(4) 0.3380(2) 0.2326(2) 0.1245(2) 0.0921(3) 0.1628(3) 0.2677(3) 0.3023(2) y/b 0.263(3) 0.462(3)
Comparing the bond lengths and angles of both tautomers of HOBt [10] with those of the OBt core of the H2OBt ÷ cation (atoms C13...C18, N1...N3 and O5), it seems that the cation has an analogue constitution like the more polar N-oxide tautomer -O-+BtH. The double bond character of the bond N 1 - N 2 increases from H-OBt (distance: 1.319,~) and -O-+BtH (1.313 A) to HzOBt + (1.304(3) ,~) and decreases for N 2 - N 3 from H-OBt (1.321 A) to HzOBt + (1.327(3),~) and -O-+BtH (1.337 ,~). Like the HOBt-tautomers HzOBt + is planar. The angle between the least-squares planes through the non-hydrogen atoms of both sub-rings (C13...C18 and C13, C18, N1, N2, N3) is close to zero (0.6°).
z/c
Ueq
0.4805(1) 0.4168(1) 0.5883(1) 0.5301(I) 0.4264(I) 0.2309(2) 0.1891 (2) 0.1755(2) 0.1269(2) 0.6625(2) 0.7289(2) 0.8056(2) 0.8159(3) 0.7505(3) 0.6716(2) 0.4654(2) 0.4312(2) 0.3735(3) 0.3515(3) 0.3866(3) 0.4450(3) 0.1503(2) 0.1482(2) 0.1005(3) 0.0574(3) 0.0602(2) 0.1088(2) Jc 0.323(4) 0.111(2)
0.049(I) 0.064(1) 0.057(1) 0.068(1) 0.066(1) 0.070( 1) 0.055(1) 0.065(1) 0.067( 1) 0.051(1) 0.065(1) 0.083(1) 0.094(1) 0.096(2) 0.074(1) 0.054(1) 0.078(1) 0.106(2) 0.119(2) 0.120(2) 0.084( 1) 0.052(1) 0.070( 1) 0.088(1) 0.087(1 ) 0.074(1) 0.056(1) Ui~o 0.050(5) 0.035(4)
3.2. Crystal packing 3.2.1. Hydrogen bonds As can be seen in Fig. 1, the most striking features of the crystal structure of HOBt/DPP are the hydrogen bonds between 0 4 . . . 0 5 and O1...N3a (symmetry code for N3a: 0.5 - x, - 0.5 + y, 0.5 - z) and/or N 3 . . . O l a (symmetry code for Ola: 0.5 - x, 0.5 + y, 0.5 - z). They are almost linear (angles O . . . H - O : 174(4) °, O . . . H - N : 177(3) °) and very short (distances O...O: 2.418(3) ,~, N...O: 2.572(3) A). Phosphates with similar strong O . . . N hydrogen bonds were reported for pyridinium 2-hydroxyphenyl phenylphosphonate-catechol [12] (N...O: 2.600(5) A, O... H - N : 172(5) °) or 1,2,3-benzotriazolium
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
117
Table 3 Selected bond lengths and angles in HOBt/DPP (E.S.D.s in parentheses) Atoms
Distance (,~)
Atoms
HOBt/DPP
Standard b
Phosphate group P 1- O 1 P 1-04 P 1-02 P1-O3 O2-C1 O3-C7
1.460(2) 1.492(2) 1.580(2) 1.582(2) 1.405(3) 1.398(3)
1.494(10) 1.494(10) 1.607(14) 1.607(14) 1.394(9) 1.394(9)
Benzotriazolium ion O5-N1 N l-N2 N2-N3 N 1-C 13 N3-C 18 C13-C18
1.338(2) 1.304(3) 1.327(3) 1.364(3) 1.353(3) 1.378(3)
Hydrogen bonds O5-H(O5) 05...04 H(O5)...04 N3-H(N3) N3...OlaC/N3a d...O1 H(N3)...O 1aC/H(N3a)...O 1
1.15(4) 2.418(3) 1.27(4) 0.89(3) 2.572(3) 1.68(3)
Angle (o) HOBt/DPP
Standard b
116.8(1) 112.8(1)
116.9(1.4) 110.8(1.2)
O 1- P 1 - 0 4 O 1- P 1-02 O 1- P 1-03 04-PI-O2 O4-P1-O3 O2-P1-O3 CI -O2-P1 C7-O3-P1
112.5(1)
110.8(1.2)
104.8(9) 108.7(1) 99.7(1) 122.7(1) 122.2(1)
105.8(2.1 ) 105.8(2.1) 102.6(2.3) 124.0(2.1) 124.0(2.1)
O5-N l - N 2 O5-N 1-C 13 N 2 - N 1 - C 13 N I-N2-N3 N 2 - N 3 - C 18 N1-C13-C18 N3-C18-C13
119.9(2) 126.5(2) 113.4(2) 104.3(2) 112.4(2) 104.3(2) 105.5(2)
O5-H(O5)...04
174(4)
N3-H(N3)...Ola c and N3aO-H(N3a)... O 1
177(3)
b According to values given for phosphates with charge - 1 in Ref. [14]. c Symmetry code relating Ola to O1:0.5 - x, 0.5 + y, 0.5 - za Symmetry code relating N3a to N3:0.5 - x, - 0.5 + y, 0.5 - z. d i h y d r o g e n p h o s p h a t e [131 ( N . . . O : 2.611 ,~, n o a n g l e given). A review with comments of hydrogen bonded p h o s p h a t e esters is g i v e n in Ref. [14]. In H O B t / D P P , e a c h p h o s p h a t e i o n is c o n n e c t e d b y hydrogen bonds with two neighbouring benzotriazolium
ions a n d vice versa. In this m a n n e r , h y d r o g e n - b o n d e d infinite s c r e w - s h a p e d c h a i n s are f o r m e d . A u s e f u l tool to d i a g n o s e h y d r o g e n - b o n d p a t t e r n s is a n a n a l y s i s b a s e d o n g r a p h t h e o r y [15]. A c c o r d i n g to this t h e o r y t h e u n i t a r y set o f g r a p h s f o r t h e h y d r o g e n
Table 4 Selected torsion angles in HOBt/DPP (E.S.D.s in parentheses) Atoms Phosphate group O1-PI-O2-C1 O4-P1-O2-C1 P1-O2-CI-C2 PI-O3-C7-C8 Benzotriazolium ion O5-N1-N2-N3 O5-N 1- C 13-C 14 CI3-NI-N2-N3 N1-C13-C18-C17 NI-C13-C14-C15
Angle (o)
Atoms
52.2(2) 179.2(2) 74.9(3) - 83.3(3)
OI-P1 - O 3 - C 7 O4-P1-O3-C7 P 1 - O 2 - C 1-C6 P1-O3-C7-C12
58.3(2 - 72.6(2 - 109.5(2 101.3(3
O5-N1-C13-C18 N 1- N 2 - N 3 - C 18 N1-C13-C18-N3 N3-C18-C13-C14 N3-C18-C17-C16
175.3(2 0.6(3 0.4(2 - 179.1(2 179.6(3
- 176.0(2) - 5.3(4) - 0.3(3) - 179.2(2) 179.6(2)
Angle (~)
118
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119 QC3
".
CS
O
J
N2
NI
Fig. 1. Molecularstructure, labellingschemeand sectionof a screwshaped hydrogen-bonded molecular chain of HOBt/DPP. The dotted lines represent directionsof hydrogen-bondinteraction.
bond O 5 - H ( O 5 ) . . . O 4 (a) has to be designated as N~ = D owing to the lack of any symmetry relation between both molecules. The same result is found for N 3 - H ( N 3 ) . . . O l a . However, more information can be received from the binary set of graphs N2(ab) with the designation C~(9) implying hydrogen bonded chains with two different donors and acceptors, respectively, and nine atoms in the repetitive unit (see Fig. 1; N 3 a - H - O I - P 1 - O 4 - H - O 5 - N 1 N 2 ( - N 3 ) or O l a - H - N 3 - N 2 - N 1 - O 5 - H - O 4 - P 1 (O1) etc.). These chains are screw-shaped and the set of graphs C2(9) leads here to a half screw period. Consequently, the designation N2(ab) = C~(9) reveals the characteristics of the screw-shaped chains of HOBt/DPP in terms of graph theory. Discussing these results in terms of space group symmetry the twofold screw axis creates this arrangement. It should be mentioned here that all molecules related by a
Fig. 2. Crystal packingof HOBt/DPPin a projectionalongthe crystallographicy-axis.Hydrogenatoms have been omittedfor clarity. Hydrogen bonds are depicted by dotted lines. Hydrogen-bondedchains pass perpendicularto the drawingplane.
F. Hoffmann, C. Griehl/Journal of Molecular Structure 440 (1998) 113-119
mirror plane or an inversion centre belong to neighboured chains (not depicted in Fig. 1) and hence no R-motif (hydrogen bonded rings) can be found in this structure.
3.2.2. Packing Crystal packing is illustrated in Fig. 2. The hydrogen-bonded chains are twisted parallel to the crystallographic y-axis. Abstracting from the molecular structure and considering the chains as infinite rods or trunks we observe sheets of parallel arranged rods in the bc-plane. Stacking up those sheets in a-direction the sheets are shifted in such a way that the rods of one sheet fit into the hollows between the rods of the neighbour sheet. In this manner the condition of a high economy of space [16] is fulfilled.
References [1] W. Krnig, R. Geiger, Chemische Berichte 103 (1970) 788. [2] B. Castro, J.R. Domroy, G. Evin, C. Selve, Tetrahedron Letters 31 (1972) 1219. [3] V. Dourtoglou, B. Gross, V. Lambropoulou, C. Zioudrou, Synthesis (1984) 572.
119
[4] C. Griehl, L. Jfiger, M. Plass, A. Kolbe, Peptides 1996, 24th EPS, Edinburgh, in press. [5] G.M. Sheldrick, SHELXS-86, Program for the Solution of Crystal Structures, University of Grttingen, Germany, 1986. [6] G.M. Sheldrick, SHELXL-93, Program for the Refinement of Crystal Structures, University of Grttingen, Germany, 1993. [7] SIEMENS XP/PC, Molecular Graphics Program Package for Display and Analysis of Stereochemical Data. V. 4.2. for MS-DOS, Siemens Analytical X-ray Instruments (1990). [8] B. Schneider, M. Kabel~c, P. Hobza, Journal of the American Chemical Society 118 (1996) 12207. [9] D.W.J. Cruickshank, Journal of the Chemical Society (1961) 5486. [10] R. Bosch, G. Jung, W. Winter, Acta Crystallographica Section C 39 (1983) 1089. [11] W. Schilf, L. Stefaniak, M. Witanowski, G.A. Webb, Magnetic Resonance in Chemistry 23 (1985) 181. [12] C.A. Poutasse, R.O. Day, R.R. Holmes, Journal of the American Chemical Society 106 (1984) 3814. [13] J. Emsley, N.M. Reza, H.M. Dawes, M.B. Hursthouse, Journal of the Chemical Society Section D: Chemical Communications (1985) 1458. [14] R.R. Holmes, R.O. Day, Y. Yoshida, J.M. Holmes, Journal of the American Chemical Society 114 (1992) 1771. [15] J. Berustein, R.E. Davis, L. Shimoni, N.-L. Chang, Angewandfe Chemie 107 (1995) 1689. [16] A.I. Kitaigorodski. Molekiilkristalle, Akademie Verlag, Berlin, 1979.