Structural studies of organoboron compounds. XLV.' 5,s-Difluoro-2,2-pentamethylene- 7,7-diphenyl-l,4,6-trioxa-3a-azonia-5-borata-2,3,4,5,6,7-hexahydroindene

WOLFGANG KLIEGEL AND UTE SCHUMACHER Institut fur Pharmazeutische Chemie der Technischen Universitat Braunschweig, Beethovenstrasse 55, 3300 Braunschweig,

Bundesrepublik Deutschland

AND

STEVEN J. RETTIG AND JAMES TROTTER Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B .C . , Canada V6T 1Z1

Received August 10, 1990

WOLFGANG KLIEGEL, UTE SCHUMACHER, STEVEN J. RETTIG, and JAMES TROTTER. Can. J. Chem. 69, 681 (1991).

The reaction of N,2-dihydroxy-N-(1 -hydroxycyclohexyl)methyl-2,2-diphenylacetamide with dimethyl ether-boron trifluoride gives 5,5-difluoro-2,2-pentamethylene-7,7-diphenyl-,4,6-trioxa-3a-azonia-5-borata-2,3,4,5,6,7-hexahydroindene in nearly quantitative yield. Crystals of the product are triclinic, a = 9.4555(5), b = 9.9813(6), c = 10.5139(9) A, a = 72.654(7), P = 77.140(5), y = 88.542(6)", Z = 2, space group p i . The structure was solved by direct methods and was refined by full-matrix least-squares procedures to R = 0.044 and R,,. = 0.060 for 2971 reflections with I 2 3u(I). The molecule has a six-membered difluoroboron chelate structure, confirming that the regioselective alkylation of N-substituted hydroxamic acids under non-basic conditions leads to imidate N-oxides in cases where intramolecular alkylation occurs. Bond lengths (corrected for libration): (N)O--B = 1.530(3), (C)O--B = 1.45 1(2), F-B = 1.389(3) and 1.379(3) A indicate relatively strong binding of the BF2 +

moiety by the 0,O-chelating ligand. Key words: organoboron compound, crystal structure, boron compound.

WOLFGANG KLIEGEL, UTE SCHUMACHER, STEVEN J. RETTIG et JAMES TROTTER. Can. J . Chem. 69, 681 (1991). La reaction du N,2-dihydroxy-N-(l-hydroxycyclohexyl)m~thyl-2,2-diphCnylac~tamide avec le complexe (CH3)20/BF3 four-

nit le 5,5-difluoro-2,2-pentamCthyl~ne-7,7-diphnyl-l,4,6-trioxa-3a-azonia-5-borata-2,3,4,5,6,7-hexahydroindne avec un rendement pratiquement quantitatif. Les cristaux de ce produit sont tricliniques, groupe d'espace P i , avec a = 9,4555(5), b = 9,9813(6) et c = 10,5139(9) A, a = 72,654(7), P = 77,140(5) et y = 88,542(5)" et Z = 2. On a rCsolu la structure par des mkthodes directes et on l'affinee par la methode des moindres canes jusqu'a des valeurs respectives deR = 0,044 et R, = 0,060 pour 2971 reflexions avec I 2 3 4 0 . La molCcule comporte une structure a six chainons impliquant une coordination du difluorure de bore; ces donnkes confirment que, dans les cas oh une alkylation intramolCculaire se produit, l'alkylation r6giostlective des acides hydroxamiques N-substitues, dans des conditions qui ne sont pas basiques, conduit a des N-oxydes d'imidate. Les longueurs des liaisons (corrigkes pour la libration): (N)O-B = 1,530(3), (C)O--B = 1,451(2), F-B = 1,389(3) et 1,379(3) A indiquent la presence d'une liaisonrelativement forte de la portion B F ~ + avec le coordinat 0,O-chelatant. Mots cl is : compos&s organoborks, structure cristalline, compost bore.

[Traduit par la redaction]

Introduction The reaction of the bis(hydroxyalky1) substituted hydroxamic

acid 1 with boron trifluoride did not lead to the difluoroboron chelate 2 having the "normal" BF2 hydroxamate structure that usually results from reactions of N-alkylhydroxamic acids with boron trifluoride (I), and which has been established by an X-ray crystallographic study of the simple prototype 3 (2). The crystalline compound obtained from the reaction of 1 with BF3-0Me2 produced spectra and elemental analyses showing not only HF elimination but also loss of H20. Neither infrared bands for 0-H stretching vibrations nor OH-proton signals in the 'H nmr spectra, both of which would arise from the hydroxyl groups of 2, were observed. These data suggest an intra- or intermolecular condensation of 1 and difluoroboron chelate formation leading to structures such as 4-7.

A possible intermediate 2 could form the cyclic ether 4 by intramolecular condensation and still feature the five-membered BF2 hydroxamate chelate, similar to the cyclic ether compound 8 with an identical difluoroboron chelate ring portion within the molecule (3). Another intramolecular condensation reaction of 1 in the presence of BF3 could give rise to the difluoroboron chelate 5 with the newly formed 2-oxazoline N-oxide moiety as one of the chelating ligands. A similar intramolecular cycliza-

'~revious paper in this series: ref. 3. Pnnled In Canada 1 Irnpr~rne au Canada

tion of an N-(2-hydroxyalkyl) hydroxamic acid in the presence of BF3, including the formation of a BF2 chelate, has already been documented by the synthesis and structure analysis of the salicylohydroxamic acid derivative 9 (4). Less likely under the applied conditions of BF3 catalysis is an intramolecular alkyla- tion of the N-hydroxy group of 1 by the N-(2-hydroxyalkyl) residue giving the four-membered oxazetidine ring with subse- quent (or concerted) formation of a BF2+ chelate (compound 6). Also unlikely is the intermolecular condensation product 7 con- taining eight-membered boron chelate rings, although eight- membered boron chelate rings are known and have been struc- turally characterized (5) and the 1,4,2,5-dioxadiazine ring sys- tem is thought to exist in certain dimers of nitrile oxides (6). However, an EI mass spectrum of the isolated crystals displays a molecular ion peak consistent only with a monomer like 4,5, or 6. The fragmentation pattern does not allow for a definite assign- ment of one of these isomeric structures, nor do the infrared and 'H nmr spectral data. An X-ray crystallographic analysis has been carried out in order to provide an unambiguous decision between the possible isomeric structures 4-6

Experimental N,2-Dihydroxy-N-(1 -hydrox)lcyclohex)ll)methyl-,2-diphenylacet-

amide, Z I-(HydroxyaminomethyI)cyclohexanol (7) (4.35 g, 30 mrnol) is

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CAN. 1. CHEM. VOL. 69, 1991

reacted with ethyl oxalyl chloride (30 mrnol) and phenylmagnesium cooling. Yield: 0.89 g (77%). Colorless crystals. Melting point 192- bromide (225 mmol) according to literature methods (8). The product 193°C (from toluene). Anal. calcd. for CzlHzzBFzNO3: C 65.48, H crystallizes from ether/~etroleum ether. Yield: 4.47 g (42%). Color- 5.76, N 3.64; found: C 65.57, H 5.74, N 3.60. Infrared (KBr): 1670 less crystals. Melting point 124-126°C (from ether/petroleum ether). cm-I (C=O/C=N). 'H nrnr (90 MHz, d6-DMSOlTMS): 6 (ppm) = Anal. calcd. ~ O ~ C ~ ~ H ~ ~ N O ~ : C70.96, H7.09, N3.94; found: C70.89, 1.22-1.63, 1.67-2.00(2m, 3:2(CH2)5), 4.33 (s, N-CH2),7.34(s, 2 H 7.07, N3.91. Infrared(KBr): 3400-3360, 3140 (0--H), 1615 cm-I C6HS). Crystals suitable for X-ray analysis are obtained by recrystal- (C=O). 'H nmr (90 MHz, CDC13/TMS): 6 (ppm) = 1.47 (s, (CH2)5), lization from toluene. 2.40 (s, broad, exchangeable, 20H), 3.75 (s, N--CH2), 5.40 (s, broad, exchangeable, OH), 7.13-7.60 (m, 2C6H5).

5,5-Dij7uoro-2,2-pentamethylene-7,7-diphenyl-1,4,6-trio.xa-3a- azonia-5-boratn-2,3,4,5,6,7-hexahydroindene, 5

1 (1.07 g, 3 mmol) is dissolved in 30-40 mL toluene and, after addition of dimethyl ether-boron trifluoride (0.34 g, 3 mmol), refluxed for 30 min. The solvent is removed in vacuo, until the volume of the reaction mixture is reduced to 3-5 mL. Crystallization starts during

X-ray crystallographic analysis of 5 A crystal ca. 0.28 X 0.32 X 0.53 mm in size was mounted on a glass

fiber. Unit-cell parameters were refined by least-squares on 2 sin O / A values for 25 reflections (20 = 38.6-41.4") measured on a diffracp- meter with Mo-K, radiation (AKal = 0.70930, hKu2 = 0.71359 A). Crystal data at 21°C are as follows

Cz1H22BFzN03 fw = 385.22

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KLIEGEL ET AL.: 2 683

TABLE 1. Final positional (fractional X lo4) and isotropic thermal parameters (U X lo3 A2) with estimated standard deviations in

parentheses

Atom x Y z Ue,

Triclinic, a = 9.4555(5), b = 9.9813(6), c = 10.5139(9) A, a = 72.654(7), P = 77.140(5), y = 88.542(5)", Z = 2, p, = 1.387 Mg m-3, F(000) = 404, p(Mo-K,) = 0.98 cm-' . Absent reflections: none, space group ~1 (No. 2, reduced cell) from structure analysis.

Intensities were measured with graphite-monochromated Mo-K, radiation on an Enraf-Nonius CAD4-F diffractometer. An 0-20 scan at 1.2-10.0" min-' over a range of (0.80 + 0.35 tan 0)" in o (scan extended by 25% on each side for background measurement) was employed. Data were measured to 20 = 55'. The intensities of three check reflections, measured every hour of X-ray exposure time throughout the data collection, showed only small random variations. The data were processed2 and corrected for Lorentz and polarization effects. Of the 4232 independent reflections measured, 2971 (70.2%) had intensities greater than or equal to 3u(4 above background where u2(r) = [C + 2B + (0.040(C 7 B ) ) ~ ] with C = scan count, B = normalized total background count.

The analysis was initiated in the centrosymmetric space group p i o n the basis of the E-statistics, this choice being confirmed by the subse- quent successful solution and refinement of the structure. The structure was solved by direct methods, the coordinates of all non-hydrogen atoms being determined from an E-map. The non-hydrogen atoms were refined with anisotropic thermal parameters and the hydrogen atoms were refined with isotropic thermal parameters. Scattering factors for

all atoms and anomalous dispersion corrections for the non-hydrogen atoms were taken from ref. 9. The weighting scheme w = l/u2(F) gave uniform average values of w(lFol - IFcl)' over ranges of both IF,^ and sin 0/h and was employed in the final stages of full-rnatrix least- squares refinement of 341 variables. Reflections with I < 3 4 4 were not included in the refinement. Convergence was reached at R = 0.044 and R, = 0.060 for 2971 reflections with I 2 3 4 4 . The function minimized was Zw(lF,I - Fc)2 , R = ZllFoi - lFcll/ZIFol, R,,. = I I (ZW(~F,~ - IF,~)~/ZWIF,~')' 2. On the final cycle of refinement the maximum parameter shift corresponded to 0 . 0 7 ~ . The mean error in an observation of unit weight was 2.13. The final difference map showed maximum fluctuations of -0.3 1 to +0.24 e A-3.

The thermal motion has been analyzed in terms of the TLS model (10). The rms error in the temperature factors Uij (derived from the least-squares analysis) is 0.0009 A'. Five structural subunits were separately analyzed (rms AUii = 0.0013-0.0023 A'). The bond lengths have been corrected for liberation (10, 11) using shape para- meters q2 of 0.08 for all atoms. The final positional and (equivalent) isotropic thermal parameters for the non-hydrogen atoms appear in Table 1. Bond lengths (corrected and uncorrected) and angles are given in Tables 2 and 3 and intra-annular torsion angles in Table 4. Hydrogen atom parameters, anisotropic thermal parameters, bond lengths and angles involving hydrogen, torsion angles, and structure factors have been deposited.3

Results and discussion As the structure analysis reveals, the intramolecular alkyla-

tion of 1 in the presence of BF3 does not lead to the cyclic ether compound 4 having a BF2 hydroxamate partial structure, but rather gives the 2-oxazoline N-oxide derivative 5 with a six- membered difluoroborn chelate ring (Fig. 1). This confirms the results of regioselective alkylation of N-substituted hydroxamic acids under non-basic conditions, leading to cyclic imidate N-oxides (4, 12) in the case of intramolecular alkylation or to acyclic imidate N-oxides (13) or thioimidate N-oxides (14) in the case of intermolecular alkylation.

The structure 5 contains a six-membered boron chelate ring analogous to the seven-membered chelate ring in compound 9, which also has a cyclic imidate N-oxide oxygen atom serving as one of the donors of the bidentate ligand. The difference be- tween these two compounds is found in the functionality of the second donor which is an alcoholate oxygen atom in 5 and a phenolate oxygen atom in 9. To the best of our knowledge this is the first example of a six-membered boron chelate with this particular heterocyclic B,N-betaine structure. The formulation of 5 as an intramolecular iminium salt is justified by the extreme- 1 short C(2)-N bond4 of the imidate N-oxide function: 1.28 1 1 , which is even shorter than the comparable C=N+ bond in 9 (1.294 A) (4), and also shorter than the C=E+ bonds in the BF2 hydroxamates 3 (1.289 A) (2) and 8 (1.294 A) (3). The n-bond order of the C ( 2 t N bond, estimated from bond length vs. T-bond order plots (15, 16), lies between 0.8 and 1.0 and is similar to that of C=N+ bends in boron complexes of oximes with bond lengths of 1.283 A (17) and 1.287A (18).

In spite of the 0-alkylation of the carbonyl oxygen atom 0(3), the C(2)--0(3) bond shows some double bond character with a bond length of 1.310 A. The estimated (16) T-bond order

2Computer programs used include locally written programs for data processing and locally modified versions of the following: MULTANSO, multisolution program by P. Main, S. J. Fiske, S. E. Hull, L. Lessinger, G. Germain, J. P. Declercq, and M. M. Woolfson; ORFLS, full-matrix least-squares, and ORFFE, functions and errors, by W. R. Busing, K. 0 . Martin, and H. A. Levy; FORDAP, Patterson and Fourier syntheses, by A. Zalkin; ORTEP 11, illustrations, by C. K. Johnson.

3Supplementary material mentioned in the text may be purchased from the Depository of Unpublished Data, Document Delivery, CISTI, National Research Council of Canada, Ottawa, Ont., Can- ada KlAOS2.

4~ibration-corrected bond distances are employed throughout the discussion and are compared with similarly treated (10) bond lengths for other compounds in this series of papers and uncorrected distances otherwise.

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CAN. J. CHEM. VOL. 69, 1991

TABLE 2. Bond lengths (A) with estimated standard deviations in parentheses

Length Length

Bond Uncorr. Corr. Bond Uncorr. Corr .

F( 1 &B 1.365(3) 1.389 C(5)--C(6) 1.507(3) 1.513 F ( 2 t B 1.357(3) 1.379 C ( 6 t C ( 7 ) 1.516(3) 1.524 o ( 1 &N 1.362(2) 1.367 c ( 7 t c ( 8 ) 1.519(3) 1.526 o ( l t B 1.5 15(3) 1.530 W)--C(9) 1.517(3) 1.522 W)--C(l) 1.410(2) 1.415 C( lO tC(11 ) 1.391(2) 1.399 0 ( 2 t B 1.434(2) 1.451 c(lO)--C(15) 1.378(2) 1.385 0(3)--C(2) 1 .306(2) 1.310 c ( l l W ( 1 2 ) 1.380(3) 1.384 0(3)--C(3) 1.530(2) 1.536 C(12)--C(13) 1.374(3) 1.381 N A ( 2 ) 1.276(2) 1.281 C(13 tC(14 ) 1.372(3) 1.379 N 4 ( 4 ) 1.449(2) 1.452 C(14 tC(15 ) 1.392(3) 1.395 C(l)--C(2) 1.5 18(2) 1.522 c(16)--C(17) 1.388(2) 1.394 c(l)--C(lo) 1.530(2) 1.534 C(16tC(21) 1.389(2) 1.395 C(l)--C(16) 1.538(2) 1.541 C(17)-C(18) 1.381(3) 1.384 c(3)--C(4) 1.537(3) 1.542 C ( l 8 t C ( l 9 ) 1.383(3) 1.388 c(3)--C(5) 1.5 lO(3) 1.518 C( 19&C(20) 1.373(3) 1.379 c(3)--C(9) 1.510(3) 1.519 C ( 2 0 ) 4 ( 2 1) 1.386(3) 1.389

TABLE 3. Bond angles (deg) with estimated standard deviations in parentheses

Bonds Angle (deg) Bonds Angle (deg)

between 0.4 and 0.5 indicates the participation of the C(2)- 1 O(3) bond in the imidate T-bond system incorporating the

1 adjacent C=N+ bond. A similar situation has been noted for compounds of the type 9 (4). The C(3)--0(3) bond is very long (1.536 A) compared to any other (sp3)C--0 bond lengths re-

I ported (19), and is also longer than the identical bond in com- pound9 (1.512 A) (4).

The boron atom has a slightly distorted tetrahedral geometry (see Table 3). The 0-B bonds of 5 have the same average

length of 1.491 A as those in the seven-membered chelate 9 (4), but - as in 9 - they are markedly different from one another (by -0.08 A), B-ON = 1.530, B-OC = 1.451 A. The distance between the N-oxide oxygen atom and the boron atom is longer than the distance between an alcoholate (or phenolate) oxygen atom and boron. This has also been noted for five- to seven-membered diphenylboron chelates of various N-o~ides (4, 20-23). The B-F bond length! in 5 (average 1.384 A) are similar to those in 9 (average 1.387 A), but distinctly longer than

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KLIEGEL ET AL.: 2

FIG. 1. Stereoview of 5; 50% probability thermal ellipsoids are shown for the non-hydrogen atoms

TABLE 4. Intra-annular torsion angles (deg) stan- dard deviations in parentheses

Atom Value (deg)

those in the five-membered hydroxamate 8 (1.358 A) and slight- ly longer than those in 3 (average 1.377 &. The mean F- B/mean 0-B bond length ratio of 0.929 for 5 is at the high end of the range 0.884-0.949 (average 0.915) observed for other "F2B0," compounds having six-membered chelate rings (ref. 4 and references therein), indicating relatively strong binding of the difluoroborenium ion (F2B+) by the chelating ligand.

The six-membered BONCCO chelate ring has an O(l),C(l)- twist-boat conformation, flattened somewhat at the C(1) end. The five-membered oxazoline ring, fused to the N,C(2) side of the above-mentioned six-membered ring, has a flattened C(3)- envelope conformation. O(3) and C(4) of the oxazoline ring are in axial and equatorial positions with respect to the cyclohexane ring, which has a relatively undistorted chair conformation (see Table 4 for torsion angles). The phenyl substituents at C(1) are

oriented nearly perpendicular to one another (dihedral angles between normals to the mean planes is 8 1.3"), the bond to the pseudo-axial substituent being slightly longer than the other (1.541(2) vs. 1.534(2) A). The 0(3)<(2+N<(4) and C(l>-C(2+N-4(1) groups are both approximately planar (all six of these atoms are coplanar to within 0.015(2) A), the former being planar within experimental error as a result of the more extended n-system of the imidate function. The most significant intermolecular contact in the solid state of 5 cor- responds to a weak C-H...F interaction; C(20)- H(20)...F(2)(2 - x, - y, - z), H...F = 2.51(2) A, C..-F = 3.240(2) A, C-H...F = 131(2)".

Acknowledgements We thank the Natural Sciences and Engineering Research

Council of Canada and the Fonds der Chemischen Industrie, Frankfurt am Main, for financial support.

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