754 Notizen
5 -B rom o-2-(ch lo ro acetam id o )b en zo - p h en on e - a Synthetic Precursor to 6-B rom oviridicatina
K arl P e te rs* , E v a -M a ria P e te rs
Max-Planck-Institut für Festkörperforschung, D-70506 Stuttgart, Germany
G e r h a r d B rin g m a n n , T h o m a s M a d e r
Institut für Organische Chemie der Universität, D-97074 Würzburg, Germany
Z. Naturforsch. 51b, 754-755 (1996);
received November 20, 1995
Crystal Structure, Naturally Occurring Benzo
diazepines, 5-Bromo-2-(chloroacetamido)-benzo- phenone. Intramolecular Hydrogen Bonding
The title compound 4 was obtained by amida- tion of 2-amino-5-bromobenzophenone and chlo- roacetic anhydride. It crystallizes from chloro
form in the monoclinic system, space group P 2x!n\
a = 2561(1), b = 586.1(1), c = 969.2(6) pm, and ß = 97.18(5)°. An intramolecular hydrogen bond quasi forms an additional six-membered ring.
I n tro d u c tio n a n d S y n th esis
F o r se v e ra l d ec ad e s, th e h e te ro c y c lic b e n z o d ia z e p in e rin g sy stem h as b e e n u se d , i.e. in th e fo rm o f w e ll-k n o w n d e riv a tiv e s like d ia z e p a m (1, V ali
u m 1*), m o st successfu lly as sy n th e tic h y p n o tic s a n d se d a tiv e d ru g s [2]. V ery rec en tly , d ia z e p a m (1) a n d h a lo g e n -fre e a n a lo g s h av e b e e n fo u n d to o c c u r in n a tu re , e.g. in ra t b ra in , a n d also in p la n t so u rc e s such as p o ta to e s a n d c e re a ls [3]. T his u n e x p e c te d d e te c tio n o f su ch p re v io u sly m e re ly sy n th e tic c o m p o u n d s in n a tu re w a rra n ts a n in v e stig a tio n o f th e b io g e n e sis o f th is b io sy n th e tic a lly u n u su a l rin g sys
te m . A s a b io sy n th e tic p re c u rs o r to b e n z o d ia z e p ines, w e h av e re c e n tly p ro p o s e d [4] th e w ell- k n o w n [5] m o u ld m e ta b o lite v irid ic a tin (2 ), w hich is p ro d u c e d by se v e ra l P en icilliu m sp e c ie s [6 ]. F o r th e d e v e lo p m e n t o f an e ffic ie n t tra c e an a ly sis o f v irid ic a tin (2 ) in b io lo g ica l m a trix , th e h ith e r to u n k n o w n 6 -b ro m o v irid ic a tin (2 ) w as n e e d e d as an in te rn a l an a ly tic a l s ta n d a rd . In a n a lo g y to a k n o w n sy n th e sis o f v irid ic a tin (2) [7], 3 w as p la n n e d to b e p r e p a re d fro m th e b ro m in a te d c h lo ro a c e ta m id e 4 ,
by tr e a tm e n t w ith N a O H . 4 w as sy n th e siz e d fro m
a “Naturally Occurring Diazepam-like Benzodiazep
ines”. part 5; for part 4. see: Lit. [1],
* Reprint requests to K. Peters.
th e c o rr e s p o n d in g 2 -a m in o -5 -b ro m o b e n z o p h e - n o n e by a m id a tio n re a c tio n w ith c h lo ro a c e tic a n h y d rid e . F ro m c h lo ro fo rm , w e m a n a g e d to get c o l
o rle ss cry sta ls o f 4 , s u ite d fo r a n X -ra y s tru c tu re analysis.
1 X = H 2 4
X = Br 3
X-ray Investigation
F o r th e cry sta l s tru c tu re an aly sis a cry stal o f th e size 0 .2 5 x 1 .0 x 0 .1 5 m m w as ch o se n . T h e d e te r m i
n a tio n o f th e cell p a r a m e te r s fro m 22 re fle c tio n s (9.7° < 0 < 12.9°) a n d th e m e a s u re m e n t o f 2275 o b s e rv e d (F > 3ct(F)) u n iq u e re fle c tio n in te n sitie s (1.75° < G < 27.5°; h m.dX = 33, k max = 7, /min = -12.
/max = 12) w e re c a rrie d o u t o n a S iem e n s R 3 m /V fo u r-circ le d iffra c to m e te r ( M o K a , W yckoff-scan.
e m p iric a l a b s o rp tio n c o rre c tio n ). T h e stru c tu re w as so lv e d b y d ire c t p h a s e d e te r m in a tio n (S ie m e n s S H E L X T L -P L U S ). T h e p a r a m e te r s o f th e c o m p le te s tru c tu re co u ld b e re fin e d by fu ll-m atrix a n is o tro p ic le a s t-s q u a re s to R = 0.051, R w = 0.041:
r e fle c tio n d a ta to p a r a m e te r r a tio = 12.30. T h e e le c tro n d e n s ity o f th e la rg e st d iffe re n c e p e a k w as f o u n d to b e 0.47, w hile th a t o f th e la rg e st d iffe r
e n c e h o le w as 0.49 e A '3.
Results and Discussion
C ^ H n N O ^ C lB r , 352.62 g m ol"1, crystallizes in th e m o n o c lin ic sy ste m , sp a ce g ro u p P 2 x!n, w ith a - 2 5 6 1 (1 ), b = 586.1(3), c = 969.2(6) pm , ß = 9 7 .18(5)°, V = 1443(1) p m 3 • 106 a n d Z = 4. T he d e n s ity w as c a lc u la te d to b e 1.623 g c m '3. A to m ic p a r a m e te r s a re liste d in T ab le I ac c o rd in g to th e a to m la b le s o f Fig. 1+. T h e X -ra y s tru c tu re analysis
+ Further crystal structure data may be obtained from the Fachinformationszentrum Karlsruhe, Gesellschaft für wissenschaftliche Information mbH. D-76344 Eggenstein-Leopoldshafen. by quoting the Registry No. CSD 401325. the names of the authors and the journal citation.
0932-0776/96/0500-0754 $06.00 © 1996 Verlag der Zeitschrift für Naturforschung. All rights reserved. D
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Notizen 755
Table I. Positional parameters (xlO4) and equivalent isotropic displacement parameters (p n rx lO -1).
Atom X y z u eq
Br 2025(1) 1107(1) 2340(1) 72(1)
CI - 75(1) 12794(2) 3812(1) 71(1)
C (l) - 331(2) 11191(9) 2358(4) 82(2)
C(2) - 36(2) 9078(10) 1988(5) 67(2)
0 (2 ) - 240(1) 7811(7) 1092(3) 105(2)
N(3) 448(2) 8745(7) 2713(4) 56(2)
C(4) 798(2) 6948(7) 2629(4) 46(1)
C(5) 1212(2) 6638(7) 3724(4) 43(1)
C(6) 1290(2) 8196(7) 4948(4) 47(2)
0 (6 ) 1141(1) 10180(5) 4877(3) 59(1)
C(7) 1570(2) 4864(7) 3609(4) 48(1)
C(8) 1527(2) 3449(7) 2463(4) 51(2)
C(9) 1104(2) 3698(8) 1434(4) 57(2)
C(10) 752(2) 5448(8) 1506(4) 58(2)
C (ll) 1545(2( 7284(7) 6312(4) 47(1)
C(12) 1861(2) 8803(9) 7157(4) 60(2)
C(13) 2057(2) 8177(10) 8511(5) 79(2)
C(14) 1932(2) 6071(11) 8994(5) 82(2)
C(15) 1625(2) 4562(9) 8184(5) 74(2)
C(16) 1433(2) 5149(7) 6817(4) 57(2)
first o f all c o n firm s th e c o n s titu tio n o f th e m o le cule as a n tic ip a te d fro m its syn th esis. O f in te re st is th e c o n fo rm a tio n a l o r ie n ta tio n o f th e tw o a r o m a tic rin g s re la tiv e to th e k e to fu n c tio n th a t jo in s th e m to g e th e r. A p p a r e n tly fo r ste ric re a so n s, th e a ro m a tic rin g sy stem s c a n n o t b o th ac h ie v e a con- ju g a tiv e s ta b ilis a tio n b y a d o p tin g a c o p la n a r a rra y w ith re s p e c t to th e c a rb o n y l fu n c tio n : T h e u n s u b s titu te d p h e n y l rin g C ( l l ) - C ( 1 6 ) is c le a rly tw isted o u t o f th e c a rb o n y l p la n e , w h e re a s th e su b s titu te d C (4 )-C (1 0 ) rin g is n e a rly c o p la n a r w ith th e C = 0
Cu
Fig. 1. Perspective drawing of 4 with the labelling of the atoms corresponding to Table I.
g ro u p , o n e o f th e p r o b a b le r e a s o n s b e in g th e N - s u b s titu e n t, w h ich c a n d isp la y its + A /-effect o nly in th a t c o n fo rm a tio n . T h e o th e r re a so n , as su g g e s te d by th e r a th e r s h o rt d is ta n c e o f 211 p m b e tw e e n 0 ( 6 ) a n d H (3 ), s h o u ld b e in tr a m o le c u la r h y d ro g e n b o n d in g th u s fo rm in g a n o th e r p la n a r six -m e m b e re d rin g sy stem . T h e N -c h lo ro a c e ty l su b s titu e n t, by c o n tra s t, is tw iste d o u t o f this p la n e.
Acknowledgments
We thank the Fonds der Chemischen Industrie for fi
nancial support and a fellowship to T. M.
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