Crystal Structure of Ethyl 42benzoyl21a ,2 ,3 ...

18 卷 4 期 1999. 7.

结　构　化　学 ( J I EGO U HUA X U E) Chi nese J . S t ruct . Chem .

Vol. 18 , No. 4 J uly 1999

Crystal Structure of Ethyl 42benzoyl21a ,2 ,3 ,42tetrahydro2 32methyl21a2( 42methylphenyl) 21 H2azirino〔1 ,22 a 〕〔1 ,5〕 benzodiazepine212carboxylate ( C28 H28 N2 O3 ) WAN G Hong2Zhong 　XU Jia2Xi 　M I Bao2 Yu 　J IN Sheng 3 ( College of Chem ist ry an d M olecul ar Engi neeri n g , Peki n g U ni versit y , Beiji ng 100871)

ABSTRACT 　　The crystal st ruct ure of t he title compound , et hyl 42benzoyl21a ,2 ,3 ,42 tet rahydro232met hyl21a2 ( 42met hylp henyl ) 21 H2azirino〔1 , 22 a 〕〔1 , 5 〕benzodiazepine212 ( ) carboxylate C28 H28 N 2 O3 , M r = 440. 55 , has been determined. It crystallizes in or2 t horhombic space group Pbca wit h cell dimensions a = 16 . 407 ( 5 ) , b = 16 . 462 ( 4) , c = 18 . 372 ( 9) ~ , V = 4962 . 1 ( 5) ~ 3 , Z = 8 , D c = 1. 180 gcm - 3 , Cu Kα(λ = 1. 5418 ~ ) , F ( 000 ) = 1014 , μ = 0. 58 mm - 1 . The st ruct ure was solved by direct met hods and re2

fined by f ull2mat rix least2squares met hods , and t he final discrepancy factor is 0. 058 for 2216 observed reflections. The molecular backbone is a t ricyclic system wit h t he cent ral seven2membered 1 ,52diazepine ring in twisted boat2like conformation and cis2f used to bot h aziridine ring and benzene ring. Keywords : crystal structure , azirino〔1 , 22 a 〕〔1 , 5 〕benzodiazepine , 1 , 52benzodi2 azepine

1 　INTROD UCTION Benzodiazepine compounds are important p harmaceutical agents〔1 ,2〕. Recently it has been found t hat benzodiazepine tricyclic derivatives , t hose f used wit h ot her five or six2membered heterocycle , are also of potential p harmaceutical interests〔3 ,4〕. Hence , much attention has been paid to t he synt heses of t hem , such as 1 ,32oxazino〔3 ,22 d 〕〔1 ,5〕benzodiazepin212one〔5 ,6〕, 1 ,2 ,42triazolo〔4 ,32 d 〕〔1 ,5 〕benzodiazepine〔7〕, 1 ,2 , 42oxadiazolo〔4 ,52 d 〕〔1 ,5〕benzodiazepine〔8〕by our research group . In t his paper , we report t he crystal structure of t he title compound , a novel 1 ,52benzodiazepine tricyclic derivative , which was generated f rom t he cycloaddition reaction of dihydro21 ,52ben2 zodiazepine wit h et hoxycarbonyl carbene. 2 　EXPERIMENTAL The title compound was prepared by t he cycloaddition reaction of 12benzoyl222 met hyl242 ( 42met hylp henyl) 22 ,32dihydro21 H21 ,52benzodiazepine wit h et hoxycarbonyl carbene generated f rom et hyl diazoacetate using a catalyst copper powder in refluxing Received 7 October 1998 ; accepted 25 March 1999

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结构化学 ( J I EGOU HUA X U E) Chi nese J . S t ruct . Chem . 　　　1999 　Vol. 18 　

cyclohexane solution , followed by t he separation on a silica gel chromatograp hic col2 umn wit h et hyl acetate and cyclohexane as eluent〔9〕. Colorless and prismatic crystals suitable for X2ray analysis were obtained by slow evaporation f rom et hanol solution. A crystal wit h approximate dimensions of 0. 2mm × 0. 2mm ×0. 3 mm was selected for X2ray diff raction. A total of 2448 independent reflections , of which 2216 wit h I ≥3σ( I ) were employed for structure determination and refinement , was collected on an R3m/ E four2circle diff ractometer wit h Cu Kα(λ = 1. 5418 ~ ) radiation using ω/ 2θ scan mode in t he range of 0°< θ < 57°at room temperature and corrected for L p and empirical absorption. All of t he calculations were carried out on a Micro VAX211 computer wit h SHEL X86 program. The struc2 ture was solved by direct met hods and t hen difference Fourier synt heses. All non2hy2 drogen atoms were refined anisotropically. Hydrogen atoms were located and added to t he structure factor calculation , but t heir positions were fixed isotropically during t he refinement . The final cycle of refinement converged to t he discrepancy factors R = 0. 058 and R w = 0. 072 , wit h w - 1 = σ2 ( F ) + 0 . 0001 F2 , S = 1 . 34 , ( Δρ) max = 0. 233e/ ~ 3 , (Δ/ σ) max = 0. 017. 3 　RESUL T AND D ISCUSSION The final positional and t hermal parameters wit h associated estimated standard deviations of all non2hydrogen atoms are given in Table 1. The selected bond lengt hs and bond angles are listed in Tables 2 and 3 , respectively. Table 1. 　Atomic Coordinates and Thermal Parameters( ~ 2 ) Atom

Ueq

Atom

C(1)

0. 5411 (3)

0. 2176 (3)

0. 0762 (3)

0. 040

C(17)

0. 6463 (3)

0. 3085 (3)

- 0. 0740 (3) 0. 039

C(2)

0. 6089 (3) 0. 5556 (3)

0. 2586 (3) 0. 0492 (3) 0. 2929 (3) - 0. 0750 (3)

0. 036

C(18)

0. 035

C(19)

0. 6825 (3) 0. 7216 (7)

0. 3833 (4) 0. 5188 (5)

- 0. 1078 (3) 0. 044 - 0. 0954 (5) 0. 086

0. 5293 (3) 0. 4544 (4)

C(20)

0. 045

C(21)

0. 7723 (8) 0. 4682 (3)

0. 5530 (6) 0. 4178 (3)

C(6)

0. 6844 (3)

0. 2039 (3) - 0. 0791 (3) 0. 1881 (3) - 0. 0319 (3) 0. 2456 (4) 0. 0810 (3)

0. 044

C(5)

0. 048

C(22)

0. 4097 (3)

0. 4704 (4)

- 0. 1581 (9) 0. 089 - 0. 0622 (3) 0. 045 - 0. 0892 (3) 0. 050

C(7)

0. 6912 (4)

0. 1941 (4)

0. 1407 (4)

0. 061

C(23)

0. 3760 (4)

0. 4603 (4)

- 0. 1576 (3) 0. 047

C(8)

0. 6240 (4)

0. 1542 (4)

0. 1678 (3)

0. 062

C(24)

0. 4040 (4)

0. 3965 (4)

- 0. 1996 (3) 0. 051

C(9)

0. 1646 (4) 0. 2514 (4)

0. 1349 (3) 0. 0762 (3)

0. 051

C(25)

C(10)

0. 5496 (4) 0. 3949 (3)

0. 049

C(26)

0. 4630 (3) 0. 4957 (3)

0. 3437 (4) 0. 3531 (3)

C(11)

0. 4023 (3)

0. 2994 (4)

0. 1451 (3)

0. 047

C(27)

0. 3115 (4)

0. 5169 (4)

- 0. 1738 (3) 0. 043 - 0. 1043 (3) 0. 033 - 0. 1857 (4) 0. 073

C(12)

0. 3609 (4) 0. 4114 (5)

0. 1549 (4) 0. 2150 (4)

0. 059

C(13)

0. 4604 (4) 0. 4572 (5)

C(28) N (1)

0. 4362 (6) 0. 4634 (3)

0. 0977 (4) 0. 2274 (3)

C(14)

0. 3971 (4)

0. 4002 (4)

0. 2663 (4)

0. 070

N (2)

0. 5982 (3)

0. 3173 (3)

- 0. 0233 (4) 0. 082 0. 0408 (2) 0. 040 - 0. 0074 (2) 0. 035

C(15)

0. 3403 (4)

0. 3388 (4)

0. 2582 (4)

0. 066

O (1)

0. 6859 (3)

0. 4460 (2)

- 0. 0643 (2) 0. 061

C(16)

0. 3421 (4)

0. 2893 (4)

0. 1985 (4)

0. 054

O (2) O (3)

0. 7085 (3) 0. 3273 (2)

0. 3821 (3) 0. 2382 (3)

- 0. 1692 (2) 0. 068 0. 0506 (3) 0. 074

x

C(3) C(4)

y

z

0. 074

x

y

Ueq is defined as one t hird of t he trace of t he ort hogonalized Uij tensor.


z

Ueq

　No. 4 　　　　　WAN G H Z et al . : Crystal Structure of C28 H28 N2 O3

Table 2. 　Selected Bond Lengths ( ~ ) Bond C(1) C(1) C(2) C(3) C(3) C(3) C(3)

Dist . -

Bond

1. 393 (8) 1. 441 (7) 1. 429 (7) 1. 528 (8) 1. 510 (7) 1. 496 (7) 1. 481 (7)

C(2) N (1) N (2) C(4) C(17) C(26) N (2)

C(4) - C(5) C(5) - C(28) C(5) - N (1) C(10) - C(11) C(10) - N (1) C(10) - O (3)

Dist .

Bond

1. 527 (8) 1. 526 (9) 1. 493 (7) 1. 496 (9) 1. 357 (7) 1. 225 (7)

C(17) C(17) C(18) C(18) C(19) C(23)

Dist . -

C(18) N (2) O (1) O (2) O (1) C(27)

1. 502 (8) 1. 462 (7) 1. 306 (7) 1. 206 (7) 1. 452 (8) 1. 503 (9)

Table 3. 　Selected Bond Angles ( ° ) Angle C(2) - C(1) - N (1) C(1) - C(2) - N (2) C(4) - C(3) - C(17) C(4) - C(3) - C(26) C(4) - C(3) - N (2) C(17) - C(3) - C(26) C(17) - C(3) - N (2) C(26) - C(3) - N (2) C(3) - C(4) - C(5)

(° ) 119. 4 (5) 119. 3 (5) 116. 2 (4) 115. 6 (4) 115. 8 (4) 122. 6 (4) 58. 5 (3) 115. 6 (4) 111. 2 (4)

Angle C(4) - C(5) - C(28) C(4) - C(5) - N (1) C(28) - C(5) - N (1) C(11) - C(10) - N (1) C(11) - C(10) - O (3) N (1) - C(10) - O (3) C(3) - C(17) - C(18) C(3) - C(17) - N (2) C(18) - C(17) - N (2)

(° ) 112. 5 (5) 110. 8 (5) 110. 5 (5) 119. 5 (5) 119. 5 (5) 120. 9 (5) 121. 7 (5) 59. 7 (3) 118. 6 (5)

Angle C(17) - C(18) - O (1) C(17) - C(18) - O (2) O (1) - C(18) - O (2) C(1) - N (1) - C(5) C(1) - N (1) - C(10) C(5) - N (1) - C(10) C(2) - N (2) - C(3) C(2) - N (2) - C(17) C(3) - N (2) - C(17)

(° ) 114. 3 (5) 120. 9 (5) 124. 7 (6) 116. 3 (4) 123. 3 (5) 118. 3 (4) 119. 0 (4) 118. 4 (4) 61. 8 (3)

The molecular structure of t he title compound and t he atomic designations are shown in Fig. 1. The molecular backbone is a tricyclic system com2 posed of a benzene ring , a seven2 membered diazepine ring and an aziri2 dine ring. The central seven2mem2 bered 1 ,52diazepine ring adopts twist2 ed boat2like conformation wit h t he di2 hedral angle 20. 0°between t he plane N ( 1) - N ( 2) - C ( 3) and t he plane N ( 1) - N ( 2 ) - C ( 5 ) , and is cis2f used to t he aziridine ring at C ( 3 ) and N ( 2 ) , cis2f used to t he benzene ring at C ( 1) and C ( 2) , respectively. The 42 met hylp henyl group attached to C ( 3 ) Fig. 1 　St ruct ure of t he title compound is axial , while t he met hyl on C ( 5) is equatorial. The conformation of t his title com2 pound is similar to t hat of 1 , 12dichloro21a , 32dip henyl21 , 1a , 2 , 32tetrahydro2azirino 〔2 ,12 d 〕〔1 ,5〕benzot hiazepine , cycloadduct of 1 ,52benzot hiazepine wit h dichlorocar2 〔10〕 bene . The aromatic rings in t he molecule show usual features , and t he bond lengt h ( mean 1. 38 ~ ) and bond angles are wit hin t he range of normal values. The dihedral ・265 ・ © 1995-2004 Tsinghua Tongfang Optical Disc Co., Ltd. All rights reserved.

结构化学 ( J I EGOU HUA X U E) Chi nese J . S t ruct . Chem . 　　　1999 　Vol. 18 　

angles are 40. 6°between t he plane of t he benzo ring 〔C ( 1) - C ( 2) - C ( 6) - C ( 7) C ( 8) - C ( 9) 〕and t he plane defined by atoms N ( 1) , N ( 2) and C ( 3) , 60. 6°between t he benzo ring plane and t he plane defined by atoms N ( 1 ) , N ( 2 ) and C ( 5 ) respec2 tively. The aziridine ring plane possesses t he dihedral angles of 27. 6°and 29. 2°wit h t he plane 〔N ( 1) - N ( 2) - C ( 3) 〕and t he plane 〔N ( 1) - N ( 2) - C ( 5) 〕. The molecule contains t hree chiral carbon atoms , C ( 3) , C ( 5) and C ( 17 ) . The atoms C ( 3) and C ( 17) show t he same configurations , while t he atom C ( 5) possesses t he relative configuration to t he atom C ( 3) according to t he R. S. Rule. REFERENCES 1 　 Bock M G , Dipardo R M , Evans B E et al . Benzodiazepine Gastrin and Brain Cholecystokinin Receptor Ligands : L2365 ,260. J . Med. Chem . , 1989 , 32 : 13～16.

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7 　 Xu Jiaxi , Jin Sheng. New Heterocyclic System Synt hesis V I : The Cycloaddition Derivatives of 1 ,52Benzot hiazepine and 1 ,52 Benzodiazepine. Chi n . Chem . L etts. , 1994 , 5 : 557～560. 8 　 Xu Jiaxi , Wu Haitao , Jin Sheng. Cycloaddition Reaction of Benzoheteroazepine II : Reactions and conformations of cy2 cloadducts on 1 ,52Benzot hiazepines and 1 ,52Benzodiazepines wit h nitrile imine and nitrile oxides. Chi n . J . Chem . , 1999 , 17 : 8491. 9 　 Mi Baoyu , Jin Sheng. New Heterocyclic System Synt hesis I : Reaction of Dihydro21 ,52Benzodiazepines and Thiazepines wit h Et hoxycarbonyl Carbenes. Chi n . Chem . L etts. , 1991 , 2 : 925～926. 10 　Xu Jiaxi , Lan Ruoxi , Jin Sheng. Crystal Structure of 1 ,12dichloro21a ,32diphenyl21 ,1a ,2 ,32tetrahydro2azirino〔2 ,12 d 〕〔1 ,5〕 benzot hiazepine , (C22 H17Cl 2NS) . Chi n . J . S t ruct . Chem . , 1998 , 17 : 349～352.
