C(3) aurated 1,4-benzodiazepin-2-ones. Synthesis and characterization. Crystal structure of (L)Au[P(C6H4CH3-4)3] (HL=7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, DIAZEPAM)

Article abstract of DOI:10.1016/S0022-328X(97)00624-4

The synthesis of a series of gold(I) metallated derivatives of some 1,4-benzodiazepin-2-ones is described. They include mononuclear (L)Au(PR₃) (R=C₆H₅, C₆H₄CH₃-4 or C₂H₅) as well as dinuclear species (L)Au(Ph₂P(CH₂)_nPPh₂)Au(L), n=2, 3 (HL=7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, DIAZEPAM or 7-chloro-1-(cyclopropylmethyl)-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, PRAZEPAM). The deprotonated ligand is bonded to the AuPR₃ moiety through the C(3) atom. Activation of the C(sp³)-H bond is achieved by means of a strong base in the presence of the phosphinegold chloride intermediate. The structure of (L)Au[P(C₆H₅CH₃-4)₃] has been determined by X-ray diffraction. Some aspects of the reactivity of the metallated species is also reported.

Full text of DOI:10.1016/S0022-328X(97)00624-4

Ž
.
Journal of Organometallic Chemistry 553 1998 405–415
ž /
C 3 aurated 1,4-benzodiazepin-2-ones. Synthesis and characterization.
ž / w ž / x
Crystal structure of L Au P C6 H4CH3-4 3
ž
HLs7-chloro-1,3-dihydro-1-
/
methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, DIAZEPAM
a
a
a
Giovanni Minghetti a,), Antonio Zucca , Maria Agostina Cinellu , Sergio Stoccoro ,
Mario Manasserob,), Mirella Sansoni
b
a
Dipartimento di Chimica, UniÕersita di Sassari, Õia Vienna 2, 07100 Sassari, Italy
`
b
Dipartimento di Chimica Strutturale e Stereochimica Inorganica, UniÕersita di Milano, Centro CNR, Õia Venezian 21, 20133 Milano, Italy
`
Received 26 July 1997
Abstract
Ž .
The synthesis of a series of gold I metallated derivatives of some 1,4-benzodiazepin-2-ones is described. They include mononuclear
Ž .
Ž
. Ž Ž . Ž .
.
Ž
Ž
.
.
Ž
L Au PR3 RsC6H5, C6H4CH3-4 or C2H5 aswell as dinuclear species L Au Ph2P CH2 nPPh2 Au L , ns2, 3 HLs7-chloro-
Ž
.
1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, DIAZEPAM or 7-chloro-1- cyclopropylmethyl -1,3-dihydro-5-phenyl-2H-
Ž .
.
1,4-benzodiazepin-2-one, PRAZEPAM . The deprotonated ligand is bonded to the AuPR3 moiety through the C 3 atom. Activation of
3
Ž
.
the C sp –H bond is achieved by means of a strong base in the presence of the phosphinegold chloride intermediate. The structure of
Ž . w Ž
. x
has been determined by X-ray diffraction. Some aspects of the reactivity of the metallated species is also
3
L Au P C6H5CH3-4
reported. q 1998 Elsevier Science S.A.
Keywords: Gold; 1,4-benzodiazepin-2-ones; DIAZEPAM; PRAZEPAM
1. Introduction
1,4-Benzodiazepines are psychotropic drugs widely employed in therapy for their anti-anxiety, sedative, hypnotic,
w
x
myorelaxing and anti-convulsive properties 1–3 .
Complexes of neutral 1,4-benzodiazepin-2-ones with transition metal ions 4–14 have been reported; in most cases
Ž .
w
x
the ligand is bonded through the N 4 atom. Metal derivatives of deprotonated 1,4-benzodiazepin-2-ones are likewise
Ž . Ž . w x
known: besides N 1 bonded molecules arising from N 1 -unsubstituted ligands 8 , examples include C-bonded
2
w
x
Ž
.
molecules where C is an ortho carbon atom of the 5-phenyl substituent 13,15 . The C sp –metal bond is usually
Ž .
assisted by coordination of the N 4 atom, to give a five-membered C,N ring. In contrast, at least to the best of our
knowledge, no metal derivative has been synthesized with the ligand bonded through the C 3 atom of the
Ž .
seven-membered 1,4-diazepine ring.
Ž .
Here we report the synthesis of some C 3 aurated 1,4-benzodiazepin-2-ones, HL: they include mononuclear
Ž . . Ž Ž . Ž .
Ž
.
Ž
Ž
.
.
L Au PR3 RsC6 H5, C6 H4CH3-4 or C2 H5 as well as dinuclear species L Au Ph2 P CH2 nPPh2 Au L , ns2,
Ž
3
Ž
HL s 7-chloro-1, 3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, DIAZEPAM or 7-chloro-1-
.
.
cyclopropylmethyl -1,3-dihydro-5-phenyl-2H-1,4- benzodiazepin-2-one, PRAZEPAM .
1
13
31
Ž .
Ä1
4
Ä1
4
The new gold I derivatives have been fully characterized in solution by H, C H and P H NMR spectra.
The structure of L Au P C6 H4CH3-4
Ž .
w
Ž
.
3x
Ž
.
HLsDIAZEPAM has been solved by an X-ray structure determination.
)
Corresponding authors.
0022-328Xr98r$19.00 q 1998 Elsevier Science S.A. All rights reserved.

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)
406
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
w
Ž
.
xq
Ž .
fragment through the N 4 atom,
Some of the aurated 1,4 benzodiazepin-2-ones are able to coordinate a Au PR3
w
Ž .
Ä
Ž
.
42 xq
giving cationic derivatives L Au PR3 .
2. Results and discussion
Although the reactivity of 1,4-benzodiazepin-2-ones with transition metal ions has been the subject of several
Ž .
9,15 and platinum II 13 derivatives where the metal–carbon sp bond is supported by coordination of the N 4
studies, very few metallated 1,4-benzodiazepin-2-ones have been reported. Actually they are restricted to palladium II
2
w
x
Ž
.
w
x
Ž
.
Ž
.
atom to give a five-membered cyclometallated C,N ring.
Ž
.
w x
Ž . w x
In the field of gold chemistry, adducts of both Au III 7 and Au I 8 have been described previously but no
activation of C–H bonds has been achieved in spite of several attempts carried out under different experimental
conditions.
Ž .
We describe here that under controlled conditions, C 3 aurated 1,4-benzodiazepin-2-ones 1–5 can be obtained in
fairly good yields according to reaction 1.
Ž .
1
The reaction requires that the ethanolic solution of the base is added at room temperature drop by drop to a
Ž
.
suspension of R3P AuCl and the ligand in the same solvent; in many cases a certain amount of the starting gold
complex is recovered.

(
)
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
407
Ž
.
It is worth noting that the auration is achieved by means of the gold chloride complex R3P AuCl and does not
Ž
.
w
Ä
Ž
.
4
xq
require the tris triphenylphosphinegold oxonium cation, R3P Au O , which is known to display a remarkable
3
w
x
‘aurating’ ability 16,17 .
Reaction 1 can be extended to the synthesis of dinuclear species,
Ž .
w x
Under the same experimental conditions, complex 8, an N 1 -aurated species previously described 8 , does not
react to give the corresponding C 3 aurated derivative:
Ž .
The new species 1–5 are white solids stable to air, soluble in most of the common organic solvents. The IR spectra
show strong absorptions in the range 1700–1500 cmy1 typical of the ligands, suggesting that the diazepine ring is
1
Ž .
untouched. Evidence for the C 3 auration is given mainly by NMR spectra. In the H spectra the AB spin system due
Ž .
to the diastereotopic C 3 protons is missing and a new signal, corresponding to one proton, appears at lower field
31
Ž
.
Ž3
see Table 1 : a small coupling to the P nucleus is observed J HP sca. 10 Hz .
Ž
.
.

Table 1
1H and
31
a
Ä1
4
P
H NMR data
Ž .
H 3
Compound
CH3
Aromatics
Other signals
.w
31 P
w
x
x
Ž
.
1
2
3.33 s
3.32 s
5.55 d 9.5
5.27 d 9.6
7.04–7.66 m, 23H
7.12–7.65 m, 8H
39.9
39.3
w
Ž .
Ž
xŽ
.
0.94 dt, 9H 17.8 7.7 C H3 –CH2
Ž
.w xŽ
.
1.49 dq, 6H 9.3 7.7 CH3 –C H2
w
w
x
x
Ž
Ž
.
.
Ž
.Ž .
3
4
3.33 s
5.53 d 9.5
5.52 d 9.6
7.03–7.65 m, 20H
6.94–7.65 m, 23H
2.37 s, 9H C6 H4C H3
38.1
40.2
Ž
.
Ž
. Ž
.
.
.
.
0.91 m, 1H CH
3.53 dd 6.4 14.4
Ž
.
Ž
. Ž
0.04–0.43 m, 4H CH2
ca 0.9 CH
0.06–0.40 m, 4H
4.13 dd 7.8 14.4
b
Ž
.
Ž
. Ž
. Ž
w
x
Ž
.
Ž
. w
xŽ
.
.
5
3.51 dd 6.1 14.4
5.23 d 9.5
7.11–7.63 m, 8H
0.94 dt, 9H 17.9 7.6 C H3 –CH2
39.5
Ž
.
Ž
Ž
. w xŽ
4.10 dd 7.8 14.4
1.48 dq, 6H 9.3 7.6 CH3 –C H2
Ž
.
.
.
.
Ž
.
6
7
9
10
3.29 s
3.29 s
3.48 s
5.49 m
5.46 d 9.5
5.34 d 8.7
5.32 d 8.8
6.83–7.62 m, 36H
2.10 m, 4H CH2
38.5, 38.6
33.8, 33.9
29.3, 40.1
29.4, 40.2
w
x
x
x
Ž
Ž .
6.98–7.62 m, 36H
1.35–2.70 m, 6H CH2
w
Ž
6.88–7.73 m, 38H
Ž
6.94–7.71 m, 38H
Ž
.
Ž
. Ž
. Ž
.
.
w
1.01 m, 1H CH
3.74 dd 6.1 14.4
Ž
.
Ž
0.18–0.60 m, 4H CH2
4.16 dd 7.9 14.4
a
Ž
.
Ž
.
Ž31
. Ž . Ž .
P , coupling constants in Hz, J H,H in parentheses, J P,H in square brackets.
CDCl3, room temperature, 300 MHz 1H , chemical shifts in ppm from internal TMS 1H and external H3PO4
b Partially overlapping with C H3 –CH2.

(
)
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
409
The 31 P H spectra of complexes 1–5 display one signal around d 40 significantly at low field with respect to the
w x
Ä1
4
shift of the gold complexes having a benzodiazepine bonded through a nitrogen atom 8 .
13
31
Ä1
4
Ž3
Ž
.
.
In the C H spectra, a resonance in the range d 77–80, coupled to
to a methinic carbon through an APT Attached Proton Test experiment. The resonances at very close values,
P
J CP sca. 73 Hz has been assigned
Ž
.
Ž
ascribed in the free ligand to the 2- and 5- quaternary carbons of the diazepine ring e.g., DIAZEPAM: d 170.1 and
Ž .
.
Ž
Ž
.
Ž
.
169.1 split remarkably in the C 3 aurated derivatives complex 1: d 179.6, J CP s4.6 Hz and 160.4, J CP s5.2
.
Hz and cannot be unambiguously assigned.
In the NMR spectra of the dinuclear complexes 6 and 7 r.t. , some of the signals are broad H or split into two
Ž
.
Ž1
.
Ž31 Ä1
4
. Ž
.
resonances P H e.g., 6: d 38.5 and 38.6 which very likely have to be assigned to the diastereomers due to the
presence in the molecule of two asymmetric carbons.
Ž .
Ž
.
w
qx
All the C 3 aurated species 1–7 show in the mass spectra FABq the molecular ion M : in addition peaks at
w
Ž
.
Ä
Ž
.
24q
x
higher mass, corresponding to dinuclear unities L–H Au2 PPh3
are sometimes observed, likely arising from
w
Ž
.
qx
w Ž .
and Au PPh3 , respectively are present in
qx
reaction in vapour phase. Peaks at mrz 721 and 459 due to Au PPh3
2
the spectra of compounds 1 and 4, as usually observed in the case of gold complexes of PPh3.
The structure of complex 3 in the solid state has been solved by an X-ray determination.
Ž .
w
Ž
.
x
The structure consists of the packing of L Au P C6 H4CH3-4 and acetone molecules in the molar ratio 1:1 with
3
no unusual van der Waals contacts. Principal bond lengths and angles are reported in Table 2. An ORTEP view of the
complex molecule is shown in Fig. 1.
w
x
In the free DIAZEPAM molecule 18 , the N1–C2–C3–N4–C5–C11–C10 seven membered ring is in a boat
conformation and the sp3 C3 atom is the bow of the boat; of the two hydrogen atoms bonded to C3, one points
towards the inside of the boat and the other towards the outside. In the present metal complex the seven-membered
ring retains the boat conformation and the gold atom replaces the C3 hydrogen atom that points toward the inside of
w
Ž .
x
Ž .
the boat. The P–Au–C3 interaction is essentially linear angle 172.2 3 8 with Au–P and Au–C3 distances of 2.289 3
˚
Ž
.
Ž
.
and 2.109 11 A, respectively. These values are very similar to those found in fluorenyl triphenylphosphine gold
3
w
x
19 , where the sp carbon atom bonded to gold belongs to a fused cyclopentadiene ring: Au–P 2.275 and Au–C
Table 2
Selected bond distances A and angles 8 with e.s.d.’s in parentheses for L Au P C6 H4CH3-4 , compound 3
˚
Ž .
Ž .
Ž . w Ž
. x
3
Ž .
2.289 3
1.435 16
Ž
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Au–P
N1–C2
C2–C3
N4–C5
C11–C10
C11–C6
C7–C8
C8–C9
C10–N1
C5–C12
C12–C17
C14–C15
C16–C17
P–C26
P–Au–C3
Au–C3–N4
N1–C2–C3
C2–C3–N4
N4–C5–C11
C11–C10–N1
C10–N1–C18
C5–C11–C6
C11–C6–C7
C6–C7–Cl
C7–C8–C9
C9–C10–C11
N4–C5–C12
C5–C12–C17
C13–C12–C17
C13–C14–C15
C15–C16–C17
Au–C3
C2–O
C3–N4
C5–C11
C10–N1
C6–C7
C7–Cl
C9–C10
N1–C18
C12–C13
C13–C14
C15–C16
P–C19
P–C33
AU–C3–C2
N1–C2–O
C3–C2–O
C3–N4–C5
C5–C11–C10
C10–N1–C2
C2–N1–C18
C10–C11–C6
C6–C7–C8
C8–C7–Cl
C8–C9–C10
C9–C10–N1
C11–C5–C12
C5–C12–C13
C12–C13–C14
C14–C15–C16
C16–C17–C12
2.109 11
Ž
1.204 13
Ž
.
.
.
.
.
.
.
.
.
.
.
.
.
Ž
Ž
1.448 13
1.496 15
Ž
Ž
1.501 15
1.290 15
Ž
Ž
1.414 14
1.392 13
Ž
Ž
1.401 17
1.391 16
Ž
Ž
1.760 13
1.357 15
Ž
Ž
1.435 16
1.362 18
Ž
Ž
1.485 16
1.414 14
Ž
Ž
1.389 15
1.469 14
Ž
Ž
1.395 18
1.408 18
Ž
Ž
1.387 19
1.338 20
Ž
Ž
1.821 11
1.371 17
Ž
Ž
1.824 12
1.820 11
Ž .
111.3 7
Ž .
172.2 3
Ž .
Ž
.
112.9 7
Ž .
119.4 1.0
Ž
.
.
115.4 9
125.3 1.1
Ž .
Ž .
114.1 9
121.7 9
Ž .
Ž
123.5 9
122.0 1.0
Ž
.
.
Ž .
121.4 1.0
122.4 9
Ž .
Ž
119.7 1.0
116.0 9
Ž .
Ž
.
.
.
.
118.1 9
119.9 1.0
Ž .
Ž
120.7 1.1
119.5 9
Ž .
Ž
121.0 1.0
118.2 8
Ž
.
.
Ž
119.1 1.0
121.6 1.1
Ž
Ž .
119.3 1.0
119.3 9
Ž .
Ž .
118.8 9
117.6 9
Ž
.
.
.
.
Ž
.
.
.
.
121.1 1.0
123.4 1.1
Ž
Ž
121.8 1.2
115.5 1.0
Ž
Ž
118.1 1.1
121.6 1.2
Ž
Ž
121.6 1.1
121.3 1.3

(
)
410
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
Ž . w Ž
. x
3
Fig. 1. An ORTEP view of L Au P C6 H4CH3-4 , compound 3. Thermal ellipsoids are drawn at the 30% probability level.
˚
Ž
.
2.102 A each value is the average of three bond lengths found in three crystallographically independent molecules .
Bond lengths and angles within the C3-coordinated DIAZEPAM molecule are very similar to those found in the free
w
x
Ž .Ž
.
Ž
. w x
ligand 18 and in the N4-bonded DIAZEPAM molecule found in Pt L HL Cl 11 13 . The most significant
˚
˚
Ž .
w
Ž
.
Ž .
differences are the lengthening of the N1–C2 bond length 1.435 16 A here, 1.365 2 and 1.378 6 A in DIAZEPAM
x
w
Ž .
Ž .
and 11, respectively and the increase of the N4–C3–C2 and C3–N4–C5 angles 114.1 9 and 121.7 9 8 here,
Ž . Ž . Ž . Ž .
x
110.5 2 and 118.1 2 in DIAZEPAM, 109.4 3 and 118.2 3 8 in 11, respectively . In the present seven-membered
Ž .
Ž .
ring the N1–C2–N4–C5 atoms are strictly coplanar and form dihedral angles of 50.9 7 and 40.6 8 8 with the bow
and stern planes of the boat, formed by atoms C2–C3–N4 and N1–C10–C11–C5, respectively. The C6–C11 and
C12–C17 aromatic rings are also strictly planar.
Ž
.
Reaction 1 is reversible: the gold–carbon bond can be cleaved by HCl to give the free ligand reaction 2 :
Ž .
2
Ž .
w
x
Reaction with bromine is more complex, as reported in the case of the simple gold I alkyl derivatives 16,17 .
Ž
.
Ž
.
Ž
.
Ž
.
Although isolation of Ph3P AuBr molar ratio Au:Brs1:1 or Ph3P AuBr3 Au:Brs1:2 gives evidence for the
cleavage of the Au–C bond, we were unable to separate the expected 3-bromo-1,4-benzodiazepin-2-one.

(
)
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
411
w
Ž
.
Ž
.
xq
Ž .
as obtained by removal of chloride from Ph3P AuCl with
The C3 aurated complexes react with PPh3 Au Sol
silver fluoborate in acetone solution, to give cationic species, according to reaction 3:
Ž .
3
31
Ä1
4
Clear evidence for the C3 and N4 bonding of the bridging ligand is given by the P H NMR spectrum: the
chemical shift of the two signals, d 29.3 and 40.1, 9, and 29.4 and 40.2, 10, are comparable with that of compounds 1
Ž .
w x
and 2, and with that of the N 4 bonded adducts 8 , respectively.
3. Experimental
Syntheses of compounds 2 and 5 were performed under dry nitrogen by using standard Schlenk techniques.
Ligands DIAZEPAM and PRAZEPAM were provided by Roche and Parke-Davis, respectively.
31
13
1H, P H and C H NMR spectra were recorded with a Varian VXR 300 spectrometer operating at 299.9
Ä1
4
Ä1
4
Ž1
.
Ž31
H , 121.4 P and 75.4 MHz C . Chemical shifts are given in parts per million relative to internal TMS 1H and
C and external 85% H3PO4
.
Ž13
.
Ž
13
.
Ž31
.
P .
IR spectra were recorded with Perkin Elmer spectrophotometers 983 and 1310 using Nujol mulls. Mass spectra
were obtained with a VG 7070 instrument operating under FAB conditions, with 3-nitrobenzyl alcohol as supporting
matrix. Conductivity measurements were obtained using a Philips PW 9505 conductimeter at 258C. Elemental
Ž
Analyses were performed with a Perkin-Elmer elemental analyzer 240 B by Mr A. Canu Dipartimento di Chimica,
.
Universita di Sassari .
`
( )
(
) [
( ) ( )
( )
3.1. Synthesis of compounds: general procedure for the synthesis of L Au PR3 HLsDIAZEPAM: 1 , 2 and 3 ;
( ) ( )]
PRAZEPAM: 4 and 5
3
3
Ž
.
Ž
.
Ž
.
An ethanol solution 10 cm of KOH 1.1 mmol was added dropwise to an ethanol suspension 30 cm of HL
Ž
.
Ž
.
Ž
.
1.0 mmol and PR3 AuCl 1.0 mmol . The mixture was stirred at room temperature, then filtered to separate some
Ž
.
unreacted PR3 AuCl and evaporated to dryness.The residue was taken up with dichloromethane, filtered and
concentrated to small volume: addition of diethyl ether gave a white solid. Recrystallization from dichloromethane–
diethyl ether gave the analytical sample.
( ) ) ( )
(
3.2. L Au PPh3 1
Ž
.
Yield 63%, m.p. 1628C dec. . Anal. Found: C, 53.64; H, 3.58; N, 3.86%. C34 H27 AuClN2OP.0.25CH2Cl2 Calc.:
13
y1
Ž
.
Ž
.
C, 53.82; H, 3.63; N, 3.66%. IR Nujol, cm
n: 1639 s, 1582 m, 1100 s, 690 s, 535 s, 504 s. C NMR CD2Cl2
2
Ž
.
Ž
Ž
.
.
Ž
Ž
.
d: 35.1 s, CH3 , 77.6 d, J CP s73.8 Hz, CH , 122.3, 128.3, 128.7, 129.0, 129.2, 130.0, 129.4 d, J CP s10.9
.
Ž
Ž
.
.
Ž
Ž
.
.
Ž
Ž
.
.
Ž
Hz , 131.6 d, J CP s2.4 Hz , 134.3 d, J CP s13.7 Hz , 160.4 d, J CP s5.2 Hz, CO or C5N , 179.7, d,
Ž
Ž
.
.
Ž
.
w
qx
w
Ž
.
qx
w
Ž
.
qx
J CP s4.6 Hz, CO or C5N ; FAB mass spectrum mrz : 742 M , 721 Au PPh3 , 459 Au PPh3 , 1200
2
w
.Ž
L–H AuPPh3
.
qx
.
2
( ) ) ( )
(
3.3. L Au PEt3 2
Ž
.
Yield 66%, m.p. 1058C dec. . Anal. Found: C, 44.32; H, 4.48; N, 4.67%. C22 H27 AuClN2OP Calc.: C, 44.12; H,
n: 1627 s, 1411 s, 1305 m, 1253 m, 1104 s, 703 s, 539 s, 526 m. 13C NMR
.
y1
Ž
4.54; N, 4.68%. IR Nujol, cm

(
)
412
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
2
Ž
.
Ž
.
Ž
Ž
.
.
Ž
.
Ž
Ž
.
.
CDCl3 d: 8.6 s, CH3CH2 P , 17.6 d, J CP s29.7 Hz, CH2 P , 34.8 s, CH3N , 78.8 d, J CP s72 Hz, CH ,
Ž
.
Ž
.
121.8, 127.3, 128.0, 128.5, 128.6, 128.9, 129.6, 145.7 and 180.5 CO or C5N . FAB mass spectrum mrz : 598
w
M
qx
w
Ž
.Ž
.
qx
, 912 L–H AuPEt3
.
2
( ) [ (
) ] ( )
3
3.4. L Au P C6 H4CH3 y4 3
Ž
.
Yield 60%, m.p. 125–1308C dec . Anal. Found: C, 54.06; H, 4.23; N, 3.21%. C37 H33 AuClN2OPP0.5CH2Cl2
y1
Ž
.
n: 1676 s, 1594 m, 1104 s, 700 s, 537 m, 524 s, 507 s, 498 s.
Calc.: C, 54.43; H, 4.14; N, 3.38%. IR Nujol, cm
( ) ) ( )
(
3.5. L Au PPh3 4
Ž
.
Yield 52%., m.p. 1358C dec. . Anal. Found: C, 55.49; H, 4.12; N, 3.49%. C37 H31AuClN2OPP0.25CH2Cl2 Calc.:
13
y1
Ž
.
Ž
.
C, 56.62; H, 3.95; N, 3.48%. IR Nujol, cm
n: 1636 s, 1435 s, 1100 s, 694 s, 533 m, 504 m. C NMR CD2Cl2
2
Ž
.
Ž . Ž Ž . .
, 51.2 s, CH2 N , 77.8 d, J CP s74.4 Hz, CH , 124.8, 128.4, 128.5, 129.1,
d: 3.4, 4.8 and 10.9 3xs,
Ž
Ž
.
.
Ž
Ž
.
.
Ž
Ž
.
.
Ž
Ž
.
129.4 d, J CP s10.8 Hz , 129.8, 131.6 d, J CP s2.5 Hz , 134.3 d, J CP s13.6 Hz , 160.3 d, J CP s4.9
.
Ž
Ž
.
.
Ž
.
w
qx
Hz, CO or C5N , 178.6 d, J CP s4.5 Hz, CO or C5N . FAB mass spectrum mrz : 783 MH , 721
w
Ž
.
qx
Au PPh3 , 459 Au PPh3 , 1240 L–H AuPPh3
w
Ž
.
qx
wŽ
.Ž
.
qx
.
2
2
( ) ) ( )
(
3.6. L Au PEt3 5
Ž
.
Yield 46%, m.p. 110–1158C dec. . Anal. Found: C, 45.35; H, 4.53; N, 4.29%. C25 H31AuClN2OPP0.25CH2Cl2
n: 1627 s, 1288 m, 707 w, 591 m, 547 m, 496 w, 480 w. 13C
.
y1
Ž
Calc.: C, 45.94; H, 4.81; N, 4.24%. IR Nujol, cm
NMR CDCl3 d: 3.2, 4.8 and 10.5 3xs,
Ž
.
Ž
Ž
.
Ž . Ž Ž . . Ž
, 8.6 s, CH3CH2 P , 17.7 d, J CP s29.7 Hz, CH2 P 50.6 s,
2
.
Ž
.
.
Ž
.
CH2 N ; 79.1 d, J CP s72.8 Hz, CH , 124.3, 128.1, 128.4, 128.6, 128.8, 129.3 144.1 and 179.7 CO or C5N .
Ž
.
w
qx
w
Ž
.Ž
. x
FAB mass spectrum mrz : 638 M , 952 L–H AuPEt3 .
2
[( ) ] (
) [
( )
( )]
3.7. General procedure for the synthesis of L Au P–P HLsDIAZEPAM: P–Psdppe 6 ; dppp 7
2
3
3
Ž
.
Ž
.
Ž
.
An ethanol solution 10 cm of KOH 1.1 mmol was added dropwise to an ethanol suspension 30 cm of HL
Ž
.
Ž
.
Ž
.
1.0 mmol and P–P Au2Cl2 0.5 mmol . The mixture was stirred at room temperature for 36 h,32q13 then filtered
and evaporated to dryness. The residue was taken up with dichloromethane, filtered and concentrated to small volume:
addition of diethyl ether gave a white solid. Recrystallization from dichloromethane–diethyl ether gave the analytical
sample.
[( ) ] (
) ( )
6
3.8. L Au dppe
2
Ž
.
Yield 25%, m.p. 160–1658C dec. . Anal. Found: C, 50.15; H, 3.64; N, 3.92%. C58 H48 Au2Cl2 N4O2 P2 P0.5CH2Cl2
y1
Ž
.
Calc.: C, 50.10; H, 3.52; N, 3.99%. IR Nujol, cm
FAB mass spectrum mrz : 1358 M , 1075 M–L
n: 1637 s, 1481 s, 1104 s, 695s, 591 m, 583 m, 541 s m, 482 m.
Ž
.
w
qx
w
qx
.
[( ) ] (
) ( )
7
3.9. L Au dppp
2
Ž
.
Yield 25%, m.p. 135–1408C dec. . Anal. Found: C, 50.21; H, 3.79; N, 3.86%. C59 H50 Au2Cl2 N4O2 P2 P0.5CH2Cl2
y1
Ž
.
n: 1637 s, 1435 s, 1103 s, 697 m, 542 m, 521 s, 483 w.
Calc.: C, 50.45; H, 3.49; N, 3.96%. IR Nujol, cm
[( )
{
(
)
}
][
] [
( )
( )]
3.10. General procedure for the synthesis of L Au PPh3
BF4 HLsDIAZEPAM: 9 ; PRAZEPAM: 10
2
3
Ž
.
Ž
.
A methanol solution of AgBF 0.0708 g, 0.32 mmol was added to a methanol suspension 15 cm of PPh3 AuCl
4
Ž
.
Ž .
Ž
.
0.1587 g, 0.32 mmol . After removal of AgCl, a methanol solution of L AuPPh3 0.32 mmol was added. The
resulting suspension was stirred for about 5 h at room temperature and then evaporated to dryness; the residue was
dissolved in chloroform, filtered and concentrated to small volume. Addition of diethyl ether gave a yellow
precipitate. Recrystallization from acetone–diethyl ether gave the analytical sample.

(
)
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
413
3.11. Compound 9
Ž
.
Yield 85.3%, m.p. 1588C dec . Anal. Found: C, 47.82; H, 3.15; N, 2.29%. C52 H42 Au2yB1ClF4 N2OP2 Calc.: C,
y4
y1
cm2 moly1. IR Nujol, cm
n: 1651 s, 1434 s,
qx
Ž
.
Ž
.
48.45; H, 3.28; N, 2.17%. LM 5=10 M, acetone 132 V
1101 s, 1054 s broad , 693 s, 544 s, 507 s. FAB mass spectrum mrz : 1201 M , 721 PPh3 2 Au , 459
Ž
.
Ž
.
w
qx
w
Ž
.
w
Ž
.
qx
PPh3 Au
.
3.12. Compound 10
Ž
.
Yield 88%, m.p. 1488C dec. . Anal. Found: C, 49.28; H, 3.45; N, 2.23%. C55 H46 Au2 BClF4 N2OP2 Calc.: C,
y4
y1
y1
cm2 moly1. IR Nujol, cm
n: 1643 s, 1101s,
Ž
.
Ž
.
49.70; H, 3.49; N, 2.11%. LM 5=10
M, acetone : 116 V
Ž
.
Ž
.
w
qx
w
Ž
.
qx
1053 s broad , 693 s, 544 s, 507 s. FAB mass spectrum mrz 1241 M , 841 Au2 PPh3 2-Ph , 721 Au PPh3
w
Ž
.
qx
,
2
w
Ž
.
qx
459 Au PPh3 .
( ) )
(
)( )
(
3.13. Reaction of L Au PPh3 1 with Br2 molar ratio 1:1
Ž .
Ž
. Ž . Ž
.
Ž
.
To a solution of L Au PPh3
1
0.1194 g, 0.16 mmol in benzene was added Br2 0.16 mmol . The mixture was
stirred for 45X in a cold water bath, then concentrated to small volume; addition of n-hexane gave a white precipitate
Ž
.
which was filtered off and recrystallized from benzene–n-hexane. The product was identified as Ph3P AuBr; yield
87.5%
Table 3
Crystallographic data
Ž
.
Compound
Formula
M
3P CH3 2CO
C40 H39 Au1Cl1N2O2 P1
843.2
Colour
colourless
Crystal system
triclinic
Space group
P1
˚
Ž .
a A
Ž .
9.956 2
˚
Ž .
b A
Ž .
13.595 2
˚
Ž .
Ž .
14.215 2
c A
Ž .
Ž .
87.29 1
a 8
Ž .
Ž .
b 8
g
89.44 1
Ž .
Ž .
8
77.29 1
3
˚
Ž
.
Ž .
1874.8 5
U A
Z
2
840
Ž
.
F 000
Dc g cm
Crystal dimensions mm
m MoK a cm
y3
Ž
.
1.494
0.23=0.28=0.42
40.6
Ž
.
.
y1
Ž
. Ž
Min. and max. transmission factors
Scan mode
0.65–1.00
v
Frame widthr8
0.3
20
Ž .
Time per frame s
No. of frames
Detector-sample distance cm
Ž .
2500
5.50
2–25
"h, "k, "l
21030; 8294
5220
0.054, 0.076
424
Ž
.
u-range 8
Reciprocal space explored
Ž
.
No. of reflections total; independent
Ž .
Unique observed reflections with I)3gs I
Final R and RX indicesa
No. of variables
Goodness of fitb
1.47
y3
˚
Ž
.
Ž . Ž .
q3.6 3 ,y2.1 3
Max. and min. residual electron density e A
a
X
1r2
Rs Ý FO yk Fc rÝFO , R s Ýw FO yk FC rÝwFO2
.
w Ž<
<
<<.
x
w
Ž
<
<.2
w
x
bw
Ž
<
<.2
Ž
.x
Ž
.x
Ž
.
w
2Ž
.
Ž
2 .2 x
1r2
2
2
Ýw FO yk FC r NO y NV
, where ws1r s FO , s FO s s FO q 0.06FO 1r2r2FO, NO is the number of observations and
NV the number of variables.

(
)
414
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
( ) )
(
) ( )
(
3.14. Reaction of L Au PPh3 4 with Br2 molar ratio 1:2
Ž
.
Ž .
Ž
. Ž . Ž
.
Addition of Br2 1.0 mmol to a suspension of L Au PPh3
4
0.3914 g, 0.5 mmol in benzene resulted in an
immediate colour change to red. The suspension was stirred for about 3 h and then filtered off. The solid product was
Ž
.
identified as Ph3P AuBr3; yield 82%.
( )
(
) ( )
3.15. Reaction of L Au PPh3 1 with HCl
3
Ž
.
Ž
.
Addition of 2M HCl 0.06 cm , 0.12 mmol to a solution of 1 0.0822 g, 0.11 mmol in EtOH gave a white
Ž
.
precipitate which was filtered off and identified as Ph3P AuCl. The filtered solution was evaporated to dryness and
extracted with diethyl ether: after removal of the solvent DIAZEPAM was recovered 80% .
Ž
.
Table 4
Ž . w Ž
. xŽ
.
Ž
Fractional atomic coordinates with e.s.d.’s in parentheses for the non-hydrogen atoms of L Au P C6 H4CH3-4 CH3 2CO compound 3
3
3
Ž
.
.
CH 2CO
Atom
x
y
z
Ž .
y0.36473 4
Ž .
0.22459 3
0.3698 3
Ž .
0.10803 3
Au
Cl
P
O
O2
N1
N4
C2
C3
C5
C6
C7
C8
C9
C10
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
C24
C25
C26
C27
C28
C29
C30
C31
C32
C33
C34
C35
C36
C37
C38
C39
C40
C41
C42
Ž .
0.0421 4
Ž .
Ž .
0.3198 3
Ž .
Ž .
Ž .
0.2629 2
y0.4097 3
0.1905 2
Ž .
Ž .
Ž .
y0.1306 6
y0.4368 8
0.3722 6
Ž .
y0.102 2
Ž .
Ž .
0.370 1
y0.325 2
Ž .
Ž .
Ž .
y0.0347 6
y0.2823 9
0.4197 7
Ž .
y0.1525 9
Ž .
Ž .
y0.0441 6
0.2010 7
Ž .
Ž .
Ž .
y0.0715 8
y0.349 1
0.3461 8
Ž .
y0.299 1
Ž .
Ž .
y0.0322 8
0.2404 8
Ž .
Ž .
Ž .
y0.0029 8
y0.062 1
0.2392 8
Ž .
Ž .
y0.022 1
Ž .
0.1485 8
0.3115 8
Ž .
Ž .
Ž .
0.2172 8
y0.059 1
0.3831 9
Ž .
0.4633 9
Ž .
y0.166 1
Ž .
0.2026 9
Ž .
Ž .
Ž .
0.1228 9
y0.244 1
0.4754 8
Ž .
0.4030 8
Ž .
y0.209 1
Ž .
0.0514 8
Ž .
Ž .
Ž .
0.0659 8
y0.098 1
0.3213 8
Ž .
0.084 1
Ž .
Ž .
y0.0192 8
0.1964 8
Ž .
Ž .
Ž .
y0.027 1
0.138 1
0.0939 9
Ž .
Ž .
Ž .
y0.049 1
0.277 1
0.0566 9
Ž .
Ž .
Ž .
y0.057 1
0.366 1
0.117 1
Ž .
Ž .
Ž .
y0.049 1
0.316 1
0.220 1
Ž .
Ž .
Ž .
y0.031 1
0.179 1
0.2589 9
Ž .
Ž .
Ž .
y0.077 1
y0.325 1
0.524 1
Ž .
Ž .
Ž .
0.3270 7
y0.513 1
0.2934 9
Ž .
y0.593 1
Ž .
Ž .
0.4047 9
0.274 1
Ž .
Ž .
Ž .
0.4566 9
y0.663 1
0.353 1
Ž .
y0.658 1
Ž .
Ž .
0.4310 9
0.452 1
Ž .
Ž .
Ž .
0.356 1
y0.580 2
0.4700 9
Ž .
y0.508 1
Ž .
Ž .
0.3030 8
0.3895 9
Ž .
Ž .
Ž .
0.487 1
y0.735 2
0.538 1
Ž .
y0.487 1
Ž .
Ž .
0.2798 8
0.0814 8
Ž .
Ž .
Ž .
0.351 1
y0.444 2
0.007 1
Ž .
y0.507 2
Ž .
Ž .
0.359 1
y0.075 1
Ž .
Ž .
Ž .
0.295 1
y0.605 1
y0.090 1
Ž .
Ž .
Ž .
y0.646 1
y0.015 1
0.2239 9
Ž .
y0.586 1
Ž .
0.068 1
Ž .
0.2156 8
Ž .
Ž .
Ž .
y0.662 2
y0.185 1
0.301 1
Ž .
y0.247 1
Ž .
0.1572 8
Ž .
0.3265 8
Ž .
Ž .
Ž .
0.2851 8
y0.136 1
0.091 1
Ž .
Ž .
Ž .
0.329 1
y0.005 1
0.071 1
Ž .
0.014 1
Ž .
Ž .
0.4148 9
0.1118 9
Ž .
Ž .
Ž .
0.455 1
y0.098 1
0.174 1
Ž .
Ž .
Ž .
y0.229 1
0.196 1
0.4125 9
Ž .
0.460 1
Ž .
Ž .
0.156 1
0.086 1
Ž .
Ž .
Ž .
0.303 1
y0.051 2
y0.293 1
Ž .
0.067 2
Ž .
y0.354 1
Ž .
0.253 1
Ž .
y0.095 3
Ž .
y0.185 2
Ž .
0.274 2

(
)
G. Minghetti et al.rJournal of Organometallic Chemistry 553 1998 405–415
415
4. X-ray data collection and structure determination
Crystal data and other experimental details are summarized in Table 3. The diffraction experiment was carried out
Ž
on a Siemens SMART CCD area-detector diffractometer at room temperature using MoK a radiation ls0.71073
˚
.
A with a graphite crystal monochromator in the incident beam and the generator working at 50 kV and 35 mA. Cell
parameters and orientation matrix were obtained from the least-squares refinements of 90 reflections measured in
three different sets of 15 frames each, in the range 2-u-238. At the end of data collection the first 50 frames,
containing 379 reflections, were recollected to have a monitoring of crystal decay, which was not observed, so that no
time-decay correction was needed. The 2500 collected frames were processed with the software SAINT, and an
Ž
.
absorption correction was applied SADABS, written by G. Sheldrick to the 21 030 collected reflections, 8294 of
2
2
2
Ž
<
<
.
which are unique with Rint s0.0287 Rint sÝ FO yFmean rÝFO .
The calculations were performed on an AST Power Premium 486r33 computer using the Personal Structure
w
x
Determination Package 20,21 and the physical constants tabulated therein. Scattering factors and anomalous
w
x
dispersion corrections were taken from Ref. 22 . The structure was solved by Patterson and Fourier methods and
refined by full-matrix least-squares, minimizing the function Ýw FO yk F 2. Anisotropic thermal factors were
Ž
<
<.
c
refined for all the non-hydrogen atoms. The hydrogen atoms of the solvent molecule were ignored. Those of the CH3
groups of the complex molecule were detected in the final Fourier maps and included in the calculations but not
˚
Ž
refined. All the other hydrogen atoms were placed in their ideal positions C–Hs0.97 A, Bs1.15 times that of the
.
carbon atom to which they are attached and also not refined. The atomic coordinates of the structure model are listed
in Table 4.
Acknowledgements
Ž
.
Ž
.
Financial support by C.N.R. Rome is gratefully acknowledged. We thank Roche Milano and Parke-Davis
Ž
.
Lainate for a gift of DIAZEPAM and PRAZEPAM, respectively.
References
w x
Ž .
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w x
2
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¨
w x
3
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¨
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.
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Ž . Ž .
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w x
Ž .
Ž
.
6
w x
7
w x
Ž .
Ž
.
8
w x
Ž .
Ž .
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w
w
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w
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w
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w
w
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Ž .
Ž
.
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Ž .
Ž
.
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Ž .
Ž
.
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Ž .
Ž
.
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x
Ž .
Ž
.
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x
Ž
.
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x
Ž
.
16 R.J. Puddephatt, in: R.J.H. Clark Ed. , The Chemistry of Gold, Elsevier, Amsterdam, 1978.
x
Ž
.
17 K.J. Grandberg, V.P. Dyadchenko, J. Organomet. Chem. 474 1994 1.
x
Ž
.
18 A. Camerman, N. Camerman, J. Am. Chem. Soc. 94 1972 268.
x
Ž
.
19 Yu.T. Struchkov, Yu.L. Slovokhotov, D.N. Kravtsov, T.V. Baukova, E.G. Perevalova, K.I. Grandberg, J. Organomet. Chem. 338 1988
269.
w
w
w
x
Ž
.
20 B.A. Frenz, Comput. Phys. 2 1988 42.
x
21 Crystallographic Computing 5, Chap. 11, Oxford Univ. Press, Oxford, UK, 1991, p. 126.
x
22 International Tables for X-ray Crystallography, Vol. 4, Kynoch Press, Birmingham, UK, 1974.