Large-scale preparation of 1,1′-ferrocenedicarboxylic acid, a key compound for the synthesis of 1,1′-disubstituted ferrocene derivatives

Article abstract of DOI:10.1021/om4004972

Efficient and simple methods for the large-scale preparation of 1,1′-ferrocenedicarboxylic acid, fc(COOH)₂, involving the sodium salts of cyclopentadienecarboxylic methyl and ethyl esters, Na(C ₅H₄COOR) (R = Me, Et), are presented. With fc(COOH) ₂ at hand, the syntheses of various 1,1′-disubstituted compounds of the type fcX₂ (X = CH₂OH, COCl, CON ₃, NCO, NHCOOMe, NHBoc, NH₂) were optimized and scaled up. The X-ray crystal structures of fc(COOEt)₂, fc(NCO) ₂·¹/₂C₆H₆, and fc(NHCOOMe)₂·MeOH are reported.

Full text of DOI:10.1021/om4004972

Article
pubs.acs.org/Organometallics
Large-Scale Preparation of 1,1′-Ferrocenedicarboxylic Acid, a Key
Compound for the Synthesis of 1,1′-Disubstituted Ferrocene
Derivatives
Alex R. Petrov, Kristof Jess, Matthias Freytag, Peter G. Jones, and Matthias Tamm*
Institut fu
Germany
̈
̈
r Anorganische und Analytische Chemie, Technische Universitat Braunschweig, Hagenring 30, 38106 Braunschweig,
*
S Supporting Information
ABSTRACT: Efficient and simple methods for the large-scale
preparation of 1,1′-ferrocenedicarboxylic acid, fc(COOH) ,
2
involving the sodium salts of cyclopentadienecarboxylic methyl
and ethyl esters, Na(C H COOR) (R = Me, Et), are
5
4
presented. With fc(COOH) at hand, the syntheses of various
2
1
,1′-disubstituted compounds of the type fcX (X = CH OH,
2
2
COCl, CON , NCO, NHCOOMe, NHBoc, NH ) were
3
2
optimized and scaled up. The X-ray crystal structures of
1
f c ( C O O E t ) 2 , f c ( N C O ) · / C H , a n d f c -
2
2
6
6
(
NHCOOMe) ·MeOH are reported.
2
+
−
INTRODUCTION
sodium cyclopentadienides of the type Na (C H Z) (Z =
5 4
■
1
CHO, C(O)Me, COOEt/Me) were employed for the
syntheses of nickelocenes and cobaltocenes, titanocene
dichlorides, and several half-metallocene complexes that
are not available by electrophilic substitution of the
corresponding metallocene. These reagents were also success-
fully employed for the syntheses of heterosubstituted
Ever since the first synthesis of ferrocene and the discovery of
1
8
2
3
its sandwich (or “Doppelkegel”) structure and aromatic
19
20
4
characteristics, the interest in this iconic molecule has never
5
abated. Indeed, ferrocene and its derivatives are among the
most important metallocenes, and the 1,1′-disubstituted
derivatives especially have found numerous applications in
7b
6
7a
ferrocenes of the type [(C H R)Fe(C H COOMe)] and
asymmetric catalysis, biochemistry, and material sciences
5
4
5
4
2
1
7c
[
(Me C )Fe(C H COOMe)].
and as chelating ligand systems. In particular, 1,1′-bis-
5 5 5 4
Although the first preparation of cyclopentadienecarboxylic
esters by Thiele dates back to 1900, the first report by
(
diphenylphosphino)ferrocene (dppf) and several related chiral
22
and nonchiral 1,1′-diphosphinoferrocenes have attracted
considerable attention because of their relevance for a number
of metal-catalyzed reactions for the production of fine
Me
Osgerby and Pauson on the use of Na(C H COOMe) (1 )
5
4
Me
for the synthesis of dimethyl 1,1′-ferrocenedicarboxylate (2 )
did not appear until the early 1970s. The reported low yield
of only 28.5% might be ascribed to inefficient generation of 1
from sodium cyclopentadienide (NaCp) and methyl chloro-
formate. Curiously, even after the discovery of superior
7
d,8,9
23
chemicals.
Me
Although ferrocene is nowadays commercially produced on
the ton scale and is therefore a relatively cheap starting material,
its 1,1′-disubstituted derivatives are still significantly more
1
0
expensive. The most common methods for derivatization of
8b,12
methods for the production of Na(C H Z), which were used
5 4
1
1,12
ferrocene are Friedel−Crafts acylation,
lithiation,
for the synthesis of derivatized metallocenes (vide supra), no
attempts were reported toward the syntheses of related,
symmetrically substituted ferrocenes of the type fc(COOR)2.
Initially, we were interested in obtaining significant amounts
of 1,1′-disubstituted ferrocenes such as 1,1′-diisocyanatoferro-
8
b
8b,12
borylation, and mercuration.
As a consequence, 1,1′-
disubstituted ferrocenes of the type fcY with Y = C(O)Me, Li,
BX , and HgX represent frequently used starting materials, and
the following group of versatile derivatives can easily be
2
2
1
3
14
15
24
25
prepared therefrom: Y = COOH, CHO, CH OH,
cene, fc(NCO) , or 1,1′-diaminoferrocene, fc(NH ) . The
2
2
2 2
8b,16
17
B(OR)2,
Br, I. For the latter species, a rather elaborate
former, fc(NCO) , can be conveniently produced from 1,1′-
2
method for the efficient separation of mono- and dibromo/-
iodo-substituted ferrocenes, prepared from the lithiated species,
by “oxidative purification” was reported recently.
An alternative method toward 1,1′-disubstituted metal-
locenes is derivatization of the five-membered ring prior to
construction of the metallocene core. This synthetic route is
well established and routinely used for the synthesis of
cyclopentadienyl transition metal complexes. For instance, the
ferrocenedicarboxylic acid, fc(COOH) (4), according to the
2
26
four-step procedure optimized by van Leusen and Hessen via
Curtius rearrangement of 1,1′-bis(azidocarboxy)ferrocene, fc-
17
Special Issue: Ferrocene - Beauty and Function
Received: May 31, 2013
©
XXXX American Chemical Society
A
dx.doi.org/10.1021/om4004972 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
2
4
Et
Me
(
CON3). The classical preparative route toward 4 makes use
Scheme 1. Preparation of Diesters 2 and 2
of the haloform reaction starting from 1,1′-diacetylferrocene
1
3a
and NaOX solutions at temperatures below +5 °C (X = Br)
13b
or at ca. 50 °C (X = Cl). The main drawback of this method
for larger scale preparations is clearly the production of large
volumes of aqueous waste contaminated with significant
amounts of halogenated organics (for example, up to 270 g
of CHBr for the production of 100 g of product), which is
3
obviously not environmentally benign.
For fc(NH ) (10), an improved, large-scale synthesis was
2
2
27
reported in 2000 by Arnold et al. as an alternative to previous
methods. However, this route requires isolation of 1,1′-
dilithiated ferrocene [Li fc·TMEDA], which is generally
2
5
2
difficult to handle without a glovebox or Schlenk techniques
because of its highly pyrophoric nature, and in addition, the
copper-catalyzed coupling of fc(Br) to fc(N ) was found to be
2
3 2
2
8
difficult. Moreover, precautions were recommended for
handling the intermediate 1,1′-diazidoferrocene, fc(N ) ,
because of its explosive nature (mp = 56 °C, dec). Finally, it
3
2
should be noted that Kostyuk and Hierso et al. also found
larger scales, handling the isolated NaCp becomes more and
more difficult.
We regarded the encouraging results described above as a
fc(NHBoc) (9, Boc = tert-butoxycarbonyl) to be an excellent
2
28
precursor for the synthesis of 10, and a modified protocol for
this reaction has been independently developed by us (see
below). In addition, we wish to present herein a rapid and
convenient, low-cost route for the preparation of 1,1′-
ferrocenedicarboxylic acid (4). Several reliable and scaled-up
procedures toward valuable symmetrically substituted ferrocene
derivatives, including fc(CH OH) (3), fc(NCO) (7), and
challenge to develop an even larger scale method (method 2).
Et
Since the only byproduct in the synthesis of 1 is ethanol and
since NaCp can also be generated easily by deprotonation of
cyclopentadiene (CpH) with alkali-metal alkoxides, we decided
to generate NaCp from CpH by reaction with sodium ethoxide
(NaOEt). Thus, careful addition of freshly cracked CpH to a
cooled suspension of commercial NaOEt (96% purity) in DEC,
followed by heating the reaction mixture to 95−97 °C, afforded
2
2
2
fc(NH ) (10), are also described.
2
2
Et
33
1
in spectroscopically pure form. The concomitant
RESULTS AND DISCUSSION
■
formation of significant amounts of highly polar EtOH
facilitates the processing of the following reaction with FeCl2,
which was added as several aliquots in solid form to the
reaction mixture. Heating was continued for 4 h, and workup
proceeded as described for method 1 (vide supra; for slight
modifications, see Experimental Section). Method 2 finally
Synthesis of 1,1′-Ferrocenedicarboxylic Acid (4). For
the preparation of the key compound fc(COOH) (4), we
2
aimed at the preparation of the diesters fc(COOR) (R = Me,
2
Me
Et
2
; R = Et, 2 ), which should be accessible by the reaction of
FeCl with the sodium salts Na(C H COOR) (R = Et, 1 ; R =
Me, 1 ). In previous protocols, the esters 1 were synthesized
Et
2
5
4
Me
Et
afforded 2 in ca. 200 g quantity, corresponding to a ca. 60%
by reaction of NaCp with an excess of dimethyl or diethyl
yield in sufficient purity for further saponification to the diacid
1
8,20a
carbonate (DMC and DEC) in THF.
Similarly, our initial
4
. Although this convenient one-pot method uses exceptionally
method (method 1) also started from NaCp, which was
prepared in pure form from dicyclopentadiene according to the
cheap starting materials and avoids the time-consuming
synthesis and isolation of large amounts of highly air-sensitive
NaCp and 1 , it should be noted that the use of commercial
29
Et
procedure established by Panda et al. (Scheme 1). It was
found that the following reaction can be carried out directly in
concentrated DEC solution (∼3 M), and quantitative
Et
grade NaOEt (96%) generally affords 2 in slightly lower
purity compared to method 1. For higher demands, the diester
Et
formation of 1 was observed within 2 h.
At this stage, the slightly air-sensitive sodium salt 1 can be
can be further purified by distillation at 180 °C/0.015 mbar,
Et
Et
which afforded 2 in only slightly lower yield (ca. 55%).
Me
isolated as a crystalline material in 83% yield by recrystallization
from hot acetonitrile after filtration. However, the crude
reaction mixture obtained after evaporation of all volatiles
We also prepared dimethyl 1,1′-ferrocenedicarboxylate (2 )
following method 1 by using dimethyl carbonate as solvent.
Me
Because of the lower solubility of Na(C H COOMe) (1 ) in
5
4
Me
(
DEC and EtOH) could also be directly used without further
DMC and the higher melting point of the product 2 (mp =
34
purification for the subsequent reaction with ferrous chloride,
113.5−114.5 °C), both reaction steps were found to require
significantly more solvent (∼10 equiv) than was used for the
which was preferably carried out in concentrated acetonitrile
3
0,31
Et
Me
solution (∼5 M) by stirring at 80 °C for 14−16 h.
Thereby,
synthesis of 2 . 2 was isolated as a yellow solid in 87%
Et
Et
the low-melting nature of the resulting diester 2 (mp = 41.5−
overall yield, albeit on a significantly smaller scale than 2 . The
3
2
4
2 °C)
ensures that the reaction mixture remains
diesters themselves are valuable precursors in ferrocene
35
homogeneous during this transmetalation step. After evapo-
ration, hexane and a small amount of DMF for assisting the
agglomeration of NaCl were added, and the mixture was
filtered through Celite and concentrated under high vacuum to
chemistry; various amides, monoesters of the type fc-
32,36
(COOR)(COOH),
and the diol 1,1′-bis(hydroxymethyl)-
15
ferrocene, fc(CH OH) (3), can be prepared from them. The
2
2
latter (3) had previously been synthesized by reduction of
Et
15b
15c
afford 2 as a dark orange, viscous oil in 84% overall yield. This
fc(COOH) ,
fc(CHO)2,
4
and, more conveniently,
2
Me 15c−f
procedure (method 1) allowed the production of a maximum
2 ,
with LiAlH or NaBH . In our hands, the reduction
of 2 was accomplished in 85% yield by using 1.75 equiv of
4
Et
Et
of 70 g of 2 in a single run by use of a 0.5 L reaction flask. On
B
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Organometallics
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LiAlH , and 3 was isolated as a yellow microcrystalline powder
4
on a 63 g scale (Scheme 2).
Scheme 2. Preparation of Dialcohol 3 and Diisocyanate 7
Figure 1. Screw-cap bottles containing 200 g of 7, 300 g of 3, and 300
Et
g of 2 (left to right). Higher quality images can be found in the
Supporting Information.
synthesis of fc(COCl) (5), the use of chloroform instead of
2
dichloromethane not only shortened the reaction time
considerably from over 14 h to only 2.5 h, but also allowed
the amount of oxalyl chloride to be reduced from 4.8 to 3.1
equiv. Recrystallization of the crude red-brown product from
hot n-heptane resulted in isolation of a bright red, crystalline
material of analytical purity in 95% yield. Compound 5
appeared to be only slightly sensitive toward air and moisture
and can be stored for months in tightly closed vessels.
1
,1′-Bis(azidocarbonyl)ferrocene, fc(CON ) (6), was pre-
3
2
pared according to the previous procedures by addition of an
aqueous solution of sodium azide to an acetone solution of
recrystallized 5. After extraction with dichloromethane,
filtration through a silica pad, drying over Na SO , and
It should be noted that most previous protocols for the
2
4
Et
Me
syntheses of the diesters 2 and 2 involved esterification of
evaporation, 6 was isolated in analytically pure form as a red-
orange powder. This method proved to be superior to the
synthesis of 6 without isolation and purification of 5, since
phase separation after addition of CH Cl and therefore the
1
3,32,37
fc(COOH) (4),
while here the opposite approach was
2
Et
pursued, with the ester 2 serving as a precursor for the
preparation of 4. Hence, saponification of the diester 2 on
Et
2
2
scales up to 150 g was performed at elevated temperature by
complete removal of water proved difficult. It should be noted
that the diazide 6 is susceptible to self-ignition upon contact
with hot surfaces, and although 6 decomposes at considerably
addition of aqueous NaOH solution to an ethanol solution of
Et
2
, producing the sodium salt fc(COONa) , which was isolated
2
27
by filtration, dissolved in water, and protonated by addition of
higher temperature (>100 °C) than fc(N ) (56 °C), care
3 2
concentrated HCl. The precipitated diacid fc(COOH) (4) was
should be taken upon handling the pure compound! The final
Curtius rearrangement of 6 was performed on a 60 g scale by
heating a 0.5 M toluene solution at 100 °C for 2 h, and the
diisocyanate 7 was isolated as a yellow crystalline solid in 81%
yield after filtration and crystallization from toluene solution.
To obtain the final target compound 1,1′-diaminoferrocene
(10) from 7, the carbamate route was chosen. Two 1,1′-
2
isolated by filtration and dried by heating at 60−70 °C in a
large crystallizing dish overnight to afford 4 as an orange
powder. Thereby, the yields varied depending on the starting
Et
Et
material. When 2 , prepared by method 1, or distilled 2 ,
prepared by method 2, were employed, 4 was isolated in nearly
quantitative yield. Saponification of the crude product obtained
by method 2 gave lower yields of 69−77%, which corresponds
to overall yields of 40−49% starting from cyclopentadiene. In
2
5b
dicarbamates, fc(NHCOR) with R = OMe (8)
and R =
2
38
OtBu (9), were simply prepared from 7 by treatment with the
corresponding alcohols and were isolated in high yields as
bright yellow, air-stable compounds (Scheme 3). Alternatively,
9 was also prepared directly from the diazide 6 in a similar
Et
most cases, however, 2 was not distilled and was used as
received after workup according to method 2. By combination
of this method with the subsequent saponification protocol, 90
g of 4 can routinely be prepared in a single run within 3 days,
and we have reliably repeated this procedure at least 10 times in
38
fashion to that initially reported by Kraatz et al. In our hands,
addition of tBuOH to the toluene solution of fc(NCO) (7)
2
order to prepare and commercialize the compounds fc-
that was obtained after heating fc(CON ) (6) for 2 h at 110
3
2
Et
(
COOEt) (2 ), fc(CH OH) (3), and fc(NCO) (7) in
°C in toluene afforded a solution of 9, which was isolated in
81−86% yield as an orange, microcrystalline solid after
evaporation, dissolving in ethyl acetate/hexane, and filtration
through silica.
2
2
2
2
amounts of 300 g (Figure 1).
Syntheses of 1,1′-Disubstituted Ferrocene Deriva-
tives from 1,1′-Ferrocenedicarboxylic Acid (4). The
transformation of 4 to 1,1′-diisocyanatoferrocene (7) was
The hydrolysis of methyl carbamate 8 under basic conditions
24
performed according to Petrovitch’s method, which had been
(5% KOH in methanol/H O, 1:1, reflux) was adopted from the
2
26
further optimized by van Leusen and Hessen, with small
procedure reported by Arimoto and Haven for O-benzylcarba-
39
modifications shown in Scheme 2. In particular, for the
mato-ferrocene, Fc-NHCOOBn. In our case, prolonged
C
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Scheme 3. Syntheses of Dicarbamates 8 and 9 (Boc =
−COOtBu) and Their Hydrolysis to Diamine 10
Figure 2. ORTEP diagram of 2Et and 7· / C H shown with 50%
1
2
6
6
thermal ellipsoids. Solvent molecules C H for 7 and hydrogen atoms
6
6
have been omitted for clarity. Selected bond lengths (Å) and (torsion)
Et
angles (deg) for 2 : Fe−Ct 1.653, Fe−Ct 1.659, C1−C11 1.468(2),
1
2
C6−C14 1.478(2), C11−O1 1.213(2), C14−O3 1.213(2), C11−O2
1
1
.343(2), C14−O4 1.241(2); Ct −Fe−Ct 178.7, C1−C11−O1
1
2
23.53(16), C6−C14−O3 124.55(16), O1−C11−O2 123.72(16),
1
O3−C14−O4 124.38(16), C1−Ct −Ct −C6 0.1. Data for 7· / C H :
1
2
2
6
6
Fe−Ct 1.651, Fe−Ct 1.651, C1−N1 1.3880(19), C6−N2
1
2
1
.3935(19), C11−N1 1.185(2), C12−N2 1.189(2), C11−O1
.1751(18), C12−O2 1.1739(19); Ct −Fe−Ct 178.52, C1−N1−
1
1
2
C11 147.90(15), C6−N2−C12 142.54(15), N1−C11−O1
1
72.33(17), N2−C12−O2 172.82(18), C1−Ct −Ct −C6 0.2.
1
2
reaction times up to 6 h were necessary to achieve high
conversions. In contrast, the acidic hydrolysis of tert-
butoxycarbonyl-protected (Boc) amines is known to proceed
40
under milder conditions. The method recently reported by
Kostyuk and Hierso et al. utilized comparatively expensive
trifluoroacetic acid, CF COOH, as an anhydrous acid source in
3
excess of 10 equiv, albeit proceeding under very mild
2
8
conditions (CH Cl /−30 °C) and affording high yields.
2
2
Figure 3. ORTEP diagram of 8·MeOH shown with 50% thermal
ellipsoids. Only one of the two independent molecules is shown.
Solvent molecules MeOH and hydrogen atoms, except those of the
NH groups, have been omitted for clarity. Selected bond lengths (Å)
However, we decided to use a solution of HCl in MeOH,
produced in situ by reaction of acetyl chloride, CH COCl, with
3
anhydrous MeOH, according to the original procedure
41
developed by Nudelman et al. This method is clearly
superior, since only a slight excess of acid and relatively
and (torsion) angles (deg) for 8·MeOH: Fe−Ct
.652/1.654, C1−N1 1.401(5)/1.397(6), C6−N2 1.410(5)/1.395(6),
N1−C11 1.353(3)/1.350(5), N2−C13 1.349(5)/1.343(5), C11−O1
.221(5)/1.221(5), C13−O3 1.213(5)/1.229(5), C13−O4 1.342(5);
1
1.661/1.656, Fe−Ct
2
1
42
cheap starting materials are required. Thus, treatment of
1
dicarbamate 9 with HCl/MeOH (3 equiv, 75 min at 65 °C)
43
Ct −Fe−Ct 178.5/178.13, C1−N1−C11 125.2(4)/124.8(4), C6−
1
2
resulted in a quick reaction with vigorous gas evolution, and
the diamine 10 was conveniently isolated in 84−93% yield after
appropriate workup. Whereas aqueous workup proved to be
N2−C13 124.5(4)/126.1(4), N1−C11−O1 126.2(4)/125.9(4), N2−
C13−O3 125.1(4)/126.4(4), N1−C11−O2 109.3(3)/109.4(4), N2−
C13−O4 110.4(4)/109.3(3), C1−Ct −Ct −C6 −0.7/−1.6.
28
1
2
convenient for small-scale preparation of 10, we developed an
alternative water-free procedure that involved addition of a
methanolic KOH solution and removal of KCl by filtration
through silica followed by extraction with CH Cl . Pure
lengths; for instance, the isocyanate groups in 7 are almost
linear, as indicated by NCO angles of 172.33(17)° and
172.82(18)° with NC and CO distances of 1.185(2)/
1.189(2) Å and 1.1751(18)/1.1739(19) Å, which resemble
those in other structurally characterized isocyanates, cf. (p-
2
2
samples of yellowish-brown 10 were obtained by recrystalliza-
tion from MeOH.
Crystal Structures. The ferrocene derivatives 2 , 7, and 8
Et
4
6
were characterized by X-ray diffraction analysis. Single crystals
OCN-C H ) CH . Analysis of the crystal packing reveals only
6 4 2 2
Et
1
Et
of the composition 2 , 7· / C H , and 8·MeOH were obtained
weak intermolecular contacts in the case of 2 , with CH···O
contacts ranging from 2.54 to 2.71 Å, which falls just slightly
below the van der Waals cutoff criterion of 2.72 Å (rvdW(H) =
2
6
6
by slow evaporation of their concentrated hexane, benzene, and
MeOH solutions, respectively. Their molecular structures are
presented in Figures 2 and 3, and selected crystallographic
parameters are assembled in Table 1. In all three structures, the
molecules adopt eclipsed, synperiplanar conformations with
regard to the relative orientations of the Cp rings and of the
47
1.20 Å, r (O) = 1.52 Å). Weak hydrogen bonding is also
vdW
1
found in 7· / C H , with each molecule displaying two CH···O
2
6
6
contacts of 2.38 and 2.53 Å with one of the neighboring
molecules to afford chains of fc(NCO) molecules parallel to
2
substituents, as indicated by very small torsion angles C1−Ct −
2
the b axis, which are additionally linked by benzene molecules
through weak CH···O contacts of 2.52 and 2.70 Å (Figure 4).
The crystal structure of 8·MeOH features significantly stronger
hydrogen bonds with two molecules forming a hydrogen-
bonded pair through two NH···O contacts of 2.08 Å; these
pairs are linked by NH···O and OH···O contacts of 1.93/2.00
and 2.05/2.00 Å involving the methanol solvate molecules to
form chains of alternating molecules of 8 and methanol parallel
to [101], with ferrocene moieties oriented perpendicularly to
the chain (see Figure 5).
1
Et 44
Ct −C6 (Ct = centroid of the Cp ring) of 0.1° (for 2 ), 0.2°
(
for 7), and −1.2° (average value for two independent
molecules of 8 in the asymmetric unit). Whereas the anti-
orientation of the functional groups in the structures of 2 and
Et
8
7
renders the molecules almost C -symmetric, the diisocyanate
2
exhibits an almost C -symmetric structure with a syn-
s
conformation of the two aligned NCO moieties.
The ferrocene moieties do not feature any unusual structural
4
5
features, and the substituents show the expected bond
D
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Organometallics
Article
Table 1. Selected Crystallographic Data for Compounds
were established, involving the preparation of the correspond-
Et
1
fc(COOEt) (2 ), fc(NCO) (7· / C H ), and
ing acid chloride and azide fc(COCl) (5) and fc(CON ) (6).
2
2
2
6
6
2
3 2
fc(NHCOOMe) (8·MeOH)
Furthermore, 1,1′-diaminoferrocene (10) can be made
accessible in larger quantities from 6 or 7 via the carbamate
2
2Et
7· / C H
6
1
8·MeOH
2
6
fc(NHBoc) (9). Although most of the reaction steps discussed
2
empirical formula
fw
C H FeO
C H FeN O
C H FeN O
1
6
18
4
15 11
2
2
15 20
2
5
herein have precedence in the literature, we feel that our
protocols might be very useful for numerous other research
groups interested in ferrocene chemistry and might therefore
have a significant impact on further development of this
research area, which is still unremittingly vivid more than 60
years after the discovery of ferrocene.
330.15
307.11
364.18
wavelength/Å
cryst syst
space group
a/Å
0.71073
monoclinic
1.54184
triclinic
1.54184
monoclinic
Pc
P2 /c
1
P1
̅
13.7576(4)
10.1798(2)
10.6675(2)
90
7.8985(7)
9.1385(8)
10.3167(8)
112.101(8)
91.731(7)
112.435(8)
624.46(9)
2
11.2801(8)
13.1742(8)
b/Å
c/Å
12.0254(10)
90
EXPERIMENTAL SECTION
α/deg
■
β/deg
104.088(2)
90
117.540(10)
90
General Remarks. Standard Schlenk-line techniques under inert
Et Et Me
gas atmosphere (N ) were used for the syntheses of 1 , 2 , 2 , 3, 7,
γ/deg
V/Å3
2
8, 9, and 10. Solvents (toluene, n-heptane) and tert-butanol were dried
over molecular sieves 3 Å; other common solvents were of solvent
grade quality. Solvents for the synthesis of fc(NH ) were degassed
1449.04(6)
4
1584.6(2)
4
Z
−
3
2 2
Dcalc/g cm
μ/mm−
1.513
1.633
1.527
prior to use. Reagent grade diethyl carbonate, dimethyl carbonate,
1
1.053
9.707
7.883
EtONa (Acros, 96%), oxalyl chloride (Acros, 98%), and sodium azide
indep reflns
R(int)
R1
3305
2583
4826
48
29
were used without purification. FeCl2 and Na(C H ) were
5
5
0.0457
0.0289
0.0653
1.099
0.0518
0.0637
0.0432
0.1026
1.026
prepared according to literature procedures. NMR spectra were
recorded on Bruker DPX-200, AV II-300, and DRX-400. EI mass
spectra were recorded on a Finnigan MAT 8400-MSS I or Finnigan
MAT 4515. Melting points were determined with an MPM-HV2.
Elemental analyses were performed at the Microanalytical Department
of the Technical University of Braunschweig. Dimensions for diameter
0.0249
wR2
0.0667
GOF
1.105
(
⦶) and height (H) are given in millimeters.
X-ray Diffraction Studies. Data were recorded on various
diffractometers from Oxford Diffraction, using monochromated Mo
Kα or mirror-focused Cu Kα radiation. Absorption corrections were
applied on the basis of multiscans. Structures were refined anisotropi-
cally on F2 using the program SHELXL-97 (G. M. Sheldrick,
̈
University of Gottingen, Germany). Treatment of hydrogen atoms:
NH and OH hydrogens were refined freely, methyls as idealized rigid
groups allowed to rotate but not tip, other H using a riding model
starting from calculated positions. Numerical details are summarized in
Table 1. Complete data have been deposited at the Cambridge
Crystallographic Data Centre under the numbers CCDC 942084
1
Figure 4. Packing diagram of 7· / C H viewed perpendicular to the
2
6
6
bc plane (slightly rotated for clarity). Hydrogen bonds C−H···O are
indicated by dashed lines. Hydrogen bonds to the benzene molecules,
which link the chains in the third dimension, are omitted for clarity.
Et
1
(
2 ), 942085 (7· / C H ), and 942086 (8·MeOH). These data can be
2 6 6
obtained free of charge from www.ccdc.cam.ac.uk/data_request/cif.
Synthesis of Sodium (Ethoxycarbonyl)cyclopentadienide,
Et
Na(C H COOEt) (1 ). Diethyl carbonate (160 mL, 2.5 equiv) was
5
4
added to solid Na(C H ) (45.9 g, 0.52 mol) in a 0.5 L Schlenk flask,
5
5
accompanied by mild warming (ca. 40 °C). The resulting thick
suspension was placed in a preheated oil-bath (100−105 °C). The
reaction mixture slowly liquefied, and a clear cherry-red solution
formed. After stirring for 2.5 h, the volume of the reaction mixture was
reduced in vacuo to two-thirds at 100 °C/3 mbar. Drying the syrup-like
mass at 100 °C/<0.5 mbar for 30 min resulted in formation of a pale
red semisolid residue (collected volume of condensate: 80−90 mL).
Et
This material was used without further purification to prepare 2
according to method 1. If desired, the compound could be isolated in
analytically pure form by crystallization from hot filtered MeCN
solution. An additional crop of the product was obtained by
concentration of the mother liquor. Isolated yield: 83% (69.1 g).
Figure 5. Packing diagram of 8·MeOH showing chains of molecules
parallel to [101]. Classical hydrogen bonds are indicated by dashed
lines.
1
The compound is soluble in water, THF, acetone, and DMSO. H
3
NMR (DMSO-d , 300.1 MHz, 300 K): δ 1.17 (t, J = 7.1 Hz, 3H,
6
HH
CONCLUSION
A convenient method for the preparation of diethyl
ferrocenedicarboxylate, fc(COOEt) (2 ), on a very large
3
3,4
CH ), 3.96 (q, J = 7.1 Hz, 2H, CH ), 5.51 (m, HC ), 6.10 (m,
HC ) ppm. C{ H} NMR (DMSO-d , 75.5 MHz, 300 K): δ 13.3
(CH ), 56.1 (CH ), 108.4 (C ), 108.9 (C ), 111.2 (br s, C ), 165.9
■
3
HH
2
2
,5
13
1
6
1
3,4
2,5
Et
3
2
2
(
CO) ppm.
scale (∼200 g) from cheap, common starting materials (CpH,
Method 1: Synthesis of Diethyl 1,1′-Ferrocenedicarboxylate,
EtONa, DEC, and FeCl , no additional solvent) was presented,
Et
Et
2
fc(COOEt) (2 ), Starting from 1 . To the semisolid, nonpurified
2
allowing the production of ∼100 g of ferrocenedicarboxylic
material, obtained from the synthesis of Na(C H COOEt) (vide
5
4
acid, fc(COOH) (4), in a single run upon saponification. With
2
supra), solid FeCl (36 g, 0.28 mol, theoretical amount of ca. 0.55
2
large amounts of this material in hand, scaled-up procedures for
equiv) and MeCN (100 mL) were added successively with water-bath
the synthesis of the 1,1′-ferrocenediisocyanate fc(NCO) (7)
cooling. An exothermic reaction took place, with warming to ca. 50 °C
2
E
dx.doi.org/10.1021/om4004972 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
and formation of a thin orange suspension. The slurry was heated to
mbar; the orange, more viscous tails from distillation contain mainly a
8
0 °C with an overpressure-controller and stirred for 14−16 h. The
volatiles were first evaporated in vacuo, and the solid was dried at 75−
0 °C (0.5 mbar) and further at 100−110 °C (0.05 mbar) for 0.5 h.
The isolation of the product was performed by addition of hexanes
150 mL), filtration of the resulting suspension through a short Celite
mixture of unidentified impurities). Yield: ca. 55% (ca. 180 g) of an
1
orange oil that quickly solidifies upon standing. H NMR (CDCl ,
3
3
3
8
300.1 MHz, 300 K): δ 1.34 (t, J = 7 Hz, 3H, CH ), 4.27 (q, J
=
HH
3
HH
2,5
3,4
7 Hz, 2H, CH ), 4.39 (m, 2H, HC ), 4.82 (m, 2H, HC ) ppm.
2
13
1
(
C{ H} NMR (CDCl , 75.5 MHz, 300 K): δ 14.5 (CH ), 60.4
3
3
2,5
3,4
1
pad (⦶150, H30), and rinsing the residue with hexanes until the
filtrate was colorless. The filtration of the very fine suspension of NaCl
was significantly accelerated by dropwise addition of DMF (7.0 mL)
under vigorous stirring and further stirring for 30 min at 50 °C. If a
low-quality batch of Na(C H ) was used, an additional tarry, brown
(OCH ), 71.5 (C ), 72.7 (C ), 73.1 (C ), 170.4 (CO) ppm. Anal.
2
Calcd for C H FeO (330.16): C 58.21, H 5.50. Found: C 58.50, H
16
18
4
5.64.
Synthesis of Dimethyl 1,1′-Ferrocenedicarboxylate, fc-
Me
Et
(COOMe) (2 ). The synthesis was performed as described for 2
5
5
2
residue forms at this stage; an acidic aqueous workup, involving
extraction with EtOAc, is recommended in this case. Volatiles from the
collected filtrates were removed in vacuo (100 mbar) and further dried
at 100 °C (0.5 → 0.05 mbar) to yield a dark orange oil. Overall yield
from Na(C H ): 84% (71.5 g) of a viscous, dark orange oil with sweet
odor that solidifies on prolonged standing. An analytically pure sample
was obtained by crystallization from hexane at 0 °C as a yellow,
crystalline solid.
(method 1) starting from NaCp (2.24 g, 25.7 mmol) and dimethyl
carbonate (25 mL, 297 mmol, 12 equiv), to yield the crude
Me
Na(C H COOMe) (1 ). Further treatment with FeCl2 (1.80 g,
5
4
14.2 mmol, 0.55 equiv) in 20 mL of MeCN according to method 1
Me
resulted in formation of the ferrocene 2 , which could be obtained in
5
5
Me
1
87% overall yield after workup (3.38 g, 11.2 mmol). For 2 : H NMR
(CDCl , 300.1 MHz, 300 K): δ 3.77 (s, 3H, OMe), 4.35 (s, 2H,
3
2
,5
3,4
13
1
HC ), 4.77 (s, 2H, HC ) ppm. C{ H} NMR (CDCl , 75.5 MHz,
300 K): δ 51.7 (OMe), 71.5 (C ), 72.5 (C ), 72.7 (C ), 170.7
(COOMe) ppm. Anal. Calcd for C H FeO (302.11): C 55.66, H
4.67. Found: C 55.51, H 4.83. For sodium salt 1 : H NMR (DMSO-
d , 300.1 MHz, 300 K): δ 3.47 (OMe), 5.52 (C ), 6.11 (C ) ppm.
3
2,5
3,4
1
Method 2: Synthesis of Diethyl 1,1′-Ferrocenedicarboxylate,
Et
fc(COOEt) (2 ) Starting from Cyclopentadiene. A 2 L three-
2
14 14
4
Me
1
necked flask, equipped with an effective mechanical stirrer and a reflux
condenser with a bubbler, was charged with powdered EtONa (140 g,
ca. 2.0 mol) and diethyl carbonate (700 mL, ca. 3 equiv). The
suspension was cooled with an ice-bath and deaerated. Freshly
prepared cyclopentadiene (130 g, ca. 160 mL, 2.0 mol) was added in
two portions with an interval of 10 min, whereupon a thick, pale red to
yellow suspension formed. The reaction mixture was vigorously stirred
for 30 min without cooling. The flask was then immersed in a
preheated oil-bath (110 °C). At an inner temperature of the reaction
mixture of 40−50 °C, the reaction mixture liquefies; it was heated
further for 4 h, maintaining the temperature at 95−97 °C with slight
overpressure. The color of the reaction mixture fades from cherry-red
or brown to pale yellow or light brown, depending on the purity of
reagents used and efficacy of deaeration. The heating bath was
3,4
2,5
6
1
3
1
C{ H} NMR (DMSO-d , 75.5 MHz, 300 K): δ 48.7 (OMe), 108.0
6
1
3,4
2,5
(
C ), 109.2 (C ), 111.2 (br s, C ), 166.3 (CO) ppm.
Synthesis of 1,1′-Bis(hydroxymethyl)ferrocene, fc(CH OH)
2
2
(3). A 1 L three-necked flask equipped with a reflux condenser, a 0.25
L dropping funnel, and magnetic stirring bar was charged with dry
THF (250 mL). Powdered LiAlH (20 g, 1.75 equiv) was added to the
4
ice-cooled solvent under nitrogen atmosphere. A solution of distilled
fc(COOEt) (100 g, 0.303 mol) in THF (80 mL) was placed in a
2
dropping funnel and was added to the stirred ice-cooled suspension of
the reductant dropwise over 1 h. After the addition was completed, the
reaction mixture was allowed to come to ambient temperature (0.5 h)
and was heated with a water-bath to 45−50 °C for 1 h. The progress of
the reaction can be monitored by TLC. After the reaction was
complete, it was poured in small portions into ice-cooled EtOAc (250
mL) with vigorous stirring. After each addition, significant, but
temporary, thickening of the mixture took place. To the thick, bright
yellow suspension, water was carefully added (180−200 mL) in
portions; the last 20−40 mL should be added in small portions and
larger intervals, whereupon the inorganics separate as a compact
creamy material. The brown organic phase was easily separated by
decantation; the inorganics were thoroughly rinsed with EtOAc (5 ×
20 mL). The combined organic phases were dried with K CO (3 × 25
removed, and solid FeCl (130 g, 1.02 mol) was added at ca. 80 °C in
2
five portions of 20 g at the beginning and in three smaller portions of
1
0 g at the end over 1 h. Each addition causes a short, but exothermic
reaction (the use of low-purity FeCl or too rapid addition of FeCl
2
2
without noticeable reactiondissolution of added FeCl and deep-
2
ening of orange colorcan result after an induction period in a
vigorous reaction that can be controlled by the use of an effective
reflux condenser). After addition of FeCl the reaction mixture was
2
stirred for 4 h at 95−97 °C. The further workup was performed
similarly to that described in method 1. The volatiles (0.50 L) were
first removed in vacuo, and the further workup should be performed in
air. Hexane (0.60 L) and DMF (30 mL, dropwise) were added
successively, and the brown reaction mixture was stirred at 50 °C for
2
3
g, pearls) with stirring. The brown organic phase was carefully
concentrated in a rotary evaporator until the total volume was 200 mL.
Crystallization was facilitated by scratching with a spatula and cooling
with an ice-bath. The yellow powdery solid was filtered off, washed
with toluene, and dried in vacuo (54 g). The volatiles from the mother
liquor were completely removed, and the remaining solid was
recrystallized from toluene (1 g/7 mL solvent), yielding an additional
30 min, whereupon a precipitate forms. The latter was conveniently
filtered off using a Celite pad (⦶150, H30) and washed with hexane
until the washings were almost colorless. The collected washings (1.4−
1.6 L) were left for 1 h in a large beaker with air contact (some amount
of black impurity precipitates). From the collected washings, a portion
of 250 mL was diluted with hexane (250 mL), and the resulting
suspension was stirred vigorously with 30 g of silica gel. The
supernatant was collected by decantation, filtered using a folded filter
paper, and evaporated on a rotary evaporator (650 mbar/70 °C). The
collected volatiles (mainly hexane, ca. 300 mL) were used again for
dilution of the next portion of 250 mL in the same flask, charged with
used silica gel. The procedure was repeated, and concentrated product
as a clear bright orange solution was collected. A small amount of solid
impurity can form upon air contact. It was removed by filtration with
the aid of a Celite pad (⦶50, H30), and the filtrate was concentrated
on a rotary evaporator (600 → 50 mbar/75 °C) and then in vacuo (5.0
amount of product. The total amount of 63 g of product was obtained
1
as a yellow solid (yield: 85%). H NMR (CDCl , 300.1 MHz, 300 K):
3
2
,5
δ 3.67 (br s, ν = 5.5 Hz, 2H, OH), 4.17 (m, 4H, HC ), 4.21 (m,
4H, HC ), 4.40 (br s, ν = 3.3 Hz, 4H, CH O) ppm. C{ H} NMR
(CDCl , 75.5 MHz, 300 K): δ 60.3 (−CH O), 67.0 (C ), 68.0 (C ),
89.3 (C ) ppm. Anal. Calcd for C H FeO (246.09): C 58.57, H
1/2
3
,4
13
1
1/2
2
2,5
3,4
3
2
1
12
24
2
5.73. Found: C 58.75, H 5.73.
Synthesis of 1,1′-Ferrocenedicarboxylic Acid, fc(COOH) (4).
2
To a solution of fc(COOEt) (150 g, 0.454 mol), prepared by method
2
2, dissolved in hot EtOH (750 mL), was added a hot aqueous solution
of NaOH (150 g, 8.2 equiv) in water (750 mL) in a 2 L round-bottom
Et
flask. (The entire amount of crude 2 obtained by method 2 can be
→
0.05/100 °C) using a short-path external trap cooled with liquid
used by changing to a larger flask.) The reaction mixture was placed in
a preheated water-bath (70−75 °C) with an overpressure controller.
Soon after, precipitation of an orange solid began, and the mixture was
held at that temperature for 2 h without stirring. After cooling to 0 °C,
the precipitated disodium salt was isolated by filtration and washed
with ethanol to remove dark red-brown impurities. The bright orange
N . Yield of the crude, dark orange, oily product: 58−63% (192−208
2
g). This material was used directly for further hydrolysis without
purification. Higher purity product was obtained by air-cooled
fractional short-path distillation (pot temperature for collecting
Et
forerun (ca. 20 g): 160 °C/0.060 mbar; for 2 : 160−180 °C/0.015
F
dx.doi.org/10.1021/om4004972 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
salt was placed in a 2 L beaker and diluted with hot water to a total
volume of 1.8 L with stirring. The dark brown solution was carefully
acidified with concentrated HCl (0.20 L), whereupon the product
precipitated as an orange solid. The ice-cooled slurry was filtered by
dried over Na SO . The solvent was removed on the rotary
2
4
evaporator. Trace amounts of moisture were removed by drying in
oil-pump vacuum (0.03 mbar) at 50 °C. Yield: 92−97% (59.8−62.8 g)
of a red-orange powder. The compound is slightly light-sensitive;
therefore it should be stored in a dark, cool place in tightly closed
flasks.
̈
means of a large Buchner funnel, washed thoroughly with water until
the washings were almost colorless, dried at 60−70 °C on a large plate
overnight, and ground to a powder. Yield: 69−77% (86−96 g) of a
bright orange solid. The compound tends to electrostatic charging if
powdered and is insoluble in all common solvents, except DMSO,
b. Synthesis of 1,1′-Bis(azidocarbonyl)ferrocene, fc(CON )
3
2
(6), Starting from 4. In a 1 L round-bottom flask fc(COOH) (61 g,
2
0.22 mmol) was suspended in 225 mL of CHCl , followed by addition
3
DMF, MeOH/water mixtures, and aqueous alkalis. Solutions of 4 are
of pyridine (0.5 mL 3 mol %) and oxalyl chloride (60 mL, 3.2 equiv)
(alternatively, 210 mL of a 1.1 M solution from previous synthesis, vide
supra, and stoichiometric amount of oxalyl chloride (40 mL, 0.47
mmol) can be used). The mixture was heated to reflux and stirred at
this temperature for 3 h. The major evolution of gas, including HCl,
was observed in the first two hours of heating and was neutralized by a
10% NaOH solution. The solvent and excess oxalyl chloride were
1
slightly air-sensitive, turning darker. H NMR (DMSO-d , 300.1 MHz,
6
2,5
3,4
3
00 K): δ 4.45 (m, 2H, HC ), 4.69 (m, 2H, HC ), 12.29 (br s, 1H,
COOH) ppm. C{ H} NMR (DMSO-d , 75.5 MHz, 300 K): δ 71.4
1
3
1
6
2,5
3,4
1
(
br s, C ), 72.6 (C ), 73.4 (C ), 171.3 (br s, CO) ppm. Anal.
Calcd for C H FeO (274.05): C 52.59, H 4.08. Found: C 53.11, H
12
10
4
3
.90.
Synthesis of 1,1′-Bis(chlorocarbonyl)ferrocene, fc(COCl) (5).
removed in vacuo to yield crude fc(COCl)
residue was dissolved in 675 mL of acetone and stirred vigorously
while adding NaN (31.6 g, 2.2 equiv) dissolved in 90 mL of water.
This solution was stirred for 1.5 h at 50 °C, whereupon NaCl forms,
and after that treated with 100 mL of saturated NaHCO and divided
2
as a dark red solid. This
2
In a 1 L one-necked flask containing a suspension of finely powdered
fc(COOH)2 (90 g, 0.33 mol) in CHCl3 (0.3 L) were added
successively pyridine (1.2 mL, 5 mol %) and oxalyl chloride (90
mL, 3.2 equiv). The reaction mixture was heated at 60 °C with a reflux
condenser until complete dissolution (ca. 2 h). The reaction was
accompanied by vigorous gas evolution (neutralized by bubbling
through a 10% solution of NaOH; fume hood!) and formation of a
deep red solution. After the gas evolution ceased, it was stirred at that
temperature for an additional 0.5 h to complete the reaction. All
volatiles were removed under reduced pressure into a trap cooled with
liquid nitrogen (this condensate containing oxalyl chloride can be
3
3
into two 2 L beakers, which were then each filled to 2 L with water.
The mixtures were cooled with ice to ensure the complete
precipitation of the product. The mixture was filtered through a
large glass frit-filter and washed thoroughly with water (ca. 3−4 L).
The red solid was dried first by sucking air through it and later in
vacuo. At the end of the drying procedure the product was powdered
and passed through a sieve. By this method 65.1 g (200 mmol, 91%) of
49
continuously used for the next syntheses of 5). The remaining dark
red-brown solid can be used without purification for the synthesis of
fc(CON ) according to the procedure b (vide infra). High-purity
fc(CON ) of a very fine reddish-brown powder was obtained. The
3 2
product synthesized by method b is slightly more impure than that
synthesized by method a, containing a brown impurity. Nevertheless, it
3
2
1
crystalline material was obtained as follows: the powdered crude
material was dissolved in boiling n-heptane (300 mL for ca. 30 g; the
mother liquor from the first crystallization was continuously reused for
the residual part of the crude product), and the slightly cooled
supernatant was decanted from a sticky black residue, followed by slow
cooling to ambient temperature (with stirring) and after that on an ice-
bath. The bright red microcrystalline solid was collected by quick
filtration using a frit-filter, rinsed with small amounts of hexane, and
dried in vacuo. Yield: 95% (97 g, 0.31 mol) of odorless, red,
can be used for further reaction to fc(NCO)
2
and fc(NHBoc)
2
. H
2,5
3,4
NMR (CDCl , 300.1 MHz, 300 K): δ 4.55 (HC ), 4.89 (HC ) ppm.
3
13
1
2,5
3,4
C{ H} NMR (CDCl , 75.5 MHz, 300 K): δ 72.1 (C ), 74.1 (C ),
3
1
74.3 (C ), 175.5 (CO) ppm. Anal. Calcd for C H FeO N
1
2
8
2
6
(324.08): C 44.47, H 2.49, N 25.93. Found: C 44.37, H 2.72, N 25.57.
Synthesis of 1,1′-Diisocyanatoferrocene, fc(NCO) (7). A 1 L
2
round-bottom flask, equipped with a reflux condenser and a bubbler,
was charged with dry fc(CON ) (64 g, 0.20 mol) in dry toluene (0.6
3
2
L), and the suspension was placed in a preheated oil-bath (110 °C).
1
microcrystalline solid, which hydrolyzes only slowly in moist air. H
After the bath temperature rose to 95 °C, vigorous N evolution began
2
2
,5
NMR (CDCl , 300.1 MHz, 300 K): δ 4.77 (s, 4H, HC ), 5.05 (s, 4H,
(bath temp: 100 °C). Because of the exothermic nature of the
decomposition, after a sluggish effervescence at the beginning, the
progress of the reaction was controlled by the degree of immersion of
the reaction flask into the oil-bath. After the gas evolution had
completely ceased (ca. 2 h), the warm, deep yellow suspension was
freed from a black precipitate by quick filtration in air through a short,
dry Celite pad. Concentration of the filtrate in vacuo to ca. 75 mL and
slow cooling to 0 °C led to crystallization of the product. This was
isolated by filtration, rinsed with a toluene/hexane mixture (2:1), and
dried in vacuo, leaving a yellow, crystalline solid. An additional crop of
product was obtained from the concentrated mother liquor. The
compound can be stored at 5 °C for months; nevertheless, slow
decomposition with darkening can take place. It is therefore
recommended to protect the product from moisture. Yield: 81%
3
3,4
1
HC ) ppm. H NMR (C D , 300.1 MHz, 300 K): δ 3.92 (s, 4H,
6
6
2,5
3,4
13
1
HC ), 4.52 (s, 4H, HC ) ppm. C{ H} NMR (C D , 75.5 MHz,
6
6
2,5
3,4
1
3
00 K): δ 74.3 (C ), 76.1 (C ), 77.5 (C ), 168.1 (CO) ppm.
Anal. Calcd for C H Cl FeO (310.95): C 46.35, H 2.59. Found: C
12
8
2
2
4
6.50, H 2.51.
a. Synthesis of 1,1′-Bis(azidocarbonyl)ferrocene, fc(CON )
3
2
(6), Starting from 5. CAUTION! Avoid any contact with hot objects!
In air and at temperatures over 100 °C intensive combustion might
occur! Even small amounts (1−2 mg) of the compound decompose
vigorously with self-ignition at temperatures close to the melting point
5
0
(
mp = 112−115 °C). In our case, we were unable to cause
detonations by impacts with a hammer, nevertheless protective clothing
should be worn! To a vigorously stirred solution of purified fc(COCl)2
1
(
63 g, 0.20 mol) in acetone (0.6 L) was added a solution of NaN (29
(43.4 g) of a yellow-brownish, microcrystalline solid. H NMR
3
3
,4
g, 2.2 equiv) in 90 mL of water in four portions. After a mildly
exothermic reaction (spontaneous precipitation of the product is
possible), the reaction mixture was stirred at 45−50 °C for an
additional 1 h. After that time, a concentrated solution of NaHCO3
(CDCl , 300 MHz, 300 K): δ 4.07 (m, 2H, HC ), 4.34 (m, 2H,
3
2,5
13
1
2,5
HC ) ppm. C{ H} NMR (CDCl , 75.5 MHz, 300 K): δ 65.9 (C ),
66.7 (C ), 90.7 (C ), 123.5 (br s, NCO) ppm. Anal. Calcd for
3
3,4
1
C H FeN O (268.053): C 53.77, H 3.01, N 10.45. Found: C 53.62,
12
8
2
2
(50 mL) was added dropwise, resulting in the formation of a red thick
H 3.21, N 10.33.
suspension. Further slow addition of water (200 mL) was performed
with manual swirling of the flask. The reaction mixture was further
diluted with ice-cold water until the total volume was 2.0 L. The fine,
deep red precipitate was filtered off using a large frit-filter and washed
thoroughly with water. The sticky residue was taken up with 400 mL
of CH Cl , the organic layer was separated, and the aqueous phase was
Synthesis of 1,1′-Bis[(methoxycarbonyl)amino]ferrocene,
fc(NHCOOMe) (8). A suspension of fc(NCO)2 (968 mg, 3.61
mmol) in 10 mL of dry methanol was heated to boiling and stirred
while it cooled to room temperature. The yellow to orange precipitate
was allowed to crystallize overnight. The supernatant was removed by
decantation; the solid filtered and dried in vacuo to yield 93% (1.11 g,
2
2
1
extracted twice with CH Cl (150 mL each). The combined organic
3.35 mmol) of a yellow crystalline solid. H NMR (Me CO-d , 300
2
2
2
6
3,4
layers were passed through a short plug of silica (H20, ⦶40). The
product was eluted with the same solvent (R (CH Cl ) = 0.36) and
MHz, 300 K), δ 3.65 (s, 3H, MeO), 3.92 (s, 2H, HC ), 4.47 (br s, 2H,
2,5
13
1
HC ), 7.66 (br s, 1H, NH) ppm. C{ H} NMR (Me CO-d , 75.5
f
2
2
2
6
G
dx.doi.org/10.1021/om4004972 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
2
,5
3,4
1
MHz, 300 K): δ 52.1 (MeO), 62.2 (br s, C ), 65.3 (C ), 98.0 (C ),
solvent in vacuo, the product was obtained as a brown solid in yields of
84−93% (10.5−11.6 g). The use of a larger excess of KOH sometimes
made it necessary to repeat the filtration steps. Analytically pure
samples could be obtained by recrystallization from methanol. Mp =
1
55.5 (CO) ppm. Anal. Calcd for C H FeN O (332.14): C 50.63,
14
16
2
4
H 4.86, N 8.43. Found: C 50.90, H 4.95, N 8.31.
a. Synthesis of 1,1′-Bis[(tert-butoxycarbonyl)amino]-
1
ferrocene, fc(NHCOOtBu) (9), Starting from 7. A stirred solution
180 °C. H NMR (200.1 MHz, CDCl , 300 K): δ 2.56 (br s, ν = 17
2
3
1/2
2,5
3,4
of fc(NCO) (5.0 g, 19 mmol) in 20 mL of dry diethyl ether was
Hz, 2 H, NH ), 3.80 (m, 2 H, HC ), 3.92 (br s, m, 2 H, HC ) ppm.
C{ H} NMR (75.5 MHz, CDCl , 300 K): δ 60.5 (C ), 64.5 (C ),
3
2
2
13
1
2,5
3,4
treated with dry, molten tert-butanol (3.0 g, 2.2 equiv). This solution
was stirred for 24 h at room temperature, at which time a yellow
powder had precipitated. The powder was filtered off, washed with
hexane, and dried in vacuo to yield a first fraction of 6.2 g of the
product as a yellow powder. The filtrate was dried in vacuo, dissolved
in 15 mL of hot ethyl acetate, and diluted with 45 mL of hexane. The
solution was flushed through a short column with silica (H20, ⦶40)
and eluted with ca. 200 mL of a 1:3 mixture of ethyl acetate and
1
103.7 (C ), ppm. Anal. Calcd for C H FeN (216.07): C 55.59, H
1
0
12
2
5.60, N 12.97. Found: C 55.01, H 5.66, N 12.45. MS (EI, 70 eV): m/z
+
+
(%) = 216.0 (100) [M] , 80.0 (30) [C H NH ] .
5
4
2
ASSOCIATED CONTENT
Supporting Information
■
*
S
hexane (R = 0.31). This solution was concentrated to a small volume
Crystallographic information files (cif) and additional pictures
showing selected ferrocene derivatives. This material is available
free of charge via the Internet at http://pubs.acs.org.
f
of hot ethyl acetate, where the product crystallized. The supernatant
was decanted, and the crystals were dried in vacuo to yield another 0.7
g of the product as orange crystals. Overall yield: 6.86 g (17 mmol,
8
9%).
AUTHOR INFORMATION
Corresponding Author
*E-mail: m.tamm@tu-bs.de. Fax: (+49) 531 391 5387.
Notes
■
b. Synthesis of 1,1′-Bis[(tert-butoxycarbonyl)amino]-
ferrocene, fc(NHCOOtBu) (9), Starting from 6. In a 1 L Schlenk
flask, finely powdered fc(CON ) (32.1 g, 0.10 mol) was suspended in
0
recommend using a flask with at least three times the volume of the
solvent employed. This mixture was stirred at 110 °C for 2 h and then
cooled to room temperature. The progress of the reaction can be
monitored by TLC in toluene (R [fc(CON ) ] = 0.26, R [fc(NCO) ]
2
3
2
.2 L of dry toluene. Because of the very vigorous gas evolution, we
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
f
3
2
f
2
=
0.82, R [fc(NHBoc) ] = 0.07) since the intermediate product
We wish to thank Janin Schlo
̈
sser, Celia Bonilla, and Sam
f
2
fc(NCO) is moderately stable for a short period of time. Careful
2
Harker for preparative assistance. The collaboration with Dr.
Zeljko Tomovic and Dr. Dejan Petrovic (BASF AG) is
gratefully acknowledged.
addition of dry, molten tert-butanol (35 mL, 3.0 equiv) to the cooled
(
0 °C) reaction mixture and heating to reflux for 5 min resulted in the
formation of a brown solution. After removal of the volatiles, the
residue was completely dissolved in 100 mL of warm ethyl acetate; 100
mL of hexane was added, and the mixture was passed through a short
silica pad (H15, ⦶100, R = 0.85 (EtOAc/n-C H , 1:1), >0.95
REFERENCES
■
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6
14
(
EtOAc), 0.23 (CH Cl )), thus removing a black solid and a polar,
2 2
dark brown impurity. Further elution with the same mixture of
solvents (ca. 600 mL) and successive removal of the volatiles in vacuo
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8
3
1
3% (33.7−34.5g). Mp = 146−147 °C. H NMR (200.1 MHz, CDCl ,
3
3
,4
00 K): δ 1.44 (s, 9H, C(CH ) ), 3.90 (m, 2H, HC ), 4.28 (m, 2H,
3
3
2,5
1
HC ), 6.05 (br s, ν = 12 Hz, 1H, NH) ppm. H NMR (300.1 MHz,
MeCN-d , 300 K): δ 1.47 (s, 9H, Me C), 3.93 (m, 2H, HC ), 4.32
1/2
3
,4
3
3
2,5
13
1
(
br s, 2H, HC ), 6.80 (br s, 1H, NH) ppm. C{ H} NMR (75.5
2,5
3,4
MHz, CDCl , 300 K): δ 28.4 (CMe ), 62.9 (br s, C ), 65.0 (C ),
8
C H FeN O (416.30): C 57.70, H 6.78, N 6.73. Found: C 57.65,
3
3
1
0.0 (CMe ), 95.9 (C ), 154.1 (CO) ppm. Anal. Calcd for
3
20
28
2
4
+
H 6.87, N 6.85. MS (EI, 70 eV): m/z (%) = 416.2 (16) [M] , 304.0
100) [fc(NHCOOH) ], 286.0 (41) [fc(NCO) ], 268.0 (44)
(
2
2
[
fc(NCO)(NHCOOH)], 216.1 (36) [fc(NH ) ], 180 (32) [Fe-
2 2
(
C H −NHCOOH], 162.0 (36) [Fe(C H −NCO)].
5
4
5
4
Synthesis of 1,1′-Diaminoferrocene, fc(NH ) (10). To an ice-
2
2
bath-cooled fine suspension of fc(NHBoc) (24.0 g, 57.8 mmol) in
2
deaerated methanol (160 mL) was added acetyl chloride (12.9 g, 2.9
equiv) via a syringe, whereupon dissolution of the solid and darkening
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at 65 °C for 1.25 h, at which time the hydrochloride salt often
precipitated as a yellow solid. The mixture was then cooled to room
temperature, and a solution of KOH (9.7 g, 3.0 equiv) in 40 mL of
deaerated methanol was added. During addition of the base, the solid
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KCl precipitated. To this yellow suspension triethylamine (4 mL, 2 vol
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2
H
dx.doi.org/10.1021/om4004972 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
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(
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5
(
2
(
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(
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4
I
dx.doi.org/10.1021/om4004972 | Organometallics XXXX, XXX, XXX−XXX