Intraannular functionalization of the 1,3-phenylene-19-crown-6 system via bromine-lithium exchange

Article abstract of DOI:10.1016/S0022-328X(98)00884-5

In contrast to the behavior of its lower homologue 1,3-phenylene-16-crown-5 (1), the direct lithiation of 1,3-phenylene-19-crown-6 (2) with n-BuLi at the intruannular position-2 was found to be slow and not quantitative. Therefore, (2-bromo-1,3-phenylene)-19-crown-6 (8) was synthesized by the reaction of the dicesium salt of 2-bromo-resorcinol (7) with pentaethylene glycol dibromide. The crystal structure of 8 revealed the existence of three chemically identical residues in the unit cell; in all cases, the bromine atom sticks out of the crown ether ring. The bromine-lithium exchange reaction of 8 with n-BuLi to furnish the desired (2-lithio-1,3-phenylene)-19-crown-6 (4) was quantitative after 2 h at -65°C in THF. Derivatization of 4 with deuterium oxide, dimethyl disulfide, iodine, carbon dioxide, mercuric bromide (1 or 0.5 molar equivalents), and magnesium bromide yielded (2-deuterio-1,3-phenylene)-19-crown-6 (2a), (2methylthio-1,3-phenylene)-19-crown-6 (10), (2-iodo-1,3-phenylene)-19-crown-6 (11), (2-carboxy-1,3-phenylene)-19-crown-6 (12), (2-bromomercurio-1,3-phenylene)-19-crown-6 (13), bis[(1,3-phenylene-19-crown-6)-2-yl]mercury (14), and (2-bromomagnesio-1,3-phenylene)-19-crown-6 (15), respectively. The synthesis of the Grignard reagent 15 was also carried out by the direct reaction of 8 with magnesium; contrary to the corresponding 1,3-xylylene crown ethers, cleavage of the crown ether ring during the formation of 15 was not observed. At room temperature, the solution of crude 4 (prepared from 8) gave rise to ether cleavage and to the formation of (2-n-butyl-1,3-phenylene)-19-crown 6 (16).

Full text of DOI:10.1016/S0022-328X(98)00884-5

Journal of Organometallic Chemistry 572 (1999) 93–104
Intraannular functionalization of the 1,3-phenylene-19-crown-6 system
via bromine–lithium exchange1
Ioannis D. Kostas 2,a, Otto S. Akkerman a, Friedrich Bickelhaupt a,*, Nora Veldman 3,b
Anthony L. Spek 4,b
,
a Valgroep Organische en Anorganische Chemie, Faculteit der Scheikunde, Vrije Uni6ersiteit, De Boelelaun 1083,
NL-1081 HV Amsterdam, The Netherlands
b Bij6oet Center for Biomolecular Research, Vakgroep Kristal-en Structuurchemie, Utrecht Uni6ersity, Padualaan 8,
NL-3584 CH Utrecht, The Netherlands
Received 9 July 1998
Abstract
In contrast to the behavior of its lower homologue 1,3-phenylene-16-crown-5 (1), the direct lithiation of 1,3-phenylene-19-
crown-6 (2) with n-BuLi at the intruannular position-2 was found to be slow and not quantitative. Therefore, (2-bromo-1,3-
phenylene)-19-crown-6 (8) was synthesized by the reaction of the dicesium salt of 2-bromo-resorcinol (7) with pentaethylene glycol
dibromide. The crystal structure of 8 revealed the existence of three chemically identical residues in the unit cell; in all cases, the
bromine atom sticks out of the crown ether ring. The bromine–lithium exchange reaction of 8 with n-BuLi to furnish the desired
(2-lithio-1,3-phenylene)-19-crown-6 (4) was quantitative after 2 h at −65°C in THF. Derivatization of 4 with deuterium oxide,
dimethyl disulfide, iodine, carbon dioxide, mercuric bromide (1 or 0.5 molar equivalents), and magnesium bromide yielded
(2-deuterio-1,3-phenylene)-19-crown-6 (2a), (2methylthio-1,3-phenylene)-19-crown-6 (10), (2-iodo-1,3-phenylene)-19-crown-6 (11),
(2-carboxy-1,3-phenylene)-19-crown-6 (12), (2-bromomercurio-1,3-phenylene)-19-crown-6 (13), bis[(1,3-phenylene-19-crown-6)-2-
yl]mercury (14), and (2-bromomagnesio-1,3-phenylene)-19-crown-6 (15), respectively. The synthesis of the Grignard reagent 15
was also carried out by the direct reaction of 8 with magnesium; contrary to the corresponding 1,3-xylylene crown ethers, cleavage
of the crown ether ring during the formation of 15 was not observed. At room temperature, the solution of crude 4 (prepared from
8) gave rise to ether cleavage and to the formation of (2-n-butyl-1,3-phenylene)-19-crown 6 (16). © 1999 Elsevier Science S.A. All
rights reserved.
Keywords: Crown ethers; Lithium; Mercury; Magnesium; Crystal structure
1. Introduction
Recently, we reported the intraannular functionaliza-
tion of 1,3-phenylene-16-crown-5 (1) via direct lithia-
tion with n-BuLi [1]. It was selective and quantitative; a
* Corresponding author. Tel.:+ 31 20 4447479; fax: +31 20
4447488; e-mail: bicklhpt@chem.vu.nl.
deuterium oxide quench of the organolithium 3 yielded
the deuterated crown ether 5 (98% deuterium incorpo-
ration) (Scheme 1).
Unfortunately, it turned out that the analogous lithi-
ation of the larger crown ether 1,3-phenylene-19-crown-
6 (2) with n-BuLi was not quantitative; a deuterium
oxide quench of the intermediate (2-lithio-1,3-
1 Dedicated to Dr Constantinos G. Screttas on the occasion of his
65th birthday.
2 National Hellenic Research Foundation, Institute of Organic and
Pharmaceutical Chemistry, Vas. Constantinou 48,;116 35 Athens;
Greece.
3 Deceased.
4 Correspondence concerning the crystallography should be ad-
dressed to this author.
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII S0022-328X(98)00884-5

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I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
Scheme 1.
2.2. Synthesis and crystal structure of
(2-bromo-1,3-phenylene)-19-crown-6 (8)
phenylene)-19-crown-6 (4) yielded a mixture of 2/2a
(Scheme 1). For that reason, we investigated the syn-
thesis of 4 by bromine–lithium exchange, a reaction
which had been applied successfully to (2-bromo-1,3-
xylylene)-crown ethers [2]. The synthesis and the crys-
tal structure of (2-bromo-1,3-phenylene)-19-crown-6
(8) will be presented also. The bromine–lithium ex-
change of 8 led to functional derivatives of the title
compound 2 via the organolithium precursor 4.
Previously, we had reported the reaction of the (2-
bromo-1,3-xylylene)-crown ethers with magnesium
metal to prepare the (2-bromomagnesio-1,3-xylylene)-
crown ethers; however, the formation of these Grig-
nard reagents was accompanied by (sometimes)
extensive crown ether cleavage [3]. Therefore, the syn-
thesis of these Grignard reagents by the reaction of
the organolithium analogue with magnesium bromide
was more convenient [4]; this was also the case in the
Although the synthesis of (2-bromo-1,3-xylylene)-
crown ethers is known [2,5] (2-bromo-1,3-phenylene)-
crown ethers have not been reported. The preparation
of 8 was carried out by the reaction of equivalent
amounts of the dicesium salt 7 of 2-bromo-resorcinol
(6) (obtained from 6 and cesium carbonate) and pen-
taethylene glycol dibromide in DMF (Scheme 2); the
advantage of cesium salts in crown ether synthesis is
well established [6]. The separation of 8 from its
dimeric byproduct 9 was achieved by column chro-
matography.
1
The NMR spectra of a solution of 8 in toluene-d8
at different temperatures (163.5–365 K) revealed the
existence of five patterns for the five groups of the
non-aromatic protons, indicating that expectedly, the
crown ether ring flips over the bromine atom. At tem-
synthesis
of
(2-bromomagnesio-1,3-phenylene)-16-
1
peratures below 163 K, the H-NMR spectra are more
crown-5 [1]. Surprisingly, and in contrast to (2-bromo-
1,3-xylylene)-crown ether analogues, the reaction of 8
with magnesium metal led to the corresponding Grig-
nard reagent 15 without cleavage of the crown ether
ring.
complicated, probably because this flipping motion
stops gradually.
Crystals suitable for X-ray crystal structure determi-
nation were obtained by recrystallization of 8 from
diethyl ether. The unit cell of 8 contains three chemi-
cally identical molecules which differ slightly in their
conformations. An ORTEP illustration of molecule
no. 1 is presented in Fig. 1. Fig. 2 gives a comparison
of the three molecules; the conformation of the major
disorder component of molecule no. 3 is very similar
to that of molecule no. 1, while molecule no. 2 ex-
hibits a significantly deviating puckering pattern. A
selection of bond distances, angles and torsion angles
is presented in Table 1.
2. Results and discussion
2.1. Lithiation of 1,3-phenylene-19-crown-6 (2)
In contrast to the previously reported quantitative
lithiation of 1 [1], lithiation of 2 with n-BuLi was
found to be slow and not quantitative. The reaction
was performed at −30°C for 7 h, after which the
reaction mixture was quenched with deuterium oxide.
Two compounds were detected by GC/MS and 1H-
NMR spectroscopy: 2 and 2a (ratio 56:44, according
to 1H-NMR spectroscopy) (Scheme 1). The metalla-
tion reaction was also attempted with n-BuLi/
TMEDA, n-BuLi/t-BuOK, t-BuLi; however, in all
cases, hydrogen–lithium exchange was not complete.
When the reaction mixtures were allowed to warm
above −30°C, cleavage of the crown ether ring oc-
curred.
The C(122)–Br(10) distance in molecule no. 1 (the
corresponding values for molecules no. 2 and no. 3 are
in the square brackets) of 1.890(8) [1.889(2), 1.885(8)]
˚
A is normal. The bromine atom is coplanar with the
aromatic ring with Br to least squares plane distance
˚
0.011(1) [0.057(1), 0.182(1)] A. The angle between the
aromatic ring and the least squares plane of the crown
ether ring is 73.7(3) [88.4(3), 78.8(3)]°, so that the
bromine sticks out of the crown ether ring in a nearly
perpendicular fashion (72.0(3) [86.4(3), 75.5(3)]°). The
torsion angles of the OCH2CH2O units vary from

I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
95
Scheme 2.
61.4(9) to 76.3(8)° with the exception of the torsion
angle O(108)–C(109)–C(110)–O(111) (−175.8(6)°).
(Scheme 3). Both 13 and 14 were identified by 1H-, 13C-,
199Hg-NMR spectroscopy, MS and elemental analysis.
2.3. Synthesis of (2-lithio-1,3-phenylene)-19-crown-6
(4) and its reactions with electrophiles
2.4. Synthesis of
(2-bromomagnesio-1,3-phenylene)-19-crown-6 (15)
Bromine–lithium exchange of 8 with n-butyllithium
proceeded in high yield. The reaction conditions re-
ported previously for the bromine–lithium exchange of
the (2-bromo-1,3-xylylene)-crown ethers [2] were
modified slightly. Best results were obtained when n-
butyllithium (1.1 molar equivalents) was added to a
solution of 8 in THF (about 0.1 M) at −65°C and the
reaction mixture was kept for 2 h at this temperature
(Scheme 3). The crown ether ring is stable under these
conditions. The organolithium reagent 4 was quite solu-
ble in THF at this concentration (0.1 M); this is in
contrast to the low solubility of 3 which gave a cloudy
suspension at the same concentration [1].
The yield of 4 was determined by quench reactions
with deuterium oxide or dimethyl disulfide (Scheme 3);
the products 2a and 10, respectively, were obtained in
good yields (72 and 82%, respectively), while starting
material was not detected by GC/MS and 1H-NMR
spectroscopy. Compound 4 was used for further func-
tionalizations. In these reactions with electrophiles, 2
(hydrolyzed material) was formed as a byproduct, pre-
sumably because at the small scale of the reactions
(usually 0.20 mmol), even minimal traces of water give
a significant amount of hydrolysis.
The preparation of crown ether Grignard reagents by
the reaction of the organolithium precursors with mag-
nesium bromide has been reported [1,4]. This method
was also successful for the synthesis of 15 (Scheme 3).
Because this reaction was carried out in standard glass-
ware with ground joints, and due to the small scale of
the reaction (0.50 mmol), a significant amount of the
Grignard reagent 15 was hydrolyzed by the traces of
moisture. A deuterium oxide quench of the reaction
mixture at room temperature yielded 2/2a (66% deu-
terium incorporation, according to GC/MS), while no
traces of ether cleavage products were detected; as the
crown ether ring of the organolithium compound 4 is
not stable at room temperature, this indicates that the
conversion of 4 to 15 had been complete.
Compound 15 was also synthesized by the reaction of
8 with magnesium metal at room temperature. In this
case, the reaction was carried out in a high vacuum
glass apparatus in order to reduce hydrolysis. In a
previous paper, we discussed the specific ether cleavage
of the (2-bromomagnesio-1,3-xylylene)-crown ethers
which occurs during their formation from the corre-
sponding bromides [3]; the cleavage was ascribed to the
attack of a carbanionic intermediate on the Grignard
reagent already formed [3]. Compound 15 was stable
for a long period; 3 months after the preparation,
hydrolysis of the reaction mixture and titration of the
aqueous phase revealed that the starting bromide 8 had
been transformed completely into a Grignard reagent,
while deuterolysis, followed by GC/MS analysis, confi-
rmed the absence of 8 and of ether cleavage products,
and the product (2/2a) was highly deuterated (ratio
2:2a=9:91). The crown ether ring of 15 was also stable
Reaction of 4 with solid iodine or carbon dioxide
yielded (2-iodo-1,3-phenylene)-19-crown-6 (11) and (2-
carboxy-1,3-phenylene)-19-crown-6 (12), respectively,
(Scheme 3) in analogy with the synthesis of the
analogous derivatives of 1 [1]. The mercury compound
13 was synthesized by the reaction of 4 and mercuric
bromide in a molar ratio of 1:1, while dropwise addi-
tion of 0.5 molar equivalents of mercuric bromide to 4
yielded the bis (crown ether) mercury compound 14

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I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
Fig. 1. ORTEP drawing (50% probability level) of one of the three similar, crystallographically independent molecules of 8. Hydrogen atoms are
omitted for clarity.
ether with n-butyllithium was warmed to room temper-
ature [4].
even when a tenfold molar excess of bromobenzene and
magnesium was reacted in the presence of 15 under the
same conditions; a deuterium oxide quench of the
reaction mixture yielded 2/2a (ratio 2:2a=11:89), while
only traces of ether cleavage products were detected.
Under identical conditions, (2-bromomagnesio-1,3-xy-
lylene)-15-crown-4 was completely consumed by ether
cleavage through attack by the phenyl anion which is
an intermediate in the formation of phenylmagnesium
bromide [3]. The high stability of the crown ether ring
of 15 is in contrast to the lower stability of its lower
homologues and of 1,3-xylylene-crown ethers; this
might be ascribed to two factors: the ether functionali-
ties in 15 may be less susceptible towards attack by the
intermediate carbanion due to less favorable coordina-
tion between oxygens and magnesium, but in addition,
the low solubility of 15 in THF will protect it against
attack by the carbanion in solution.
2.6. Conclusions
In contrast to 1,3-phenylene-16-crown-5 (1), the
larger crown ether 2 could not be lithiated quantita-
tively at the intraannular position-2. On the other hand,
(2-lithio-1,3-phenylene)-19-crown-6 (4) was quantita-
tively formed by bromine–lithium exchange from 8,
thus providing a convenient method for further intraan-
nular functionalization of the crown ether system via 4.
Interestingly, the synthesis of the Grignard reagent
15 from 8 and magnesium occurred without cleavage of
the crown ether ring, in contrast to the analogous
reaction of (2-bromo-1,3-xylylene)-crown ethers.
3. Experimental section
2.5. Stability of 4 in the presence of n-butylbromide
3.1. General
While the solution of 4 as prepared from 8 and
n-butyllithium was reasonably stable at low tempera-
ture, warming it up to room temperature led to the
formation of appreciable amounts of (2-n-butyl-1,3-
phenylene)-19-crown-6 (16) formed by reaction of 4
with n-butylbromide (in addition to the formation of 2
and unknown products (crown ether cleavage?), appar-
ently arising by selfdecomposition of 4). A GC/MS
analysis of the residue of a deuterium oxide quench of
the reaction mixture indicated a product distribution of
49% of 16 and 51% of a 2/2a mixture (ratio 85:15). The
formation of appreciable amounts of 2-n-butylated
product has also been observed when the reaction
mixture of an analogous (2-bromo-1,3-xylylene)-crown
The crown ether 2 was obtained by a known proce-
dure [6]. Pentaethylene glycol dibromide was prepared
by the reaction of pentaethylene glycol with phospho-
rus tribromide [7]; the 1H-NMR spectrum of pen-
taethylene glycol dibromide was similar to the one
reported previously [8]. Pentaethylene glycol [5] and
2-bromo-resorcinol [9] were obtained by literature pro-
cedures. Lithiation reactions were performed in stan-
dard glassware with ground joints under argon. THF
was predried and distilled from LiAlH4. The reaction of
8 with magnesium was carried out in fully sealed glass-
ware by using high vacuum techniques; for its synthesis,
extremely dry THF was prepared by distillation from

I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
97
Fig. 2. Comparison of the conformation of the three crystallographically independent molecules (nos. 1, 2, 3) of 8.
liquid Na/K alloy after predrying on NaOH. A solution
of dry magnesium bromide was prepared by the reac-
tion of dibromoethane and doubly sublimed magne-
sium in THF. Concentrations of ‘total base’ and Mg2+
of the organomagnesium solution were determined by
titration of a hydrolyzed sample with acid–base and
EDTA complexon, respectively [10]. The starting
materials ethylene glycol (Baker), 1,2-bis (2-
chloroethoxy)ethane (Janssen), phosphorus tribromide
(Merck), bromine (Baker), resorcinol (Baker), cesium
carbonate (Janssen), n-butyllithium (Janssen, Acros),
deuterium oxide (Janssen), dimethyl disulfide (Aldrich),
iodine (Janssen), mercuric bromide (Baker), dibro-
moethane (Janssen), bromobenzene (Merck) were avail-
able commercially. Column chromatography was
performed over aluminium oxide 90, activity II-III
(Merck). TLC chromatography was carried out on
aluminium sheets, silica gel 60 F254 (Merck). Purifica-
tion of 16 was carried out by preparative gas chro-
matography (Intersmat GC 120, katharometer

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I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
(1H-NMR, NOESY, 400.13 MHz; 199Hg-NMR, 71.60
MHz). The 13C chemical shifts were obtained from the
13C{1H}-NMR and the coupling constants J(13C–1H)
from the 13C-NMR spectra. The correlation between
carbons and hydrogens was found by 2D{13C, 1H}-
NMR. GC/MS analyses were performed on a HP 5890
II GC/5971 A MSD combination, operating at 70 eV
and equipped with a Chrompack CP sil SCB 50-m/0.21-
mm column. Mass spectra and HRMS measurements
were performed on a Finnigan MAT 90 mass spectrom-
eter (direct inlet); in the case of 14, CI with NH3 was
used to characterize the compound by its mass spec-
trum. Melting points were measured on a Buchi melting
point apparatus and are not corrected. Elemental
analyses were carried out at the Micro Analytical De-
partment, Rijksuniversiteit Groningen, The Nether-
lands.
Table 1
˚
Selected bond distances (A), bond angles (°) and torsion angles (°) of
8
˚
Bond distances (A)
Br(10)–C(122)
1.890(8)
1.355(11)
1.425(10)
1.418(11)
1.409(10)
1.422(9)
1.395(10)
1.417(12)
1.432(11)
1.428(11)
1.426(11)
1.450(11)
1.342(10)
117.1(8)
O(102)–C(101)
O(102)–C(103)
O(105)–C(104)
O(105)–C(106)
O(108)–C(107)
O(108)–C(109)
O(111)–C(110)
O(111)–C(112)
O(114)–C(113)
O(114)–C(115)
O(117)–C(116)
O(117)–C(118)
O(102)–C(101)–C(122)
O(117)–C(118)–C(119)
O(117)–C(118)–C(122)
125.4(8)
116.6(8)
Torsion angles (°)
C(121)–C(101)–C(122)–Br(10)
O(117)–C(118)–C(119)–C(120)
C(119)–C(118)–C(122)–Br(10)
O(102)–C(103)–C(104)–O(105)
O(102)–C(101)–C(122)–Br(10)
O(105)–C(106)–C(107)–O(108)
O(117)–C(118)–C(122)–Br(10)
O(108)–C(109)–C(110)–O(111)
O(102)–C(101)–C(122)–Br(118)
O(111)–C(112)–C(113)–O(114)
O(102)–C(101)–C(121)–C(120)
O(114)–C(115)–C(116)–O(117)
O(117)–C(118)–C(122)–C(101)
179.7(7)
176.7(7)
179.4(7)
61.4(9)
2.5(10)
68.3(9)
3.1(10)
175.8(6)
177.7(7)
71.4(9)
176.9(8)
76.3(8)
176.7(7)
3.2. 1,3-Phenylene-19-crown-6 (2)
Crown ether 2 was synthesized by a known proce-
dure [6]. Its purification was performed by column
chromatography over aluminium oxide. It was obtained
as a pure oil (Lit. [6]: oil). We report the spectra data
and the mass spectrum of 2 which have not been
reported previously [6].
2: H-NMR (200.13 MHz, CDCl3, ref. CHCl3=7.27
ppm): l 3.61–3.72 (m, 12H, O(2)CH2CH2O(3)CH2),
3.78–3.82 (m, 4H, O(1)CH2CH2O(2)), 4.19–4.23 (m,
detection, 10% OV 101 column, 2.03 m, chromosorb
WHP) at appropriate oven temperature. The yields of
the products are based on the amount of the starting
material. NMR spectra (for numbering, see Formula of
(2-X-1,3-phenylene)-19-crown-6) were measured on a
Bruker AC 200 (1H-NMR, 200.13 MHz; 13C-, 13C{1H}-,
1
1
2D{13C, H}-NMR, 50.32 MHz) or a Bruker MSL 400
Scheme 3.

I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
99
3
4
4H, O(1)CH2CH2O(2)), 6.48 (dd, J=8.2 Hz, J=2.3
Hz, 2H, aryl H(4,6)), 6.86 (t, 4J=2.3 Hz, 1H, aryl
ually changed in 10% increments from pure petroleum
ether (40–60) to pure THF. The crown ether 8 (0.91 g,
yield 23%) was isolated as an oil and crystallized upon
standing. Repeated crystallizations were achieved from
diethyl ether/pentane, yielding a white solid. It crystal-
lized in two different modifications with m.p. 49–51°C
and 55–57°C, respectively; the m.p. of a mixture of
equal amounts of these modifications was 54–57°C.
Colorless crystals suitable for X-ray crystal structure
determination were obtained by slow recrystallization
from diethyl ether by cooling from room temperature
to −20°C.
H(2)), 7.12 (t, J=8.2 Hz, 1H, aryl H(5)). 13C-NMR
3
(50.32 MHz, CDCl3, ref. CDCl3=77 ppm): (68.14 (t,
1J=143 Hz, 2C, O(1)CH2CH2O(2)), 69.85 (t, J=140
1
Hz, 2C, O(1)CH2CH2O(2)), 70.58, 70.70 and 71.17
1
(3×t, J=141 Hz, 6C, O(2)CH2CH2O(3)CH2), 103.49
(dtd, 1J=160 Hz, 3J=5 Hz, 4J=1.9 Hz, 1C, aryl
1
C(2)), 108.23 (dm, J=160 Hz, 2C, aryl C(4,6)), 129.46
(d, 1J=158 Hz, 1C, aryl C(5)), 160.12 (s, 2C, aryl
C(1,3)). GC/MS: m/z (relative intensity) 312 (M+,
C16H24O6, 86), 180 (15), 154 (14), 137 (56), 136 (47), 133
(12), 117 (10), 110 (59), 92 (100), 89 (26), 76 (40), 73
(49), 64 (42), 45 (69).
The dimeric byproduct [2,2%-dibromo-[bis(1,3-
phenylene)]]-38-crown-12 (9) was also isolated as a pure
oil (0.39 g, yield 10%) and crystallized from diethyl
ether, m.p. 79–82°C. By increasing the polarity of the
eluent using mixtures of ethano/methanol, 0.66 g of a
mixture of compounds with higher molecular weight
was isolated, which were not identified further.
3.3. Reaction of 2 with n-butyllithium
To a solution of 2 (0.096 g, 0.31 mmol in 3 ml of
THF) under argon, 0.20 ml (0.32 mmol) of n-butyl-
lithium (1.6 M in n-hexane) was added, at −30°C.
After 7 h of stirring at this temperature, an excess of
deuterium oxide (0.50 ml, 27.63 mmol) was added after
which the cooling bath was removed and the reaction
mixture was stirred for 0.5 h, and then 5 ml of 1 M HCl
was added. The volatile materials were removed by
evaporation, the residue was extracted with
dichloromethane (3×10 ml), the combined organic lay-
ers were washed with 5 ml of water, dried over MgSO4,
filtered and evaporated to dryness, yielding 0.068 g of a
pale yellow oil, which was identified by GC/MS and
1H-NMR spectroscopy as 2/2a (44% deuterium incor-
1
8: H-NMR (200.13 MHz, CDCl3, ref. CHCl3=7.27
ppm): l 3.43 (s, 4H, O(3)CH2CH2O(3)), 3.50–3.56 (m,
4H, O(2)CH2CH2O(3)), 3.63–3.69 (m, 4H, O(2)CH2-
CH2O(3)), 3.79–3.83 (m, 4H, O(1)CH2CH2O(2)), 4.32–
3
4.36 (m, 4H, O(1)CH2CH2O(2)), 6.60 (d, J=8.3 Hz,
3
2H, aryl H(4,6)), 7.15 (t, J=8.3 Hz, 1H, aryl H(5)).
The 1NMR spectrum was analyzed with the help of
NOESY spectrum (1H-NMR, 400.13 MHz). 13C-NMR
(50.32 MHz, CDCl3, ref. CDCl3=77 ppm): (69.35 (t,
1
1J=144 Hz, 2C, O(1)CH2CH2O(2)), 69.63 (t, J=141
1
Hz, 2C, O(1)CH2CH2O(2)), 70.14 (t, J=141 Hz, 2C,
1
O(2)CH2CH2O(3)), 70.41 (t, 1J=142 Hz, 2C,
O(3)CH2CH2O(3)), 71.48 (t, 1J=141 Hz, 2C,
O(2)CH2CH2O(3)), 104.03 (td, 3J=8.3 Hz, 4J=1.7 Hz,
poration, according to the H-NMR spectrum).
3.4. (2-Bromo-1,3-phenylene)-19-crown-6 (8) and
[2,2%-dibromo-[bis(1,3-phenylene)]]-38-crown-12 (9)
1
3
1C, aryl C(2)), 107.24 (ddd, J=161 Hz, J=8.4 Hz,
2J=1.7 Hz, 2C, aryl C(4,6)), 127.55 (d, J=160 Hz,
1
To a solution of 2-bromo-resorcinol (6) [9] (1.92 g,
10.16 mmol in 500 ml of methanol) under nitrogen,
cesium carbonate (3.31 g, 10.16 mmol) was added.
Once the cesium carbonate was dissolved, the methanol
was removed under reduced pressure. Then 500 ml of
dry DMF was added, which was removed under high
vacuum along with the traces of remaining water and
methanol. The dry precipitate was suspended in 500 ml
DMF and the dibromide of pentaethylene glycol [7,8]
(3.70 g, 10.16 mmol) was added. The reaction mixture
was stirred at 65°C for 5 days. Then it was cooled down
to room temperature and the DMF was evaporated
under high vacuum. The residue was dissolved in
dichloromethane (200 ml), the organic layer was
washed once with 50 ml of a 10% aqueous NaCl and
once with 50 ml of 1% aqueous KOH. The organic
layers were dried over Na2SO4, filtered, and the solvent
was evaporated, yielding 4.08 g of an oil. Purification
was carried out by column chromatography over alu-
minium oxide. During the elution, the eluent was grad-
3
aryl C(5)), 156.66 (d, J=11.2 Hz, 2C, aryl C(1,3)).
GC/MS: m/z (relative intensity) 392/390 (M+;
C16H23BrO6, 59), 311 ([M–Br]+, 21), 216/214 (19), 205
(20), 179 (19), 177 (9), 172/170 (87), 161 (35), 151 (32),
133 (27), 107 (29), 89 (48), 73 (35), 45 (100). HRMS:
79
23
Anal. Calc. for C16H BrO6 390.0678, found
390.067890.0008. Anal. Calc. (%) for C16H23BrO6: C,
49.12; H, 5.92. Found (%): C, 48.93; H, 5.89.
1
9: H-NMR (200.13 MHz, CDCl3, ref. CHCl3=7.27
ppm): l 3.67–3.70 (m, 16H, CH2O(3)CH2CH2O(3)-
CH2), 3.77–3.82 (m, 8H, O(2)CH2CH2O(3)), 3.88–3.93
(m, 8H, O(1)CH2CH2O(2)), 4.14–4.19 (m, 8H,
O(1)CH2CH2O(2)), 6.56 (d, 3J=8.3 Hz, 4H, aryl
3
H(4,6)), 7.17 (t, J=8.3 Hz, 2H, aryl H(5)). 13C-NMR
(50.32 MHz, CDCl3, ref. CDCl3=77 ppm): (69.25 (t,
1
1J=145 Hz, 4C, O(1)CH2CH2O(2)), 69.41 (t, J=142
1
Hz, 4C, O(1)CH2CH2O(2)), 70.61 and 70.62 (2 (t, J=
1
141 Hz, 8C, CH2O(3)CH2), 71.14 (t, J=141 Hz, 4C,
O(2)CH2CH2O(3)), 102.19 (td, 3J=8.5 Hz, 4J=1.5

100
I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
1
3
Hz, 2C, aryl C(2)), 106.14 (dd, J=161 Hz, J=8.4
work up procedure was as described for 2a, yielding the
sulfide 10 (0.059 g, 82%, \95% pure according to
GC/MS and H-NMR spectroscopy) as an oil. It was
1
Hz, 4C, aryl C(4,6)), 128.02 (d, J=160 Hz, 2C, aryl
C(5)), 156.52 (d, 3J=11.0 Hz, 4C, aryl C(1,3)). MS
(direct inlet, Finnigan MAT 90): m/z (relative intensity)
46
1
crystallized from diethyl ether at (20°C, yielding a white
solid, m.p. 43–44.5°C.
782 (M+; C32H Br8lBrO12, 72), 701 ([M–Br]+, 79Br,
79
15), 700 ([M–HBr]+, 79Br, 7), 436/434 (10), 392/390
10: 1H-NMR (200.13 MHz, CDCl3, ref. CHCl3=
(19), 311 (14), 216/214 (11), 205 (8), 179 (17), 177 (9),
172/170 (56), 161 (23), 151 (26), 133 (25), 107 (21), 89
(40), 73 (33), 45 (100). HRMS: Anal. Calc. for
C32H4679Br2O12 780.1356, found 780.135290.0006.
Anal. Calc. (%) for C32H46Br2O12: C, 49.12; H, 5.92.
Found (%): C, 49.07; H, 6.04.
7.27 ppm):
l 2.42 (s, 3H, SMe), 3.41 (s, 4H,
O(3)CH2CH2O(3)), 3.49–3.53 (m, 4H, O(2)CH2CH2O-
(3)), 3.64–3.68 (m, 4H, O(2)CH2CH2O(3)), 3.80–3.84
(m, 4H, O(1)CH2CH2O(2)), 4.34–4.38 (m, 4H,
O(1)CH2CH2O(2)), 6.60 (d, 3J=8.3 Hz, 2H, aryl
H(4,6)), 7.15 (t, J=8.3 Hz, 1H, aryl H(5)). 13C-NMR
3
(50.32 MHz, CDCl3, ref. CDC13=77 ppm): l 17.74
1
(q,1J=140 Hz, 1C, SMe), 68.81 (t, J=144 Hz, 2C,
3.5. (2-Lithio-1,3-phenylene)-19-crown-6 (4)
O(1)CH2CH2O(2)), 69.71 (t, 1J=141 Hz, 2C,
O(1)CH2CH2O(2)), 70.21 (t, 1J=141 Hz, 2C,
O(2)CH2CH2O(3)), 70.41 (t, 1J=142 Hz, 2C,
O(3)CH2CH2O(3)), 71.30 (t, 1J=141 Hz, 2C,
O(2)CH2CH2O(3)), 106.67 (dd, 1J=160 Hz, 3J=7.9
Hz, 2C, aryl C(4,6)), 115.23 (s, 1C, aryl C(2)), 128.24
(d, 1J=159 Hz, 1C, aryl C(5)), 159.94 (s, 2C, aryl
C(1,3)). GC/MS: m/z (relative intensity) 358 (M+;
C17H26O6S, 87), 311 ([M–SMe]+, 1), 226 (11), 200 (11),
182 (20), 167 (20), 156 (100), 139 (15), 123 (22), 111
(11), 95 (12), 73 (9), 45 (65). HRMS: Anal. Calc. for
C17H26O362S 358.1450, found 358.145590.0005. Anal.
Calc. (%) for C17H26O6S: C, 56.96; H, 7.31. Found (%):
C, 56.60; H, 7.40.
To a solution of 8 (0.079 g, 0.20 mmol in 2 ml of
THF) under argon, 1.1 molar equivalent of n-butyl-
lithium (1.6 M in n-hexane) was added at −65°C. The
exchange was completed after 2 h, and 4 was reacted
with the corresponding electrophile (vide infra).
3.6. (2-Deuterio-1,3-phenylene)-19-crown-6 (2a)
An excess of deuterium oxide (0.20 ml, 11.05 mmol)
was added at −65°C to the solution of 4 (0.20 mmol in
2 ml of THF). The reaction mixture was warmed slowly
to room temperature, after which 5 ml of 1 M HCl was
added. The volatile materials were removed by evapo-
ration and the organic material was extracted with
dichloromethane (3×10 ml). The combined organic
layers were washed with 5 ml of water, dried over
MgSO4, filtered and evaporated to dryness, to yield an
oil of 2/2a (0.051 g, 72, 88% deuterium incorporation,
3.8. (2-lodo-1,3-phenylene)-19-crown-6 (11)
An excess of solid iodine (0.111 g, 0.44 mmol) was
added at −65°C to the solution of 4 (0.20 mmol in 2
ml of THF) and the reaction mixture was warmed
slowly to room temperature overnight, after which 5 ml
of an aqueous solution of sodium thiosulphate (2 g,
12.65 mmol) was added. The standard work up yielded
0.080 g of the crude product as a slightly yellow oil,
which solidified upon standing. It was identified by
GC/MS analysis as a mixture of 2 (18%) and 11 (82%).
The crude product was recrystallized from diethyl ether,
yielding a white solid (0.066 g, 75%), m.p. 69–70°C.
11: The 1H-NMR (200.13 MHz, CDCl3, ref.
CHCl3=7.27 ppm) is in accordance with that of 8. The
13C-NMR (50.32 MHz, CDCl3, ref. CDCl3=77 ppm)
is also in accordance with that of 8 except for the
chemical shifts for the signals of the aryl C, being
(81.41 (C(2)), 106.54 (C(4,6)), 129.06 (C(5)), 159.03
(C(1,3)). GC/MS: m/z (relative intensity) 438 (M+;
C16H23IO6, 100), 311 ([M–I]+, 2), 262 (9), 236 (12), 218
(56), 161 (12), 151 (10), 133 (10), 107 (14), 89 (17), 73
(14), 45 (61). HRMS: Anal. Calc. for C16H23IO6
438.0538, found 438.053690.0005. Anal. Calc. (%) for
C16H23IO6: C, 43.85; H, 5.29. Found (%): C, 43.23; H,
5.33.
1
according to GC/MS and H-NMR spectroscopy).
2a: The 1H-NMR spectrum (200.13 MHz, CDCl3,
ref. CHC13=7.27 ppm) is identical with that of 2
except for the signal of the aryl H(4,6), being a doublet
3
l 6.49, d, J=8.2 Hz, 2H) and the absence of the aryl
H(2) signal. The 13C-NMR spectrum (50.32 MHz,
CDCl3, ref. CDCl3=77 ppm) is identical with that of 2
except for the signal of the aryl C(2), being a triplet (l
1
103.12, t, J(C–2H)=24 Hz, 1C) of low intensity, and
1
the signal of the aryl C(4,6) (l 108.17, ddd, J=161
3
2
Hz, J=7.7 Hz, J=1.3 Hz, 2C). GC/MS: m/z (rela-
tive intensity) 313 (M+; C16H232HO6, 100), 181 (10),
155 (9), 138 (33), 137 (36), 133 (7), 117 (7), 111 (42), 93
(70), 89 (22), 77 (31), 73 (42), 65 (34), 45 (87). HRMS:
Anal. Calc. for C16H232HO6 313.1636. Found
313.164090.0007.
3.7. (2-Methylthio-1,3-phenylene)-19-crown-6 (10)
An excess of dimethyl disulfide (0.10 ml, 1.11 mmol)
was added at −65°C to the solution of 4 (0.20 mmol in
2 ml of THF), after which the cooling bath was re-
moved and the reaction mixture was stirred for 1 h. The

I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
101
3.9. (2-Carboxy-1,3-phenylene)-19-crown-6 (12)
(32%) and 13 (68%). Purification of 13 was achieved by
recrystallization from acetone at −20°C, yielding a
white solid (0.027 g, 41%), m.p. 123–125°C.
Carbon dioxide was bubbled through the solution of
4 (0.20 mmol in 2 ml of THF) at −65°C for 30 min.
Then the reaction mixture was poured rapidly into a
beaker containing a slurry of crushed dry ice and
anhydrous diethyl ether. When the carboxylation mix-
ture had reached room temperature, water was added,
and the volatile materials were removed by evapora-
tion. The aqueous phase was washed once with 10 ml of
toluene and once with 10 ml of hexane, after which 5
ml of 20% H2SO4 was added to liberate the acid, which
was extracted with dichloromethane (4×10 ml). The
combined organic layers were washed with 5 ml of
water and dried over MgSO4. After filtration, the sol-
vent was evaporated, yielding 12 (0.055 g, 77%) as an
oil, which solidified upon standing; it was identified by
1H-NMR spectroscopy as pure 12. Repeated crystal-
lizations from dichloromethane/pentane yielded a white
solid, m.p. 104–106°C.
Upon dropwise addition of a mercuric bromide solu-
tion (0.035 g, 0.10 mmol in 5 ml of THF) during 30 min
to the solution of 4 (0.20 mmol in 2 ml of THF) and
the standard work up, 0.075 g of a crude solid was
obtained. According to 1H-NMR spectrum, it con-
tained: 2 (42%) and 14 (58%). Purification of 14 was
achieved as described for 13, yielding a white solid
(0.022 g, 27%), m.p. 121–123°C.
13: 1H-NMR (200.13 MHz, CDCl3, ref. CHCl3=
7.27 ppm): l 3.51–3.62, 3.66–3.82 and 3.89–4.00 (3×
m, 16H, CH2O(2)CH2CH2O(3)CH2), 4.06–4.16 (m, 4H,
O(1)CH2CH2O(2)), 6.64 (d, 3J(1H–lH)=8.1 Hz, Hg
4
satellites J(199Hg–lH)=80 Hz, 2H, aryl H(4,6)), 7.20
3
(t, J=8.1 Hz, 1H, aryl H(5)). 13C-NMR (50.32 MHz,
1
CDCl3, ref. CDCl3=77 ppm): l 68.83 (t, J=140 Hz,
1
2C, OCH2), 69.78 (t, J=142 Hz, 2C, OCH2), 70.05 (t,
1J=141 Hz, 2C, OCH2), 70.43 (t, 1J=142 Hz, 2C,
12: 1H-NMR (200.13 MHz, CDCl3, ref. CHCl3=
7.27 ppm): l 3.56–3.61 (m, 8H, CH2O(3)CH2CH2-
O(3)CH2), 3.68–3.73 (m, 4H, O(2)CH2CH2O(3)),
3.76–3.81 (m, 4H, O(1)CH2CH2O(2)), 4.25–4.29 (m,
OCH2), 71.50 (t, J=140 Hz, 2C, OCH2), 107.50 (ddd,
1
3
2
3
1J=160 Hz, J=7.7 Hz, J=1.5 Hz, Hg satellites J
(13C–199Hg)=107 Hz, 2C, aryl C (4,6)), 130.63 (d,
1J=159 Hz, 1C, aryl C(5)), 132.72 (s, low intensity, 1C,
3
3
4H, O(1)CH2CH2O(2)), 6.59 (d, J=8.4 Hz, 2H, aryl
aryl C(2)), 161.59 (d, J (13C–13C)=12.6 Hz, Hg satel-
3
2
H(4,6)), 7.26 (t, J=8.4 Hz, 1H, aryl H(5)), 10.18 (brs,
lites J (13C–199Hg)=43 Hz, 2C, aryl C(1,3)). 199Hg-
1H, COOH). 13C-NMR (50.32 MHz, CDCl3, ref.
CDCl3=77 ppm): (68.89) (t, 1J=141 Hz, 2C,
O(1)CH2CH2O(2)), 69.26 (t, 1J=144 Hz, 2C,
NMR (71.60 MHz, CDCl3, ref. Me2Hg=0 ppm): l
−1242.70 (s, 1Hg). MS (direct inlet, Finnigan MAT
90):
m/z
(relative
intensity)
592
(M+;
1
O(1)CH2CH2O(2)), 70.16 and 70.35 (2 (t, J=142 Hz
C16H Br202HgO6, 1), 513 ([M–79Br]+, 202Hg, (20), 311
79
23
and 1J=141 Hz, 4C, CH2O(3)CH2CH2O(3)CH2),
(11), 45 (100). The signal of M+; was too weak for
exact mass determination. Parent ion mass calc. for
23
1
70.85 (t, J=142 Hz, 2C, O(2)CH2CH2O(3)), 107.15
1
3
198
(dd, J=162 Hz, J=7.0 Hz, 2C, aryl C(4,6)), 116.68
C16H HgO6 ([M–Br]+) 509.1163, found 509.11599
(s, 1C, aryl C(2)), 130.92 (d, 1J=160 Hz, 1C, aryl
C(5)), 156.38 (d, J=10.9 Hz, 2C, aryl C(1,3)), 165.76
0.0006. Anal. Calc. (%) for C16H23BrHgO6: C, 32.47; H,
3
3.92. Found (%): C, 32.48; H, 4.38.
(s, 1C, COOH). MS (direct inlet, Finnigan MAT 90):
m/z (relative intensity) 356 (M+; C17H24O8, 31), 339
([M–OH]+, 100), 311 ([M–COOH]+ (2), 269 (11), 225
(10), 207 (17), 180 (61), 163 (24), 136 (39), 108 (30), 89
(14), 73 (19), 45 (63). HRMS: Anal. Calc. for C17H24O8
356.1471, found 356.147290.0007. Anal. Calc. (%) for
C17H24O8: C, 57.30; H, 6.79. Found (%): C, 57.22; H,
6.92.
14: 1H-NMR (200.13 MHz, CDCl3, ref. CHCl3=
7.27 ppm): l 3.37–3.65 and 3.70–3.90 (2×m, 32H,
6×C2H4 and 4×O(1)CH2CH2O(2)), 4.17–4.38 (m,
3
8H, O(1)CH2CH2O(2)), 6.68 (d, J(1H–1H)=8.0 Hz,
4
Hg satellites J(199Hg–1H)=39 Hz, 4H, aryl H(4,6)),
3
7.13 (t, J=8.0 Hz, 2H, aryl H(5)). 13C-NMR (50.32
1
MHz, CDCl3, ref. CDCl3=77 ppm): l 68.54 (t, J=
1
142 Hz, 4C, OCH2), 69.50 (t, J=140 Hz, 4C, OCH2),
70.14 (t, 1J=142 Hz, 4C, OCH2), 70.51 (t, 1J=142 Hz,
1
3.10. (2-Bromomercurio-1,3-phenylene)-19-crown-6
(13) and bis[(l,3-phenylene-19-crown-6)-2-yl]mercury
(14)
4C, OCH2), 71.13 (t, J=141 Hz, 4C, OCH2), 107.17
1
3
2
(ddd, J=157 Hz, J=7.0 Hz, J=3.0 Hz, 4C, aryl
1
C(4,6)), 129.14 (d, J=158 Hz, 2C, aryl C(5)), 146.45
(s, 2C, aryl C(2)), 163.80 (d, 3J=11.1 Hz, 4C, aryl
C(1,3)). The Hg satellites were not observed due to the
low concentration. 199Hg-NMR (71.60 MHz, CDCl3,
ref. Me2Hg=0 ppm): l −708.84 (s, 1 Hg). MS (CI,
A solution of mercuric bromide (0.042 g, 0.12 mmol
in 2 ml of THF) was added rapidly to the solution of 4
(0.11 mmol in 1 ml of THF) at −65°C. Then it was
warmed slowly to room temperature overnight, after
which the clear solution turned slightly cloudy. Then 5
ml of water was added, and after the standard work up
0.043 g of a crude solid was obtained. According to the
1H-NMR spectrum, two compounds were present: 2
NH3, Finnigan MAT 90): m/z (relative intensity) 842
202
(M·NH4+,
C32H HgNO12,
100),
530
50
([aryl202Hg·NH3]+, 75), 513 (aryl202Hg+, 19). Anal.
Calc. (%) for C32H46HgO12: C, 46.68; H, 5.63. Found
(%): C, 46.16; H, 5.59.

102
I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
quenched carefully with deuterium oxide (0.70 ml,
38.68 mmol). After evaporating to dryness,
dichloromethane (10 ml) and 5 ml of aqueous saturated
solution of ammonium chloride were added. After a
thorough extraction with dichloromethane, the organic
layer was dried over MgSO4, filtered, and evaporated to
3.11. Reaction of 4 with magnesium bromide
In standard glassware with ground joints under ar-
gon, a solution of 0.21 M magnesium bromide in THF
(2.50 ml, 0.53 mmol) was added at −65°C to the
solution of 4 (0.50 mmol in 2 ml of THF), after which
the reaction mixture was warmed slowly to room tem-
perature overnight. Owing to its low solubility in THF,
the Grignard reagent was present in suspension. A
sample of the reaction mixture was quenched with an
excess of deuterium oxide. Standard acidic work up
1
dryness. According to its H-NMR spectrum, the oily
residue was essentially pure 2/2a (89% deuterium incor-
poration). GC/MS analysis of this residue revealed only
3% of unidentified products, possibly ether cleavage
products which, however, were not identified.
1
yielded a pale yellow oil, which was identified by H-
NMR spectroscopy and GC/MS as 2/2a (66% deu-
3.14. (2-n-Butyl-1,3-phenylene)-19-crown-6 (16)
terium incorporation).
A solution of 4 (0.20 mmol) in THF (2 ml), prepared
at −65°C from 8 and n-butyllithium, was allowed to
warm to room temperature overnight and then
quenched with deuterium oxide (0.50 ml, 27.63 mmol).
The standard work up procedure yielded 0.040 g of a
pale yellow oil, which was analyzed by GC/MS and
1H-NMR spectroscopy. In addition to unknown prod-
ucts, three compounds were identified by GC/MS anal-
ysis: a mixture of 2/2a (51%, ratio 85:15), and 16 (49%).
Purification of 16 was performed by preparative GC,
3.12. Reaction of 8 with magnesium in THF
In a high-vacuum glass apparatus, 8 (0.079 g, 0.20
mmol) was stirred with an excess of doubly sublimed
magnesium (0.102 g, 4.20 mmol) in dry THF (10 ml) at
room temperature. Gradually, a white precipitate
formed. After 13 days of stirring, the black magnesium
dust and the precipitate was allowed to settle, and the
vessel was stored at room temperature for a long
period. After 3 months, a sample (3.70 ml) of the clear
supernatant was decanted into a second vessel con-
nected to the reaction vessel, after which it was discon-
nected by sealing off at a capillary. Titration of this
sample showed that 0.019 mmol of ‘total base’ and
0.018 mmol of Mg2+ were present [10]. The solubility
Table 2
Numerical data of the structure determination for 8
Crystal data
Empirical formula
Formula weight
Crystal system
Space group
C16H23Br1O6
391.26
Orthorhombic
P212121 (No. 19)
8.451 (2)
23.171 (6)
25.837 (6)
5059 (2)
1
of 15 in THF was too low for H-NMR spectroscopy.
The remaining reaction mixture was quenched with
an excess of deuterium oxide (0.50 ml, 27.63 mmol).
Standard acidic work up yielded 0.043 g of a pale
yellow oil, which was identified by 1H-NMR spec-
troscopy and GC/MS as 2/2a (91% deuterium incorpo-
ration). The presence of about 0.02 mmol of 15 in the
sample which was titrated and 0.13 mmol in the re-
maining mixture which was quenched with deuterium
oxide, indicates a total yield of about 75% of 15.
˚
a (A)
˚
b (A)
˚
c (A)
3
˚
V (A )
Z
12
1.541
Dcalc. (g cm−3
)
F(000) (electrons)
v (Mo–Kh) (cm)
Crystal size (mm)
2424
24.7
0.25×0.45×0.50
Data collection
Temperature (K)
Radiation (A) Mo–Kh (with
150
0.71073
˚
3.13. Reaction of bromobenzene with magnesium in the
presence of 15
monochromator)
q min-max (°)
1.2, 22.5
Scan type, scan (°)
Data set
Total, unique data
Observed data [I\2.0|(I)]
DELABS transmission range
ꢀ, 0.90+0.35 Tan(q)
0:9/0:24/0.27
3761, 3730
2993
In sealed glass apparatus, a solution of bromoben-
zene (0.20 ml, 1.91 mmol) in THF (10 ml) was added at
room temperature to a vessel containing excess of mag-
nesium, and 15 (0.20 mmol) in THF (10 ml), prepared
from 8 with an excess of doubly sublimed magnesium
(0.170 g, 6.99 mmol) as described above. In order to
prevent a too vigorous reaction, the bromobenzene was
added in small portions during 2 h, after which the
stirring was continued for additional 45 min. The reac-
tion vessel was opened and the reaction mixture
0.533, 1.000
Refinement
Nref, Npar
R, wR, S
Maximum and average shift/error
Largest difference peak and hole (e A
Flack absolute structure parameter
3730, 622
0.0396, 0.0831, 1.05
0.000, 0.000
−0.32, 0.49
0.02 (1)
−3
˚
)
w=1/[|2(Fo2)+(0.0345P)2+1.8276P] where P=(Fo2+2F2c)/3.

I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
103
Table 3 (continued)
Table 3
Final coordinates and equivalent isotropic thermal parameters of the
non-hydrogen atoms for 8
2
˚
Atom
x
y
z
Ueq (A )
2
˚
C(212) −0.3258(12)
C(213) −0.2290(12)
0.2678(4)
0.3180(4)
0.3014(4)
0.2811(4)
0.1801(4)
0.1919(4)
0.1463(4)
0.0897(4)
0.1231(4)
0.2275(3)
0.2427(4)
0.2572(4)
0.2977(4)
0.2807(3)
0.2391(4)
0.2134(3)
0.2262(3)
0.2939(3)
0.035(4)
0.040(4)
0.040(3)
0.040(4)
0.027(3)
0.036(4)
0.036(3)
0.032(3)
0.022(3)
Atom
x
y
z
Ueq (A )
C(215)
C(216)
C(218)
C(219)
C(220)
C(221)
C(222)
0.0433(14)
0.1533(12)
0.2043(11)
0.3018(12)
0.3740(12)
0.3483(11)
0.1787(10)
Br(30)
O(302)
O(305)
O(308)
O(311)
O(314)
O(317)
C(301)
C(303)
C(304)
C(306)
C(307)
C(309)a
C(310)
C(312)
C(313)
C(315)
C(316)
C(318)
C(319)
C(320)
C(321)
C(322)
C(409)a
Br(10)
O(102)
0.47086(13)
0.5656(8)
0.3585(9)
0.2823(8)
0.2810(9)
0.4744(8)
0.6533(7)
0.6567(11)
0.5717(13)
0.5207(13)
0.3141(13)
0.3683(13)
0.3501(17)
0.2650(14)
0.2261(12)
0.3449(11)
0.6191(11)
0.7196(11)
0.7029(11)
0.8251(11)
0.8637(11)
0.7810(10)
0.6244(10)
0.351(4)
.38009(4) −0.00551(3) −0.0369(3)
0.4887(2)
0.5309(3)
0.4164(3)
0.2740(3)
0.1889(3)
0.2898(2)
0.4458(4)
0.5450(4)
0.5479(4)
0.5164(5)
0.4582(4)
0.3671(6)
0.3305(4)
0.2314(4)
0.2151(4)
0.1887(4)
0.2387(3)
0.3425(4)
0.3508(4)
0.4059(4)
0.4539(4)
0.3909(4)
0.3830(15)
0.11002(4)
0.0037(2)
0.0445(2)
0.1262(3)
0.1658(3)
0.1386(2)
0.0883(2)
0.0495(2)
0.0637(3)
0.0670(3)
0.1228(3)
0.1778(3)
0.1936(4)
0.1646(7)
0.1215(5)
0.1039(4)
0.0635(3)
0.0590(3)
0.0721(3)
0.0659(3)
0.1004(3)
0.1158(3)
0.0980(3)
0.0465(3)
0.1309(16)
0.65837(3)
0.6208(2)
0.5368(2)
0.5022(2)
0.5111(2)
0.5830(2)
0.6266(2)
0.6068(3)
0.5948(3)
0.5391(3)
0.4871(3)
0.4716(3)
0.4953(3)
0.5230(3)
0.5437(3)
0.5934(3)
0.6245(3)
0.6156(3)
0.6119(3)
0.5859(3)
0.5705(3)
0.5802(3)
0.6222(3)
0.35084(3)
0.2836(2)
0.1925(2)
0.1677(2)
0.2014(2)
0.2785(2)
0.3101(2)
0.2669(3)
0.2484(3)
0.2229(3)
0.1680(3)
0.1383(3)
0.2030(3)
0.2334(3)
0.0277(19)
0.048(3)
0.069(3)
0.049(3)
0.035(2)
0.026(2)
0.022(3)
0.035(3)
0.042(4)
0.048(4)
0.052(4)
0.040(5)
0.072(6)
0.040(4)
0.033(3)
0.026(3)
0.025(3)
0.021(3)
0.026(3)
0.029(3)
0.025(3)
0.020(3)
0.025(12)
0.0293(3)
0.0267(19)
0.027(2)
0.030(2)
0.034(2)
0.027(2)
0.0230(19)
0.020(3)
0.030(3)
0.021(3)
0.027(3)
0.027(3)
0.033(3)
0.032(3)
0.035(3)
0.027(3)
0.030(3)
0.031(3)
0.022(3)
0.025(3)
0.026(3)
0.027(3)
0.020(3)
0.0301(3)
0.028(2)
0.036(2)
0.036(2)
0.033(2)
0.032(2)
0.031(2)
0.023(3)
0.039(4)
0.033(3)
0.035(3)
0.038(3)
0.033(3)
0.027(3)
Ueq, one-third of the trace of the orthogonalized U.
a C(309)/C(409) are disordered in the ratio 0.73:0.27; atom sites have
a population less than 1.0.
although complete separation from 2/2a was not
possible.
1H-NMR (200.13 MHz, CDCl3, ref. CHCl3=7.27
3
ppm): l 0.93 (t, J=6.8 Hz, 3H, n-C3H6–CH3), 1.26–
3
1.59 (m, 4H, CH2CH2CH2CH3), 2.81 (t, J=7.3 Hz,
2H, CH2–C3H7), 3.49–3.89 (m, 16H, CH2O(2)CH2-
CH2O(3)CH2), 4.06–4.33 (m, 4H, O(1)CH2CH2O(2)),
3
3
6.54 (d, J=8.2 Hz, 2H, aryl H(4,6)), 7.04 (t, J=8.2
Hz, 1H, aryl H(5)). 13C{1H}-NMR (50.32 MHz,
CDC13, ref. CDCl3=77 ppm): l 14.18, 22.94, 23.22
and 31.84 (4C, n-Bu), 68.71, 69.68, 70.34, 70.60 and
71.29 (10C, C2H4), 106.78, 108.30, 125.83 and 157.63
(6C, aryl C). GC/MS: m/z (relative intensity) 368 (M+;
C20H32O6, 63), 192 (19), 177 (8), 164 (26), 149 (37), 133
(21), 124 (23), 117 (9), 107 (13), 91 (18), 89 (27), 73 (28),
45 (100). HRMS: Anal. Calc. for C20H32O6 368.2199,
found 368.219490.0010.
−0.05348(11)
0.0963(7)
O(105) −0.0955(7)
O(108) −0.1752(7)
O(111) −0.1440(8)
O(114)
O(117)
C(101)
C(103)
C(104)
−0.0329(3)
0.0850(2)
0.2382(3)
0.3125(2)
0.2034(2)
0.0488(4)
0.0330(8)
0.1625(7)
0.1890(11)
0.1156(12) −0.0501(4)
0.0674(11) −0.0474(3)
C(106) −0.1463(11) −0.0161(4)
C(107) −0.0959(11)
C(109) −0.1108(11)
C(110) −0.2097(11)
C(112) −0.2057(12)
C(113) −0.1191(11)
C(115)
C(116)
C(118)
C(119)
C(120)
C(121)
C(122)
Br(20)
O(202)
O(205)
O(208) −0.2295(7)
O(211) −0.2379(7)
O(214) −0.1094(8)
O(217)
C(201)
C(203)
C(204)
C(206)
0.0430(3)
0.1399(4)
0.1835(4)
0.2828(4)
0.2883(4)
0.3060(4)
0.2556(4)
0.1531(4)
0.1470(4)
0.0930(4)
0.0448(4)
0.1037(4)
0.10723(4)
0.0233(2)
0.0118(3)
0.1047(3)
0.2239(3)
0.3029(3)
0.2209(2)
0.0774(4)
3.15. X-ray structure determination of 8
Numerical data on the structure determination have
been collected in Table 2. X-ray data were collected for
a colorless transparent crystal cut to shape and trans-
ferred into the cold dinitrogen stream on an ENRAF-
NONIUS CAD4 diffractometer (rotating anode,
Mo–Kh radiation). Intensity data were corrected for
absorption (PLATON/DELABS [11]). The structure
was solved with standard direct methods (SHELXS-86
[12]) and difference Fourier techniques and refined on
F2 with SHELXL-93 [13]. Molecule no. 3 was refined
with a disorder model (0.73(3):0.27) for the pair C309/
C409. Hydrogen atoms were taken into account at
calculated positions and refined riding on the atoms
they are attached to with isotropic displacement
parameters related to Ueq of the carrier atom (Table 3).
Geometrical calculations and the illustrations were per-
formed with PLATON [11]. Final coordinates are given
in [3]. Full details may be obtained from the author,
A.L. Spek.
0.1428(12)
0.2510(11)
0.2271(11)
0.3683(11)
0.4190(10)
0.3333(11)
0.1401(10)
0.04532(12)
0.2089(8)
0.0257(8)
0.1316(7)
0.2435(10)
0.2218(13) −0.0245(4)
0.0649(12) −0.0361(4)
0.1263(11)
0.0047(4)
0.0593(4)
0.1298(4)
0.1759(4)
C(207) −0.1637(12)
C(209) −0.1211(11)
C(210) −0.2047(11)

104
I.D. Kostas et al. / Journal of Organometallic Chemistry 572 (1999) 93–104
[3] P.R. Markies, O.S. Akkerrnan, F. Bickelhaupt, W.J.J.
Acknowledgements
Smeets, A.L. Spek, J. Am. Chem. Soc. 110 (1988) 4284.
[4] P.R. Markies, A. Villena, O.S. Akkerman, F. Bickelhaupt,
W.J.J. Smeets, A.L. Spek, J. Organomet. Chem. 463 (1993)
7.
[5] M. Newcomb, S.S. Moore, D.J. Cram, J. Am. Chem. Soc.
99 (1977) 6405.
[6] B.J. van Keulen, R.M. Kellogg, O. Piepers, J. Chem. Soc.
Chem. Commun. (1979) 285.
[7] (a) The method of its preparation was analogous to that of
bis (2-bromoethyl)ether. (b) K. Ziegler, H. Holl, Ann. Chem.
528 (1937) 143.
[8] J.F.W. Keana, G.S. Heo, J.S. Mann, F.L. Van Nice, L. Lex,
V.S. Prabhu, G. Ferguson, J. Org. Chem. 53 (1988) 2268.
[9] E. Kiehlmann, R.W. Lauener, Can. J. Chem. 67 (1989) 335.
[10] A.D. Vreugdenhil, C. Blomberg, Recl. Trav. Chim. Bays-gas
82 (1963) 453.
We thank Dr F.J.J. de Kanter for the NMR mea-
surements on the Bruker MSL 400 and Dr B.L.M. van
Baar for measuring the mass spectra and for the
HRMS measurements. This work was supported by the
Human Capital and Mobility Programme of the Eu-
ropean Union (I.D. Kostas) and by the Netherlands
Foundation of Chemical Research (SON) with financial
aid from the Netherlands Organization for Scientific
Research (NWO) (N. Veldman and A.L. Spek).
References
[11] A.L. Spek, PLATON, A multipurpose crystallographic tool,
Utrecht University, Utrecht, The Netherlands, 1998.
[12] G.M. Sheldrick, SHELXS-86, Program for crystal structure
determination, University of Go¨ttingen, Germany, 1986.
[13] G.M. Sheldrick, SHELXL-93, Program for crystal structure
refinement, University of Go¨ttingen, Germany, 1993.
[1] I.D. Kostas, G.J.M. Gruter, O.S. Akkerman, F. Bickelhaupt,
H. Kooijman, W.J.J. Smeets, A.L. Spek, Organometallics 15
(1996) 4450.
[2] M. Skowronska-Ptasinska, V.M.L.J. Aarts, R.J.M. Egberink,
J. van Eerden, S. Harkema, D.N. Reinhoudt, J. Org. Chem.
53 (1988) 5484.
.