Use of 9-methylfluorene as an indicator in the titration of common group IA and group IIA organometallic reagents

Article abstract of DOI:10.1021/jo0111208

9-Methylfluorene was tested as an indicator in the titration of commonly used organometallic reagents. This indicator is readily prepared in three steps from fluorenone. In THF solution the deprotonated indicator is red and exhibits a sharp endpoint. The highly basic reagents secbutyllithium and tert-butyllithium can be titrated in ether solution, where the color of the deprotonated indicator is yellow.

Full text of DOI:10.1021/jo0111208

SCHEME 1. Syn th esis of 9-Meth ylflu or en e (1)
Use of 9-Meth ylflu or en e a s a n In d ica tor in
th e Titr a tion of Com m on Gr ou p IA a n d
Gr ou p IIA Or ga n om eta llic Rea gen ts
Martina E. Bowen, Bhasker Reddy Aavula, and
Eugene A. Mash*
Department of Chemistry, The University of Arizona,
Tucson, Arizona, 85721-0041
Received December 3, 2001
Abstr a ct: 9-Methylfluorene was tested as an indicator in
the titration of commonly used organometallic reagents. This
indicator is readily prepared in three steps from fluorenone.
In THF solution the deprotonated indicator is red and
exhibits a sharp endpoint. The highly basic reagents sec-
butyllithium and tert-butyllithium can be titrated in ether
solution, where the color of the deprotonated indicator is
yellow.
aliquot of the organometallic solution was added to
solvent containing 1, and in most cases a color change
was observed immediately (vide infra). THF solutions of
deprotonated 1 were deep red,4 while ether solutions were
bright yellow. These colored solutions were then titrated
with a standard solution of sec-butanol in THF. In both
THF and ether, visible endpoints were observed as a
sharp change from colored to colorless or cloudy white
solutions. In cases where the solution remained colorless,
additional titrations could be performed in the same
vessel by injecting another aliquot of the titrand and re-
titrating. Results obtained over several runs were con-
sistent and, where comparable, in close agreement with
parallel titrations using 2 as the indicator. Compound 2
gave a yellow to clear endpoint in THF or ether, which
was often more difficult to distinguish than the endpoint
of 1.
Indicator 1 was more generally useful than 2 for the
group IA organometallics tested. It worked well for
determination of the concentrations of alkyllithium re-
agents, including sec-butyllithium and tert-butyllithium
(Table 1, entries 1-7); of the amide bases lithium
diisopropylamide, sodium hexamethyldisilazane, and
potassium hexamethyldisilazane (entries 12-14); and of
dimsylsodium and lithiated methyl phenyl sulfone (en-
tries 15-16). In contrast, indicator 2 was more useful
than 1 for the group IIA organometallics tested (entries
Organometallic reagents containing group IA and
group IIA metals play important roles in organic chem-
istry. Often their use requires accurate knowledge of the
concentration of the organometallic reagent in a solution.
Many methods and indicators have been employed for
the titrimetric determination of organometallic reagent
concentrations.1 An ideal indicator should have a single,
cleanly removable proton with a pKa lower than that of
the conjugate acid of the titrand and higher than that of
the conjugate acids of hydroxide or alkoxide impurities
that contribute to the total base concentration. The rate
of transfer of proton from the indicator to the titrand
must be greater than the rate of transfer from titrant to
deprotonated indicator. The indicator should be colorless
in its protonated state and intensely colored when
deprotonated in solution. It should also be readily avail-
able, stable in storage, recyclable, and nontoxic. We have
examined the utility of 9-methylfluorene (1) as an indica-
tor in titrimetric determinations of the concentrations of
several group IA and group IIA organometallic reagents
and report our results herein.2
(1) (a) Gilman, H.; Haubein, A. H. J . Am. Chem. Soc. 1944, 66,
1515-1516. (b) Gilman, H.; Cartledge, F. K. J . Organomet. Chem.
1964, 2, 447-454. (c) Eppley, R. L.; Dixon, J . A. J . Organomet. Chem.
1967, 8, 176-178. (d) Watson, S. C.; Eastham, J . F. J . Organomet.
Chem. 1967, 9, 165-168. (e) Kofron, W. G.; Baclawski, L. M. J . Org.
Chem. 1976, 41, 1879-1880. (f) Duhamel, L.; Plaquevent, J .-C. J . Org.
Chem. 1979, 44, 3404-3405. (g) Winkle, M. R.; Lansinger, J . M.;
Ronald, R. C. J . Chem. Soc., Chem. Commun. 1980, 87-88. (h) Lipton,
M. F.; Sorensen, C. M.; Sadler, A. C.; Shapiro, R. H. J . Organomet.
Chem. 1980, 186, 155-158. (i) Bergbreiter, D. E.; Pendergrass, E. J .
Org. Chem. 1981, 46, 219-220. (j) J uaristi, E.; Martinez-Richa, A.;
Garcia-Rivera, A.; Cruz-Sanchez, J . S. J . Org. Chem. 1983, 48, 2603-
2606. (k) Suffert, J . J . Org. Chem. 1989, 54, 509-510. (l) Aso, Y.;
Yamashita, H.; Otsubo, T.; Ogura, F. J . Org. Chem. 1989, 54, 5627-
5629. (m) Kiljunen, H.; Hase, T. A. J . Org. Chem. 1991, 56, 6950-
6952. (n) Love, B. E.; J ones, E. G. J . Org. Chem. 1999, 64, 3755-3756.
(2) Although the acidity of fluorene derivatives has been widely
studied (e.g., see Bowden, K.; Cockerill, A. F. J . Chem. Soc. B 1970,
173-179), their general utility as titrimetric indicators has not been
described.
Compound 1 was prepared using published methods
(see Scheme 1 and Supporting Information).3 A descrip-
tion of the titration method appears in the Experimental
Section. Results from titrations using 1, and for com-
parison purposes N-phenyl-1-naphthylamine (2),1i are
given in Table 1.
Tetrahydrofuran was commonly used as the solvent in
titrations employing 1 as indicator. Ether was used as
the solvent only when titrating very basic organometal-
lics, such as sec-butyllithium and tert-butyllithium. An
(3) Badger, G. M. J . Chem. Soc. 1941, 535-538. Details of our
synthesis based on this method appear in the Supporting Information
for this note.
(4) The reported values of λmax and ꢀ for the cesium salt of 1 in THF
are 376 nm (12350), 478 nm (980), 503 nm (1250), and 539 nm (890).
See: Bors, D. A.; Kaufman, M. J .; Streitwieser, A., J r. J . Am. Chem.
Soc. 1985, 107, 6975-6982.
10.1021/jo0111208 CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/15/2002
J . Org. Chem. 2002, 67, 9087-9088
9087

TABLE 1. Titr a tion s of Or ga n om eta llic Solu tion sa
titrated concentration, M
entry
organometallic
solvent
hexanes
hexanes
hexanes
cyclohexane
pentane
ether
cyclohexane/ether
THF
THF
ether
THF
concentration, Mb,c
9-methylfluorene
N-phenyl-1-naphthylamine
1
2
3
4
5
6
7
8
BuLi
BuLi
BuLi
sec-BuLi
tert-BuLi
MeLi
1.6 (N)
1.6 (O, S)
1.6 (O)
1.3 (O)
1.7 (O)
1.6 (N)
1.8 (N)
3.0 (O)
1.0 (N)
3.0 (O)
1.0 (O)
2.0 (N)
1.0 (N)
0.5 (N)
∼0.5l
1.56 ( 0.05d
1.29 ( 0.04e
1.65 ( 0.04f
1.06 ( 0.11f
1.64 ( 0.13e
1.59 ( 0.06f
1.63 ( 0.05d
no resulti
1.56 ( 0.04f
1.31 ( 0.03f
1.65 ( 0.04e
0.99 ( 0.08f
no resultg,h
1.66 ( 0.09f
1.63 ( 0.07d
1.65 ( 0.29d,j
no resulti
PhLi
MeMgCl
tert-BuMgCl
phenyl MgBr
vinyl MgBr
LDA
NaN(SiMe3)2
KN(SiMe3)2
NaCH2S(O)CH3
LiCH2SO2Ph
9
no resulti
10
11
12
13
14
15
16
no resulti
3.07 ( 0.11d
1.01 ( 0.02f
1.93 ( 0.10f
no resultk
1.08 ( 0.08f
2.04 ( 0.06f
0.97 ( 0.05e
0.78 ( 0.06e
0.35 ( 0.08d
0.17 ( 0.02d
heptane/THF
THF
toluene
THF
no resultg
no resultg
THF
∼0.25m
no resultg
a
b
Titrations were performed using THF as solvent except for sec-BuLi and tert-BuLi, which were performed in ether. Original molarity
according to the label. c N ) new bottle, O ) previously opened bottle, S ) sediment present. Average of 4 titrations. e Average of 5
d
titrations. f Average of 6 titrations. g Addition of organometallic to indicator in THF gave a yellow solution that never exhibited an endpoint.
h
i
j
Ref 1i reports the titration of tert-BuLi using sec-BuOH in xylenes. Addition of organometallic gave no color change. Endpoint difficult
to distinguish. Addition of organometallic gave a black solution. Anticipated concentration; prepared by reaction of NaH with an excess
of dry DMSO. Anticipated concentration; prepared by reaction of BuLi with an excess of methyl phenyl sulfone in dry THF.
k
l
m
8-11). Neither 1 nor 2 was useful for determination of
the concentrations of lithium hexamethyldisilazane, lithi-
ated phenylacetylene, or the lithium enolate of cyclohex-
anone. The last two failures can be attributed to the
comparable thermodynamic acidities of phenylacetylene,
cyclohexanone, and the indicators.5,6 The apparent failure
of most Grignard reagents and lithium hexamethyldisi-
lazane to deprotonate 1 is more difficult to rationalize.
A significant kinetic barrier to deprotonation of 1 must
exist and may be attributable to differences in ion-pairing
and organometallic aggregation for these reagents.7
Compound 2 was an adequate indicator for the less basic
organolithiums, for LDA, and for three of the four
Grignard reagents tested. However, its yellow endpoint
was often obscured by residual coloration of the solution.
Exp er im en ta l Section
HAZARDOUS CHEMICAL WARNING: 9-Methylfluorene
has been shown to be mutagenic; see ref 9. Tetrahydrofuran and
diethyl ether were distilled from sodium metal and benzophe-
none prior to use. sec-Butanol was distilled from calcium hydride
and stored over 3 Å sieves. A standard solution was prepared
by weighing dry sec-butanol (4-5 g) into a 100 mL class A
volumetric flask that had been dried in an oven for several days
and diluting to the mark with freshly distilled THF.
Titr a tion P r oced u r e. A flame-dried 25 mL three neck
round-bottom flask under argon was charged with indicator (ca.
15 mg) and THF or ether (5 mL). The flask was fitted with two
rubber septa and a class A 10 mL buret that had been dried in
an oven and inserted through a third rubber septum. The buret
was filled with the standard solution of sec-butanol in THF. The
organometallic solution to be titrated (1.00 mL) was then added
via syringe. The organometallic solutions containing indicator
normally turned red (THF) or yellow (ether) for 1 and yellow
for 2. The standard solution of sec-butanol in THF was added
dropwise until the color just disappeared. The concentration of
the organometallic was then calculated from the volume of the
standard solution dispensed. If the organometallic was not
colored to begin with, another aliquot of organometallic could
be added and the titration repeated (often several times) in the
same flask. If the organometallic was colored, or for highly basic
organometallics, such as sec-butyllithium and tert-butyllithium,
multiple titrations were performed in separate flasks to facilitate
observation of the endpoint.
9-Methylfluorene offers some advantages over other
indicators used in organometallic titrations. It has a
single removable proton with a pKa of 22,5 which is lower
than those of the conjugate acids of organometallic
species normally titrated and higher than those of the
conjugate acids of hydroxide or alkoxide impurities that
contribute to the total base concentration.8 It is colorless
in its protonated state and intensely colored when
deprotonated in THF or ether solution. The titration
endpoint is easily discernible. 9-Methylfluorene is ex-
pected to be stable in storage and recyclable when
warranted. Although it is presently commercially un-
available, it is readily prepared in three steps from
inexpensive fluorenone.3
Note Ad d ed a fter ASAP : A typographical error was
introduced in the first paragraph of the version posted
ASAP 11/15/2002; the corrected version was posted
11/27/2002.
Su p p or tin g In for m a tion Ava ila ble: Details of the syn-
thesis of 1 from fluorenone. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O0111208
(5) The reported pKa value for 1 in THF is 21.85. See ref 4.
(6) Values of pKa reported for phenylacetylene and cyclohexanone
vary. See: (a) Cram, D. J . Fundamentals of Carbanion Chemistry;
Academic Press: New York, 1965. (b) J ones, J . R. The Ionization of
Carbon Acids; Academic Press: New York, 1973. (c) Bates, R. B.; Ogle,
C. A. Carbanion Chemistry; Springer-Verlag: Berlin, 1983, and
references cited in the these books.
(8) This was demonstrated by adding potassium tert-butoxide to a
solution of 9-methylfluorene in THF. No color was observed over 48 h.
(9) For studies bearing on the toxicological properties of 9-meth-
ylfluorene, see: (a) Rice, J . E.; Rivenson, A.; Braley, J .; LaVoie, E. J .
J . Toxicol. Environ. Health 1987, 21, 525-532. (b) Veith, G. D.;
Mekenyan, O. G.; Ankley, G. T.; Call, D. J . Chemosphere 1995, 30,
2129-2142.
(7) Parris, G. E.; Ashby, E. C. J . Am. Chem. Soc. 1971, 93, 1206-
1213, and references therein.
9088 J . Org. Chem., Vol. 67, No. 25, 2002