The Use of Salicylaldehyde Phenylhydrazone as an Indicator for the Titration of Organometallic Reagents

Full text of DOI:10.1021/jo982433e

J . Org. Chem. 1999, 64, 3755-3756
3755
Sch em e 1
Th e Use of Sa licyla ld eh yd e
P h en ylh yd r a zon e a s a n In d ica tor for th e
Titr a tion of Or ga n om eta llic Rea gen ts
Brian E. Love* and Edward G. J ones
Department of Chemistry, East Carolina University,
Greenville, North Carolina 27858
Received December 14, 1998
Though there are a number of reagents available which
can serve as indicators for the titration of organolithium
compounds,1 only a few are suitable for use with Grignard
reagents. Those that can be used with Grignard reagents
such as 1-pyreneacetic acid3 and diphenyl ditelluride4
tend to be expensive and/or have other limitations.5 Other
reagents such as N-phenyl-1-naphthylamine7 and 1,10-
phenanthroline8 are more reasonably priced but must be
used in conjunction with a standardized anhydrous
solution of 2-butanol in xylene, which is tedious to
prepare. Potentiometric titration is perhaps the most
accurate means of determining the concentration of a
Grignard reagent, but it too requires a standardized
2-butanol solution, as well as expensive electrochemical
equipment.9
Ta ble 1. Titr a tion of Gr ign a r d Rea gen ts
calculated
calculated
molarity using PhTeTePh
reagent
molarity using 1a
MeMgBr
2.18 ( 0.06
1.60 ( 0.13
1.50 ( 0.04
1.31 ( 0.17
1.75 ( 0.08
1.45 ( 0.03
1.19 ( 0.08
2.10
1.58
1.53
1.27
b
n-PrMgCl
i-PrMgCl
n-BuMgCl
t-BuMgCl
n-C6H13MgBr
PhMgCl
1.42
1.22
a
b
Average of three trials. Titration of tert-butyl magnesium
chloride with diphenyl ditelluride as an indicator was impractical
due to the slow reaction ratessmore than a minute was required
between addition of a drop of tert-butyl magnesium chloride and
the observation of its effect on the color of the diphenyl ditelluride
solution.
Resu lts a n d Discu ssion
Ta ble 2. Titr a tion of Or ga n olith iu m Rea gen ts
Here we report the use of salicylaldehyde phenyl-
hydrazone 1 (Scheme 1) as an indicator for the titration
of organometallic species, including Grignard reagents.
It is easily prepared in good yield from inexpensive
starting materials and is simple to isolate in pure form.
Addition of an organometallic reagent to a solution of 1
produces the yellow monoanion 2, and further addition
of the reagent produces a red color, attributed to the
dianion 3. The first drop of organometallic reagent in
excess of 1 equiv is manifested by a change in the color
of the solution from yellow to bright orange, which thus
serves as the end point of the titration. Prior to reaching
the end point, each drop of organometallic reagent
produces a localized formation of the dianion (which
quickly dissipates with efficient stirring) but provides a
preview of the color change to be observed at the end
point. Though there is not a large chromatic shift (yellow
calculated
calculated
molarity using NPOT
b
reagent
molarity using 1a
MeLi
1.15 ( 0.04
1.28 ( 0.05
0.96 ( 0.01
0.99 ( 0.12
1.20
1.28
0.98
1.08
n-BuLi
s-BuLi
t-BuLi
a
b
Average of three trials. NPOT ) N-pivaloyl-o-toluidine.
to orange), the end point is nevertheless distinct and easy
to observe.
The titration can be carried out simply by dissolving
an accurately weighed sample of 1 in freshly distilled
THF and maintaining this solution under an atmosphere
of dry nitrogen while the organometallic reagent is added
by means of a gastight syringe. The results are quite
reproducible, given the accuracy of the syringe,10 and
agree well with values obtained using previously reported
indicators (Tables 1 and 2).
Not only Grignard reagents and organolithiums but
also solutions of hydridic species such as lithium alumi-
num hydride (LAH) and sodium bis(2-methoxyethoxy)-
aluminum hydride (Vitride or Red-Al) can be titrated
using 1 as an indicator (Table 3). The concentration of
these solutions is commonly determined by iodometric
titration11 or by treatment with benzyl alcohol and either
measurement of evolved hydrogen gas12 or observation
of the development of color in the presence of 1,10-
(1) Some commonly used examples include the following: diphenyl-
acetic acid,2a 1,3-diphenyl-2-propanone p-tosylhydrazone,2b 4-biphenyl-
methanol,2c and N-pivaloyl-o-toluidine,2d though a number of others
have been reported.
(2) (a) Kofron, W. G.; Baclawski, L. M. J . Org. Chem. 1976, 41, 1879.
(b) Lipton, M. F.; Sorensen, C. M.; Sadler, A. C.; Shapiro, R. H. J .
Organomet. Chem. 1980, 186, 155. (c) J uaristi, E.; Martinez-Richa, A.;
Garcia-Riviera, A.; Cruz-Sanchez, J . S. J . Org. Chem. 1983, 48, 2603.
(d) Suffert, J . J . Org. Chem. 1989, 54, 509.
(3) Kiljunen, H.; Hase, T. A. J . Org. Chem. 1991, 56, 6950.
(4) Aso, Y.; Yamashita, H.; Otsubo, T.; Ogura, F. J . Org. Chem. 1989,
54, 5627.
(5) 1-Pyreneacetic acid now costs approximately $28 per gram,6 and
the commercial material often contains colored impurities which
obscure the end point. Diphenyl ditelluride now costs approximately
$20 per gram6 and produces malodorous alkylphenyl tellurides which
are potentially toxic.
(10) A 1.00 mL syringe with calibration marks every 0.02 mL was
used. With the amounts of 1 employed (60.0-80.0 mg), an error of 0.01
mL in the amount of titrant used changes the calculated molarity by
approximately 0.05-0.1 M. Use of larger amounts of 1 generally gave
more precise results.
(11) Felkin, H. Bull. Soc. Chim. Fr. 1951, 347.
(12) Rickborn, B.; Quartucci, J . J . Org. Chem. 1964, 29, 3185.
(6) Aldrich Chemical Co.
(7) Bergbreiter, D. E.; Pendergrass, E. J . Org. Chem. 1981, 46, 219.
(8) Watson, S. C.; Eastham, J . F. J . Organomet. Chem. 1967, 9, 165.
(9) Silverman, G. S., Ed. Handbook of Grignard Reagents; Marcel
Dekker: New York 1996; pp 89-92.
10.1021/jo982433e CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/22/1999

3756 J . Org. Chem., Vol. 64, No. 10, 1999
Notes
Ta ble 3. Titr a tion of Hyd r id e Rea gen ts
In summary, salicylaldehyde phenylhydrazone 1 has
been found to be a useful indicator for the titration of a
wide range of commonly used reagents.16 It can be
prepared easily from inexpensive starting materials and
provides clear and accurate end point determinations.
calculated
calculated
molarity using 9-fluorenone
reagent
molarity using 1a
LiAlH4
Red-Al
3.71 ( 0.03
2.69 ( 0.09
3.57
2.78b
a
b
Average of three trials. In this case the end point was
indicated by the development of a dark color, rather than the
disappearance of the yellow color, as was reported (and observed)
for LAH.
Exp er im en ta l Section
Gen er a l Meth od s. THF was freshly distilled under nitrogen
from sodium benzophenone ketyl.
phenanthroline.13 More recently, a procedure which
utilizes 9-fluorenone has also been reported.14 As with
the previous organometallic species, sharp end points
were observed, that for LAH being more distinct than
that observed with the other organometallic species, and
the Red-Al being less so.
All four of the hydrogens on LAH take part in the
reaction, and thus the calculated molarity is four times
the actual molarity of the reagent.15 With sodium bis(2-
methoxyethoxy)aluminum hydride, both of the hydrogens
react, and thus the calculated molarity is double the
actual molarity of the reagent.
The phenylhydrazones of the isomeric compounds
m-hydroxybenzaldehyde and p-hydroxybenzaldehyde were
also tested for their ability to serve as indicators for the
titration of organometallic species. Both exhibited very
similar characteristics to those of 1, but since they offered
no significant advantage over the indicator derived from
the less expensive salicylaldehyde, their use was not
investigated further.
Sa licyla ld eh yd e P h en ylh yd r a zon e (1) A 2.92 g (27.0
mmol) sample of phenylhydrazine was dissolved in 10 mL of 95%
ethanol and stirred while 3.30 g (27.0 mmol) of salicylaldehyde,
dissolved in 15 mL of ethanol, was added. The solution was
stirred for 30 min at room temperature (a precipitate formed
within a minute) and then cooled to -15 °C. The white solid
was collected by vacuum filtration and washed with ice cold
ethanol to give (after drying in vacuo) 4.73 g (82.5%) of product
melting at 140-145 °C (lit.17mp 142 °C). The product can be
recrystallized from CHCl3 (recovery: 85%), but the melting point
is not changed significantly, and the product obtained prior to
recrystallization is typically suitable for use as a titration
indicator. 1H NMR (CDCl3) δ 10.96 (s, 1H), 7.78 (s, 1H), 7.50 (s,
1H), 7.4-7.2 (m, 3H), 7.2-6.8 (m, 6H); 13C NMR (CDCl3) δ
157.48, 143.89, 141.69, 130.53, 130.08, 129.91, 121.39, 120.04,
119.05, 117.09, 113.17.
Titr a tion P r oced u r e. An accurately weighed sample of 1
(typically between 60.0 and 80.0 mg) is dissolved in 10 mL of
freshly distilled THF and stirred at room temperature under
nitrogen while the organometallic reagent is added slowly by
means of a gastight syringe. A yellow color (the monoanion)
forms initially, the end point being indicated by a change in this
color to bright golden orange.
(13) Villieras, J .; Rambaud, M.; Kirschleger, B. J . Organomet. Chem.
1983, 249, 315.
J O982433E
(14) Brown, E.; Le´ze´, A.; Touet, J . Tetrahedron Lett. 1991, 32, 4309.
(15) Titration of LAH required the use of larger amounts of 1 than
were necessary for organolithium and Grignard reagent titrations. Use
of approximately 200 mg of 1 gave accurate and reproducible results,
while lesser amounts (50 mg) led to greater variations in calculated
molarity.
(16) This reagent did not, however, exhibit a satisfactory end point
when titrated with a solution of LDA.
(17) Rappoport, Z., Ed. Handbook of Tables for Organic Compound
Identification, 3rd ed.; The Chemical Rubber Co.: Cleveland, 1967.