In the Laboratory

A Guided-Inquiry Approach to the Sodium Borohydride W

Reduction and Grignard Reaction of Carbonyl Compounds
Robert E. Rosenberg†
Department of Chemistry and Physics, Salem State College, Salem, MA 01970; rrosenberg@transy.edu

Over the years, numerous articles in this Journal have
discussed the advantages of inquiry- or discovery-based labo-
ratories over traditional (cookbook or verification) labs (1).
In short, the two major advantages of the inquiry approach
are giving students a sense of excitement and allowing them
to participate in the scientific process. In many cases, these
gains are achieved without sacrificing any of the skills learned
from the traditional approach. These advantages have led
some programs to incorporate discovery-based laboratories
into part or all of their laboratory curricula (2). Nonethe-
less, most laboratory texts, most second-year organic cur-
ricula, and most organic experiments published in this Journal
feature the traditional approach (3).
In this work, the guided-inquiry approach is applied to
two standard experiments from the second semester of or-
ganic chemistry: sodium borohydride reduction of a ketone
and the Grignard addition of phenyl magnesium bromide to
a carbonyl compound (Table 1). Each student works in a team
of four and performs these two reactions on an unknown car-
bonyl compound from the following list of possible un-
knowns: benzaldehyde, benzophenone, benzoic anhydride,
and ethyl benzoate.1 IR spectral and melting point data of
the reaction products are used to establish both product and
starting material identities. Students use their team data to
draw conclusions about relative reactivity (esters are the least
electrophilic species of the four carbonyl compounds stud-
ied, the Grignard reagent is more nucleophilic than NaBH4)
and about reaction mechanism (carboxylic acid derivatives
undergo substitution reactions via an addition–elimination
†
Current address: Department of Chemistry, Transylvania Uni-
versity, Lexington, KY 40508.
mechanism). For maximum benefit, this three-period experi-
ment should commence while studying the addition of nu-
cleophiles to aldehydes and ketones and conclude before the
mechanism of nucleophilic addition to carboxylic acid de-
rivatives is revealed.
Experimental
The procedures for NaBH4 reduction (4) and synthesis
and reaction of phenyl magnesium bromide (5) are adapted
from standard procedures and are included in the Supple-
mental Material.W
Hazards
Methanol and sodium borohydride are both highly flam-
mable and toxic. Bromobenzene is an irritant. Magnesium is
flammable. The unknowns are either irritants (benzoic an-
hydride, benzophenone) or harmful (benzaldehyde). Ether
is harmful and extremely flammable. Hydrochloric acid is
corrosive. Students should have adequate eye protection, wear
gloves, and work in a well ventilated space at all times dur-
ing both of these procedures.
Discussion
NaBH4 Reduction
The first week of the experiment involves the NaBH4 re-
duction of an unknown. After the reaction, students will iden-
tify their unknown by using (i) the physical state of their
unknowns at ambient temperature, (ii) IR spectra and melt-

Table 1. Unknowns and Their Potential Reaction Products

Substitution +
Entry Unknown No Reaction Addition Substitution
Addition
Reaction with NaBH4
1 PhCHO(l) –– PhCH2OH(l) –– ––
2 Ph2CO(s) –– Ph2CHOH(s) –– ––
3 PhCO2Et(l) PhCO2Et(l) PhCH(OH)OEt PhCHO PhCH2OH
4 (PhCO)2O(s) (PhCO)2O PhCH(OH)OBz PhCHO PhCH2OH(l)
Reaction with PhMgBr
5 PhCHO –– Ph2CHOH(s) –– ––
6 Ph2CO –– Ph3COH(s) –– ––
7 PhCO2Et PhCO2Et Ph2C(OH)OEt Ph2CO Ph3COH(s)
8 (PhCO)2O (PhCO)2O Ph2C(OH)OBz Ph2CO Ph3COH(s)
Abbreviations: Ph = phenyl = C6H5; Et = ethyl = CH3CH2; Bz = benzoyl = C6H5CO. For reactions of PhCO2Et and
(PhCO)2O, the actual product is underlined.

1474 Journal of Chemical Education • Vol. 84 No. 9 September 2007 • www.JCE.DivCHED.org

 In the Laboratory

ing point data of their products, and (iii) an instructor-pro-

vided list of possible products, shown in Table 1. The reac-
tion products for the aldehyde and ketone are given explicitly,
(entries 1 and 2). A series of four possible reaction outcomes
are given for the carboxylic acid derivatives, (entries 3 and 4).
Students use physical data to divide their unknowns into
a liquid group (benzaldehyde and ethyl benzoate) and a solid
group (benzophenone and benzoic anhydride), (decision 1 in
Figure 1). In the liquid group, the product of benzaldehyde
reduction is given as benzyl alcohol and is uniquely identi-
fied by the OH stretch in its IR spectrum, (analysis I, Figure
1). By elimination, ethyl benzoate is identified as the other
liquid unknown. Now, the reduction product of ethyl ben-
zoate must be identified from the four possibilities shown in
entry 3 of the table. This product has an IR spectrum with a
C⫽O stretch but not an OH stretch consistent with either
starting material or benzaldehyde (analysis II, Figure 1). This
choice can be resolved (i) by logic (benzaldehyde is known to
react with NaBH4), (ii) by smell (the product does not smell
like benzaldehyde), or (iii) by taking an IR spectrum of ei-
ther ethyl benzoate or benzaldehyde (analysis III, Figure 1).
In the solid group, the product of benzophenone reduc-
tion is given as benzhydrol, which is uniquely identified by
its melting point (analysis IV, Figure 1). By elimination, ben-
zoic anhydride is identified as the other solid unknown. Now,
the reduction product of benzoic anhydride must be identi-
fied from the four possibilities in entry 4 of Table 1. This
product must be benzyl alcohol as it is the only potential
product with an IR spectrum that has an OH stretch but
not a C⫽O stretch (analysis V, Figure 1).
With a list of known starting materials and products in
hand, students can make two conclusions about reactivity.
First, esters are the least electrophilic compounds in this set
since they do not react under these conditions. Second, car-
boxylic acid derivatives react differently than aldehydes and
ketones: they do not give addition products. Instructors in-
terested in a one-week experiment could stop at this point.
Grignard Reaction
The next two weeks involve the addition of the carbo-
nyl compounds to phenyl magnesium bromide. With the
identities of the unknown determined from the NaBH4 re-
action, students only need to identify the Grignard products.
The given products of benzaldehyde (benzhydrol, entry 5 in
Table 1) and benzophenone (triphenylmethanol, entry 6 in
Table 1) are verified by their melting points. For each of the
Figure 1. Guide to the analysis of unknown identities and reaction
two carboxylic acid derivatives, there are four possible reac- products for NaBH4 reduction.
tion outcomes, listed as entries 7 and 8 in Table 1. Both prod-
ucts are identified as triphenylmethanol as their melting
points match the benzophenone product.
Looking at both data sets, students can conclude that
Grignard reagents are stronger nucleophiles than NaBH4 since
only the Grignard reagent gives a product with esters. With group of the carboxylic acid derivative. Substitution can oc-
some leading questions, students can use the product data cur in three ways: (i) simultaneously, (ii) elimination followed
from the two reactions to propose a reasonable mechanism by addition, or by (iii) addition followed by elimination. Since
for the addition of strong nucleophiles to carboxylic acid de- the Grignard reagent undergoes addition to aldehydes and
rivatives. Since the ketone, ester, and anhydride all give the ketones, it is reasonable to assume that Grignard reagents also
same Grignard product, it is reasonable (though not neces- initially add to carboxylic acid derivatives. This fits best with
sary) to assume that all three compounds proceed through a an addition–elimination mechanism. Similar reasoning can
common intermediate, the ketone. For this to occur, the phe- be used to rationalize the product formed in the addition of
nyl group of the Grignard reagent must substitute for the X hydride to benzoic anhydride.2

www.JCE.DivCHED.org • Vol. 84 No. 9 September 2007 • Journal of Chemical Education 1475

 In the Laboratory
Conclusion
Using standard experiments (NaBH4 reduction and re-
action of a Grignard reaagent), students learn about the re-
activity and mechanism of carbonyl compounds. For
reactivity, they discover that esters are less reactive electro-
philic than ketones, aldehydes, or anhydrides and that Grig-
nard reagents are more nucleophilic than NaBH 4 .
Mechanistically, students learn that carboxylic acid deriva-
tives do not yield simple addition reactions with nucleophiles.
With a little help, students can be led to the correct mecha-
nism.
Acknowledgments
The author would like to thank the students of Salem
State College for helping to test these ideas. Also, the author
would like to thank David K. Johnson (SUNY, Geneseo) and
Irvin J. Levy (Gordon College) for their shared wisdom.
W
Supplemental Material
Instructions for the students, including prelab work and
report sheets, and notes for the instructor are available in this
issue of JCE Online.
1476 Journal of Chemical Education • Vol. 84 No. 9 September 2007
Notes
1. Many lab sizes will mandate some teams of three, in which
case the instructor can provide data on the fourth compound.
2. This argument is probably better suited to a class or team
discussion than as a postlab question.
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1084. (c) Allen, J. B.; Barker, L. N.; Ramsden, J. H. J. Chem.
Educ. 1986, 63, 533–534. (d) Wartell, M. A. J. Chem. Educ.
1973, 50, 361–362.
2. Jarrett, R. M.; McMaster, P. D. J. Chem. Educ. 1994, 71,
1029–1031.
3. Horowitz, G. J. Chem. Educ. 2003, 80, 1039.
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Laboratory, 3rd ed.; Harcourt College Publishing: New York,
2001; p 216.
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• www.JCE.DivCHED.org