Rosenberg 2007

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 mechanism). For maximum benefit, this three-period experi-
discussed the advantages of inquiry- or discovery-based labo- ment should commence while studying the addition of nu-
ratories over traditional (cookbook or verification) labs (1). cleophiles to aldehydes and ketones and conclude before the
In short, the two major advantages of the inquiry approach mechanism of nucleophilic addition to carboxylic acid de-
are giving students a sense of excitement and allowing them rivatives is revealed.
to participate in the scientific process. In many cases, these
gains are achieved without sacrificing any of the skills learned Experimental
from the traditional approach. These advantages have led
some programs to incorporate discovery-based laboratories The procedures for NaBH4 reduction (4) and synthesis
into part or all of their laboratory curricula (2). Nonethe- and reaction of phenyl magnesium bromide (5) are adapted
less, most laboratory texts, most second-year organic cur- from standard procedures and are included in the Supple-
ricula, and most organic experiments published in this Journal mental Material.W
feature the traditional approach (3).
In this work, the guided-inquiry approach is applied to Hazards
two standard experiments from the second semester of or-
ganic chemistry: sodium borohydride reduction of a ketone Methanol and sodium borohydride are both highly flam-
and the Grignard addition of phenyl magnesium bromide to mable and toxic. Bromobenzene is an irritant. Magnesium is
a carbonyl compound (Table 1). Each student works in a team flammable. The unknowns are either irritants (benzoic an-
of four and performs these two reactions on an unknown car- hydride, benzophenone) or harmful (benzaldehyde). Ether
bonyl compound from the following list of possible un- is harmful and extremely flammable. Hydrochloric acid is
knowns: benzaldehyde, benzophenone, benzoic anhydride, corrosive. Students should have adequate eye protection, wear
and ethyl benzoate.1 IR spectral and melting point data of gloves, and work in a well ventilated space at all times dur-
the reaction products are used to establish both product and ing both of these procedures.
starting material identities. Students use their team data to
draw conclusions about relative reactivity (esters are the least Discussion
electrophilic species of the four carbonyl compounds stud-
ied, the Grignard reagent is more nucleophilic than NaBH4) NaBH4 Reduction
and about reaction mechanism (carboxylic acid derivatives The first week of the experiment involves the NaBH4 re-
undergo substitution reactions via an addition–elimination duction of an unknown. After the reaction, students will iden-
†
Current address: Department of Chemistry, Transylvania Uni- tify their unknown by using (i) the physical state of their
versity, Lexington, KY 40508. 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 Notes
Using standard experiments (NaBH4 reduction and re- 1. Many lab sizes will mandate some teams of three, in which
action of a Grignard reaagent), students learn about the re- case the instructor can provide data on the fourth compound.
activity and mechanism of carbonyl compounds. For 2. This argument is probably better suited to a class or team
reactivity, they discover that esters are less reactive electro- discussion than as a postlab question.
philic than ketones, aldehydes, or anhydrides and that Grig-
nard reagents are more nucleophilic than NaBH 4 . Literature Cited
Mechanistically, students learn that carboxylic acid deriva-
tives do not yield simple addition reactions with nucleophiles. 1. (a) Monteyne, K.; Cracolice, M. S. J. Chem. Educ. 2004, 81,
With a little help, students can be led to the correct mecha- 1559–1560. (b) Mohrig, J. R. J. Chem. Educ. 2004, 81, 1083–
nism. 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.
Acknowledgments 1973, 50, 361–362.
2. Jarrett, R. M.; McMaster, P. D. J. Chem. Educ. 1994, 71,
The author would like to thank the students of Salem 1029–1031.
State College for helping to test these ideas. Also, the author 3. Horowitz, G. J. Chem. Educ. 2003, 80, 1039.
would like to thank David K. Johnson (SUNY, Geneseo) and 4. Bell, C. E., Jr.; Taber, D. F.; Clark, A. K. Organic Chemistry
Irvin J. Levy (Gordon College) for their shared wisdom. Laboratory, 3rd ed.; Harcourt College Publishing: New York,
2001; p 216.
W
Supplemental Material 5. (a) Williamson, K. L. Organic Experiments, 4th ed.; Houghton
Mifflin Co.: Boston, 2003; pp 465–470, 472–476. (b)
Instructions for the students, including prelab work and Mohrig, J. R.; Hammond, C. N.; Morrill, T. C.; Neckers, D.
report sheets, and notes for the instructor are available in this C. Experimental Organic Chemistry, 1st ed.; W. H. Freeman
issue of JCE Online. and Co.: New York, 1998; pp 122–126.
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In the Laboratory

A Guided-Inquiry Approach to the Sodium Borohydride W

Table 1. Unknowns and Their Potential Reaction Products

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

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

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

1476 Journal of Chemical Education • Vol. 84 No. 9 September 2007 • www.JCE.DivCHED.org

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