Knoevenagel Condensation to a-Phenylcinnamonitriles:

NaBH4 Reduction to Propanenitriles

Stuart S. Kulp
Moravian College, Bethlehem, PA 18018

A fast, simple Knoevenagel condensation has been uti-
lized for 10 years in our sophomore laboratory course to
synthesize a,8-unsaturated nitriles in high yields. The latter
compounds are re~resentativeof multifunctional substances
and i r e good startkg materials for subsequent synthetic and
structural elucidation experiments. One example is the re-
duction of the alkene double bond by sodium borohydride in
dimethylformamide, a reaction that readily forms the corre-
sponding saturated nitriles. The equations for these reac-
tions are
A Ar'
1 2
DMF
3 + NaBH4 -H-
z0
r ArCH2-CHCH
I
Ar'
4 2,s-Dlarylpropenenltrlles (3)and 2,3-Diarylpropanenltrlles (4)
ethanol. Add dropwise with stirring 3.0 mL of 40%aqueous NaOH,
and continue manual stirring until solidification is complete, -5
min. Collect the solid by vacuum filtration, wash with 12 mL of iee-
cold water and 3 mL of ice-cold ethanol. Dry, weigh, and determine
the melting point of the crude product. The reported melting point
of the purified product is 86-88 'CZ. Recrystallization from 95%
ethanol (3.5 mL1g) is recommended.
2,s-Diphenylpropanenitrile (4a)
Under the hood, dissolve 2.0 g (0.05 moll of 98% NaBHdin 50 mL
of dirnethylformamide3 (DMF) with vigorous shaking. Filter this
solution by gravity to remove any particulate matter. Dissolve 0.05
mol of purified 2,3-diphenylpropenenitrile(3a) in 50 mL of DMF.
Filter this solution by gravity. Combine the solutions and shake
intermittently for 45 mi". Quench the reaction with 150 rnL of ice
I
Ar' water, and carefully neutralize by dropwise addition of 2 N HCI.
3 Collect the white solid by vacuum filtration, and recrystallize from
EtOH, mp 51.0-51.5 OC, lit. 58 O C 4 .

The reactive carhonyl of benzaldehydes, 1, and active

methylene of benzyl cyanides, 2, give 2,3-diarylpropene-
nitriles, 3, with NaOH in ethanol within minutes a t room
temperature in yields of 80-3570.
Our students have synthesized 21 compounds (3a-u) from
combinations of seven different aromatic aldehydes and
three benzaldehvdes (see table).
Normally sodfum borohydride, a relatively mild reducing
aeent. does not hvdroaenate alkenes. However, activation of
the d ~ u b l bond
r ig
rt;njugnted electron withdrawers surh as
csnna, nlltnvs *odium horohvdride in d~methvlfurmnmidetu Ar Ar' mp ('C) mpibp ("C)
rkact with propenenitriles, 3, a t room temperature. The cya-
no function is not attacked by the hydride in these com- CeHs CsHs (a) 85-86.5 51-51.5
pounds. The reductions are fast (i.e., complete in 1 min for CeHs 4-ClcsH1 (b) 110-110.5 84-85
CsHs 4CHs0CsH4 ( C ) 92.5-93.5 68-69
3e, which has chlorines in the para positions). The rate data (d) 101-101.5 110-111.5
pClCsH4 C6H6
and yields have been reported' for these reductions. The PC~CBHI 4-ClCeH4 (e) 108.5-109 89-90
properties of the 2,3-diarylpropanenitriles (4a-u) prepared PCICBH, 4-cHa0CeH1 (11 108.5-109 108-109.5
hv students are also found in the table. PCH~OCBHI CeHs (g) 93.5-94.5 85.5-87
The ease, rapidity, and product flexibility of this Knoe- pCH30CsH4 4-CICsH, (h) 127.5-128.5 111-112.5
venagel reaction is emphasized. Further exploitation of the pCH30CeH4 4-CHaOCgHa (1) 107-107.5 115-1 16.5
a$-unsaturated nitrile products for synthetic and product pMeW& CeHs (1) 137-138 76-77.5
elucidation experiments will he reported later. pMezNCeH4 4-CICaH4 (kl 189-190 112-114
pMe2NCaH4 ~-CHIOC~H, (1) 149.5-150 102-104
Experimental l-naphthyi CaHr (m) 110-110.5 82-83
I-naphlhyl 4-CICeHa (n) 174-175 83-84
I-naphlhyl 4-CH,OCaHl ( 0 ) 104.5-105 94.5-96.5
Z3-Diphenylpropenenitriie (3a) a-fury1 CsHr (p) 42.5-43' 116-117121 mm
Into a 250-mL Erlenmeyer flask place 6.36 g (0.06 moll of benzal- a-fury1 4-CICeH4 (q) 80-80.5' 196-197121 mm
dehyde, 7.02 g (0.06 mol) of benzyl cyanide and 40 mL of 95% a-fury1 4CH30CsH+ (r) 61-6Zb 207-208121 mm,
a-thienyl C6Hs (s) 90-90.7 206-207121 mm
a-thienyl 4-CICsHd (I) 135-136 84.5-86
' KuID.S. S.: Caldwell..~C. 6-. J. Oro Chem. 1980.. 4 -.5 171
,~~~ ~ - 0 ~ -- ~ - - ~
~~ ~
a-thienyl 4CH30CaH. (u) 76.5-77 190-19212 mm
~&zonek,S.; Smolin, E. M. Org. Synfh. 1953,3,715.
Caution: DMF is a skin penetrant like DMSO. 'DBcompose~on standing at room tempemure several days
Oict of Org. Cpds. 4th ed.; Oxford Univ.: 1965: Vol. 3, p 1293. ' for 40 min.
Reaction mixture heated at 50 C

742 Journal of Chemical Education