Knoevenagel Condensation to a-Phenylcinnamonitriles: NaBH4 Reduction to Propanenitriles Stuart S. Kulp Moravian College, Bethlehem, PA 18018
A fast, simple Knoevenagel condensation has been utilized 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 reduction of the alkene double bond by sodium borohydride in dimethylformamide, a reaction that readily forms the corresponding saturated nitriles. The equations for these reactions are
A
Ar'
1
2 3
I
Ar' 3 DMF
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 ieecold 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 water, and carefully neutralize by dropwise addition of 2 N HCI. Collect the white solid by vacuum filtration, and recrystallize from EtOH, mp 51.0-51.5 OC, lit. 58 O C 4 .
+ NaBH4 -Hr ArCH2-CHCH I z0 Ar' 2,s-Dlarylpropenenltrlles (3)and 2,3-Diarylpropanenltrlles (4)
4
The reactive carhonyl of benzaldehydes, 1, and active methylene of benzyl cyanides, 2, give 2,3-diarylpropenenitriles, 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 rt;njugnted electron withdrawers surh as r the d ~ u b l bond csnna, nlltnvs *odium horohvdride in d~methvlfurmnmidetu rkact with propenenitriles, 3, a t room temperature. The cyano function is not attacked by the hydride in these compounds. The reductions are fast (i.e., complete in 1 min for 3e, which has chlorines in the para positions). The rate data and yields have been reported' for these reductions. The properties of the 2,3-diarylpropanenitriles (4a-u) prepared hv students are also found in the table. The ease, rapidity, and product flexibility of this Knoevenagel reaction is emphasized. Further exploitation of the a$-unsaturated nitrile products for synthetic and product elucidation experiments will he reported later.
ig
Experimental Z3-Diphenylpropenenitriie (3a) Into a 250-mL Erlenmeyer flask place 6.36 g (0.06 moll of benzaldehyde, 7.02 g (0.06 mol) of benzyl cyanide and 40 mL of 95%
' KuID.S. S.: Caldwell..~C. 6-. J. Oro Chem. 1980.. 4 -.5 171 ,~~~
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Ar'
CeHs CeHs CsHs pClCsH4 PC~CBHI PCICBH, PCH~OCBHI pCH30CsH4 pCH30CeH4 pMeW& pMezNCeH4 pMe2NCaH4 l-naphthyi I-naphlhyl I-naphlhyl a-fury1 a-fury1 a-fury1 a-thienyl a-thienyl a-thienyl
CsHs 4-ClcsH1 4CHs0CsH4 C6H6 4-ClCeH4 4-cHa0CeH1 CeHs 4-CICsH, 4-CHaOCgHa CeHs 4-CICaH4 ~-CHIOC~H, CaHr 4-CICeHa 4-CH,OCaHl CsHr 4-CICeH4 4CH30CsH+ C6Hs 4-CICsHd 4CH30CaH.
mp ('C)
mpibp ("C)
85-86.5 (b) 110-110.5 ( C ) 92.5-93.5 (d) 101-101.5 (e) 108.5-109 (11 108.5-109 (g) 93.5-94.5 (h) 127.5-128.5 (1) 107-107.5 (1) 137-138 (kl 189-190 (1) 149.5-150 (m) 110-110.5 (n) 174-175 ( 0 ) 104.5-105 (p) 42.5-43' (q) 80-80.5' (r) 61-6Zb (s) 90-90.7 (I) 135-136 (u) 76.5-77
51-51.5 84-85 68-69 110-111.5 89-90 108-109.5 85.5-87 111-112.5 115-1 16.5 76-77.5 112-114 102-104 82-83 83-84 94.5-96.5 116-117121 mm 196-197121 mm 207-208121 mm, 206-207121 mm 84.5-86 190-19212 mm
(a)
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~&zonek,S.; Smolin, E. M. Org. Synfh. 1953,3,715. Caution: DMF is a skin penetrant like DMSO. Oict of Org. Cpds. 4th ed.; Oxford Univ.: 1965: Vol. 3, p
742
Ar
1293.
'DBcompose~on standing at room tempemure several days Reaction mixture heated at 50 C ' for 40 min.
