1. Synthesis of 3-Substituted Coumarins by the Knoevenagel
Condensation Reaction BY:MARIAM ISRAIEL Mentor: Dr. Kenneth
Yamaguchi New Jersey City University (NJCU) Chemistry Department
Experimental Protocol The Knoevenagel condensation reaction is an
organic reaction named after Emil Knoevenagel. It is a modification
of the Aldol condensation. The microwave irradiation-assisted and
thermal solvent-free Knoevenagel condensations of aromatic ketones
with malononitrile catalyzed by NH4OAc or silica gel, and the
uncatalyzed Knoevenagel condensations in refluxing water have been
investigated. The preparation of heterocyclic compounds under
solvent - free conditions offers several key advantages and
represents an important class of compounds with elevated biological
activity and industrial importance .The microwave - assisted
synthesis of a series of 3-Substituted Coumarins via the
condensation of a series of 2-hydroxyaldehydes and dimethylmalonate
on silica gel was explored . 2-Hydroxyaldehyde (3mmol), dimethyl
malonate (3mmol), ammonium acetate (231 mg, 3mmol) and silica gel
or basic alumina (3g) are mixed thoroughly in a mortar.The reaction
mixture is placed in a beaker and irradiated in a microwave.The
progress of the reaction is monitored by TLC using petroleum
ether-CH 2 Cl 2(30:70).The mixture is then extracted into methylene
chloride (330-ml) then filtered and washed with water, the organic
phase is removed under reduced pressure by rotary
evaporation.Further purification by column chromatography on silica
gel gives the desired product.Crystallization can be carried out in
ethanol. Reactions Background Abstract All yields are based on pure
products 1 2 4 3 5 7 9 6 8 10 Results Infrared Spectroscopy (IR)
Results for Products: The Pechmann condensation is a synthesis of
coumarins, starting from a phenol and a carboxylic acid or esters
containing a -carbonyl group. The condensation is performed under
acidic conditions. The mechanism involves an esterification/
transesterification followed by attack of the activated carbonyl
ortho to the oxygen to generate the new ring. The final step is a
dehydration, as seen following an Aldol condensations. Active
hydrogen compounds condense with aldehydes and ketones.Known as
Knoevenagel condensations, these aldol-like condensations are
catalyzed by weak bases such as amines. With simple phenols, the
conditions are harsh, although yields may still be good Reaction
Mechanism Chemical Formula: C 11 H 7 BrO 3 Molecular Weight =
267.075 Chemical Formula: C 12 H 9 BrO 3 Molecular Weight = 281.102
Chemical Formula: C 11 H 8 O 3 Molecular Weight = 188.179 Chemical
Formula: C 12 H 10 O 3 Molecular Weig ht = 202.206 Chemical
Formula: C 15 H 12 O 3 Molecular Weight = 240.253 Chemical Formula:
C 16 H 14 O 3 Molecular Weight = 254.280 Chemical Formula: C 12 H
10 O 3 Molecular Weight = 202.206 Chemical Formula: C 13 H 14 O 3
Molecular Weight = 216.232 Chemical Formula: C 12 H 10 O 4
Molecular Weight = 218.205 Chemical Formula: C 12 H 10 O 4
Molecular Weight = 232.23 H1NMR and 13CNMR Spectrums of products4
Result were confirmed using: GC-MS 1 HNMR 13 CNMR Infrared
Spectroscopy (IR) Prep-Plates 30:70 (petroleum ether-CH2Cl2)
Crystallization (ethanol) Flash Chromatography Long Column
(Fraction Collection) Sep Packing (Fraction Collection)
Purification Methods 1 HNMR for products and Reactants Conclusion
References Silverstein, R. "Spectrometric Identification of Organic
Compounds" 6th Edition. NIST Chemistry WebBook:
http://srdata.nist.gov/gateway. Fryhle, Craig and TW Graham
Solomons.Organic Chemistry. 8th ed. New York: Wiley &
Sonshttp:// www.umich.edu"A Generalized Knoevenagel Condensation"
Aldrich Catalog Spectral Database for Organic Compounds (SDBS)
ChemFinder:http:// cambridgesoft.com
Pubchem:http://pubchem.nbci.nlm.nih.gov The reactions were carried
out under atmospheric pressure in an a closed vessel adapted to
Synthwave 402 microwave monomode reactor (Prolabo). All the
compounds were identified by GC/MS, IR, NMR and gave satisfactory
results in comparison with authentic samples. The Knoevenagel
condensations between aldehydes and malononitrile in dry media
catalyzed by silica gel and ammonium acetate (NH4OAc) basic alumina
have been studied. In summary, the method describes a noticeable
improvement in reactions conditions for the coumarin synthesis by
the Knoevenagel condensation and takes advantage of both solvent
free conditions reaction and microwave activation. 42.6% yield
71.3% yield 52.8% yield 49.2% yield 50.2% yield Results Products
Dimethyl malonate Aldehyde 39.4% yield 65.3% yield 54.8% yield
44.9% yield 43.6% yield Results Products Diethyl malonate Aldehyde
C=O (1700 cm -1 ) (1740.38 cm -1 ) C=C (1650 cm -1 ) (1655.66 cm -1
) C O (1100 cm -1 ) (1120.32cm -1 ) C=O (1700 cm -1 ) (1750.11 cm
-1 ) C=C (1650 cm -1 ) (1651.64 cm -1 ) C Br (650 cm -1 ) (655.36cm
-1 ) C O (1100 cm -1 ) (1110.81cm -1 ) C=O (1700 cm -1 ) (1772.1 cm
-1 ) C=C (1650 cm -1 ) (1652.7 cm -1 ) C Br (650 cm -1 ) (651.60cm
-1 ) C O (1100 cm -1 ) (1109.80cm -1 ) Infrared Frequencies
Structure C=O (1700 cm -1 ) (1760.46 cm -1 ) C=C (1650 cm -1 )
(1650.34 cm -1 ) C O (1100 cm -1 ) (1120.55cm -1 ) C=O (1700 cm -1
) (1760.38 cm -1 ) C=C (1650 cm -1 ) (1650.68 cm -1 ) C O (1100 cm
-1 ) (1120.36cm -1 ) C=O (1700 cm -1 ) (1740.36 cm -1 ) C=C (1650
cm -1 ) (1655.69 cm -1 ) C O (1100 cm -1 ) (1110.18cm -1 ) Infrared
Frequencies Structure C=O (1700 cm-1) (1720.72 cm-1) C=C (1650
cm-1) (1653.34 cm-1) CO (1100 cm-1) (1120.36cm-1 and 1125.68) C=O
(1700 cm-1) (1725.50 cm-1) C=C (1650 cm-1) (1653.80 cm-1) CO (1100
cm-1) (1125.56cm-1 and 1128.50)C=O (1700 cm -1 ) (1735.24 cm -1 )
C=C (1650 cm -1 ) (1655.63 cm -1 ) C O (1100 cm -1 ) (1120.39cm -1
) C=O (1700 cm -1 ) (1730.80 cm -1 ) C=C (1650 cm -1 ) (1660.79 cm
-1 ) C O (1100 cm -1 ) (1135.33cm -1 ) Infrared Frequencies
Structure 7.99(1H, d, J=2.3, H-5), 7.50(1H, dd, J=8.7 and 2.3,
H-7), 7.34(1H, d, J=8.7, H-8), 2.67(3H), s, CH3 acetyl), 2.55(3H,
s, C2-CH3), and 2.45(3H, s, C6-CH3).methyl 2-methoxy-1-naphthoate
7.39(1H, dd, J=8.2 and 1.1, H-8), 7.37(1H, ddd, J=8.4, 7.1 and 1.1,
H-6), 2.63(3H, s, CH3 acetyl), and 2.52(3H, s, C2-CH3).
4-acetyl-3-methoxyisocoumarin 7.72(1H, dd, J=8.8 and 2.4, H-7),
7.29(1H, d, J=8.8, H-8),3.823(3H) 3-butyryl-4-hydroxycoumarin 10.40
s (1H), 8.44 d(1H), 7.74 d(2H), 7.66 s (1H), 7.45 s (1H), 7.30
s(1H), 3.983 (3H) ethyl 2-methoxy-1-naphthoate 7.79-7.78(Ar), 7.686
(Ar), 7.57-7.44(Ar), 3.823(3H), 1.550
s(2H)7-methoxy-3-phenyl-4-chromanone 8.29(1H, d,J=2.5, H-5),
7.72(1H, dd, J=8.8 and 2.4, H-7), 7.29(1H, d, J=8.8, H-8), 2.53(3H,
s, CH3 acetyl), and 2.86(3H, s,
C2-CH3).5-hydroxy-2-phenyl-4-chromanone 8.14(1H, dd, J=8.4 and 1.6,
H-5), 7.64(1H, ddd, J=7.1, 8.2 and 1.6, H-7), 7.39(1H, dd, J=8.2
and 1.1, H-8), 7.37(1H, ddd, J=8.4, 7.1 and 1.1, H-6), 2.63(3H, s,
CH3 acetyl), and 2.52(3H, s, C2-CH3).
5-Hydroxy-2-ethyl-1,4-naphthoquinone 8.30(1H, d,J=2.4, H-5),
7.67(1H, dd, J=8.8 and 2.4, H-7), 7.38(1H, d, J=8.8, H-8), 7.36(3H,
s, CH3 acetyl), and 2.729(3H, s,
C2-CH3).5-Hydroxy-2-methyl-1,4-naphthoquinone 8.30(1H, d,J=2.4,
H-5), 7.76(1H, dd, J=8.8 and 2.4, H-7), 7.33(1H, d, J=8.8, H-8),
2.64(3H, s, CH3 acetyl), and 2.53(3H, s,
C2-CH3).3-probyl-6-bromocoumarine 3.37(3H), 3.47(3H), 5.46(NH),
5.49 (1H), 7.42-7.25 (Ar) 3-acetyl-6-bromocoumarine 3.375 t(3H),
3.398d(2H). Dimethylmalonate 9.966s(1H), 7.440 (Ar,d) , 7.37
(Ar,d), 3.18, (Ar,d), 3.852 s(1H) 2-Hydrovy-5-methylbenzaldehyde
9.850s(1H), 7.540 d(2H)Ar, 7.41 d(2H)Ar, 7.089 d(2H)Ar
2-Hydroxy-4-methoxybenzaldehyde 4.206 d(2H), 3.361 d(2H), 1.285
d(2H). Diethylmalonate 13.12s (1H), 10.725s(1H)Ar, 8.254t(3H)Ar,
7.903 d(2H)Ar, 7.738 d(2H)Ar, 7.540 d(2H)Ar, 7.41 d(2H)Ar, 7.089
d(2H)Ar. 2-Hydroxy-1-napthaldehyde 6.944 (t), 7.005 (Ar, t), 7.473
(Ar,t), 9.858 d(2H), 1.999t(1H)Salicyaldehyde 10.92 s(1H), 9.84
d(2H), 7.66 (Ar, t) ,7.600 (Ar,d) ,7.856t(3H)
4-Bromobenzaldehyde
