The document summarizes the synthesis of 5,5-dimethyl-3-aminocyclohex-2-ene via a condensation reaction between 5,5-dimethylcyclohexene-1,3-dione and ammonium acetate with no solvent. NMR and IR spectroscopy confirmed the identity of the enaminone product, though it had a lower melting point and yield than reported due to insufficient recrystallization. The green synthesis produced the target enaminone through a condensation reaction without solvents.

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Synthesis of an Enaminone
Rashid Alsuwaidi
7/11/14
Chem213 section: 001
Michael Banales
Synthetic FFR 1 Corrected

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Introduction
Enaminones are compounds that have an amine, alkene and ketone as their functional
groups. They can function as both nucleophiles and electrophiles as a result of their inherent
reasinance.1This interaction between the carbonyl and enamine allows them to be very useful at
synthesizing many pharmaceuticals such as dibromophenyl enaminones for epilepsy and seizure
disorders. From enaminones many compounds can be synthesized which are used for
asymmetric catalysis involving chelating agents such as quinolones, peptide and
azocompounds.2In medicine they can be used as anticonvulsants and antitumor agents.
There many different ways to synthesize enaminones and a simple method would be by
condensation of a 1,3-dicarbonyl using an amine but some methods result in low selectivity, side
products or requires toxic materials such as copper-mediated aminolysis and the reductive
cleavage of isoxazoles. Solid supported catalysts are the best way to synthesize enaminones
because they provide better surface area and yield such as silica gel that has absorbed
polyphosphoric acid which is a green method since it is solvent free.
The method used for this reaction will be by condensation of 5,5-dimethyl-3-
aminocyclohexane-1,3-dione which is 1,3-carbonyl using ammonium acetate. A carbonyl will be
replaced by an amine and an alkene will form by water molecules deprotonating the hydrogen
next to the carbonyls formed during the reaction. The mechanism for the synthesis of 5,5-
dimethyl-3-aminocyclohex-2-ene is shown in Scheme 1 and it is a green reaction which means
no solvents are used.

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Scheme 1. Mechanism of enaminone synthesis using no solvents.
The oxygen from the carbonyl removes a proton from the ammonium because it is
positively charged which results in an alcohol group and an amine. The reaction starts with the
amine from the ammonium acetate acting as a nucleophile and attacking the carbon on the
carbonyl which is the most electrophilic part and the electrons from the double bond are
transferred to the oxygen which becomes negatively charge. The nitrogen then forms a bond with
the carbon but it already has three bonds attached to it which gives it a positive charge while the
oxygen of the carbonyl has a negative charge. A proton transfer occurs between the oxygen and
nitrogen which then becomes a good leaving group. The electrons on the nitrogen are now
transferred to form a double bond with the carbon and the bond is broken with the oxygen
releasing water and forming an imine. This water then acts as a weak base and removes a proton
from the α-carbon and forms an alkene while the imine converts to an amine.
Enaminones are unique in their ability to be nucleophile and electrophiles since they
have enamines and carbonyls in their structure. These allow us enaminone derivatives and
intermediates to synthesize drugs than can used as anticonvulsant’s and antitumor agents.3The
purpose of this lab is to synthesize an enaminone using a green process which involves no
solvents by condensation reaction. The enaminone will then be purified by recrystallization and
tested using melting point, IR and NMR.

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Experimental
5,5-dimethyl-3-aminocyclohex-2-ene.5,5-dimethylcyclohexene-1,3-dione(560mg,4mmol) and
ammonium acetate(556mg,4mmol) were combined and stirred for fifteen minutes at 100 ̊ C.
The product was then recrystallized using acetonitrile and the crystal were removed by vacuum
filtration.4 Recrystallization (100% acetonitrile) yielded pale yellow crystals(223mg,40%) mp
96-99 ̊C; 1HNMR (60 MHz,d-DMSO) δ(ppm) 6.67 (s,2H), 4.91 (s,1H), 2.12 (s,2H), 1.91 (s,2H),
0.96 (s,6H); 1HNMR (400 MHz,d-DMSO) δ(ppm) 6.67 (s,2H), 4.90 (s,1H), 2.12 (s,2H), 1.90
(s,2H), 0.96 (s,6H); 13CNMR(400 MHz,d-DMSO) δ(ppm) 193.63, 165.14, 95.68, 49.64,
41.37,32.04, 27.86;IR (ATR) υmax (cm-1 ) 3297, 3095, 2955, 1679, 1524, 1470,1442.
Results and Discussion
5,5-dimethyl-3-aminocyclohex-2-ene was synthesized from heating 5,5-
dimethylcyclohexene-1,3-dione and ammonium acetate which is a condensation reaction. It is a
green reaction where the reaction was performed using no solvents by melting the mixture
together to form an orange liquid. There were no solvents used so it was not necessary to isolate
the product and the most efficient way to purify it was by recrystallization with acetonitrile
solution.
In the 1HNMR you can see a singlet peak at 6.67ppm with an integral value of 2 which
can only be from an amine. At 4.91 ppm there is a singlet with an integral value of 1 that belongs
to the hydrogen on the alkene. The peaks at 2.12ppm and 1.91ppm are both singlets with an
integral value of 2 but the hydrogens next to the carbonyl shifted the peak to the left at 2.21ppm
while at 1.91ppm it is further away from it. At 0.96ppm there is a singlet with an integral value
of 6 which can only be from the methyl groups attached to the same carbon

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In the 13CNMRyou can see the peak for the carbonyl carbon at 193.63 ppm. At 165.14
ppm is the peak for the carbon from the alkene while at 95.68ppm is the carbon from the alkene
that is closer to the carbonyl. At 49.64 ppm is the carbon that is next to the carbonyl carbon
while the carbon at 41.37 ppm is located further from it. The carbon that is attached to both
methyl groups is at 32.04 ppm while the carbons of the methyl groups are at 27.86 ppm.
The IR spectral data was used to identify the functional groups in the product.. There is an
amine stretching peak at 3297 cm-1 while at 3095 cm-1 is the stretching peak for the hydrogen
attached to the carbon double bond. At 2955 cm-1 is the peak for the aliphatic carbon and
hydrogen stretch while at 1679 cm-1 is the peak for the alkene. At 1524cm-1 is the peak for the
carbonyl and from 1440-1490cm-1 are the carbon and hydrogen stretch for the methyl groups.
Both the IR and NMR confirmed the identity of the enaminone which was 5,5-dimethyl-
3-aminocyclohex-2-ene.The product was not pure since we obtained a melting point range of 96-
99 ̊C compared to the literature value of 167-170 ̊C.4 This was because it was recrystallized in a
few hours so it was not able to form proper pure crystals and left the impurities in the crystal.
The amount of product isolated was in 40% yield which is bad compared to the 80% yield from
the literature.4 Most of the product was lost because excess acetonitrile was added and to get the
best yield, you need to use the minimum amount of solvent because the product will remain
dissolved in the solvent and not recrystallize will cooling.
Conclusion
According to the spectral data, 5,5-dimethyl-3-aminocyclohex-2-ene was successfully
synthesized with a 40% yield but due to excess solvent during recrystallization some product was

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lost. These yield was bad but it is possible to obtain a better yield if the minimum amount of
solvent was used.
References
1. Niphakis, Micah; Turunen, Brandon; Gunda. , Georg. J. Org. Chem., 2010, 75 (20), pp
6793–6805.
2. Nisar, Muhammad; Ali ,Ihsan ; Raza Shah ,Muhammad ; Qayum ,Mughal; Zia-Ul-
Haq, Muhammad; Rashid, Umer; Saiful ,Islam, Md .Molecules, 2013, 18, 15182-15192.
3. Mahmud, Tariq; Rehman, Rabia; Gulzar, Aqsa; Khalid, Amina; Anwar, Jamil;
Shafique, Umer; Waheed-uz-Zaman; Salman ,Muhammad. Arabian Journal of Chemistry, 2010,
3,219-224.
4. Wang, Guan-Wu; Miao, Chun-Bao. Green Chem., 2006, 8, 1080–1085.