Академический Документы
Профессиональный Документы
Культура Документы
NOTE: For this assignment, you must submit your report to TurnItIn and submit a PDF to Canvas. All
late penalties still apply to this assignment.
Introduction
This should include: A paragraph on the importance of the reaction class/
category, a paragraph on the importance of the chosen molecule, and a 30
paragraph on the chemistry being proposed including a full electron-
pushing mechanism in words and two schemes (reaction and
mechanism).
Experimental
Using your chosen synthesis pathway and the corresponding literature,
please write an experimental if we were to do this experiment in Chem 10
213W in the future. Please refer to the Chapter 3 of the lab guide to write
your experimental.
References
ACS Format - use reference formatting examples in Chapter 3 and
Workshop #6. MUST have AT LEAST FOUR peer-reviewed journal 5
articles in ADDITION TO the articles you were provided. If you use a
website, you will receive ZERO points.
Spectral Data 10
Obtained from the literature, annotated properly and labeled as Figures.
TOTAL 100
Helen Mendenhall
Purpose
hydroxylamine hydrochloride while kept at 158°C. This reaction can be monitored by TLC and purified
using column chromatography. The piperonylonitrile product can be analyzed by melting point analysis,
Introduction
reaction. The piperonal contains an aldehyde and is replaced by a nitrile group. Aldehydes can be used to
as a germicide or insecticide when embalming or gardening with formaldehyde, and nitriles are naturally
found in fungi and contribute to nitrile metabolism.1 Nucleophilic substitutions are one of the most used
reactions in organic chemistry and allow for the formation of intermediates when converting functional
groups. Nitriles are important in the pharmaceutical industry, agriculture, and in the formation of
materials, but often require toxic reagents and high temperatures to form.3 It is important to find a more
timely and environmentally friendly way to form nitriles. Piperonylonitrile is an example of a nitrile that
hydrochloride to piperonal. The lone pair of electrons on the oxygen of the aldehyde is protonated due to
the excess hydrochloride, then the lone pair on the nitrogen atom of hydroxylamine backside attacks the
carbon of the carbonyl to form an intermediate. The alcohol deprotonates the hydroxylamine and forms
water as a leaving group. Water deprotonates the nitrogen to leave an alcohol, which transfers protons to
Page | 1
the hydrogen and produces water as a leaving group again while forming the triple bond of the nitrile
group. Piperonylonitrile can be synthesized from an alcohol such as piperonyl alcohol, or it can be
synthesized from piperonal with sodium azide as a reagent and trifle acid as a catalyst.3,4
Page | 2
Proposal, Discussion, and Conclusions
dimethylformamide and refluxed to 158°C for 10-15 minutes. The reaction can be monitored by TLC
and worked up with water.2 On TLC plates, the starting material will have a higher Rf value because the
nitrile on the piperonylonitrile product is more polar than the aldehyde on piperonal. Water is used to
work up the reaction to remove any excess starting material by accelerating the conversion of the
aldehyde to a nitrile.
No purification occurred in this particular experiment but the product can be purified using
column chromatography since it is a solid and the polarities of the starting materials and products are
very similar. Since the polarities are similar, a longer column is suggested and a mobile phase of 25%
THF or ethyl acetate/75% hexanes. The starting material will elute first since it is slightly less polar that
Running the reaction in these conditions should produce a 90-95% yield, but may average 51%
in student labs.2 This low yield may be due to loss of crude product during vacuum filtration. To
improve this yield, increasing the number washes during the workup may help as well as purifying the
product as suggested above. Synthesizing piperonylonitrile from an alcohol such as piperonyl alcohol
Reaction success can be supported with spectral analysis. 1HNMR spectra shows the successful
isolation of the product due to the lack of the aldehyde peak that would be found around 9-10 ppm.
Spectra shows the ortho hydrogens as a doublet peak a 7.2ppm, the meta hydrogen as a doublet peak at
7.1ppm, and the secondary hydrogens as a singlet at 6.1ppm. An acetone impurity is found at 2.5 ppm
Page | 3
13CNMR data support the purity of the product. A peak around 190-220 ppm would show if there
was starting material left over in the reaction. The peaks at 148 ppm and 151.5 ppm show the aromatic
carbons closest to the oxygens. The carbon found between the two oxygen show as a peak at 102 ppm,
and the other aromatic carbons show as peaks at 128 ppm, 111.5 ppm, 109 ppm, and 105 ppm. The final
peak that shows the carbon attached to the nitrile is found at 119 ppm.
IR spectra would include a shift around 1700 cm-1 if starting material was left over, and shows
the success of the product with the carbon and nitrogen triple bond that shows as a shift at 2200 cm-1.
The aromatic carbon and hydrogens bonds are found at 2900 cm-1, and the carbon and hydrogen scissor
bend is found at 1500 cm-1. Lastly, the carbon and oxygen bonds are found at 1250 cm-1.
Melting points can also determine the success of a reaction, and should match literature
(92-93°C). If impurities such as the starting materials are found in the final product then melting points
be replicated in a Chem213W lab setting. Following this simple experiment does not require much time
and can produce proper yields (90-95%) when done correctly. It is recommended to purify the product
using column chromatography to allow for proper separation of the starting material and final product
since their polarities are similar. Not having a long enough column to allow for full separation and not
Experimental
Piperonylonitrile. Hydroxylamine hydrochloride (60 mg, 1 mmol) was dissolved DMF (0.5 mL) and
was refluxed to 158 °C, then added dropwise to a mixture of Piperonal (100 mg, 0.67 mmol) dissolved
in DMF (0.5 mL) and reheated for 10 minutes. The reaction was monitored by TLC and washed with
Page | 4
water (10 mL). The nitrile product is filtered and allowed to crystal (90-95%). M.P. 92-93C. 1HNMR
(400 MHz, DMSO-d6): δ (ppm) 7.2 (d, 2H), 7.1 (d, 1H), 6.1 (s, 2H); 13CNMR (100 MHz, CDCl3) δ
(ppm) 151.5, 148, 128, 119, 111.5, 109, 105, 102; IR (ATR) υmax (cm-1) 2900, 2200, 1500, 1250.
References
1. Martinkova, L.; Nitrile Metabolism in Fungi: A Review of its Key Enzymes Nitrilases with Focus on
their Biotechnological Impact. Fungal Biology Reviews, 2019, 33, 149-157. https://doi.org/10.1016/
j.fbr.2018.11.002
2. DeMott Jr., J.M., Kelley, C.J.; An Alternative One-Step Procedure for the Conversion of Piperonal to
3. Yin, W., Wang, C., Yong, H.; Highly Practical Synthesis of Nitriles and Heterocycles from Alcohols
under Mild Conditions by Aerobic Double Dehydrogenative Catalysis. Org. Lett., 2013, 15,
4. Rokade, B.V., Prabhu, K.R.; Chemoselective Schmidt Reaction Mediated by Triflic Acid: Selective
Synthesis of Nitriles from Aldehydes. J. Org. Chem., 2012, 77, 5364-5370. DOI: 10.1021/jo3008258
5. SciFinder; Chemical Abstracts Service: Columbus, OH; proton NMR spectrum; spectrum ID
6. SciFinder; Chemical Abstracts Service: Columbus, OH; carbon-13 NMR spectrum; spectrum ID
Page | 5
Spectral Data
Page | 6
Figure 3. FT-IR of piperonylonitrile7
Page | 7