Synthesis and Purification of Nitrophenols

Abstract

Ortho and para-nitrophenol was synthesized using an electrophilic aromatic substitution of phenol and dilute nitric acid. Isolation of the crude product used a dichloromethane followed by a short vortex and sodium sulfate for water removal. Separation of the ortho and para products was completed using column chromatography to collect the eluent in ten vials; vials #1-5 collected o- and vials #6-10 collected p-nitrophenol. Thin layer chromatography confirmed synthesis of o-nitrophenol collected in vial #3, 4 and 5 and p-nitrophenol in vial #7.¹H NMR showed o-nitrophenol being the spectrum with more peaks, due to the asymmetric structural difference creating more nuclear environments for the proton to participate in.

Introduction

Phenols, due to their rich electron density, are highly susceptible to undergo electrophilic substitution reactions. The hydroxyl group on the aromatic ring of the phenol promotes charge delocalization; thus, allowing for stabilization through resonance.  One such electrophilic substitution reaction is that of nitration. First, an electrophilic attack of the phenol takes place, resulting in a carbocation intermediate stabilized by resonance¹. Next, the nitronium ion nitrates the phenol ring, producing p-nitrophenol and o-nitrophenol (Figure 1). The hydroxyl group of the phenol is an ortho para director; therefore, the meta isomer is not produced. However, by products such as 2,4-dinitrophenol and 2,4,6,-trinitrophenol may be present in excess amounts of nitric acid. Once nitration is complete, the crude product can be purified through column chromatography and monitored through TLC.

 

Thin layer chromatography (TLC) is a chromatographic technique used to separate the components of a mixture using a thin stationary phase. TLC functions on the same principle as all chromatography: a compound will have different affinities for the mobile and stationary phases and this affects the speed at which migrates².

After a separation is complete, individual compounds appear as spots separated vertically. Each spot has a retention factor (R_f) which is equal to the distance migrated over the total distance covered by the solvent. The R_f formula is²

In this experiment the difference in R_f values will allow for identification between o- and p-nitrophenol. When comparing two different compounds under the same conditions, the compound with the larger R_f value is less polar because it does not stick to the stationary phase as long as the polar compound, which would have a lower R_f value².

Column chromatography is a useful analytical technique for small-scale separation and purification using similar principles as TLC³. The polar, stationary phase remains either silica gel or alumina and the mobile phase can be dichloromethane (DCM)/hexane or DCM/ethyl acetate depending on the polarity of the sample. Therefore, the more polar isomers will adsorb to the silica gel and take longer to elute than the less polar isomers³. In the above reaction, the ortho product should elute first as it is less polar than the para product.

Results

Total percent yield using mass values Table 1

 

Table 1: Mass of fractions #1-10

Vial Number	Empty Clean Vial (g)	Dry Vial Weight (g)	Product only (g)
1	13.3497	13.4663	0.1166
2	13.3357	13.337	0.0013
3	13.1605	13.1608	0.0003
4	13.0819	13.3543	0.2724
5	13.2054	13.3147	0.1093
6	13.2838	13.6743	0.3905
7	13.2007	13.5176	0.3169
8	13.0464	13.0977	0.0513
9	13.3157	13.4682	0.1225
10	13.5818	13.8376	0.2558

Table 2. ¹H NMR spectrum of o-nitrophenol

Atom	Atom is part of a group	Peak multiplicity	Peak observed (ppm)	Peak calculated (ppm)
A	Hydroxyl	Singlet	10.7	10.84
B	Arene	Doublet	7.15	7.07
C	Arene	Triplet	7.0	6.59
D	Arene	Doublet	8.2	8.00
E	Arene	Triplet	7.6	7.22

Table 3: ¹H NMR spectrum of p-nitrophenol

Atom	Atom is part of a group	Peak multiplicity	Peak observed (ppm)	Peak calculated (ppm)
A	Arene	Doublet	8.15	8.24
B	Arene	Doublet	6.8	7.0
C	Hydroxyl	Singlet	5.45	6.0

Table 4: IR spectrum of o-nitrophenol

Functional Group	Molecular Motion	Observed Wavenumber (cm-1)	Literature Value Range2-4 (cm-1)	Peak Intensity	Peak Shape
Aromatic alcohol	O-H Stretch	3240.31	3550-3500	Weak	Broad
Aromatic C=C	C=C Stretch	1613.37	1600-1430	Medium	Sharp
Aromatic nitro	NO2 Asymmetric Stretch	1530.13	1540-1500	Medium	Sharp
Aromatic nitro	NO2 symmetric Stretch	1471.31	1370-1330	Medium	Sharp

Table 5: IR spectrum of p-nitrophenol

Functional Group	Molecular Motion	Observed Wavenumber (cm-1)	Literature Value Range2-4 (cm-1)	Peak Intensity	Peak Shape
Aromatic alcohol	O-H Stretch	2999.35	3550-3500	Weak	Broad
Aromatic C-H	In plane C-H  bending	1259.93	1275-1000	Medium	Sharp
Aromatic nitro	NO2 Asymmetric Stretch	1517.92	1540-1500	Medium	Sharp
Aromatic nitro	NO2 Symmetric Stretch	1326.38	1370-1330	Strong	Sharp
Aromatic C=C	C=C Stretch	1600	1600-1430	Medium	Sharp

Figure 2: TLC plate A                                     Figure 3: TLC plate B

Table 6: R_f values

Compound	Retention Factor (Rf)	Relative Polarity
o-nitrophenol	0.93	Less polar
p-nitrophenol	0.07	More polar

Discussion

In this experiment a nitrophenol synthesis was carried out. The total percent yield is 42.7% as evident in Equation 2. Equations 2 and 3 show o-nitrophenol yield being 54.66% and p-nitrophenol being 45.34%. It could be assumed that not all of the organic matter was collected during the crude isolation phase.

Two TLC analyses were performed to further determine the identity of o- and p- nitrophenols. The analysis on plate A determined that the fractions collected correspond to o-nitrophenol. This was concluded based on the distance the spots traveled up the plate. The o-nitrophenol complex is less polar than both the silica gel on the TLC plate and the p-nitrophenol complex. Therefore, it was expected to travel further up the plate. The fractions collected on TLC plate B correspond to p-nitrophenol; this complex is polar and adheres to the polar silica gel of the plate. The R_f value (retention factor) obtained for o-nitrophenol is 0.93. The R_f value obtained for p-nitrophenol is 0.07. Compounds with larger retention factors are less polar as they do not stick to the polar solvent. The fractions collected on plate A are all pure as only one spot is observed per lane. Lanes 1 and 2 do not show any spots because the fractions were collected too early and no product exists. The only pure fraction collected on plate B is the one in lane 7. Lanes 8, 9, and 10 each have multiple spots suggesting that by-products are present. Lane 6 does not have any spots meaning that only solvent, not product exists.

To confirm the identity of the product, ¹ H NMR spectroscopy were used. The ¹ H NMR spectrum of p-nitrophenol it is easily distinguishable because it contains only 3 observed peaks- A, B and C at 8.15 ppm, 6.8 ppm and 5.45 ppm accordingly. Peak A is a doublet and belongs to the protons adjacent to the deshielding nitro group. The proton pair adjacent to the hydroxyl group show a doublet signal at 6.8 ppm on the spectrum. The singlet showing lack of splitting must belong to the hydroxyl group, but it is far below expected values of around 10 ppm⁴. This is due to the intermolecular hydrogen bonding in this compound. The spectrum for o-nitrophenol has five observed peaks. The hydroxyl group is just above 10.5 ppm, which is in normal range. Peak D which is a doublet belongs to the proton closest to the nitro group at 8.2 ppm. The triplet directly across the nitro group peak E has a values of 7.6 ppm. This value generally would be expected at 7.0 ppm, but the ortho and para positions are more deshielded due to the resonance structure observed in Figure 4 and 5.

 

Comparing resonance structures of p-nitrophenol and phenol explains why pnitrophenol is more acidic (Figure 4, Figure 5). Phenol can donate an electron pair to the aromatic system from the hydroxide group. P-nitrophenol has a ring deactivating nitro group that withdraws electron density from the aromatic system. This allows the hydroxyl proton to be removed because of the partial positive charge on that side of the system. The conjugate base is then stabilized by the nitro group taking away an electron pair from the negatively charged oxygen to form a double bond with the ring system. The stable conjugate base means that it can’t form a new bond with the free proton, thus making p-nitrophenol more acidic than phenol. However with phenol, there is no electron withdrawing group, allowing oxygen to retain its negative charge. The conjugate base formed is very unstable and will immediately bond with any available proton. Also, o-nitrophenol has the nitro group in close proximity to the hydroxyl, thus allowing for intramolecular hydrogen bonding to occur. This slightly lowers the acidity of o-nitrophenol compared to pnitrophenol because the hydroxyl proton is made unavailable by the negative oxygen on the nitro substituent. Whereas in p-nitrophenol, intermolecular bonding occurs between other p-nitrophenols contributing to the overall stability of the compound.

The IR spectrum of o-nitrophenol was given; however, the IR spectrum of p-nitrophenol was obtained experimentally. The IR spectrum for o-nitrophenol shows the following stretches: O-H stretch; C=C stretch; aromatic NO₂ asymmetric stretch; and an aromatic NO₂ symmetric stretch. The O-H stretch is caused by the hydroxyl group on the phenol ring. The observed value is 3240.31 cm^-1; this corresponds to the literature value range of 3550-3500 cm^-1. The peak was broad and exhibited strong intensity. The C=C stretch is caused by the aromatic ring of the phenol. The observed value is 1613.37 cm^-1; this corresponds to the literature value range of 1370-13130 cm^-1. The peak was sharp and exhibited medium intensity. The aromatic NO₂ asymmetric stretch is caused by a nitro group. The observed value is 1530.13 cm^-1; this corresponds to the literature value range of 1540-1500 cm^-1. The peak was sharp and exhibited smedium intensity. The aromatic NO₂ symmetric stretch is also caused by the nitro group.

The p-nitrophenol IR spectrum exhibited many of the same peaks. The observed peaks are as follows: O-H stretch; C-H bending; aromatic NO₂ asymmetric stretch; aromatic NO₂ symmetric stretch and C=C stretch. The O-H stretch is caused by the hydroxyl group on the phenol ring. The observed value is between 3726.38 and 2999.35 cm^-1; this corresponds to the literature value range of 3550-3500 cm^-1. The peak was broad and exhibited weak intensity. The C-H in plane bend is caused by the aromatic ring of the phenol. The observed value is 1259.93 cm^-1; this corresponds to the literature value range of 1275-1000 cm^-1. The peak was sharp and exhibited medium intensity. The aromatic NO₂ asymmetric stretch is caused by a nitro group. The observed value is 1517.92 cm^-1; this corresponds to the literature value range of 1540-1500 cm^-1. The peak was sharp and exhibited strong intensity. The aromatic NO₂ symmetric stretch is also caused by the nitro group. The observed value is 1326.38 cm^-1; this corresponds to the literature value range of 1540-1500 cm^-1. The peak was sharp and exhibited medium intensity.

Conclusion

The synthesis of o- and p-nitrophenol was performed using an electrophilic aromatic substitution of a nitro group in dilute acidic conditions. This was followed by column chromatography to separate the o- and p– forms and TLC to confirm that the synthesis and purification was successful. The capture of o-nitrophenol and of p-nitrophenol was successful due to having product in vials #3,4,5 and 7 as seen on the TLC plates (Figure 2 nand 3). IR spectra of o- and p-nitrophenol also confirm a successful synthesis due to the differences in the aromatic OH streches (Table 4, Table 5). The experiment may be considered a success because of the differences between the IR spectra confirming the synthesis of o- and p-nitrophenol. The IR spectra may be improved by more homogenous packing of the column. Also, waiting to collect a darker yellow elute may have increased yield of o-nitrophenol due to not capturing only solvent in vials #3-4.

References

1. Stawikowski, M. Experiment 5: Synthesis and Purification of Nitrophenols; BlackBoard.
2. Touchstone, Joseph C. Practice of thin layer chromatography. 2nd ed. New York: Wiley, 1983.Print
3. Smiley RA Ullmann’s Encyclopedia of Industrial Chemistry. John Wiley and Sons
4. . Richards, S. A., and Hollerton, J. C.. Essential Practical NMR for Organic Chemistry (1). Hoboken, GB: Wiley, 2010, 2.