Synthesis of Methyl-Sudan I by Diazotization

Brooke Gushen

Introduction

Diazonium salts are very valuable reagents in many organic reactions because

diazotization reactions can be coupled with many other reaction pathways to yield stable

products with few side products. In particular, the Sandmeyer reaction is an example of

diazotization coupled with a multitude of nucleophilic substitutions.1 These reactions make it

possible to add protons, halogens, alcohols, and more onto an R-group, in particular onto

aromatic rings. Strong acids play a heavy role in the diazotization reaction, and there has been

research that has found that certain acids can affect the rate of the reaction. In a kinetic study of

diazotization run with sulfuric acid instead of hydrochloric acid, researchers found that sulfuric

acid can increase the rate of the reaction.2 So this is a very valuable reaction technique in organic

chemistry.

In this specific experiment, however, the diazotization reaction of an arylamine is

coupled with an electrophilic aromatic substitution, which yields a diazo dye called Methyl-

Sudan I. Azo and diazo compounds are very characteristic because they tend to be very brightly

colored compounds that are often used as dyes. Some of these dyes are used in liquid crystal

displays in televisions,3 some are found in textiles,4 and some have even been found in food. The

particular diazo dye synthesized in this experiment was at one point being used to brighten chili

powder in the UK.5 However, since these dyes were found to have carcinogenic qualities, they

have been banned from many uses.

The reaction mechanism for this experiment is a diazotization reaction coupled with an

electrophilic aromatic substitution.

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Figure 1. Reaction Mechanism of Diazotization.

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In this mechanism, the sodium hydroxide deprotonates the 2-naphthol yielding sodium 2-

naphtholate and water. The negative charge pushes to that particular carbon because it is more

stable at that adjacent carbon due to the resonance provided by the nearby aromatic ring. In

another reaction, the 4-methyl-aniline deprotonates the hydrochloric acid. The protonated aniline

is then deprotonated by the nitrous acid. An electron pair on the aniline’s nitrogen forms a bond

with the protonated nitrous acid, pushing the water leaving group off. The water molecule then

deprotonates the nitrogen, yielding a hydronium molecule. The aniline molecule then

tautomerizes to yield a double bond between the nitrogens. The hydronium molecule protonates

the –OH group on the aniline tautomer. The electron pair on the upper nitrogen then shifts down

to form a triple bond between the nitrogens and pushes off the water leaving group. When this

diazonium salt is added to the prepared sodium 2-naphtholate, the lone pair on the aromatic ring

forms a bond with the lower nitrogen and pushes a pair of electrons from the triple bond to the

upper nitrogen. A water molecule then comes in to deprotonate the molecule where the bond was

made with the nitrogen. This pushes the electrons to form a double bond on the aromatic ring,

giving the oxygen atom a negative charge. A hydronium molecule protonates this oxygen,

yielding an alcohol group on the aromatic ring. The final product is methyl-sudan I dye.

The purpose of this experiment was to synthesize a diazo dye from an arylamine

compound through a diazonium coupling reaction, which would also be purified by

recrystallization. 1H NMR spectroscopy and UV/Vis Spectrophotometry were used for further

analysis on the product of the diazotization. These methods evaluated the purity of the product.

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Experimental6

1. Methyl-Sudan I. 4-methyl-aniline (100 mg, 0.933 mmol), 12M hydrochloric acid (0.5 mL),

and distilled water (0.05 mL) were placed in a 10 mL flask equipped with a magnetic stir bar.

The reaction mixture was stirred and warmed until dissolved. It was then cooled in an ice bath to

0ºC. Sodium nitrite solution was prepared with sodium nitrite (80 mg, 1.16 mmol) and water (1

mL) in a reaction tube and was added drop-wise to the aniline solution. Five minutes after

addition was complete, the reaction mixture was tested for excess nitrous acid using starch iodine

paper. Urea crystals are added until excess nitrous acid was neutralized, as shown by the brown

color of the starch iodine paper. Sodium 2-naphtholate solution was prepared by adding 2-

naphthol (160 mg, 1.11 mmol) to 3M sodium hydroxide (1.5 mL) and heating slightly until

dissolved. This solution was then added in small amounts to the cooled diazonium solution while

stirring. After 15 minutes in the ice bath, the solution was isolated by vacuum filtration, and the

reddish orange crystals were washed with cold water (2 mL). The crude air-dried product (201

mg, 82.1% yield) was recrystallized from ethanol. Melting point was determined to be 120 to

134ºC (lit: 135ºC). 60 MHz 1H NMR, 400 MHz 1H NMR, and UV/Vis spectra were obtained for

the purified product, methyl-sudan I (88 mg, 35.9% recovery).

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1H-NMR Data: Obtained by using deuterated chloroform solvent on a 400 MHz NMR.

Significant Peaks

Observed Splitting (Integral Value), Type of Hydrogen

2.4128 ppm S (3.037), CH3

6.9114 ppm D (0.999), H of Aromatic Ring

7.2740 ppm D (2.020), H of Aromatic Ring

7.3699 ppm T (1.032), H of Aromatic Ring

7.5367 ppm T (1.049), H of Aromatic Ring

7.6154 ppm D (1.039), H of Aromatic Ring

7.6633 ppm D (2.032), H of Aromatic Ring

7.7132 ppm D (1.038), H of Aromatic Ring

8.5955 ppm D (1.008), H of Aromatic Ring

16.1942 ppm S (0.958), O-H

UV-Vis Data: Ran on dilute solution of Methyl-Sudan I in methanol on UV/Vis spectrophotometer.

Wavelength (nm) Color Absorbed Observed Color Absorbance (AU)

420.0 Violet-Blue Yellow-Orange 0.49611

482.0 Blue-Green Red 0.53729

Results and Discussion

In this experiment, the 12M HCl was added to the aniline to be sure that all the molecules

were protonated. This protonated form could then easily transfer its proton to the nitrous acid,

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giving it a better leaving group. The nitrous acid was produced after a proton transfer occurred

between the sodium nitrite and water. There are many proton transfers that occur between the

aniline molecule and water, allowing it to eventually become a diazonium salt, which is why the

presence of water is so important. The urea was added to oxidize any remaining nitrous acid in

the solution because if the nitrous acid were present with the sodium 2-naphtholate, it would just

revert it back to 2-naphthol. When the sodium 2-naphtholate is added to the diazonium salt, the

sodium 2-naphtholate acted as the nucleophile and the diazonium salt as the electrophile creating

the nitrogen bond. Further proton transfers between the molecule and water eventually yielded

the crude product. An 1H MNR spectrum of the crude product showed presence of impurities.

The methyl-sudan I was recrystallized in ethanol to get rid of any side products that may have

formed during the synthesis. Ethanol is used because it has similar polarity to the product.

In Figure 3, the UV/Vis shows absorbance peaks at 420.0 and 482.0 nm. At 420.0 nm, the

absorbance peak means that light was absorbed at the violet-blue part of the visible light

spectrum. Because violet-blue wavelengths were absorbed, the complementary color yellow-

orange was reflected in the diazo dye. At 482.0 nm, the absorbance peak means that light was

absorbed at the blue-green part of the visible light spectrum. Because blue-green wavelengths

were absorbed, the complementary color red was reflected in the diazo dye. This proves true in

the reddish orange color the dye appears after synthesis and purification was completed.

In Figures 1 and 2, the 1H-NMR of methyl-sudan I in deuterated chloroform produced

peaks in ten distinct groupings. The first peak at 2.4128 ppm showed the splitting pattern of

Protons A, a singlet with an integral value of 3.037 because it had three chemically equivalent

protons with no adjacent protons. These protons are found at the lower end of the spectrum

because they are bonded to a methyl group. The peaks at 6.9114, 7.6154, and 7.7132 ppm

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showed the splitting pattern of Protons F, G, and K, a doublet with an integral value around

1.000 because each was adjacent to one other proton. It cannot be determined exactly which

proton goes with each doublet however. The peaks at 7.2740 and 7.6633 ppm showed the

splitting pattern of Protons B and C, a doublet with an integral value around 2.000 because each

had two chemically equivalent protons adjacent to one other proton. It cannot be determined

exactly which proton goes with each doublet however. The peaks at 7.3699 and 7.5367 ppm

showed the splitting pattern of Protons H and J, a triplet with an integral value around 1.000

because each was adjacent to two other protons. It cannot be determined exactly which proton

goes with each doublet however. The peak at 8.5955 ppm showed the splitting pattern of Proton

E, a doublet with an integral value around 1.000 because it was adjacent to one other proton. Its

chemical shift was pulled further towards 8-9 ppm because it is more deshielded due to its

proximity to the alcohol group. All the peaks from 6.9114 to 8.6166 ppm are protons bonded to

aromatic rings. The last peak at 16.1942 ppm showed the splitting pattern of Proton D, a singlet

with an integral value of 0.958 because it has no adjacent protons. This proton is found to the

higher end of the spectrum because it is directly bound to an oxygen atom, which deshields the

proton.

The melting point was expected to be around 135ºC. The melting point range was found

to be 120 to 134ºC. This shows that there may have been very trace amounts of impurity present

to cause the solid dye to melt initially at such a low temperature, however, such impurities

should have been evident on the NMR spectra. The upper end of the range comes very close to

the expected melting point, which suggests that the product was indeed in its pure form.

The percent yield was 82.1% before recrystallization. This high percent yield may have

been due to the fact that highly concentrated hydrochloric acid effectively protonated all the p-

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toluidine. Also, the urea was used to oxidize any excess nitrous acid, and the produced crystals

were washed during vacuum filtration. All of these steps effectively bind up side products and

rid the product of most impurities. Since there still appeared to be impurities from an NMR

spectrum, the product was recrystallized. The percent recovery was found to be 35.9%. The

percent recovery is much lower because some of the crude crystals were used in NMR and

melting point analysis. Also, much of the diazo dye crystals were lost in transfer from flask to

watchglass.

Overall synthesis of a pure diazo dye, methyl-sudan I, was successful by a diazotization

reaction. The 1H NMR and UV/Vis spectra supported the predicted results.

References

1. McMurry, J. Organic Chemistry, 7th ed. 2008: Brooks/Cole, pp. 941-945.2. Aboul-Seoud, A. A Kinetic Study of the Diazotization of Aniline in Dilute Sulphuric Acid.

Bulletin des Sociétés Chimiques Belges, 1966, 75, 599.3. Chigrinov, V.; Prudnikova, E.; Kozenkov, V.; Kwok, H. Synthesis and Properties of Azo

Dye Aligning Layers for Liquid Crystal Cells. Liquid Crystals, 2002, 29, 1321.4. Flintoff, R.J.; On the Relative Importance of the Stability of Diazo Compounds to Practical

Utility in the Production of Insoluble Oxy-Azo Colours on Cotton Cloth. The Journal of the Society of Dyers and Colourists, 1902, 18, 96.

5. (author unknown). Sudan Outraged at Namesake Dye, British Broadcasting Company, 2005.6. Williamson, K. L. Macroscale and Microscale Organic Experiments, 2nd ed. 1994: Houghton

Mifflin, pp 1-3.

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