Experiment

Synthesis of 1-Phenylthiourea

prepared by Itamar Luís Gonçalves*, Leonardo Davi, Fernando Cidade Torres, Rômulo Faria Santos Canto and Vera Lucia Eifler-Lima

modified by

PURPOSE OF THE

EXPERIMENT

Synthesis of 1-phenylthiourea via two-step reaction and separation with pH controlling

BACKGROUND

INFORMATION1

Carbonyl substitution and addition reaction are one of the most important categories in chemical industry. One simple example with the carbonyl group is urea. Urea is popular organic compound as first compound that artificially synthesized from inorganic materials by Friedrich Wöhler in 1828. Heated ammonium cyanate decomposes to ammonia and cyanic acid. These two undergo nucleophilic addition followed by tautomeric isomerization and finally produce urea. In a similar way, ammonium thiocyanate can produce thiourea by heating, the sulfur analogue of urea

Substituted thiourea are important building blocks in organic synthesis of many heterocyclic compounds, such as thiazoles and benzothiazoles. Recent studied have been performed actively to investigate the potential pharmacological activities of substituted thioureas.

Experiment will progress two steps.

Benzoyl chloride and ammoniumthiocynate react first, and then aniline addition occurs. The reaction completion can be decided through TLC.

Secondly, intermediate cleavage proceeds under base condition. Reaction completion can be decided from TLC analysis, diethyl ether as eluent on silica plates. Benzoate ion and 1-phenylthiourea(product) will be produced. For isolation of product only, pH control have to be applied. Ammonium chloride can make reaction medium to acidify to pH 8.

EXPERIMENTAL PROCEDURE

Two steps synthesis of 1-phenylthiourea

Reagents and Properties

substance

quantity

molar mass (g/mol)

mmol*

mp

(oC)

bp  (oC)

density (g/mL)

Ammonium thiocyanate

0.837g

76.12

11

Benzoyl chloride

1.16ml

140.6

10

1.21

Acetone

18ml

Aniline

0.911ml

93.1

10

1.03

NaOH(2.5M)

15ml

Saturated NH4Cl solution

~10ml

Diethyl ether(TLC)

~10ml

experimental stuff

(erase later)

two-neck round bottom flask(50ml), rbf(50ml)

reflux condensor

100ml beaker

pinch clamp

heating plate

vacuum filtrate

TLC & NMR analysis(Silica plates, chamber, D-CCl3)

PROCEDURE

Caution: Wear lab coats and safety goggles at all times while in the lab. Many chemicals are potentially harmful. Prevent contact with your eyes, skin, and clothing. Wearing contact lens is strictly prohibited.

Step 1

Caution:

Experiment should be performed under fume hood. Benzoyl chloride is harzardous if skin contact occurs. Aniline is harmful if inhaled and is a potential methemoglobin-forming agent. Both intermediate and product of this experiment can cause skin irritation, so they must be handled with care.

Charge two-neck round bottom flask(50ml) with 0.837 g(1.1mmol) of ammonium thiocyanate and 1.16ml of benzoyl chloride under magnetic stirring at room temperature.

Connect round bottom flask to reflux condensor and heat at 60℃ for 15 minutes. While the reaction go on, dissolve 0.911ml of aniline to 3ml of acetone and add additional 15 ml of acetone.

After 15 minutes, add aniline solution dropwise and continuously heat at 60℃ about 20 minutes more. Monitor aniline consumption with TLC.

Pour the reaction medium into 50ml of room temperature water. Gain precipitation via vacuum filtration and caculate intermediate, A’s yield(NMR analysis of intermediate can be added).

Step 2

Add 2.3g of intermediate A(8.9mmol) to 15ml of 2.5M NaOH solution in 50ml round bottom flask and stirr at 90℃ about 20 minutes. Monitor your reaction medium by TLC analysis with diethyl ether eluent. Then cool the reaction flask to room temperature.

Isolation

Acidify the reaction medium to pH 8 with saturated ammonium chloride. The precipitation isolates by vacuum filtration and washes with water. Dry your product and calculate final yield.

NMR analysis

Caution: Deutero-Chloroform is toxic and a suspected carcinogen. Dispense it in a fume hood. Wear protective gloves.

Product will dissolve in deutero-chloroform. Obtain the NMR spectrum as directed by your TA.

Pre-Laboratory Questions

Summarize all MSDS’s of chemicals used in this experiment.

Write down the detailed reaction process of 1-phenylthiourea(Need hint?).

Search the literature pKa data of benzoic acid and 1-phenylthiourea. What pH would be preferred for isolation of 1-phenylthiourea?

Post-Laboratory Questions

Assign peaks in 1H NMR spectra of product.

Calculate your intermediate’s and product’s percentage yield.

Why aniline have to be added later than thiocyanate in step 1? Propose one possible reaction if three starting components added simultaneously.

Eluent have to be decided