June 18, 2011
I am currently carrying several grams of [2,2'-biindolinylidene]-3,3'-dione (1) with me, and chances are you are too if you are wearing blue jeans. An indigo molecule, also known as indigotin (1), is an oxidized dimer of an indole ring. Thousands of tons of indigo are consumed each year making it the most produced textile dye in the world.
Indigo was also one of the most prized dyes in ancient times. It was first produced in India and was introduced to Europe through the Silk Road. In fact, the word "indigo" comes from "India." Isaac Newton was the first to use indigo as the seventh color of the rainbow. The element indium, in turn, gets its name from indigo since it was first identified by a unique spectral line of that color. It’s no surprise that the naming of the parent indole ring of indigo also originates from the word "indigo." In fact, indole is a combination of the words indigo and oleum since the reaction of indigo with oleum is the first method by which indole was synthesized.
A useful dye is a highly colored substance that is insoluble in water so that it doesn’t fade when clothes are washed. Most products easily found in the natural world such as fruit juices, plant extracts, bark, or blood are at least partially water soluble. Although it may be hard to get a blood stain out of a shirt, the initial red color produced turns into an unattractive brown that fades with washing, making it a useless dye. One very common class of dyes requires mordants. A mordant is an insoluble compound incorporated into the fabric of the clothing that increases the fastness of a dye by binding to the dye, thus rendering it insoluble and resistant to washing. The most common mordant used is alum (KAl(SO4)2), or potassium aluminum sulfate, which forms insoluble coordination complexes with many dyes.
Indigo was one of the most important dyes in ancient times not only because of its brilliant color, but because its unique chemical properties allow it to be used without a mordant. Indigo is insoluble in water so one cannot simply dunk an article of clothing into a vat of indigo in water. The two electron reduction of indigo results in the formation of the molecule leucoindigo (2). Leucoindigo is white instead of blue since its conjugated system does not extend onto the two oxygen atoms as in indigo, and for this reason is also known as indigo white. Since leucoindigo is water soluble in a mildly alkaline solution, a piece of clothing can be dipped into a solution of leucoindigo and then set to dry in air. The oxygen in air oxidizes the leucoindigo to insoluble colored indigo, which remains stuck in the fabric of the clothing. In order to create the vat of leucoindigo that is needed, ancient humans reduced indigo with fermented urine, utilizing the ammonia and microbes present as reducing agents. However, more common and less malodorous reducing agents can be used such as sodium dithionite.
In ancient times, indigo was extracted from plants that contain indican (3), a glycoside of indoxyl (4). In the Americas and Asia, Indigofera tinctoria was most commonly used whereas in Europe, Isatis tinctoria, or woad, was used. The mass concentration of indigo in the leaves of these plants usually does not exceed 1%. The leaves are fermented in water, which results in the hydrolysis of indican (3) to indoxyl (4). Indoxyl is then oxidized by air to indigo. Indigo was produced exclusively using this method until the late 1800’s. The advent of synthetic processes to manufacture indigo during this time resulted in the rapid decline of indigo plantations across the world.
I will now show you why indigo is considered a coal tar dye. The power of synthetic industrial chemistry can convert the carcinogenic black crud that is left over from heating coal into the durable and harmless blue dye in your jeans. There are two main methods by which indigo is synthesized, one uses N-phenylglycine (8) as a precursor, and the other relies on N-phenylglycine-ortho-carboxylic acid (14). Although there are many ways to synthesize these two precursors, they are most commonly made from benzene (5) and naphthalene (10), respectively, both of which are products of coal tar (or petroleum) distillation.
In the N-phenylglycine (8) route, benzene (5) is first nitrated with nitric and sulfuric acids to give nitrobenzene (6). Nitrobenzene can then be reduced with iron under acidic conditions to give aniline (7). In industry, nitrobenzene is often reduced with hydrogen gas using various metal catalysts. Aniline is then converted to N-phenylglycine (8) using chloroacetic acid, produced via the chlorination of acetic acid. Fusion of N-phenylglycine with caustic soda and sodium amide gives ring closure and results in the formation of the disodium salt of indoxyl (9). Subsequent aerial oxidation results in the formation of indigo. This method of producing indigo is largely controlled by the price of sodium metal, as this metal is reacted with ammonia to form the required sodium amide. Sodium prices are low enough for this synthetic route to dominate modern indigo production.
An alternate route to producing indigo was utilized more often in the early 1900’s when the production of sodium metal was rather difficult. This method also has the advantage of producing higher yields of indigo in the final step, resulting in a purer product, and for this reason, it is still used to some extent today. In this synthetic scheme, naphthalene (10) is first oxidized to phthalic anhydride (11). Classically, potassium permanganate is used as the oxidant, but other cheaper industrial oxidants can be used. The phthalic anhydride is then converted to ammonium 2-carbamoylbenzoate (12). The primary amide on this molecule is converted to an amine using the standard Hoffman rearrangement condition of base and sodium hypochlorite. Subsequent acidification results in anthranilic acid (13). Anthranilic acid is then converted to N-phenylglycine-ortho-carboxylic acid (14) using chloroacetic acid. Closure to form the indole ring occurs upon fusing with lye. This results in the intermediate 15, which is a carboxylic acid derivative of indoxyl. This molecule then decarboxylates to give indoxyl, which is oxidized by air to give indigo.
Now these two routes may be optimal for the industrial chemistry, but for the home chemist, they are unnecessarily cumbersome. I have thought up of two routes to indigo that should be attainable in the makeshift chemistry lab with household materials. The first starts from toluene which can be purchased in bulk from hardware stores. Toluene is first mononitrated in the cold with nitric acid and sulfuric acid to give mostly o-nitrotoluene and p-nitrotoluene with only a few percentage of m-nitrotoluene. Care would have to be taken to carefully monitor the reaction temperature and not to produce any dinitrotoluenes or worse yet trinitrotoluene (TNT). The excess toluene could then be removed through careful simple distillation under atmospheric pressure. The mononitrotoluene isomers could then be separated by fractional freezing as is described in the literature. It might not even be necessary to separate out pure 2-nitrotoluene if all is desired to is to witness the blue color of indigo in the end.
Assuming 2-nitrotoluene is in hand, this would then be oxidized to 2-nitrobenzaldehyde using manganese dioxide and sulfuric acid. Some 2-nitrobenzoic acid would also surely form, and the conditions would have to be played with in order to prevent extensive over oxidation. 2-nitrobenzaldehyde can then be converted directly to indigo by reacting it with acetone and sodium hydroxide in what is known as the Baeyer-Drewson process. The mechanism of the Baeyer-Drewsen synthesis of indigo is shown below (image courtesy of Wikipedia). The first step is a simple aldol condensation with acetone. The enolate of the formed ketone can then attack the nitrogen on the nitro group to form the indole ring backbone, which eventually couples with another indole ring to form indigo.
An alternative approach for the amateur synthesis of indigo starts form ground cinnamon! Cinnamon is first steam distilled to give oil of cinnamon, which is mostly cinnamaldehyde. The cinnamaldehyde (16) could be extracted from the distillate and vacuum distilled if necessary to further purify it. 2-nitrocinnamaldehyde (17) is then formed by nitrating cinnamaldehyde with nitric acid in the presence of glacial acetic acid and acetic anhydride. These conditions are reported to give a very high percentage of the desired ortho isomer. I would have to make acetic anhydride from bromine, sulfur, and sodium acetate and the glacial acetic acid from concentrated sulfuric acid and sodium acetate. The 2-nitrocinnamaldehyde (17) is then oxidized to 2-nitrocinnamic acid (18) using a solution of hydrogen peroxide in glacial acetic acid. The alkene of 2-nitrocinnamic acid (18) is then brominated (19) with bromine. Subsequently, this compound undergoes double dehydrohalogenation in the presence of base to give an alkyne intermediate (20). This alkyne then rearranges and decarboxylates to give isatin (21). A reducing agent in the reaction mixture, such as glucose, then reduces isatin to indigo.
