Ninhydrin, hydration

Russell and coworkers147 had found that treatment of dimsyl anion 88 or of a similar methylsulfonyl carbanion with 1,2-, 1,3- and 1,4-dicarboxylic acid esters can give five- to seven-membered cyclic compounds. By this type of cyclization, they prepared ninhydrin hydrate 106 from diethyl phthalate148,149. 

Another experimental result is also consistent with the hypothesis that cyclic 1,2,3-triketones are not stable. 2-Diazoindan-l,3-dione (9.91) is oxidized by eA butyl hypochlorite in ethanol to the 2-monoacetal 9.92 of indan-l,2,3-trione. The monoacetal undergoes hydrolysis to 2,2-dihydroxyindan-l,3-dione (ninhydrin hydrate 9.93), but the trione itself could not be identified (9-41). 

Synonyms 2,2-Dihydroxy-1,3-indandione 2,2-Dihydroxy-1 H-indene-1,3(2H)-dione 1,2,3-Indantrione, monohydrate Ninhydrin hydrate Ninhydrin monohydrate Triketohydrindene hydrate 1,2,3-Triketohydrindene monohydrate... 

Ninhydrin (hydrate form, 57) Amino acids, amines... 

Ninhydrin (hydrate form, 57)330>33i and similar reagents such as perinaphthalenetrione (hydrate form, 58)332.333 capable of oxidis-... 

Ninhydrin (also named 1 2 3-triketoindane or 1 2 3-triketohydrindene hydrate) is prepared most simply from the inexpensive phthahc anhydride (I). The latter is condensed with acetic anhydride In the presence of potassium acetate to give phthalylacetlc acid (II) reaction of the latter with sodium methoxide in methanol yields 1 3-indanedionecarboxyhc acid, which is decomposed upon warming with dilute hydrochloric or sulphuric acid to indane-1 3-dione (or 1 3-diketohydrindene) (HI). Selenium dioxide oxidation of (III) afibrds indane-1 2 3-trione hydrate (ninhydrin) (IV). 

Ninhydrin (1,2,3-triketohydrindene hydrate) [485-47-2] M 178.1, m 241-243 (dec), pK 8.82. Crystd from hot water (charcoal). Dried under vacuum and stored in a sealed brown container. 

Silylated pyrrohdone 388 reacts with formaldehyde to give 429 [41] whereas N-trimethylsilylsucdnimide 201 reacts with formaldehyde only in the presence of MesSiONa 96 at 100°C to give N-trimethylsilyloxymethylenesuccinimide ]42]. The silylating agent BSA 22a with formaldehyde at 75 °C gives the 0,N-acetal 430 [41]. Hydrated ninhydrin 431 is converted by N,0-bis-(trimethylsilyl)acetamide 22 a to the 0,N-acetal 432 ]43] (Scheme 5.12). 

Indane-1 2 3-trione hydrate (ninhydrin). In a 500 ml. threenecked flask, fitted with a reflux condenser and mechanical stirrer, place 11 g. of resublimed selenium dioxide dissolved in 240 ml. of dioxan and 6 ml. of water. Heat the stirred solution to 60-70°, remove the source of heat, add 15 g. of crude 1 3-indanedione and reflux the resulting mixture for 6 hours. A solid separates during this period. Filter the mixture, transfer the filtrate to a distilling flask and distil off about 180 ml. of dioxan then add 100 ml. of water, boil the solution to coagulate the red tarry precipitate and remove it by filtration. Concentrate the filtrate to about 50 ml. and filter. Boil the filtrate with 0- 2-0- 3 g. of decolourising carbon, filter again, concentrate to 20-25 ml. and keep at room temperature. Collect the crystals of crude ninhydrin by suction filtration, and recrystallise from hot water with the addition of a little decolourising carlran, if necessary. The yield of colourless ninhydrin is 6 g. the crystals turn red between 125° and 130° and melt at 242-243°. 

Detection powders and fingerprint development kits commonly contain cream- or yellow-colored ninhydrin crystals or a solution of dissolved ninhydrin. Ninhydrin (also known as 1,2,3-indantrione, monohydrate 2,2-dihydroxy-1,3-indandione triketohydrindene, monohydrate and triketohydrinden hydrate) has the structure presented in Fig. 13.3.1. Ninhydrin will react with a free a-amino group, -NH2. This group is contained in all amino acids, and analysis with ninhydrin is often performed to verify the presence of amino acids. When a-amino acids (i.e., amino acids with the structure NH2-CHR-COOH) react with ninhydrin, a characteris-... 

FIGURE 5.6 Reaction of ninhydrin (trioxohydrindene hydrate) with the amino group of a bound residue (A) generates the Schiff s base. Hydrolysis after shift of the double bond generates the aldehyde and another amine which reacts (B) with a second molecule of ninhydrin to give an equilibrium mixture of the anion depicted and its tetraoxo form with a maximum of absorbance at 570 nm. 

Ninhydrin (triketohydrindene hydrate) reacts with an amino acid when heated under acidic conditions (pH 3-4) to produce ammonia, carbon dioxide and a blue-purple complex. This reaction forms the basis of many widely used methods (Figure 10.11). One mole of carbon dioxide is liberated from each mole of amino acid, exceptions being the dicarboxylic amino acids, which produce two moles of carbon dioxide, and the a-imino acids, proline and hydroxyproline, which do not produce carbon dioxide. Although this formed the basis of a gasometric technique, colorimetric methods are now the most common. 

Problem 15.37 In acid, most aldehydes form nonisolable hydrates (gem-diols). Two exceptions are the stable chloral hydrate, Cl3CCH(OH)2, and ninhydrin. 

Hydration of the middle carbonyl group of ninhydrin removes both pairs of repulsions. 

Immiscible liquids, 12 boiling point of, 13, 14 vapour pressure of, 13, 14 Incongruent melting point, 31 Indane-1 2-dione, 903, 904 Indane-1 2 3-trione hydrate, see Ninhydrin Indigo, 980... 

Ninhydrin Reaction. A neutral solution of an amino acid will react with ninhydrin (triketohydrindene hydrate) by heating to cause oxidative decarboxylation. The central carbonyl of the tnketone is reduced to an alcohol. This alcohol further reacts with ammonia formed from the amino add and causes a red-purplish color. Since the reaction is quantitative, measurement of the optical density of the color produced is an indication of amino add concentration. Imino acids, such as hydroxyproline and proline, develop a yellow color in the same type of reaction. 

We shall consider the hydrate of the cyclic triketone, 18, known as ninhydrin, later in connection with amino acids ... 

Note. (1) Ninhydrin (p. 630) is the 2-hydrate of indane-l,2,3-trione. It reacts with a-amino acids to yield highly coloured products. Contact with the skin should be avoided since it produces a rather long-lasting purple discoloration. 

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