Ninhydrin condensations

Ninhydrin also forms highly reactive dicationic species in acidic solution. Whereas in the presence of H2 SO4, ninhydrin condenses with aromatic compounds... 

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). 

Further development of the chromatogram with 0.1N ammonia afforded fractions positive to ninhydrin test. From the fractions, 249 mg. of a colorless material was obtained. It was dissolved in 19 ml. of water and the solution was adjusted to pH 4.0 with dilute hydrochloric acid. A colorless material, after condensing under a reduced pressure and lyophilization, was recrystallized from aqueous methanol with a small amount... 

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°. 

Anchored amine materials can be prepared through a number of synthetic methodologies. Because of the potential importance of these materials to organic synthesis, a ninhydrin assay was developed as a rapid laboratory determination of available surface amines. The assay agreed well with expected values for aminopropyltriethoxysilane grafted onto commercial silica. The assay also distinguished between reactive amines and protonated or poisoned surface amines on co-condensed SBA-15 materials. 

Condensation of 1,2-bishydroxylamines (84) with 1,2-dicarbonyl compounds leads to derivatives of 2,3-dihydropyrazine-l,4-dioxides (85) (255), whereas the reaction with ninhydrin gives [1,2-b] pyrazine N,N -dioxides (86) (Scheme 2.32)... 

The linker 36 was prepared on pMeBHA resin using Fmoc chemistry. After the tetrapeptide was synthesized, the Fmoc group was removed by piperidine/NMP (1 4) for 20 min and the Boc group was removed by TFA/CH2C12 (1 1) for 20 min followed by neutralization with DIPEA/NMP (1 19). Fmoc-p-Ala-OH and bromoacetic acid were then condensed stepwise to the peptide-resin. Completion of each reaction was monitored by the ninhydrin test. The peptide-resin was treated with TFA/3-cresol/TfOH (9 1 1 v/v) for 1 h at rt. Subsequently, H20 was added to the mixture with cooling and the mixture was washed with pentane (2 x ) followed by Et20 (2 x ). The aqueous soln was applied to RP-HPLC, and the purified peptide analyzed by FAB-MS m/z 1067.0 Da [M + H]+ (calcd 1067.2 Da). 

The forward synthetic reaction (formulated in Expt 7.9) is thus an initial mixed Claisen ester condensation, followed by a Dieckmann cyclisation, hydrolysis and decarboxylation. Indane-l,3-dione is used for the synthesis of the trione, ninhydrin (Expt 5.99). 

A microwave-assisted one-pot three-component procedure for the condensation of ninhydrin with a phenylenediamine and malononitrile under solvent-free conditions using a catalytic amount of DMSO has been reported by Mohammadizadeh and co-workers [131] to obtain the corresponding 2-(indenoquinoxalin-ll-ylidene)mal-ononitriles 95. (Scheme 72) Further, this one-pot procedure has been extended for the preparation in good yields of dicyanomethylene derivatives 96 of tryptanthrin when potassium carbonate was used as a base (Scheme 73). 

A six-step synthesis of ninhydrin starting with a double ester condensation of dimethyl phthalate with ethyl acetate is presented as a student experiment A new synthesis involves in the first step dropwise addition of diethyl phthalate to a suspension of sodium methoxide in dimethyl sulfoxide which is stirred with a... 

Stream of nitrogen. The initial product, the jS-keto sulfoxide II, undergoes intramolecular ester condensation with formation of the 1,3-indanedione system. Ill, which in the presence of hydrochloric acid undergoes Pummerer rearrangement to 2-chloro-2-methylmercapto-l,3-indanedione (IV). This crystalline product (m.p. 63°) is obtained in yield of 80% and is hydrolyzed in boiling water nearly quantitively to ninhydrin (V). 

Condensation with ninhydrin. Proline condenses with one equivalent of ninhydrin to give proline yellow (3) and with two equivalents to give proline red (4), which forms a deep blue anion. In the first case, the reaction mixture smells strongly of pyrrolidine. An identical red pigment results from condensation of ninhydrin with pyrrolidine. 

For a student preparation of ninhydrin starting with the condensation of dimethyl phthalate with ethyl acetate, one of us developed a technique for powdering sodium which seemed safe for use by beginners. Whatever hazard remained was eliminated by Gruen and Norcross by using sodium hydride dispersion in place of powdered sodium. Their yield is better than that obtained with powdered sodium (36-72%). Both bases promote ester interchange to give the methyl ester enolate. 

Only a few amino acids are detected by the UV or visible spectrophotometers, fluorometers, or electrochemical detectors that are routinely used with HPLC analyzers. Consequently, amino acids typically are postcolumn derivatized for analysis by HPLC. The most widely used reagent for this purpose is ninhydrin. A number of colored products are formed, but the major one is presumed to result from deamination and condensation as follows ... 

Keywords ninhydrin, dimedone, ball-milling, condensation... 

---