Triones, preparation

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). 

The kinetics of /V-ch1orination of CA iu basic media have been studied by stopdow spectrophotometry (21). The A/-chloro derivatives are the most important commercial products derived from CA. Their av CI2 and other values appear iu Table 2. Trichloroisocyanuric acid [87-90-17, TCCA, or l,3,5-trichloro-j -tria2iQe-2,4,6(lJT,3JT,5J-i)-trione, is obtained iu - 90% yield by cblorination of aqueous trisodium cyanurate, prepared from CA and NaOH iu a 1 3 molar ratio (22). 

Kubota and co-workers also prepared several 1,2-diols (61) and noted that these substances give the enediones (59) in much better yields than the diosphenols (58). This is consistent with a mechanism which requires, as the first step, hydroxylation of the -double bond of (58) by manganese dioxide followed by oxidation to the intermediate trione. 

A. 2-Methyl-4-eihoxalylcyclopenlane-l,3,5-trione. A solution of sodium ethoxide is prepared in a 2-1. three-necked, round-bottomed flask fitted with a mercury-sealed stirrer, a reflux condenser carrying a drying tube, and a stopper by the addition of 69.0 g. (3 moles) of sodium to 950 ml. of absolute ethanol. The solution is cooled to 0-5° in an ice bath and stirred. The stopper is replaced by a dropping funnel, and a cold mixture (5-15°) of 108 g. (1.50 moles) of freshly distilled 2-butanone and 482 g. (3.30 moles) of diethyl oxalate (Note 1) is added gradually over a... 

B. 2-Methylcyclopenlane-l,3,5-trione hydrate. A mixture of 200 g. (0.89 mole) of the keto ester prepared above, 910 ml. of water, and 100 ml. of 85% phosphoric acid is healed under reflux for 4 hours and then cooled in an ice-salt bath to —5°. The trione mixed with oxalic acid separates and is collected by filtration and dried under reduced pressure. The dried material is extracted with boiling ether (250-300 ml.) under reflux, and the ethereal extract is separated from the undissolved oxalic acid. The original aqueous filtrate is also extracted with ether in a continuous extractor. The two extracts are combined, and ether is removed by distillation. The crude trione separates as a dark brown solid and is crystallized from ca. 250 ml. of hot water. The once-crystallized, faintly yellow product weighs 95-105 g. (74-82%), m.p. 70-74°. This product is used in the next step without further purification. A better specimen, m.p. 77-78°, which is almost colorless, can be obtained by recrystallization from hot water after treatment with Norit activated carbon. 

Methylcyclopentane-l,3-dione has been prepared in 15% yield by the catalytic reduction of 2-mcthylcyclopentane-l,3,5-trione over platinum.2 The present method is based on the original procedure 3 of Panouse and Sannie with improvements as effected by Boyce and Whitehurst4 and the submitters.6... 

Benzenediamine (358) and 5-(l,2-dihydroxyethyl)tetrahydro-2,3,4-furane-trione (359) (prepared in situ by oxidation of ascorbic acid with p-benzoqui-none) gave either 3-(2,3,4-trihydroxybutyryl)-2(17i)-quinoxalinone (360)... 

A library of l,3,7-substituted-perhydropyrazino[l,2-f]pyrimidine-2,6,8-triones was built by preparation of functionalized ketopiperazines on the solid phase, followed by N-acylation with 2-bromoacetic acid, reaction with isocyanate and with concomitant cyclization using trifluoroacetic acid (TFA) <2003W02003/013740>. 

A library of fifteen 6,7,9,9a-tetrahydro-57/-pyrazolo[l,2-tf]pyrrolo[3,4-ir]pyrazole-l,3,5(2/7,3a7/)-triones 712 was prepared by combinatorial stereoselective cycloadditions of compounds 320 to A-substituted maleimides. 

The four-, five-, and six-membered analogs (178,180, and 182) were also obtained from the diprotonation of squaric acid (3,4-dihydroxy-3-cyclobutene-l,2-dione, 177), tri-O-protonation of croconic acid (4,5-dihydroxy-4-cyclopentene-l,2,3-trione, 179), and tetra-O-protonated rhodizonic acid (5,6-dihydroxy-5-cyclohexene-l,2,3,4-tetraone, 181), respectively. These ions were prepared in either Magic Acid (1 1 FSOsH-SbFs) or fluorosulfuric acid at low temperature and characterized by NMR. Ab initio/IGLO calculations showed that di-O-protonated squaric acid (178) is planar and aromatic, whereas the polyprotonated croconic and rhodizonic acids (180 and 182) have more carboxonium ion character, and no indication was obtained for any significant contributing homoaromatic structures. 

The first pyrazolo[l,5-c]pyrimidine derivative (191) was prepared by condensing thiosemicarbazide with heptane-2,4,6-trione in the presence of perhydroacetic acid (72CB388). This reaction was adopted for the preparation of derivatives of 191 (X = O, NH), and later used to synthesize other pyrazolo[ 1,5-c] pyrimidines (71GEP2131790). 

Addition polymers consisting of pentaerythritol triallyl ether, (I), and pentaer-ythritolntetrakis(3-mercaptopropionate), (H), were previously prepared by the authors (2) and used in dental restorative materials. Other photosensitive addition polymer mixtures using triallyl l,3,5-triazine-2,4,6-trione, ( ), are also described by the authors (3). 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

When 2,2-disubstituted 1,3-dioxolanes were employed, mono- or poly-chlorination of the side chain was observed on the carbon atom a to the acetal grouping. Incidentally, it should be noted thatN-bromo-succinimide, N-chlorosuccinimide, and trichlorotetrahydrotriazine-trione were found to be effective for the preparation of bromoacetates from O-ethylidene derivatives this might be useful when O-benzyli-dene derivatives are not readily available, or when a problem arises due to the fact thatO-benzoyl groups are, in general, more difficult to remove than O-acetyl groups. 

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