Homophthalic acids

A solution of 240 g. of potassium dichromate and 720 ml. of concentrated sulfuric acid in 3.6 1. of water is stirred and heated to reflux in a 5-1. three-neck flask equipped with two 10-bulb Allihn condensers. 

Indene (72 g. of 87% pure material) is added all at once, and rapid reflux is maintained by the heat of reaction for a few minutes, after which the flask is heated to reflux and stirred for an additional 7 minutes. After the mixture is cooled to 10°, the precipitated product is removed and dissolved in 250 ml. of 10% aqueous sodium hydroxide solution. After extraction with ether to remove insoluble material, the alkaline solution is acidified with 78 ml. of 33% sulfuric acid solution and heated to boiling to dissolve the precipitated homoph-thalic acid. The hot solution is treated with activated carbon and filtered. Cooling precipitates 57 g. (58%) of homophthalic acid, m.p. 179-180°. 

Method 2. Intimately mix 99 g. of pure phthalic anhydride and 20 g. of urea, and place the mixture in a 1 litre long-necked, round-bottomed flask. Heat the flask in an oil bath at 130-135°. When the contents have melted, effervescence commences and gradually increases in vigour after 10-20 minutes, the mixture suddenly froths up to about three times the original volume (this is accompanied by a rise in temperature to 150-160°) and becomes almost solid. Remove the flame from beneath the bath and allow to cool. Add about 80 ml. of water to disintegrate the solid in the flask, filter at the pump, wash with a little water, and then dry at 100°. The yield of phthalimide, m.p. 233° (. ., it is practically pure) is 86 g. If desired, the phthalimide may be recrystaUised from 1200 ml. of methylated spirit the first crop consists of 34 g. of m.p. 234°, but further quantities may be recovered from the mother liquor. 

Homophthalic acid. Place a mixture of 25 g. of o-carboxyphenylacetonitrile and 25 g. of 50 per cent, sulphuric acid in a 100 ml. flask, heat 

Phthalide. In a 1 litre bolt-head flask stir 90 g. of a high quality zinc powder to a thick paste with a solution of 0 5 g. of crystallised copper sulphate in 20 ml. of water (this serves to activate the zinc), and then add 165 ml. of 20 per cent, sodium hydroxide solution. Cool the flask in an ice bath to 5°, stir the contents mechanically, and add 73-5 g. of phthalimide in small portions at such a rate that the temperature does not rise above 8° (about 30 minutes are required for the addition). Continue the stirring for half an hour, dilute with 200 ml. of water, warm on a water bath imtil the evolution of ammonia ceases (about 3 hours), and concentrate to a volume of about 200 ml. by distillation vmder reduced pressure (tig. 11,37, 1). Filter, and render the flltrate acid to Congo red paper with concentrated hydrochloric acid (about 75 ml. are required). Much of the phthalide separates as an oil, but, in order to complete the lactonisation of the hydroxymethylbenzoic acid, boil for an hour transfer while hot to a beaker. The oil solidifles on cooling to a hard red-brown cake. Leave overnight in an ice chest or refrigerator, and than filter at the pump. The crude phthalide contains much sodium chloride. RecrystaUise it in 10 g. portions from 750 ml. of water use the mother liquor from the first crop for the recrystaUisation of the subsequent portion. Filter each portion while hot, cool in ice below 5°, filter and wash with small quantities of ice-cold water. Dry in the air upon filter paper. The yield of phthalide (transparent plates), m.p. 72-73°, is 47 g. 

Submitted by P. A. S. Smith and R. O. Kan 1 Checked by Melvin S. Newman and Bernard Darri. 

Ten grams (0.056 mole) of 2a-thiohomophthalimide2 and a solution of 30 g. of potassium hydroxide in 125 ml. of water are placed in a 300-ml., one-necked, round-bottomed flask (Note 1). The mixture is refluxed for 48 hours, filtered, and acidified with 12N hydrochloric acid. The solid that forms on cooling is collected by filtration and recrystallized from a mixture of 25 ml. of water and as much acetic acid (about 7 ml.) as necessary to dissolve the solid in the boiling solution, with addition of a little activated carbon. The yield of homophthalic acid, m.p. 181° (Note 2), is 6.1-7.5 g. (60-73%) (Note 3). 

Because base can attack glass vessels, possibly introducing difficultly removable silicates into the reaction mixture, a copper flask is recommended for routine operations. 

The melting point depends on the rate of heating. When the solid is heated slowly, the melting range can be as low as 172-174°. 

An alternative procedure involves 3 days of refluxing in a mixture of 75 ml. of glacial acetic acid, 50 ml. of 12 A hydrochloric acid, and 30 ml. of water. The product separates on cooling in a slightly lower yield (48%). 

Place 126 ml. of glacial acetic acid, 7 5 g. of purified red phosphorus (Section 11,50,6) and 2-6 g. of iodine in a 600 ml. round-bottomed flask fitted with a reflux condenser. Allow the mixture to stand for 15-20 minutes with occasional shaking mxtil all the iodine has reacted, then add 2 5 ml. of water and 60 g. of benzilic acid (Section IV,127). Boil the mixture under reflux for 3 hours, and filter the hot mixture at the pump through a sintered glass funnel to remove the excess of red phosphorus. Pour the hot filtrate into a cold, well-stirred solution of 12 g. of sodium bisulphite in 500 ml. of water the latter should be acid to litmus, produced, if necessary, by passing sulphur dioxide through the solution. This procedure removes the excess of iodine and precipitates the diphenyl-acetic acid as a fine white or pale yellow powder. Filter the solid with suction and dry in the air upon filter paper. The yield is 45 g., m.p. 

142-144. Upon leciystaUisation from about 260 ml. of 60 per cent, alcohol, cr talline diphenylacetic acid, m.p. 144-146 (1), is obtained. 

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Homophthalic acid. This is a four-stage preparation with phthalic anhydride as the starting material ... 

Homofolic acid, 5,11-methenyl-tetrahydro-biological activity, 3, 327 Homofolic acid, tetrahydro-biological activity, 3, 327 Homoisoflavanones occurrence, 3, 722 thermoisomerization, 3, 722 thermolysis, 3, 728 Homolytic reactions heterocyclic compounds reviews, 1, 74 Homophthalic acid isocoumarins synthesis from, 3, 830 synthesis, 3, 830 Homophthalic anhydride isochroman-l-one synthesis from, 3, 860 20a-Homoporphyrin nomenclature, 1, 30 Homopterocarpin isolation, 4, 998 ( )- D- Homotestosterone synthesis, 1, 453 Homer-Emmons reaction chromene synthesis by, 3, 749 Hortiacine isolation, 3, 149 Hortiamine isolation, 3, 149... 

The first direct approach to a pentacyclic system, based on the condensation product 101 of tryptamine with a homophthalic acid or anhydride, was introduced by Clemo and Swan and extended to reduced and substituted homophthalates. Esterification of... 

Homophthalic acid may be obtained by the oxidation of in-dene,3-4 the reduction of phthalonic acid,6-6 and the hydrolysis of o-carboxyphenylacetonitrile.7 Other methods are listed in an earlier volume.3... 

This is a general method for converting 2a-thiohomophthaIim-ides to homophthalic acids. Since 2a-thiohomophthalimides are readily obtained from phenylacetyl chlorides,2 this is a convenient method for preparing homophthalic acids. 

The thioimides can be hydrolyzed to the corresponding di-carboxylic acids. The thioimides can be converted to the corresponding imides, and thiohomophthalimides can be converted to phthalimides both conversions are one-step processes.4 Thus a variety of substituted phthalic and homophthalic acids and their derivatives are available from these thioimides. 

The observed ambient organic aerosol formation rates are also consistent with those estimated by extrapolation of smog-chamber kinetic data. Other heavy unsaturates, such as styrene and indene, are present in the atmosphere and may contribute, in part, to the formation of benzoic acid and homophthalic acid, respectively. Diesel exhaust and industrial emission are possible sources of such heavy unsaturates. Diolefins of C6+ are not present in gasolines and exhaust gases and have not been found in the atmosphere, and their possible role as precursors of the Cs-7 difiinctional acidic compounds is seriously challenged. Lower diolefins are emitted in automobile exhaust. Examination of vapor-pressure data indicates that the bulk of their expected photooxidation products remains in the gas phase, including most of the less volatile C3-4 dicarboxylic acids. 

Homophthalic acid [89-51-0] M 180.2, m 182-183° (varies with the rate of heating). 

Hippuric acid, 584 Hoesch reaction, 727J, 736, 737 Hofmann reaction, 413, 414, 754, 773 Homophthalic acid, 753, 771 Hot plate, electric, 58, 61 Hydratropaldehyde, 906, 907 Hydrazine hydrate, 190, 976, 977 Hydrazines, 1075 ... 

Reaction of homophthalic acid (377) and 3-hydroxypropylamine at 215-220°C gave l-(3-hydroxypropyl)-l,2,3,4-tetrahydro-6//-pyrimido[l,2-b]isoquinoline (376, R = CH2CH2CH2OH, R1 = H) (71GEP1960375). 1-Substituted 1,2,3,4-tetrahydro-6//-pyrimido[l, 2-b]isoquinolin-6-ones (378) were obtained from homophthalic acid (377) and 1,3-propanediamines in o-dichlorobenzene at 140-150°C with removal of water by azeotropic distillation [78JAP(K)78/130435 79CPB2372 88HCA77],... 

The reactions of homophthalic acids or a-alkyl, a-phenyl, and a-benzyl derivatives (221) and 3-aminopropanethiol hydrobromide in o-... 

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