Succinic anhydrides, hydrogenation

Methanesulfonyl chloride Succinic anhydride Hydrogen hydrochloride Dibutylamine... 

Succinic anhydride [108-30-5] (3,4-dihydro-2,5-furandione butanedioic anhydride tetrahydro-2,5-dioxofuran 2,5-diketotetrahydrofuran succinyl oxide), C H O, was first obtained by dehydration of succinic acid. In the 1990s anhydride is produced by hydrogenation of maleic anhydride and the acid by hydration of the anhydride, by hydrogenation of aqueous solutions of maleic acid, or as a by-product in the manufacture of adipic acid (qv) (see Maleic ANHYDRIDE, MALEIC ACID, AND FUMARIC ACID). 

Oxidation. Succinic acid reacts with hydrogen peroxide, giving different products that depend on the experimental conditions peroxysuccinic acid [2279-96-1] (CH2COOOH)2, oxosuccinic acid [328-42-7] (oxaloacetic acid) malonic acid [141-82-2] or a mixture of acetaldehyde, malonic acid, and make acid [6915-15-7]. Succinic anhydride in dimethylformamide (DMF) with H2O2 gives monoperoxysuccinic acid [3504-13-0], HOOCCH2CH2COOOH, mp 107°C (70). 

Hydrogenation. Gas-phase catalytic hydrogenation of succinic anhydride yields y-butyrolactone [96-48-0] (GBL), tetrahydrofiiran [109-99-9] (THF), 1,4-butanediol (BDO), or a mixture of these products, depending on the experimental conditions. Catalysts mentioned in the Hterature include copper chromites with various additives (72), copper—zinc oxides with promoters (73—75), and mthenium (76). The same products are obtained by hquid-phase hydrogenation catalysts used include Pd with various modifiers on various carriers (77—80), Ru on C (81) or Ru complexes (82,83), Rh on C (79), Cu—Co—Mn oxides (84), Co—Ni—Re oxides (85), Cu—Ti oxides (86), Ca—Mo—Ni on diatomaceous earth (87), and Mo—Ba—Re oxides (88). Chemical reduction of succinic anhydride to GBL or THF can be performed with 2-propanol in the presence of Zr02 catalyst (89,90). 

V-Alkyl or A/-aryl succinimides can be prepared from the corresponding amines (107) or from succinic anhydride, ammonia, and the corresponding alcohol (108). Succinimides are also obtained by vapor-phase hydrogenation of the corresponding maleimides ia the presence of a catalyst (109). 

Reactions with Sulfur Compounds. Thiosuccinic anhydride [3194-60-3] is obtained by reaction of diethyl or diphenyl succinate [621-14-7] with potassium hydrogen sulfide followed by acidification (eq. 10). Thiosuccinic anhydride is also obtained from succinic anhydride and hydrogen sulfide under pressure (121). 

Succinic anhydride is manufactured by catalytic hydrogenation of maleic anhydride [108-31-6]. In the most widely used commercial process this reaction is performed in the Hquid phase, at temperatures of 120—180°C and at moderate pressures, in the range of 500—4000 kPa (72—580 psi). Catalysts mentioned in the patent Hterature include nickel (124), Raney nickel (125,126), palladium on different carriers (127,128), and palladium complexes (129). The hydrogenation of the double bond is exothermic Ai/ = —133.89 kJ/mol (—32 kcal/mol) (130). 

After separation of the catalyst by filtration, raw succinic anhydride is purified by distillation under reduced pressure, ie, 4—13 kPa (30—98 mm Hg), and flaked. The material of constmction of the plant is stainless steel. Typical specific consumptions for the production of one metric ton of succinic anhydride are maleic anhydride at 1050 kg hydrogen, 300 m steam, 4500 kg cooling water, 100 m electricity, 350 kW nitrogen, 100 m and methane,... 

In the early 1990s, processes were developed for the production of 1,4-butanediol and y-butyrolactone by gas-phase catalytic hydrogenation of maleic anhydride (131—134). Succinic anhydride is obtained as a partial hydrogenation by-product in these processes. It can be recycled to complete the hydrogenation to the desired products, or be separated and purified. This process could in the future become a significant commercial route for succinic anhydride. 

Under the present reaction conditions, we observed the formation of succinic anhydride almost simultaneously together with the formation of GBL. The hydrogaiation of maleic anhydride yields succinic anhydride, and the subsequent hydrogenation of succinic anhydride produces GBL. The rate of hydrogenation of maleic anhydride to succinic anhydride was very fast compare to that of succinic anhydride to GBL. When the reaction was CEuried out wifliout solvent, tetrahydrofiiran was not producal. The above results indicate that the Pd-Mo-Ni/SiOz catalyst under our experimental conditions played an important role for the selective formation of GBL. Therefore, it is inferred that the catalyst composition may influence the route by which tetrahydrofiiran was formed, probably due to the different absorption mechanism of maleic anhydride, succinic anhydride, and GBL. 

The first examples of a homogeneous reduction of this type were reported in 1971. Cobalt carbonyl was found to reduce anhydrides such as acetic anhydride, succinic anhydride and propionic anhydride to mixtures of aldehydes and acids. However, scant experimental details were recorded [94]. In 1975, Lyons reported that [Ru(PPh3)3Cl2] catalyzes the reduction of succinic and phthalic anhydrides to the lactones y-bulyrolaclone and phthalide, respectively [95], The proposed reaction sequence for phthalic anhydride is shown in Scheme 15.15. Conversion of phthalic anhydride was complete in 21 h at 90 °C, but yielded an equal mixture of the lactone, phthalide (TON = 100 TOF 5) and o-phthalic acid, which is presumably formed by hydrolysis of the anhydride by water during lactoniza-tion. Neither acid or lactone were further hydrogenated to any extent using this catalyst system, under these conditions. 

Mitsubishi have reported several processes based on Ru-catalyzed hydrogenation of anhydrides and acids. Succinic anhydride can be converted into mixtures of 1,4-butane-diol and y-butyrolactone using [Ru(acac)3]/trioctylphosphine and an activator (often a phosphonic acid) [97]. Relatively high temperatures are required ( 200°C) for this reaction. The lactone can be prepared selectively under the appropriate reaction conditions, and a process has been developed for isolating the products and recycling the ruthenium catalyst [98-100]. 

Succinic anhydride is clearly hydrogenated more readily than the acid, as was the case with phthalic acid (Scheme 15.17), but faster absolute rates were observed in the hydrogenation of o-phthalic acid and phthalic anhydride to phtha-lide. In these reactions, the problem of anhydride hydrolysis is less significant as the acid can also be reduced to the same lactone product... 

Beta-carbomethoxypropionyl chloride (Org. Synth. 25,19 (1945)). Dissolve 400 g succinic anhydride in 190 ml methanol in 1 L round bottom flask and reflux (steam bath) one-half hour. Stir until homogeneous (about twenty minutes) and reflux one-half hour. Evaporate in vacuum and cool the residual liquid to precipitate about 500 g methyl-hydrogen succinate (1). Dissolve 264 g (1) in 200 ml SOCl2 in a 1 L round bottom flask with a reflux condenser and warm at 30-40° in water bath for three hours. Evaporate in vacuum the SOCl2 (can heat flask in steam bath) to get 270 g of the title compound (can distill 92/18). 

A 500-mL, three-necked, round-bottomed flask (Note 1) equipped with an overhead mechanical stirrer, is charged with powdered succinic anhydride (10.01 g, 0.1000 mol) (Note 2) and bromobenzene (96.87 g, 0.6170 mol) (Note 2) under dry argon. The resulting white mixture is cooled to 0°C before anhydrous aluminum chloride (26.67 g, 0.2000 mol) (Note 2) is added in one portion (Note 3). The reaction conditions are maintained over a period of 4 hr before the reaction mixture is allowed to warm to room temperature. The reaction mixture is stirred for 96 hr at room temperature (completion of the reaction is indicated by cessation of the evolution of hydrogen chloride gas) and is then poured into cooled (0°C), mechanically stirred hydrochloric acid (250 ml, 37%) (Note 4) and stirred for 1 hr. The white precipitate is filtered off, washed well with water (1 L) and dried overnight on a Buchner funnel. The crude product (24.81 g, 97%) is crystallized from dry toluene (Note 5) and dried under reduced pressure (PjO, CaCI, 18 hr) to afford a white crystalline product (first fraction, 20.76 g, second fraction, 3.47 g) yield is 24.23 g (94%) (Note 6). 

The mixture is heated (Note 2) with a free flame for about fifty minutes until no more hydrogen chloride is evolved. The condenser is then removed, and the flask arranged for distillation. A tube leading to the drain is placed on the side-arm of the receiving flask to carry off the vapors. A few cubic centimeters are collected before the temperature rises to 2550, at which temperature the receiver is changed and the succinic anhydride collected from 255-260° (Note 3). The yield of product melting at 118-120° is 164-192 g. (82-96 per cent of the theoretical amount). 

A. Methyl hydrogen succinate. A mixture of 400 g. (4 moles) of succinic anhydride (Note 1) and 194 ml. (4.8 moles) of methanol (Note 2) in a 1-1. round-bottomed flask is refluxed on a steam bath. After about 35 minutes the mixture is swirled frequently until it becomes homogeneous (this requires 15-30 minutes) the flask is then half immersed in the steam bath for an additional 30-25 minutes (Note 3). 

Methyl hydrogen succinate has been prepared by heating succinic acid with methyl succinate,2 by treating ethyl succinate with sodium methoxide,3 and by heating succinic anhydride with methanol.4 5 ... 

So the decision was taken to use succinic anhydride as the electrophile (chapter 5). Pyrroles prefer to react next to nitrogen with electrophiles (chapter 39), but with a large group on nitrogen 108 (j-P Si), Friedel-Crafts reaction occurred at the other position to give the keto-acid 109. Reduction to the benzylic alcohol and catalytic hydrogenation gave 110 in excellent yield. 

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