Succindialdehyde

The oxidative reaction of furan with bromine in methanol solution or an electrochemical process using sodium bromide produces 2,5-dimethoxy-2,5-dihydrofuran (19), which is a cycHc acetal of maleic dialdehyde. The double bond in (19) can be easily hydrogenated to produce the corresponding succindialdehyde derivative. Both products find appHcation in photography and as embalming materials, as well as other uses. 

The 2,5-dialkoxy-2,5-dihydrofurans are cyclic acetals of male-aldehyde and may be used to generate this substance in situ. Also, the 2,5-dialkoxy-2,5-dihydrofurans readily undergo hydrogenation to provide the cyclic acetals of succindialdehyde." ... 

The importance of tropinone as a possible starting-point for the production of the therapeutically valuable alkaloids atropine, hyoscyamine, cocaine, tropacocaine and the artificial tropeines (p. 73) led Robinson to consider the possibility of preparing this substance by a simple method. Starting with the idea that the formula for tropinone (XXX) may be regarded as made up of the formulae of the residues of succindialdehyde (XXVII), methylamine (XXV III) and acetone (XXIX), he found that a mixture of these substances in water, when allowed to stand for thirty minutes produced tropinone, which could be detected by means of its characteristic dipiperonylidene derivative (bright yellow needles, m.p. 214°). 

The synthesis of tropinone 14, a precursor of atropine and related compounds, is a classical example. In 1917 Robinson has prepared tropinone 14 by a Mannich reaction of succindialdehyde 11 and methylamine 12 with acetone 13 better yields of tropinone were obtained when he used the calcium salt of acetonedicar-boxylic acid instead of acetone. Modern variants are aimed at control of regio-and stereoselectivity of the Mannich reaction. ... 

Furthermore, as described by Mori and coworkers, the domino aldol/cyclization reaction of the 3-keto sulfoxide 2-422 with succindialdehyde (2-423) in the presence of piperidine at r.t. afforded the chromone 2-424 which, on heating to 140 °C, underwent a thermal syn-elimination of methanesulfenic acid to provide 2-426 in 22 % overall yield (Scheme 2.100) [227]. This approach was then used for the synthesis of the natural products coniochaetones A (2-425) and B (2-427) [228]. 

Suspend 23.2 g succinaldoxime powder in 410 ml IN sulfuric acid and add dropwise with stirring at about 0° a solution of 27.6 g Na nitrite in 250 ml water over three hours. Stir two hours at room temperature (keeping air out), stir in 5 g Ba carbonate and filter. The succindialdehyde should then be extracted from the basic solution with ether and the ether dried and evaporated in vacuum. For succinaldoxime preparation, see JOC 21,644(1956) and JACS 68,1608(1946). 

It may be possible to partially oxidize butanediol to butanedial (succindialdehyde) and distill this as the reaction occurs. 

Succindialdehyde. This can be purchased, too. 23.2 g of succinaldoxime powder in 410 ml of 1 N sulfuric acid and add dropwise with stirring at 0° a solution of 27.6 g of sodium nitrite in... 

Complete Synthesis of Succindialdehyde. JACS, 68, 1608 (1946). In a 2 liter 3 necked flask equipped with a stirrer, reflux condenser, and an addition funnel, is mixed 1 liter of ethanol, 67 g of freshly distilled pyrrole, and 141 g of hydroxylamine hydrochloride. Heat to reflux until dissolved, add 106 g of anhydrous sodium carbonate in small portions as fast as reaction will allow. Reflux for 24 hours and filter the mixture. Evaporate the filtrate to dryness under vacuo. Take up the residue in the minimum amount of boiling water, decolorize with carbon, filter and allow to recrystallize in refrigerator. Filter to get product and concentrate to get additional crop. Yield of succinaldoxime powder is a little over 40 g, mp is 171-172°. 

Take the total amount of succinaldehyde (obtained from 4 of the above syntheses combined) and without further treatment or purification (this had better be 15.5 g of succindialdehyde) put into an Erlenmeyer flask of 4-5 liters capacity. Add 21.6 g of methylamine hydrochloride, 46.7 g of acetonedicarboxylic acid, and enough water to make a total volume of 2 liters. Adjust the pH to 8-10 by slowly adding a saturated solution of disodium phosphate. The condensate of this reaction (allow to set for about 6 days) is extracted with ether, the ethereal solution is dried over sodium sulphate and distilled, the product coming over at 113° at 25 mm of pressure is collected. Upon cooling, 14 g of tropinone crystallizes in the pure state. Tropinone can also be obtained by oxidation of tropine with potassium dichromate, hut I could not find the specifics for this operation. 

The synthesis involved reacdon of methylamine, succindialdehyde and acetone under mild acid condidons, and although yields were poor, tropinone was formed. This could then be reduced with sodium borohydride to give tropine. 

Limited data are available on the reaction of diaJdehydes with dinitromethane. Succindialdehyde and glyoxal gave the diaddition products, l,l,6,6-tetranitrohexane-2,5-diol (106) and 1,1,4,4-tetra-nitrobutane-2,3-diol (107), respectively 56). Whether this is due to the low tendency of these dialdehydes to form cyclization products — reaction of glyoxal with nitromethane can give di-addition 57) and cyclization products 58) — or is a general behavior of dinitromethane is not yet apparent. 

The Mannich reaction is an important biosynthetic route to natural products, mainly alkaloids, and some of these routes have been duplicated in the laboratory. A classic example is the synthesis of tropinone (17) by Robinson in 1917. Robinson synthesized tropinone by a Mannich reaction involving succindialdehyde, methylamine, and acetone 183... 

Cyclitol osazones consume the expected amount of periodate (three molar equivalents per mole), but the presumed product, 2,3-bis(phenylhydra-zono)succindialdehyde (XCVII), cyclizes to the pyrazole XCVIII.212 The... 

Total syntheses of coniochaetones A and ( )-B feature the reaction of P-ketosulfoxide 756 with succindialdehyde to form the cyclopentane-fused chromone 757 in modest yield (Scheme 196) <1998SL259>. 

Hydrogenation of 1,4- and 1,5-dioximes tends to give pyrrolidines and piperidines, respectively. Thus, the hydrogenation of succindialdehyde oxime over Raney Ni in alcoholic ammonia, which did not occur at room temperature and 10 MPa H2, afforded only pyrrolidine on warming to 60°C.77... 

Pyrrolidines can also be prepared by Mannich reactions a classical example is the synthesis of tropinone 43 from succindialdehyde, methylamine, and acetone dicarboxylic acid (Scheme 32) <1917JCS762> reactions of this type are involved in alkaloid biogenesis. 

MARSCHALK REACTION Glyoxylic acid. Piperidinium acetate. Succindialdehyde. 

Reaction of succindialdehyde, benzotriazole, and T-phenylethylenediamine provides l-phenyl-5-(benzotriazol-l-yl)hexahydro-177-pyrrolo[l,2- ]imidazole 1250. Further reaction of compound 1250 with Grignard reagents affords l-phenyl-5-substituted-hexahydro-17/-pyrrolo[l,2- ]imidazoles 1251 in good to excellent yields (Scheme 313) <2000JOC3683>. 

But the most reliable biomimetic type of synthesis of tropine was achieved in 1S17 by Robinson (27). In this method, succindialdehyde, methylamine and acetone dicarboxylic acid were mixed at pH 5.6 for 30 minutes to give tropinone in one step which was then reduced to tropine by an established process (25). A much better yield (almost 40%) was obtained by using calcium acetcndicarboxy-late the calcium salt so produced is converted into tropinone by warming with hydrochloric acid (23). 

Schopf and Lehmann (29) have also obtained a yield of 70-85% by modifying Robinson s synthesis. A dilute buffered solution of succindialdehyde, methyl-amine hydrochloride and acetone dicar-boxylate were mixed at 25 and at pH 5.0. 

Elming et al. (30) have synthesized tropinone (in 81% yield) by using methylamine hydrochloride, acetone dicarboxylic acid and generating succindialdehyde m situ by the action of acid on 2, 5-dimethoxytetrahydrofuran which is commercially available. 

Robinson s classical synthesis of tropinone was achieved by condensation of succindialdehyde and methylamine with acetonedicarboxylic acid. Schbpf later carried out the reaction in a solution buffered to pH 5 and at room temperature and... 

Several one-pot syntheses are closely related to MCRs that have irreversible final steps, although they are unions of two usually reversible M-3CRs, since their products are rather stable polyheterocyclic compounds. The first such procedure was introduced by Robinson in 1917 [48a], who synthesized the tropinone 59 from succindialdehyde 56, methylamine 2b and the methyl ester of acetonedicarbocylic acid 57 (Scheme 4.28). Two decades later, Schopf et al. accomplished some progress with a closely related synthesis [48b],... 

In an application of the chiral auxiliary technique, succindialdehyde has been transformed into mono-N-tosyloxazolidine 1.83 (n = 0, Y = CH=CHCOOH) derived from ephedrine. Treatment of 1.83 with KOC1 leads to an epoxyacid with high diastereoselectivity [1385], After nucleophilic ring opening of epoxide, the chiral auxiliary is recovered by treatment with ethanedithiol (Figure 7.35). Epoxidation of the (2, 47 )-pentane-2,4-diol monoketal of a prochiral quinone with tri-tylhydroperojdde has been performed with a moderate selectivity by Corey and Wu en route to a natural product (70%) [1386],... 

The best synthon for unstable succindialdehyde, for the ring synthesis of C-unsubstituted pyrroles, is... 

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