Succinic dialdehyde

In 1917, Sir Robert Robinson [9] suggested that tropinone (141 could be synthesised in Nature from succinic dialdehyde (151. N-methylamine (161 and acetonedicarboxylic acid (171. or some of their "equivalents", according to a double... 

It has been pointed out already that the early design of synthetic routes for the vast number of simple and complex molecules was a largely intuitive operation. Indeed even the most eminent of synthetic chemists rarely recorded in the literature the thought processes which led to the realisation of the successful synthesis of a complex structure. One notable exception was that of the Robinson tropi-none synthesis.13 In this case the molecule was submitted to an imaginary hydrolysis at the points indicated by the dotted line and resolved into succin-dialdehyde, methylamine and acetone. These reagents were then mixed together... 

There is abundant information to support the contention that the lower-melting monoisopropylidene-mannitol (m. p. 85°) is the 3,4-derivative. For example, its tetrabenzoate is identical with that obtained by acetonation of 1,2,5,6-tetrabenzoyl-mannitol,11498 the structure of which is based on independent evidence.114 The larger fragment resulting from the oxidative scission of the D-enantiomorph of the isopropylidene-man-nitol with lead tetraacetate is 2,3-isopropylidene-D-//treo-dihydroxy-succinic dialdehyde, characterized by its subsequent conversion into D-i/ireo-tartaric acid.126 When methylated and hydrolyzed, the L-enantio-morph of the monoketal affords a tetramethyl-mannitol, which, in turn, yields dimethyl-L-glyceraldehyde with lead tetraacetate.127 Each of these facts is in itself proof that the acetone residue occupies the 3,4-position in the mannitol molecule. 

Diol (165) is an intermediate in the synthesis of the symmetrical triterpene, squalene (167). Succin-dialdehyde serves as the central four carbons followed by bidirectional synthesis through diol (164). The transformation of diol (164) into its higher homolog (165) requires several operations (i) orthoacetate rearrangement s to a diester (ii) reduction to a diol (iii) oxidation to a dialdehyde and (iv) addition of iso-propenyllithium. A more convergent approach employs 3,3-dimethoxy-2-methylbut-l-ene in conjunction with diol (164), a sequence that only requires reduction of the resultant isopropenyl ketone after rearrangement to realize diol (165). ... 

The synthesis of tropine and of its esters has been made practical because succinic dialdehyde has become easily available. Furane, now available commercially, gives on anodic oxidation in methanol with ammonium bromide as electrolyte good yields of 2,5-dimethoxy-2,5-2H-furane (37a). This mixed ketal of maleic dialdehyde could be hydrogenated readily and quantitatively over Raney nickel to 2,5-dimethoxy-4H-furane (37b). The latter as a mixed ketal of succinic dialdehyde undergoes acid hydrolysis easily. Optimum conditions for the condensation of this dialdehyde formed in situ to tropinone have been recorded (38) with yield up to 93% and at a higher rate than described earlier (18). 

It is interesting to note that the substitution of succinic dialdehyde for the glutaric dialdehyde in the foregoing reaction gives rise to a lower homolog of lobelanine, V-methyl-2 5-diphenacylpyrrolidine. This base, which has not been found in nature, is obtained in 94% yield as beautiful crystals, m.p. 205-206°. Like lobelanine, it forms a hydrochloride, m.p. 205-206°, which is sparingly soluble in water. 

Robinson s synthesis of tropine (210) on the other hand was as direct (two steps) as Willstatter s was long but it involved the use of the very sensitive succinic dialdehyde (from pyrrole) (157, 219). The fragments from the hypothetical fission of the symmetrical tropinone (XLVI) suggested to Robinson the possibility of obtaining this ketone by the condensation of succinic dialdehyde and methylamine with acetone. The primary reaction was considered to be the combination of succinic dialdehyde with methyl-amine and the resulting biscarbinolamine (XLIX) in turn condensed with acetone. This synthesis was realized when these reactants, in aqueous... 

The alkaloid has been synthesized from the dioxime of succinic dialdehyde. The steps involved in the synthesis were (a) reduction (Na -1-C2H5OH) of the dioxime to putrescine, (b) conversion of putrescine to the dimethochloride of the alkaloid, and (c) pyrrolysis of the dimethochloride. 

In a related report, a one-pot synthesis of 1,5-didehydrohygrine (15) was achieved by reaction of succinic dialdehyde and methylamine hydrochloride in the presence of citric acid followed by treatment of the resulting intermediate with acetoacetic acid. A lengthier route to (15) using terminal steps described for the preparation of compound (14) was also reported. 

This process is commercialized by BASF for the formation of succinic dialdehyde and by Otsuka, Japan, for the synthesis of maltol and ethyl maltol. 

CAS 638-37-9 EINECS/ELINCS 211-333-8 Synonyms 1,4-Butandial Butanedial Succinic dialdehyde... 

Succinic anhydride, (1-octenyl)-. See 1-Octenylsuccinic anhydride Succinic anhydride, (tetrapropenyl). See Tetrapropenyl succinic anhydride Succinic dialdehyde. See Succinaldehyde Succinic dinitrile. See Succinonitrile Succinic imide. See Succinimide Succinic peroxide. See Succinic acid peroxide Succinimide... 

As pointed out by Sir Robert Robinson with regard to tropanone, almost 15 years after the work outlined above was published, it appears to be of too complicated a character to admit of development into an economical process. The critique was accompanied by a new synthesis, which required only that succinic dialdehyde react with acetonedicarboxylate and methylamine in ethanol solution (Scheme 13.6). As simple as this reaction appears, however, it clearly serves more as a proof of principle than a good preparative method as side reactions frequently intrude. Significantly more work has been carried out on tropinone since these early days, and a more recent synthesis (also containing references to other methods) is shown in Scheme 13.7. 

The last cascade reaction we report here for the synthesis of a quaternary spirocenter employs a platinum catalyst [21 ]. A regio and enantioselective diboration of 1,3-diene 44 could lead to a chiral bis(boryl) intermediates 45 (Scheme 9.12), which could then react in two subsequent asymmetric carbonyl allylations of succinic dialdehyde, leading to the creation of three stereogenic centers in good diastereomeric (9 1) and promising enantiomeric ratios (88 12) 46. 

Apart from Fluorouracil, 4-hydrohybutyraldehyde and succinic dialdehyde are also formed, which are further transformed into y-butyrolactone and4-hydrohybutyric acid [28], Tegafur was shown to be 2-5 times more potent and less toxic than 1 hence lower doses of 3 can be utilized, resulting in decreased neurotoxicity without compromising the antitnmor effects. 

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