摘要:

SECTION C Organic Chemistry Anodic Oxidation. Bart VIII.l Electrolysis of Dimethyl Sodiomalonate in Hexamethyl phosphoric Triamide By R. Brettle" and D. Seddon, Department of Chemistry, The University, Sheffield, S3 7HF Electrolysis of dimethyl sodiomalonate in hexamethylphosphoric triamide gives tetramethyl ethane-1.1.2.2-tetra- carboxylate, tetramethyl propane-1.1.3.3-tetracarboxylate, and hexamethyl propane-I ,1,2,2,3,3- hexacarboxylate. Degradation of the solvent to pentamethyl phosphoric triamide occurs ; mechanisms for the loss of the N-methyl group and for its subsequent incorporation into the second of the above products are discussed. \ WE reported earlier that the electrolysis of diethyl sodiomalonate in NN-dimethylformamide and NN-di- methylacetamide gives as one of the products tetra- ethyl propane-l,l,3,3-tetracarboxylate (I ; R = Et) con- taining a one-carbon fragment which we suggested was derived from one of the N-methyl groups of the solvent.Since this electrochemical demethylation parallels the biological oxidative demethylation of N-methyl sub- stituted carboxylic amides? recent reports that hexa- methylphosphoric triamide, a well known electrochemical solvent: undergoes biological demethylation prompted us to see if we could obtain evidence for the electro- chemical N-demethylation of this phosphoric amide. We report now on the electrolysis of dimethyl sodio- malonate in this solvent. Tetramethyl ethane-l,1 ,2,2-tetracarboxylate (11) tetramethyl propane-1,1,3,3-tetracarboxylate (I ; R = Me), and hexamethyl propane-l,l,2,2,3,3-hexacarb- oxyIate (111) could each be isoIated from the electrolysis products by a combination of fractional crystallisation and t.1.c.The structure of (111), which (RO,C),CHCH,*CH (C0,R) , (MeO,C),CH*CH(CO,Me) , (Me02C)2CHC(C0,Me)2*CH(C02Me)2 (1) (11) (111) was not fully characterised in the earlier stu+es,2 was confirmed by the microanalytical data, a molecular ion m/e 392 in the mass spectrum, and the n.m.r. spectrum which showed just two singlet absorptions, due to the ester methyl groups (z 6.19) and the hydrogen atoms at C-1 and C-3 (z 5.72), with integrated areas in the ratio 9 : 1. Analysis by g.1.c. of the water-soluble material showed the presence of hexamethylphosphoric triamide and also pent amethylphosphoric triamide (IV) (identi- fied by its retention time and by its i.r.spectrum). SOG. (C), 1969, 2499. 1 Part VII, T. D. Binns, R. Brettle, and G. B. Cox, J . Chem. a R. Brettle and J. G. Parkin, J . Chem. SOC. (C), 1967, 1352. a R. E. McMahon. T. Pharm. Sci.. 1966. 55. 457. The formation of (11) and (111) in this electrolysis is unexceptional and was expected on the basis of work in other solvents.2 The formation of both tetramethyl propane-lJl,3,3-tetracarboxylate (I; R = Me) and pentamethylphosphoric triamide (IV) strongly suggests that the ' extra methylene group in (I; R = Me) originates as one of the N-methyl-groups in the solvent. A mechanism analogous to the one suggested earlier to account for the formation of (I; R = Et) during the electrolysis of diethyl sodiomalonate in NN-dimethyi- acetamide, which requires the presence of a trace of water, could be operative here (Scheme: pathway a).Alternatively (Scheme : pathway b) the intermediates (V) and (VI) in such a pathway might combine with the anion from dimethyl malonate, or the related radical formed from it by electrochemical oxidation, to give the the intermediate (VII) , fragmentation of which would give pentamethylphosphoric triamide (initially as its anion) and dimethyl methylenemalonate, the precursor of (I ; R = Me) ; N-(2,2-diethoxycarbonylethyl)phthal- imide undergoes a similar fragmentation.6 * A. R. Jones and J. S. Bertram, Experimentia, 1968, 24, 326; A. R. Jones and H. Jackson, Biochem. Pharmacol., 1968, 17, 2247. ti H. Normant, Angew. Chem. Internat. Edn., 1967, 6, 1046; Bull.SOC. chim. Fyance, 1968. 791. . " ~ - - . 6 H. Bohme and L. Hafner, Chem. Ber., 1966, 287.1154 J. Chem. SOC. (C), 1970 Our results show that the analogy between electro- chemical and biological oxidative N-demethylation in carboxylic amides can be extended to a phosphoric arnide. EXPERIMENTAL Chloroform was evaporated on a Buchi Rotavapor R evaporator. Details of the electrolysis cell have been given previo~sly.~ For other general directions see earlier Parts of this series. Electrolysis of Dimethyl Sodiomalonate ifi Hexamethyl- phosphoric Triamide.-Dimethyl malonate (66.0 g., 0.5 mole) was added dropwise to a stirred suspension of sodium hydride (12.0 g., 0.5 mole) in anhydrous hexamethylphos- phoric triamide (200 ml.) until reaction was complete; the solution was then electrolysed using a platinum anode and a mercury cathode at 40".The initial current of 2 A at 100 v fell to 0.5 A after 16 hr. Tetramethyl ethane-1,1,2,2-tetra- carboxylate (g.l.c., mixed m.p.a determination) (1-31 g . ) de- posited during the electrolysis was filtered off. Unchanged dimethyl malonate and hexamethylphosphoric triamide were distilled from the filtrate a t 60-120°/15 mm. The residue, after 4 days, deposited more tetramethyl ethane- 1,1,2,2-tetracarboxylate (0.56 g . ) . Further material (3.13 g . ) , deposited during the next 14 days, on recrystallisation from benzene afforded hexamethyl +ropane-l,1,2,2,3,3-kexa- carboxylate (1.72 g.), m.p. 136-137: (Found: C, 46.2; H, 4.9. C,,H,,O,, requires C, 45.9; H, 5.1%). The residue was diluted with water and extracted with chloroform; the aqueous layer was examined separately (see below).The chloroform extracts were dried and the chloroform evap- orated, leaving a viscous oil which partly solidified after 2 days. Analytical g.1.c. on this solid (3.26 g.) (F and M 720; 2 column, 10% silicone-rubber, 210") showed that it was mainly tetramethyl ethane-1, 1,2,2-tetracarboxylate (RT 1.5 min.) and hexamethyl propane-l,1,2,2,3,3-hexacarb- oxylate (R, 8.6 min.). The remaining material was taken up in chloroform washed with water (3 x ) and the solution dried ; the washings were combined with the aqueous layer from the initial extraction. Evaporation of the chloroform gave a solid (12.14 g.). Preparative t.1.c. on a part of this material (1.52 g.) gave tetramethyl propane-l,l, 3,3-tetra- carboxylate (0.66 g.), m.p. 42-46" (from methanol), mixed m.p.a 43-46", T 6.24 (12H, s, Me) 6.47 (2H, t, J 7.5 c./sec., CH) and 7.54 (2H, t, J 7.5 c./sec., CH,). Continuous extraction of the combined aqueous layers, with chloroform gave an oil (11-6 g.) which was shown by g.1.c. (as above, 150') to contain only hexamethylphosphoric triamide (RT 2.9 min.) and pentamethylphosphoric triamide (RT 4.0 min.), which had an i.r. spectrum identical with that of an authentic sample. We thank Dr. A. R. Jones for a sample of pentamethyl- phosphoric triamide and the S.R.C. for a training award (to D. S.). [9/1960 Received, November 14th, 19691 Nguyen Dinh-Nguyen, Acta Chem. Scand., 1958, 585; R. Brettle, N. Polgar, and W. Smith, J . Chern. Soc., 1960, 2802; T. D. Binns and R. Brettle, J . Chem. SOC. ( C ) , 1966, 336.

ISSN:0022-4952    

DOI:10.1039/J39700001153

出版商:RSC    

年代:1970

数据来源: RSC