Some Derivatives of Tetrahydropyran as Potential Pharmacodynamic Agents. II¹

Mobility of anions within anion-neutral complexes. Cross ring hydride ion migration upon collisional activation of thepara-formylbenzyloxy anion

“…This was prepared by heating a mixture of para-carboxybenzaldehyde, trimethyl orthoformate and methanol under reflux, which yielded para carbomethoxybenzaldehyde dimethyl acetal (in quantitative yield), 10 which was reduced 11 with lithium aluminium hydride in anhydrous diethyl ether to yield para-dimethoxymethylbenzyl alcohol. Reaction 12 between para-dimethoxymethylbenzyl alcohol and methanol/H 2 18 O gave para-(formyl-18 O)benzyl alcohol (overall yield 28%, 18 O = 96%).…”

Synthesis of novel 3-heterospiro[5.5]undecanes

“…5 4-Formyl-1-piperidinecarboxylic acid-1,1-dimethylethyl ester (8) was prepared in a similar way according to the patent literature, 6 i.e., starting from 4-oxo-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (6) 7 via the enol ether intermediate which was accessible by a Wittig reaction (Table 1, X = N-COO-t-Bu). 2H-Tetrahydrothiopyran-4-carboxaldehyde (14) proved to be difficult to synthesize. In our first attempts the aldehyde was prepared in analogy to the piperidines by the Wittig reaction route (Table 1, X = S).…”

“…After detailed experimental studies appropriate reaction conditions could be developed: lithium iodide (highly concentrated, and used in a large excess, in dry THF) was found to be the only Lewis-type acid for promoting the rearrangement of 1-oxa-6-thiaspiro[2.5]octane (13) to 2H-tetrahydrothiopyran-4-carboxaldehyde (14) in a reasonable yield. Additionally, the yield could be improved remarkably by use of a Soxhlet apparatus, from which lithium iodide was gradually washed into the reaction vessel.…”

“…The reduction of 2H-tetrahydropyran-4-carboxylic acid (18) by lithium aluminum hydride according to a known method 14 gave 2H-tetrahydropyran-4-methanol (19). Subsequent Swern oxidation 15 using a procedure with modified stoichiometry yielded the desired 2H-tetrahydropyran-4-carboxaldehyde (20).…”

Competitive charge-remote and anion-induced fragmentations of the non-8-enoate anion. A charge-remote reaction which co-occurs with hydrogen scrambling

“…The reaction 41 between allyl bromide (1.2 g) and Cu 13 CN (1.1 g, 13 C = 99%) 42 gave allyl ( 13 C cyanide) in 70% yield. The allyl ( 13 C cyanide) was hydrolysed 43 to the labelled vinyl acetic acid (65% yield), which was reduced 34 with lithium aluminium hydride in refluxing tetrahydrofuran to form 1-13 C-but-3-en-1-ol in 78% yield. The alcohol was tosylated 44 with tosyl chloride.…”