Dihydro-2-methoxy-4-methyl-2H-pyran

This procedure is a modification 2 of the method of Altschul3 for preparing tert-butyl esters. Di-ferf-butyl malonate has been prepared by the reaction of malonyl chloride with tert-butyl alcohol in the presence of a tertiary amine.4 

1 Department of Chemistry, University of Wisconsin, Madison, Wisconsin. 

4-DIHYDRO-2-METHOXY-4-METHYL-2H-PYRAN (2H-Pyran, 3,4-dihydro-2-methoxy-4-methyl-) 

Submitted by Raymond I. Longley, Jr., William S. Emerson, and Albert J. Blardinelli.1 Checked by T. L. Cairns and T. E. Young. 

In a high-pressure autoclave, arranged for agitation by shaking or rocking, are placed 286 g. (336 ml., 4.08 moles) of croton-aldehyde, 294 g. (5.06 moles) of methyl vinyl ether, and 1.1 g. of hydroquinone (Notes 1 and 2). The autoclave is heated to 200° (Note 3) and held there for 12 hours. The autoclave is cooled and vented, and the black product is distilled through a 1 by 60 cm. helix-packed column. The yield of 3,4-dihydro-2-methoxy- 

---

Dihydro-2-methoxy-4-methyl-2H-pyran has been prepared only by the addition of methyl vinyl ether to crotonaldehyde.2-4... 

In a 2-1. three-necked flask equipped with a stirrer and thermometer are placed 336 g. (2.62 moles) of 3,4-dihydro-2-methoxy-4-methyl-2H-pyran,2 630 ml. of water, and 24 ml. of concentrated hydrochloric acid (sp. gr. 1.19). The mixture is stirred for 2 hours, during which the temperature may reach 50° but should not be permitted to rise higher. Solid sodium bicarbonate is then added until the solution is neutral to pH indicator paper Note 1). The entire reaction mixture weighing about 1 kg. together with 39 g. of Raney nickel is introduced into a 3-1. 

The submitters report that /3-methylglutaraldehyde may be isolated at this point from an analogous hydrolysis. The hydrolysis is carried out with 196 g. of 3,4-dihydro-2-methoxy-4-methyl-2H-pyran in 650 ml. of water and 15 ml. of concentrated hydrochloric acid for 3 hours. After neutralization with sodium bicarbonate, the solution is saturated with sodium chloride and extracted continuously with ether for 20 hours. The ether is removed by distillation, and the product is dried thoroughly by azeotropic distillation using a benzene-hexane mixture. Distillation affords /3-methylglutaraldehyde, b.p. 85-86°/15 mm., 1.4307-1.4351. Yields up to 90% have been secured. The aldehyde polymerizes on standing but is stable as a 50% solution in water or ether. The monomer may be recovered by careful destructive distillation of the polymer. 

Dihydro-2-methoxy-4-methyl-2H-PYRAN, 34, 29, 71 3, 4-Dihydro-2 (1 H) -naphth alenonf., 32, 97, 99... 

Hydrolysis, of 2-chloro-l,l,2-trifluoro-ethyl ethyl ether, 34, 49 of a,o -dicyano-/3-ethyl-3-methyl-glutarimide, 36, 29 of 3,4-dihydro-2-methoxy-4-methyl-2H-pyran, 34, 71 of dihydropyran, 30, 48 of ethyl 3-benzyl-2-cyano-3-methyl-pentanoate, 36, 8... 

H- Pyran, rrans-2-methoxy-4-methyl-3,4-dihydro-conformation, 3, 630 2H-Pyran, 4-methyl-5,6-dihydro-photolysis, 3, 719 2H-Pyran, 6-methyl-3,4-dihydro- C NMR, 3, 586... 

The steric effects involved in the cis-hydroxylation of 5,6-dihydro-2H-pyrans substituted at positions 6 and/or 2 with aqueous potassium permanganate were studied by Mochalin and co-workers. It was found that the reaction course is dependent on the steric hindrance exerted by the bulky substituent at C-2 both OH groups enter preferentially trans with respect to that substituent. In consequence, products of (x-lyxo or -erythro configuration are obtained in the case of di- or mono-substituted substrates. However, in the case of 5,6-dihydro-2-methoxy-2H-pyran, both possible stereoisomeric products, methyl 4-deoxy-a-and p-DL-eo t o-pentopyranosides, were formed in approximately equal amounts. 

Cjs-hydroxylation of 3,6-dihydro-2-methoxy-2H-pyran (341) afforded " a mixture of methyl 2-deoxy-a- and (3-DL-etyfAro-pentopyranosides (342). Hydrolysis of this mixture gave free 2-deoxy-DL-eo op ntos (2-deoxyribose). Compound 341 was obtained by the reductive removal of the p-toluenesul-fonyloxy group in methyl 3,4-dideoxy-2-0-p-toluenesulfonyl-a,p-DL-pent-3-eno-pyranoside (345). Mochalin °° obtained 341 in three steps starting from the Diels-Adler adduct 343 via the amide 344 and its Hoffman degradation in methanol solution. 

Sharpless oxyamination reagent, composed of chloramine-T and a catalytic quantity of osmium tetraoxide, was reacted with a series of 6-substituted 5,6-dihydro-2-methoxy-2H-pyrans. Both regioisomeric methyl 2,4-dideoxy-2-p-to-luenesulfonylamido- and 3,4-dideoxy-3-p-toluenesulfonylamido DL-/yjro-hexo-pyranosides (346 and 347) were obtained in yields of 40-60%, with the latter distinctly prevailing in mixtures. 

Myrtucommulone B. 4,9-Dihydro-8-hydroxy-6-methoxy-2,2,4,4-tetramethyl-5-(2-methyl-l-oxopropyl)-9-(2-methylethyl)-lH-xanthene-l,3(2H)-dione, 2161 Nor-auricepyrone. 3-[[2,4-Dihydroxy-6-methoxy-3-(2-methyl-l-oxopropyl) phenyl]methyl]-6-ethyl-4-hydwxy-5-methyl-2H-pyran-2-one, 2055 ONO-3144. l-[3-(Aminomethyl)-5-(l,l-dimethylethyl)-2-hydroxyphenyl]-l-propanone (Hydrochloride), 1917... 

---