Methyl-1,5-pentanediol

Submitted by Raymond I. Longley, Jr., and William S. Emerson.1 Checked by T. L. Cairns and John F. Harris, Jr. 

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. 85-86715 mm., d 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. 

The initial hydrogen pressure should be high enough so that it does not fall below 1000 p.s.i. during the shaking period. 

---

Write equations showing how 3 methyl 1 5 pentanediol could be prepared from a dicarboxylic acid or a diester I... 

Write equations showing how 3-methyl-1,5-pentanediol could... 

FIGURE 18 In vivo cumulative weight loss (o) and cumulative release of levonorgestrel (o) from a crossUnked polymer prepared from a 3,9-bis(ethylidene-2,4,8,10-tetraoxaspiro[5,5]undecane)/3-methyl-1,5-pentanediol prepolymer crossUnked with 1,2,6-hexane triol. Polymer rods, 2.4 X 20 mm, containing 30 wt% levonorgestrel and 7.1 mol% Mg(OH)2. Devices implanted subcutaneously in rabbits. (From Ref. 15.)... 

Oxidation of Prochiral Diol. The oxidation of prochiral diol 3-methyl-1,5-pentanediol did not give the corresponding -hydroxy aldehyde but gave the corresponding lactol at 22% yield. To determine stereochemistry of the lactol, this was chemically oxidized by Ag20 and afforded 3-(R)-methyl-pentan-l,5-olide at 38% optical purity. (Figure 9). This was determined by comparison of optical rotation with a reference (70). 

Figure , (a) Daily release of nafarelin from a cross-linked poly(ortho ester) (POE). Crossbar denotes minimum daily requirement of 0.4 //g/day for estms suppression. Conditions 7.4mm x 20 mm rods prepared from a 3-methyl-l,5-pentanediol prepolymer cross-linked with 1,2,6-hexanetriol and placed into pH 7.4 buffer at 37°C. (b) Percent of female rats showing estms suppression as a function of treatment time with nafarelin-containing POE rods. Devices were prepared from a 3-methyl-1,5-pentanediol prepolymer cross-linked with 1,2,6-hexanetriol and contained 3 wt.% LHRH analog. (After Heller et al, 1987.)... 

Hexanedioic acid, polymer with 3-methyl- 1,5-pentanediol... 

---