L-Phenoxy-2-propanol

The unsaturated compound first formed from the o-alkylphenol then undergoes ring closure. Some phenoxylated alcohols, looked upon as forerunners of compounds (104), such as l-phenoxy-2-propanol, also undergo ring closure with dehydrogenation (400°, A1203) to benzofuran derivatives, viz., to 2-methylbenzofuran (mixed with the 2,3-dihydro derivative).290... 

Epoxides are sensitive to nucleophilic ring-opening reactions. Phenoxide ion attacks the less hindered carbon to yield l-phenoxy-2-propanol. 

Therapeutic Function Choleretic Chemical Name 3-n-Butoxy-l-phenoxy-2-propanol Common Name -Structural Formula ... 

Example 1. Enantiomeric Separation of l-Phenoxy-2-Propanol. The following example, the enantiomeric separation of l-phenoxy-2-propanol, roughly illustrates the individual steps for the design of a suitable SMB process. Details, especially for the determination of the adsorption isotherms and the description of the SMB system, can be taken from the literature [124]. 

The tracer pulse method was also used by Bliimel et al. [112] to determine the binary isotherms of the enantiomers of l-phenoxy-2-propanol on Chiralcel OD, by Lindholm et al. [113] to determine the binary isotherms of methyl-mandelate on Chiral AGP, and by Mihlbachler et al. [1] to determine those of the enantiomers of Troger s base on Chiralpak AD. In this last case, an imusual isotherm was obtained, illustrated in Figure 4.28. The adsorption of the more retained (+) enantiomer is not competitive the amoimt adsorbed by the chiral stationary phase at equilibrium with a constant concentration of the (+) enantiomer is independent of the concentration of the (-) enantiomer. On the other hand, the adsorption of the less retained enantiomer is cooperative the amoimt of this (-) enantiomer adsorbed by the CSP at equilibrium with a constant concentration of this enantiomer increases with increasing concentration of the (+) enantiomer. The isotherm data are best accounted for by an isotherm model derived assuming multilayer adsorption. 

Furukawa et al. explored the use of methanol and ethanol as additives for diethylzinc-based epoxide polymerization systems, and found that both the yield and crystallinity of the resulting polymers were inferior to those for polymers synthesized with the ZnEt2/H20 system. The use of achiral alcohols as cocatalysts was revisited in 1994 when Kuran and Listos reported the polymerization of propylene oxide and cyclohexene oxide (a meso molecule) with ZnEt2/polyhydric phenol (such as 4-tert-butyl-catechol), phenol, or l-phenoxy-2-propanol. The poly(propylene oxide) formed from these systems contained mostly isotactic dyads (72% m), whereas the poly(cyclohexene oxide) contained mostly syndiotactic dyads (80% r) (Scheme 24.8). 

SCHEME 24.8 Polymerization of epoxides with ZnEt2/l-phenoxy-2-propanol/4-ferf-butylcatechol. 

Kuran, W. Listos, T. Polymerization of 1,2-epoxypropane and 1,2-epoxycyclohexane by diethylzinc-polyhydric phenol and/or phenol or l-phenoxy-2-propanol as catalysts. Macromol. Chem. Phys. 1994, 795,401 11. 

CN 1 - [(1,1 -dimethy lethy l)amino]-3- [2- [(tetrahydro-2-furanyl)methoxy ]phenoxy ]-2-propanol... 

CN l-[(l-methylethyl)amino]-3-[2-(2-propenyloxy)phenoxy]-2-propanol hydrochloride... 

Metoprolol Metoprolol, l-(wo-propylamino)-3-[4 (2-methoxyethyl)phenoxy]-2-propanol (12.1.5), is synthesized by reacting 4-(2-methoxyethyl)phenol with epichlorhy-dride in the presence of a base, isolating l,2-epoxy-3-[4 (2-methoxyethyl)phenoxy] propane (12.1.4), the subsequent reaction of which, analogous to that described before, with jio-propylamine, gives an opening of the epoxide ring and leads to the formation of metoprolol (12.1.5) [7,8]. 

Metroprolol Metroprolol is l-(/xo-propylamino)-3-[4 (2-methoxyethyl)phenoxy]-2-propanol (12.1.5). The synthesis of this drug is described in Chapter 12. 

Another alternate pathway for the synthesis of racemate product (6) is shown in Scheme 2 [6]. l-phenoxy-2-bromopropane (8) was obtained in 38% yield by the bromination of 1-phenoxy-2-propanol (7) with PBr3. Compound (8) was refluxed in butanol with l-(4-hydroxyphenyl)-2-amino-1-propanol (9) to yield racemate product (6). 

It was prepd by heating l,3-bis-(2,4-dinitro-phenoxy)-2 propanol with aq nitric acid coned sulfuric acid (Refs 3 6)... 

More recently Bradley and co-workers288 demonstrated a fourth significant product in this reaction to be l,3-dichloro-2-propanol. formed by addition of hydrochloric acid to epiehlorohydrin. These authors then showed that under suitable conditions phenyl glycidyl ether can be mode to react wjth a chlorohydrin. There are formed in this manner a new epoxide and l-chloro-D-phenoxy-2-propanol, ah... 

To a solution of 1 gramm equivalent (g-eq.) of l-bromo-3-[2-(tetrahydrofuran-2-yloxy)phenoxy]propan-2-ol in 30 ml of ethanol is added 1 g-eq. of t-butylamine, the mixture is refluxed for 6 hours, and then the ethanol is distilled off. The residue is dissolved in benzene and the solution is extracted twice with 5% oxalic acid. The aqueous extract is made alkaline with potassium hydroxide and the isolated oil is extracted with benzene. The benzene extract is dried over potassium carbonate and the benzene is distilled off to give of oily l-(t-butylamino)-3-(o-((tetrahydrofurfuryl)oxy)phenoxy)-2-propanol. The corresponding acid fumarate melts at 128°-132°C. 

Step 1 In a 500 ml flask equipped with gas inlet tube, dropping funnel and reflux condenser is placed 139 grams of 1-phenoxy-2-propanol. A stream of dry air is bubbled through the alcohol while 55 grams of thionyl chloride is added dropwise with external cooling. The stream of dry air is continued for about six hours or until most of the hydrogen chloride has been expelled and then another 55 grams of thionyl chloride is added. The reaction mixture is allowed to stand twenty-four hours, a few drops of pyridine are added and the mixture heated 4 hours on the steam bath. The cooled reaction mixture is poured into water, the crude product is washed with dilute sodium bicarbonate solution and finally taken up in benzene. The benzene is distilled at ordinary pressure and the residue distilled in vacuo to yield 60-70% of l-phenoxy-2-chloropropane, BP 93°-94°C/5 mm. 

Figure 9. Acetophenone-mediated electroenzymatic reduction of l-phenoxy-2-propanone to (5 )-1 -phenoxy-2-propanol using lipoamide dehydrogenase (LiDH) or ferredoxin-NADP reductase (FNR) and an alcohol dehydrogenase [46].

Elsinga, P.H., Van Waarde, A., Visser, G.M., Vaalburg, W., 1994. Synthesis and preliminary evaluation of (R,5)-l-[2-((carbamoyl-4-hy-droxy)phenoxy)ethylamino]-3-[4-( I -[" C]-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol (["C]CGP 20712A) as a selective beta-1-adrenoceptor ligand for PET. Nucl. Med. Biol. 21, 21-217. 

Table 10-6 represents a summary of empirically arrived at structure-activity relationships, The exception of para-aryl substitutions for cardioselective P-blockers (IIB 1 and 4) should be noted but cannot be satisfactorily explained. In fact, not all the para substituents are as lipophilic as the amide ones in practolol, acebutolol (No. 11), atenolol (No. 12), or the ester group in esmolol (No. 14). The methoxyethyl group of metoprolol (No. 15) and the large hydrocarbon nature of the cyclopropylmethoxyethyl function of betaxolol (No. 13) would hardly be expected to increase aqueous solubility of these compounds (see Table 10-4). Still, all the -selective compounds are much less lipophilic than propranolol. Such apparent data correlations may have contributed to a belief that a cardioselectivity-hydrophilicity relationship exists due to some putative hydrophilic site on the Pj receptor. This notion, however, was dispelled by a study comparing hydrophilicity, substituent positions, and cardioselectivity in three sets of l-(2-propylamino)-3-phenoxy-2-propanols. The data clearly show that for each set of compounds even with identical lipophilicities (log P) the Pi-activity resided primarily in the para isomer.

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