1.3-Propanolamine

Alkanolamines with at least one NCH2CHOHCH,i grouping. Important materials include monoisopropanolamine NHX H CHOHCH, b.p. 159 C di-iso-propanolamine NH(CH CHOHCH b.p. 248 C triisopropanolamine NtCH -CHOHCHi). , b.p. 300 C. Manufactured from ammonia and propylene oxide. U ed, is weedkillers, as stabilizers for plastics, in detergents, alkanolaniine soaps for sweetening natural gas and in synthesis. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Chemical Reactivity - Reactivity with Water A slow, non-hazardous reaction occurs, forming propanolamine Reactivity with Common Materials No reactions Stability During Transport The product is stable if it is kept in contact with solid caustic soda (sodium hydroxide) Neutralizing Agents for Acids and Caustics Dilute with water and rinse with vinegar solution Polymerization This material will polymerize explosively when in contact with any acid Inhibitor of Potymerization Solid sodium hydroxide (caustic soda). 

The propanolamine obtained by hydrolysis of ergometrine and ergometrinine is dextrorotatory, but belongs to the I- series and appears to be fully described as Z-(-)-)- 3-aminopropyl alcohol. 

Dihydro-l,3-4H-oxazines (33) can be formed from 0-acyl derivatives of 3-propanolamine even where the formation of smaller rings would also have been possible/ e.g. ... 

A number of other reagents cyclize 3-propanolamines to 5,6-dihydro-1,3-4/f-oxazines, These reagents are acetylenic ethers (which act as... 

N,N -Bis( -chloroethyl)phosphoric acid amide dichloride T riethylamine 1,3-Propanolamine... 

A solution of 75 g (Mo mol) of 1,3-propanolamine and 202 g of triethylamine in 100 cc of absolute dioxane Is added dropwise at 25°C to 30°C while stirring well to a solution of 25.9 g (Vio mol) of N,N-bis-( -chloroethyl)-phosphorlc acid amide dichlorlde in 100 cc of absolute dioxane. After the reaction is complete, the product is separated from the precipitated triethylamine hydrochloride and the filtrate Is concentrated by evaporation In waterjet vacuum at 35°C. The residue Is dissolved in a large amount of ether and mixed to saturation with water. The N,N-bis-( -chloroethyl)-N,0-propylene phosphoric acid diamide crystallizes out of the ethereal solution, after it has stood for some time in a refrigerator, in the form of colorless water-soluble crystals. MP 48 C to 49°C. Yield 65% to 70% of the theoretical. 

Sulphinol sulpholane, water, di-2-propanolamine sulpholane will decompose and give sulfur poisoning... 

The preparation of purine derivatives substituted at the C-2 position via amine displacement of a halogen is known as a difficult reaction step requiring several days of reaction time. However, Al-Obeidi and coworkers have recently prepared 2,6,9-trisubstituted purines on soUd-phase by employing a synthetic route in which the critical step was performed with microwave irradiation (Fig. 37) [62]. PS resin-bound 2-iodosubstituted purine was treated with diethanolamine or propanolamine in NMP with microwave irradiation at 200 °C for 30 min. Trifluoroacetic acid-mediated cleavage resulted in the 2-amino substituted purines in 45-59% yields and 77-89% purities. 

Tang, A.H. Cangelosi, A.A. Code, R.A. and Franklin, S.R. Phencyclidine-like behavioral effects of 2-methyl-3,3-diphenyl-3-propanolamine (2-MDP). Pharmacol Biochem Behav 20 209-213,... 

Condensation of that intermediate with epichlorohydrin in the presence of a catalytic amount of piperidine affords the chlorohydrin 213, admixed with some epoxide. Reaction with tertiary butylamine completes construction of the propanolamine side chain. Displacement of the remaining halogen atom of 214 with morpholine under more strenuous conditions affords timolol (215). ... 

Figure 3. Some /3-blocking agents of the propanolamine series...

Figure 4. Cardiac 0-blocking activity of the aryloxy-propanolamines—modification of the side-chain...

As an example I would like to consider the para-aoylamino "class" of propanolamines as developed from practolol. These have the general formula -... 

A similar enzyme-catalyzed stereoselective synthesis of enantiomers of propanolamines has been recently reported30. Addition of a lipozyme from the fungus Mucor miehei to the epoxide ( )-8 in toluene and then a slightly more than one half molar equivalent of 2-propylamine gave a 29% conversion of ( )-8 to (S)-9 with an ee of 90%. For some benzene ring-substituted epoxides, both the percent conversion of the epoxide and the ee of product are slightly higher30. 

Kaye and Fainstat 1987 Wooten et al. 1983). The risk of cerebral hemorrhage is even greater when combining ephedrine with other catecholamine stimulants such as the over-the-counter stimulant phenyl-propanolamine (StoessI et al. 1985). Pseudoephedrine may be safer than ephedrine in some respects (Porta et al. 1986). In a large sample (n > 100,000) of pseudoephedrine users, there were no reports of cerebrovascular disorders within 15 days after administration. The incidence of myocardial infarction, seizures, and neuropsychiatric disorders were no greater than base rates in the general population. 

Fig. 7. Idealized structure of hyperbranched polyesteramide resin based on HHPA and diiso-propanolamine (molar ratio 7 8, respectively, molecular weight 2016 g/mol)...

GaiUard, P., Carrupt, R A., Testa, B., and Schambel, R (1996) Binding of arylpiper-azines, (aryloxy)propanolamines and tetrahydropyridyl-indoles to the 5-HT1A receptor contribution of the molecular lipophilicity potential to three-dimensional quantitative structure-activity relationship models. J. Med. Chem. 39, 126-134. 

Fig. 15. Hydrolytically stable borate esters of hinder phenols (R = alkyl) and tri-n-propanolamine...

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