2- Hydroxyethylamine, reaction with

Suzuki-Miyaura reactions with aryl bromides and triflates have been reported in the synthesis of plasmepsin I and II inhibitors using a hydroxyethylamine transition-state-mimicking scaffold [73], Four libraries of similar compounds were prepared where the Suzuki-Miyaura reaction was used for direct derivatization of the PI -position without protection of the hydroxyethylamine center. It was noted in this context that no epimerization occurred during the reaction and that exchange of cesium carbonate for sodium carbonate resulted in better yields (Scheme 15.33) [74]. 

By the same token, reaction with participation by one water molecule will be relatively slow when both reactive sites are firmly hydrated. In that case, we may observe fast reaction with participation of two water molecules. However, in no case is reaction with solvent participation expected to be fast unless the conformation of the firmly bound solvent molecule is favourable for proton transfer. Thus, the relatively small values of the rate constants for reaction of tris- -hydroxyethylamine compared to triethylamine in water (Table 1) and of N,N-diethyl-w-toluidine compared to p-toluidine in methanol (Table 2) suggest that polar substituents or centres of van der Waals attraction can modify the hydrogen-bonded structure in the solvation shell. 

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

Deacetylvinblastine acylazide (62) was later shown to be an exceptionally versatile intermediate for the preparation of C-3 amides. Since nucleophilic displacement of azide occurs at relatively low temperatures under mild conditions, a wide variety of C-3 derivatives have been prepared (Scheme 1, Table III). This observation is in contrast to the direct amino-lysis of vinblastine which usually fails when the amine employed is substituted (e.g., p-hydroxyethylamine) or secondary (dimethylamine). The reactions can be conveniently followed by the disappearance of the CO—N, infrared band at 2135 cm" with the concomitant appearance of the CO—NHj band in the region 1665-1675 cm". Acetylation of the... 

Sharpless and co-workers first reported the aminohydroxyIation of alkenes in 1975 and have subsequently extended the reaction into an efficient one-step catalytic asymmetric aminohydroxylation. This reaction uses an osmium catalyst [K20s02(OH)4], chloramine salt (such as chloramine T see Chapter 7, section 7.6) as the oxidant and cinchona alkaloid 1.71 or 1.72 as the chiral ligand. For example, asymmetric aminohydroxylation of styrene (1.73) could produce two regioisomeric amino alcohols 1.74 and 1.75. Using Sharpless asymmetric aminohydroxylation, (IR)-N-ethoxycarbonyl-l-phenyl-2-hydroxyethylamine (1.74) was obtained by O Brien et al as the major product and with high enantiomeric excess than its regioisomeric counterpart (R)-N-ethoxycarbonyl-2-phenyl-2-hydroxyethylamine (1.75). The corresponding free amino alcohols were obtained by deprotection of ethyl carbamate (urethane) derivatives. 

Normal nucleophilic substitution reactions of alkyl and aryl chloropyrazines have been examined as follows 2-chloro-3-methyl- and 3-chloro-2,5-dimethyl(and diethyl)pyrazine with ammonia and various amines (535, 679, 680) 2-chloro-3(and 6)-methylpyrazine with methylamine and dimethylamine (681, 844), piperidine and other amines (681, 921) 2-chloro-5(and 6)-methylpyrazine with aqueous ammonia (362) alkyl (and phenyl) chloropyrazines with ammonium hydroxide at 200° (887) 2-chloro-3-methylpyrazine with aniline and substituted anilines (929), and piperazine at 140° (759) 2-chloro-3-methyl(and ethyl)pyrazine with piperidine (aqueous potassium hydroxide at reflux) (930,931) [cf. the formation of the 2,6-isomer( ) (932)] 2-chloro-3,6-dimethylpyrazine with benzylamine at 184-250° (benzaldehyde and 2-amino-3,6-dimethylpyrazine were also produced) (921) 2-chloro-3,5,6-trimethylpyrazine with aqueous ammonia and copper powder at 140-150° (933) and with dimethylamine at 180° for 3 days (934,935) 2-chloro-6-trifluoromethylpyrazine with piperazine in acetonitrile at reflux (759) 2-chloro-3-phenylpyrazine with aqueous ammonia at 200° (535) 2-chloro-5-phenylpyrazine with liquid ammonia in an autoclave at 170° (377) 2-chloro-5-phenylpyrazine with piperazine in refluxing butanol (759) but the 6-isomer in acetonitrile (759) 5-chloro-2,3-diphenylpyrazine and piperidine at reflux (741) and 5-chloro-23-diphenylpyrazine with 2-hydroxyethylamine in a sealed tube at 125° for 40 hours (834). 

Sommer et al. published the synthesis of the polycyclic 1,3,2-oxazarsinanes (263) and (264) by the reaction of 3-hydroxypropyl-2-hydroxyethylamine and bis(3-hydroxypropyl)amine with As(NMe2)3. With bis(3-aminopropyl)amine a more complex product (265) was formed, with five arsenic atoms to three of the triamine <70ZAAC(379)48>. 

The discovery of peptide-based substrate-mimicking HIVPI was directed towards the synthesis of substrate analogs in which the scissile bond was replaced by a non-cleavable isostere with tetrahedral geometry that could mimic the tetrahedral transition-state of the proteolytic reaction. Thus, several inhibitors with hydroxyethylene or hydroxyethylamine isostere replacement were prepared to bind with the enzyme as shown in Fig. 3a [31]. However, the clinical development of peptide-derived compounds was hindered by their poor pharmacokinetics, including low oral bioavailability, rapid excretion and complex (expensive) synthesis [44,45]. Therefore, recently more... 

Different kinetic behavior was observed when secondary hydroxy-alkylic amines, methyl-2-hydroxyethylamine and butyl-2-hydroxy-ethylamine, were employed as nucleophiles. Autoacceleration appeared in dioxane for both secondary amines however, normal second order kinetics were followed in DMF when the nucleophile is methyl-2-hydroxyethylamine which has less bulky substituents. In the reaction of butyl-2-hydroxyethylamine with CMPS in DMF, rate retardation began when the conversion reached about 75% owing to the steric hindance of the bulky butyl groupThus the sensitivity of the rate profiles to reaction media and nucleophile structure complicates assessment of "polymeric effects". 

Stabilizers UVA 2-hydroxy-4-methoxybenzophenone 2,4-dihydroxy-benzophenone 2-benzotriazol-2-yl-4,6-di-tert-butylphenol 2-(2H-benzotriazole-2-yl)-4,6-di-tert-pentylphenol N-(2-ethoxyphenyl)-N -(4-isododecylphenyl)oxamide HAS decane-dioic acid, bis(2,2,6,6-tetramethyl-1-(octyloxy)-4-piperidinyl) ester, reaction products with 1,1-dimethylethylhydroperoxide and octane 2,4-bis[N-butyl-N-(1-cyclohexyloxy-2,2,6,6-tetra-methylpiperidin-4-yl)amino]-6-(2-hydroxyethylamine)-1,3,5-trlazlne bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate 2-dodecyl-N-(2,2,6,6-tetramethyl-4-piperidinyl)succinimide polymer of 2,2,4,4-tetramethyl-7-oxa-3,20-diaza-dispiro [5.1.11,2]-hene-lcosan-21-on and epichlorohydrin Screener Ti02 Phosphite phosphoric acid, (2,4-di-butyl-6-methylphenyl)ethylester ... 

The observed kinetic data summarized in Table 7.1 and Table 7.2 follow the simple first-order rate law for less than nine half-lives of the reactions. However, the observed kinetic data for the reaction of methylamine with phthalimide at 0.08-M CH3NH2 buffer of pH 10.93 do not follow strictly a first-order rate law if the data analysis includes all the observed data points within observed t range 20 to 2220 sec, as is evident from the A,.a. <, values in Table 7.3. But, the rate of methylaminolysis of phthalimide follows the first-order rate law for the reaction period of < 10 half-lives, as is evident from the data analysis shown in Table 7.3. Similarly, the rate of 2-hydroxyethylaminolysis of phthalimide at 0.20-M2-hydroxyethylamine buffer of pH 9.84 follows the first-order rate law for the reaction period of < 3.5 half-lives. The chemical reasons for the deviation of observed data points from the first-order rate law in these reactions are described in detail elsewhere."... 

Kinetic studies on nucleophilic cleavage of phthalimide (SH) in the buffers of RNHj (= 2-hydroxyethylamine and 2-methoxyethylamine) reveal nonlinear plots of k bs vs. [BuHt (tohil buffer concentration) at constant pH, which fit to Equation 7.51 with replacement of [PipJr by [Buf]x. These observations have been explained in terms of a brief reaction mechanism as shown in Scheme 7.7 in... 

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