Amino alcohols, reaction with

Phthalimidoglutaric acid (18), readily prepared from glutamic acid and phthalic anhydride, has served as a precursor for the preparation of several interesting condensation polymers (76MI1110l). For example, it is readily transformed (Scheme 7) into diisocyanate (19), which was utilized for the preparation of a number of optically active polyureas (by reaction with diamines), polyurethanes (by reaction with diols) and polyurea-urethanes (by reaction with amino alcohols). 

Syntheses of quaternary l-alkyl-3-perfluoroalkyl-4,5-dimethyl-l,2,4-triazolium iodides have led to the disclosure of a variety of new quaternary salts <04JOC1397>. Arylation of 3-alkylthio-5-aryl-l,2,4-triazoles under basic conditions gave 5-alkylthio-l,3-diaryl-l,2,4-triazoles in moderate yields <04JHC201>. Acyl hydrazides 155 reacted with imidates 156 to yield 1,2,4-triazoles 157 followed by Mitsunobu reactions with amino alcohols 158 to give regioisomeric... 

It is worth noting that the reaction of metals with functional alcohols forming stable complexes with metal cations is most often much more facile than with the aliphatic ones. Both alkaline earth (Mg, Ca, Sr) and rare earth elements do react with alkoxy alcohols such as 2-methoxy-ethanol (now prohibited from use in European Union because of its toxicity) on reflux without the need of addition of a catalyst. Even tin can be converted into Sn(II) alkoxides by a catalyst-free reaction with amino alcohols under high temperatures and pressures [112]. 

Several p-block compounds have been employed in this acid-amine coupling reaction these include bismuth, indium and antimony. Indium metal has been found useful for the N-formylation of amines. This reaction requires only 10 mol% indium catalyst and can be used for formic acid reactions with amino alcohols resulting in no side reaction on the alcohol terminus. Electron-rich triarylbismuthanes have been reported to couple carbo>ylic acids to amines within reaction times of 12 hours. In numerous cases, high yields were obtained although little amine scope is explored and in some cases where hindered carbojq lic acids were used, only starting materials were recovered. ... 

Reaction with Amino Alcohols and Related Compounds. Both secondary and tertiary carbamates bearing a vicinal hydroxyl group react with carboxylic acids in the presence of DEAD and TPP to afford the corresponding esters with inversion of configuration (eq 34). Reaction of N-t-butoxycarbonylserine with methanol, DEAD, and TPP gives the corresponding methyl ester in >98% yield (eq 35). Without methanol, TV-benzyloxycarbonyl- or A-f-butoxycarbonylserine reacts with the preformed adduct of DEAD and TPP to afford the P-lactone (eq 35). The W-protected serine methyl ester (37a) and threonine methyl ester (37b) react with DEAD and TPP to give the dehydrated products (38a) and (38b) (eq 36). ... 

With active methylene compounds, the carbanion substitutes for the hydroxyl group of aHyl alcohol (17,20). Reaction of aHyl alcohol with acetylacetone at 85°C for 3 h yields 70% monoaHyl compound and 26% diaHyl compound. Malonic acid ester in which the hydrogen atom of its active methylene is substituted by A/-acetyl, undergoes the same substitution reaction with aHyl alcohol and subsequendy yields a-amino acid by decarboxylation (21). 

Acrylic Esters. A procedure has been described for preparation of higher esters from methyl acrylate that illustrates the use of an acid catalyst together with the removal of one of the products by azeotropic distillation (112). Another procedure for the preparation of butyl acrylate, secondary alkyl acrylates, and hydroxyalkyl acrylates using -toluenesulfonic acid as a catalyst has been described (113). Alurninumisopropoxide catalyzes the reaction of amino alcohols with methyl acrylate and methyl methacrylate. A review of the synthesis of acryhc esters by transesterification is given in Reference 114 (see... 

In a related reaction the amino alcohol (413) was cyclized with HBr to the 3-methyl-1,2,3,4-tetrahydro derivative (414) <65JCS1558), whilst the Isay reaction itself has been shown (Section 2.15.15.6.1) to probably occur, at least in some cases, via a [6 + 0( )] cyclization of intermediate anils. 

Ring-opening of diastereomerically pure vinylaziridine 131, prepared by azir-idination of butadiene with 3-acetoxyaminoquinazolinone 130 [52], yielded acetate 132 with inversion of configuration, together with amino alcohol 133 with retention (Scheme 2.34) [53]. The formation of 133 can be explained by assuming participation by the quinazolinone carbonyl oxygen, which produces an intramolecular reaction with the aziridine carbon with retention of configuration. 

Reaction of (S)-(+)-2-aminobutyrate hydrochloride with ethyl oxalyl chloride followed by replacing of the ethyl ester with amino alcohol, oxidation with Dess-Martin periodinate and cyclization using TFA/TFAA in acetic acid gave the cyclic product, which was further converted to the bromide. Sub-... 

Cyclic phosphoramidates (phosphoric amides) were obtained by the reaction of amino alcohols with a phosphoric diimidazolide.tl933,[2]... 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

Table 16 Reaction of amino alcohols with bis-electrophiles...

The oxidation of sulfamidites to sulfamidates is a way to prepare these heterocycles, although the direct reaction of amino-alcohols with sulfuryl chloride is generally more convenient <1990TA885>. The reduction of sulfamides leads to the corresponding diamines (Equation 3) <2005JA11250>. 

Isatoic anhydride undergoes a one-step conversion to o-aminophenyloxazolines 2 with amino alcohols via elimination of carbon dioxide. The reaction is carried out in the presence of kaolinitic clay in refluxing chlorobenzene. These o-aminophenyloxazolines, in particular, those derived from chiral amino alcohols,... 

A common and effective direct approach to unsubstituted or multiply substituted oxazolines is the Lewis acid catalyzed reaction of nitriles with amino alcohols in an alcoholic or aromatic solvent (chlorobenzene) at reflux. The most common Lewis acids employed include ZnCl2, ZnBr2, NiBr2, CuCl2, and kaolinitic clay. Microwave irradiation has also been reported to facilitate the transformation. Alternatively, the condensation can be carried out in the presence of catalytic amounts of potassium carbonate. The method works well for both aliphatic and aromatic nitriles, with retention of stereochemistry. Some representative examples from the recent literature are listed in Table 8.16 (Scheme 3 40),2 35.2oi-2i3... 

Cyclic phosphonamides (tetrahydro-2//-l, 3,2-oxazaphosphorine 2-oxides) were obtained by reaction of / -amino alcohols with benzylphosphonic dichloride in moderate yield. In the case of the 6-monomethyl derivative the diastereomers were separated by chromatography. Deprotonation with /erz-butyllithium followed by alkylation occurred in a highly stereoselective manner (d.r. 96 4-99 1), independent of the nature of the alkylating reagent, counterion and solvent, as demonstrated for the 6,6-dimethyl derivative6. 

The properties and reactions of amino-alcohols, obtained largely by hydrolysis of naturally occurring alkaloids, were investigated primarily for the purposes of structural analysis and the preparation of physiologically active derivatives. Many authors have described acylation of pyrrolizidine alcohols with benzoyl chloride and acetic anhydride (see, e.g., refs. 83 and 101). Trachelanthamidine benzoate and p-aminobenzoate were prepared especially for testing of their physiological activity.102 The p-aminobenzoate was obtained by treatment of trachelanthamidine with p-nitrobenzoyl chloride and subsequent reduction of the nitro group with iron in 20% acetic acid. The compound exhibited an anesthetic activity close to that of cocaine. 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

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