Hydroxyethyl derivatives

In alkylation, phenols and amines are alkylated by sulfites in high yield and quaternary salts readily form (67). Ethylene sulfite reacts yielding hydroxyethyl derivatives and SO2 elimination, corresponding to its activity as an ethylene oxide precursor (68). 

A/-Vinylamides and /V-vinylimides can be prepared by reaction of amides and imides with acetjiene (3), by dehydration of hydroxyethyl derivatives (4), by pyrolysis of ethyUdenebisamides (5), or by vinyl exchange (6), among other methods the monomers are stable when properly stored. 

When the reaction of acetaldehyde with a 6-diazopenicillanate is catalyzed by BFs-EtiO, an epoxide of unknown stereochemistry is obtained (79H( 13)227). With ZnCh catalysis, however, the 6a-acetyl derivative is obtained, which can be stereospecifically reduced as the Mg chelate to the 6a-(/ -l-hydroxyethyl) derivative as part of an elegant synthesis of the carbapenem thienamycin (Scheme 40) (8UA6765). 

The reaction of ethylene carbonate with acid imides which yields V-hydroxyethyl derivatives w as applied to 6-azauracil. In agreement with the foregoing findings, 6-azauracil produced a 3-(2-hydroxyethyl) derivative (65) which w as treated with thionyl chloride to convert... 

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

Perhydro derivatives of pyrido[l,2-7)][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and pyrido[l,2-c][l,3]oxazines and [l,3]oxazino[3,4-u]quinolines were also used in the stereoselective syntheses of different alkaloids. Perhydropyrido[l,2-c][l,3]oxazines and their benzologs are formed form 2-(2-hydroxyethyl) piperidines and from their benzologs to justify the stereochemistry of 2-(2-hydroxyethyl) derivatives. Different optically active pipecolic acids can be prepared via 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-ones. 

Thiamine is present in cells as the free form 1, as the diphosphate 2, and as the diphosphate of the hydroxyethyl derivative 3 (Scheme 1) in variable ratio. The component heterocyclic moieties, 4-amino-5-hydroxymethyl-2-methylpyrimidine (4) and 4-methyl-5-(2-hydroxyethyl)thiazole (5) are also presented in Scheme 1, with the atom numbering. This numbering follows the rules of nomenclature of heterocyclic compounds for the ring atoms, and is arbitrary for the substituents. To avoid the use of acronyms, compound 5 is termed as the thiazole of thiamine or more simply the thiazole. This does not raise any ambiguity because unsubstituted thiazole is encountered in this chapter. Other thiazoles are named after the rules of heterocyclic nomenclature. Pyrimidine 4 is called pyramine, a well established name in the field. A detailed account of the present status of knowledge on the biosynthesis of thiamine diphosphate from its heterocyclic moieties can be found in a review by the authors.1 This report provides only the minimal information necessary for understanding the main part of this chapter (Scheme 2). 

Treatment of l,2 3,5-di-0-methylidene-6-0-tosyl-a-D-glucofuranose (310) with KF (in refl. ethylene glycol, 3 min) gave a mixture of 6-deoxy-6-fluoro (311, 60%), an alkene (312, 18%), and 6-0-(2-hydroxyethyl) derivatives (12%). 

During the vacuum fractional distillation of bulked residues (7.2 t containing 30-40% of the bis(hydroxyethyl) derivative, and up to 900 ppm of iron) at 210-225°C/445-55 mbar in a mild steel still, a runaway decomposition set in and accelerated to explosion. Laboratory work on the material charged showed that exothermic decomposition on the large scale would be expected to set in around 210-230°C, and that the induction time at 215°C of 12-19 h fell to 6-9 h in presence of mild steel. Quantitative work in sealed tubes showed a maximum rate of pressure rise of 45 bar/s, to a maximum developed pressure of 200 bar. The thermally induced decomposition produced primary amine, hydrogen chloride, ethylene, methane, carbon monoxide and carbon dioxide. 

Typically, Cl Basic Red 24 (4-97) has a structure reminiscent of a disperse dye, except that a quaternary ammonium group is carried on the pendant alkyl chain in the coupling component. This coupling component is prepared by reaction of N-ethylaniline with ethylene oxide followed by conversion of the resulting P-hydroxyethyl derivative into the p-... 

Bis-pyrimidine derivatives were prepared by the reaction of the hydroxyethyl derivatives of pyrimidine with various bifunctional compounds such as dichloro-siloxane derivatives (Figure 3) (20). 

The latter, ester-type derivatives (21) were prepared by the reaction of L-glutamic acid with hydroxyethyl derivatives of nucleic acid bases. The reaction was studied in the presence of p-toluenesulfonic acid at 100-110°C in dioxane, and water formed was removed by azeotropic distillation with dioxane ( ). 

The reactivity of the agent mechlorethamine (11.31, R = Me, Fig. 11.5) was investigated in buffer solution by means of NMR to monitor the formation of primary, secondary, and tertiary products [66], The reactive aziridin-ium derivative (11.32) mentioned above and resulting from intramolecular nucleophilic substitution was indeed observed and underwent hydrolysis first to the 2-hydroxyethyl derivative and then to A-methyl-2,2 -iminodi-ethanol. 

Everolimus (40 Afinitor Novartis, 2009), a rapamycin analog, is the 42-0-(2-hydroxyethyl) derivative of sirolimus (34), and is marketed as an immunosuppressant by Novartis under the tradename Afinitor for use in advanced renal cell carcinoma.In March 2009, the FDA approved everolimus (40) for use against advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. The drug works similarly to sirolimus as an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. Everolimus (40) binds to an intracellular protein, EKBP-12, resulting in an inhibitory... 

Octahydroazocine (1) behaves as a typical secondary amine and forms an azeotrope with water, b.p. 96 °C (52M386). It can be transformed into 1-nitroso and 1-amino derivatives in the usual way (74JMC948). The imine (1) can also be cyanoethylated, and adds ethylene oxide (59MI51900) to give the N- hydroxyethyl derivative. Attempts to convert (1) to an enamine by oxidation with silver acetate gave only a low yield of pyridine (52M386). 

There is an intriguing observation concerning the equilibratability of certain indolyltetrahydropyridine. The Nb-unsubstituted isomers undergo equilibration readily, yet the Nb-hydroxyethyl derivatives are stable [96]. 

Pyruvate is decarboxylated to form a hydroxyethyl derivative bound to the reactive carbon of thiamine pyrophosphate, the coenzyme of pyruvate dehydrogenase. 

Of the triazine compounds, the tris(2-hydroxyethyl) derivative (17) is an effective fungistat and bactericide developed to be used with emulsifiable cutting oils and coolants. The triethyl derivative (18) is used as a preservative for pigment slurries. 

Oxiranes react with the heteroaryl anions to yield, via the alkali metal salts, the N-(2-hydroxyethyl) derivatives (B-77MI30502) and, with the Grignard compounds, the analogous C-substituted compounds (e.g. 65JCS7165, 78H(9)807). 

Attempted Vilsmeier formylations (POCl3/DMF) of metalloporphyrins bearing vinyl side chains results in formylation of the vinyl group (to give 84) at a rate which is faster than methine formylation as a result, vinyl groups usually need to be protected as the 2-hydroxyethyl derivative (78) which, in one step, can be formylated and transformed into 2-chloroethyl (ready for dehydrochlorination to regenerate the vinyl) by treatment with thionyl chloride. 

R. L. Baxter, and L. Sawyer. Biotin synthesis requires three other enzymes (steps b, c, d). Step b is catalyzed by a PLP-dependent transaminase. At the left is thiamin diphosphate, in the form of its 2-(1 -hydroxyethyl) derivative, an intermediate in the enzyme pyruvate decarboxylase (Dobritzsch et al.,. Biol. Chem. 273,20196-20204,1998). Courtesy of Guoguang Lu. Thiamin diphosphate functions in all living organisms to cleave C-C bonds adjacent to C=O groups. 

---