Sulfate esters synthesis

Grignard reaction, other examples n-Butyl borate (see Phenylboronic add). r-Butylhydro-peroxide. /-Butylperbenzoate. Dibromodifluoromethane. Diethyl sulfate. Ester synthesis (see 3-Dimethylaminopropylamine). Ethoxymethyleneaniline. Ethyl chloroformate. Ethylene dibromide (entrainment). Ethylene oxide. Ethyl formate. Ethynylmagnesium bromide. Sulfur. Triethyl orthoformate. Trimethylene oxide. See also Dichloroformoxime. 

The Wenker aziridine synthesis entails the treatment of a P-amino alcohol 1 with sulfuric acid to give P-aminoethyl sulfate ester 2 which is subsequently treated with base to afford aziridine 3. Before the discovery of the Mitsunobu reaction, wbicb transforms an amino alcohol into an aziridine in one step under very mild conditions, the Wenker reaction was one of the most convenient methods for aziridine synthesis. However, due to the involvement of strong acid and then strong base, its utility has been limited to substrates without labile functionalities. 

The mechanism for the Wenker aziridine synthesis is very straightforward. As depicted by conversion 2—>3, the transformation is a simple case of intramolecular Sn2 displacement process, in which the sulfate ester is the leaving group. 

As described in Section 1.7.1, the utility of the Wenker reaction is limited to substrates without labile functionalities because of the involvement of strong acid and then strong base. The Fanta group prepared a variety of aziridines by taking advantage of the Wenker reaction.For example, 6-aza-bicyclo[3.1.0]hexane (14) was produced from the ring-closure of ( )-rra s-2-aminocyclopentanol hydrochloride (13). In a similar fashion, sulfate ester 16 was prepared from A-methyl dl-trans- >-ssmnoA-hydroxytetrahydrofuran (15). Subsequent treatment of sulfate ester 16 with NaOH then delivered aziridine I . " Additional examples of Wenker aziridine synthesis may also be found in references 15-17. 

The most commonly employed routes for the preparation of the / -sulfatoethylsulfone group, which is the essential structural feature of vinylsulfone reactive dyes, are illustrated in Scheme 8.5. One method of synthesis involves, initially, the reduction of an aromatic sulfonyl chloride, for example with sodium sulfite, to the corresponding sulfinic acid. Subsequent condensation with either 2-chloroethanol or ethylene oxide gives the / -hydroxyethylsulfone, which is converted into its sulfate ester by treatment with concentrated sulfuric acid at 20 30 °C. An alternative route involves treatment of an aromatic thiol with 2-chloroethanol or ethylene oxide to give the /Miydroxyethylsulfonyl compound which may then be converted by oxidation into the /Miydroxyethylsulfone. 

When alkenes react with concentrated sulfuric acid, the corresponding sulfate esters (alkyl hydrogen sulfate, dialkyl sulfate) are formed. Depending on the alkene structure and the acid concentration, ester formation is accompanied by polymer formation (see Section 13.1.1). Hydrolysis of the sulfate esters allows the synthesis of alcohols. The reaction, called indirect hydration, is applied in the manufacture of ethanol and 2-propanol (see Section 6.1.3). 

Alternatively, the remaining sulfate ester of 70 may serve as a leaving group for a second nucleophilic displacement reaction. When this displacement is by an intramolecular nucleophile, a new ring is formed, as was first shown in the synthesis of a cyclopropane with malonate as the nucleophile [68] and of aziridines with amines as the nucleophiles [76]. The concept is further illustrated in the double displacement on (/J,/ )-stilbenediol cyclic sulfate (72) by benzamidine (73) to produce the chiral imidazoline 74 [79]. Conversion of the imidazoline (74) to (.V,.S )-stilbenediaminc 75 demonstrates an alternative route to optically active 1,2-diamines. Acylation of 75 with chloroacetyl chloride forms a bisamide, which, after reduction with diborane, is cyclized to the enantiomerically pure trans-2,3-diphenyl- 1,4-diazabicy-clo[2.2.2]octane (76) [81],... 

The polar functionality presents a major problem in the synthesis of cylindrospermopsin because the natural product cannot be extracted into organic solvents, making its separation from water-soluble reagents difficult. Clearly, the sulfate ester should be introduced in the last step. The guanidine should also be introduced late in the synthesis and should be protected as a less basic acyl guanidine until as late as possible. Finally, the uracil is also polar and so must be either introduced late in the synthesis or protected as a dialkoxypyrimidine. 

Reaction of cyclic sulfates with intramolecular O-nucleophiles leads to cyclic ethers and other heterocycles (Table 1). For example, a hydrolysis of compound 39 has produced predominantly the cyclic alcohols 41 (Scheme 4) < 1995JA12873 >. When the reaction was buffered with pyridine, the sulfate ester 40 was isolated rather than the free alcohol. An alcohol function in an intermediate product may give a route to a polysulfate cascade cyclization, which has been successfully realized in the synthesis of poly(tetrahydrofurans) (Table 1) <1995JA12873>. 

Further improvement in the technology of methyl fatty ester synthesis can be achieved by dual esterification [4], This takes advantage of the fact that the sulfated zirconia catalyst has similar activity for normal alcohols, over the series C1-C8. However, methanol manifests about twice the activity [20], The removal of water produced by the esterification with methanol is solved simply, by employing a heavy alcohol immiscible with water, such as 2-ethyl-hexanol, which acts simultaneously as a reactant and an entrainer. As a result, the two fatty esters are obtained in the bottom product in the desired ratio by adjusting the feeds. For example, in a preferable operation mode the ratio of fresh feed reactants is acid methanol 2-ethyl-hexanol 1 0.8 0.2. 

Sulfur metabolism in algae. I. Synthesis of metabolically inert chloroform-soluble sulfate esters by two chrysomonads and Chlorella pyrenoidesa. L Protozool., 9, 33 (1962). With T. H. Haines. 

Ethylenimine is conveniently prepared from ethanolamine by heating the inner salt of the sulfate ester with aqueous alkali (37%). The method has been applied to other /3-amino alcohols to form the C-alkyl homologs of ethylenimine in which one to three of the four hydrogens may be substituted. The general procedure is illustrated by the synthesis of 2,2-dim ethyl ethylenimine (51%). The N-alkyl analogs can be made by treating the N-alkylethanolamine hydrochlorides with chlorosulfonic acid followed by the action of base on the intermediate sulfuric acid esters, as in the preparation of N-ethylethylenimine (70%). ... 

Wieland and co-workers (913) in 1931 isolated from the skin secretion of the toad two indole derivatives, bufotenin and bufotenidin, whose correct structure (diagram 24) was established soon after (914) and confirmed by synthesis (416, cf. 363). Dehydrobufotenin was isolated in 1935 (443) and the previously isolated bufothionin (915) shown to be its sulfate ester (916, cf. diagram 24). 

Conjugation of 0-, N- and S-contalnlng functional groups with sulfate Is very common In animal systems. Sulfate Is transferred from adenosine 3 -phosphate-5 -sulfatophosphate (PAPS) by a variety of transfer enzymes. The mechanisms for sulfation of xenobiotics (74,75) and the chemistry of sulfate esters and related compounds and the synthesis of these have been reviewed (75-77). Syntheses of 0-, N- and S-sulfate conjugates of xenobiotics may be carried out by the methods described below. 

Pyrosulfate (dlsulfate, 8207 ") has been used for synthesis of aryl sulfate esters from the corresponding phenols (9 ). A high yield of phenyl sulfate was obtained when phenol was heated with potassium dlsulfate In dimethyl- or dlethylanlllne. Morphlne-3-sulfate ester was Isolated from an aqueous mixture of morphine, potassium hydroxide and potassium dlsulfate after 8 h at room temperature (9 ). 

A different approach to the synthesis of sulfate esters was discussed by Buncel and co-workers (97 ). The sulfate monoester was obtained after neutral or alkaline methanolysis of methyl 4-nltro-phenyl sulfate. The methoxide Ion attacks only at the alkyl carbon with the formation of dimethyl ether and 4-nltrophenyl sulfate Ion as the leaving group. Other substituted methyl phenyl sulfates have been converted to phenyl sulfates In the same manner (98). Correspondingly l,2 5,6-dl-0-lsopropylldlne-a-D-glucofuranose was reacted with phenyl chlorosulfate to give the carbohydrate... 

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