Synthesis of alpha-Haloalkyl Esters from alpha-Arylthioalkyl Esters.

Benneche, T.; Strande, Per; Wiggen, Unni; Öhman, Lars‐Olof; Ruiz, José; Colacio, Enrique; Mulichak, A. M.; Alminger, Tomas; Erickson, Magnus; Grundevik, Inger; Hagin, Inger; Hoffman, Kurt-Jürgen; Johansson, Svante; Larsson, Sam; Löfberg, Ingalil; Ohlson, Kristina; Persson, Björn; Skånberg, Inger; Tekenbergs-Hjelte, Lija

doi:10.3891/acta.chem.scand.43-0074

Cited by 14 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The β-sulfenylacetate precursor 24 was obtained by acetylation of the corresponding hydroxyl derivative obtained from reaction of 2-bromoethanol and thiophenol under basic conditions. , The α-sulfenylacetate precursor 26 was synthesized via chlorination of ethyl phenyl sulfide with N -chlorosuccinimide with subsequent displacement of the chloride by sodium acetate in DMF. , …”

Section: Methodsmentioning

confidence: 99%

Reactions of Thiiranium and Sulfonium Ions with Alkenes in the Gas Phase

et al. 2019

View full text Add to dashboard Cite

Ion−molecule reactions between thiiranium ion 11 (m/z 213) and cyclohexene and cis-cyclooctene resulted in the formation of addition products 17a and 17b (m/z 295 and m/z 323, respectively) via an electrophilic addition pathway. Associative π-ligand exchange involving direct transfer of the PhS + moiety, which has been observed for analogous seleniranium ions in the gas phase, did not occur despite previous solution experiments suggesting it as a valid pathway. DFT calculations at the M06-2X/def2-TZVP level of theory showed high barriers for the exchange reaction, while the addition pathway was more plausible. Further support for this pathway was provided with Hammett plots showing the rate of reaction to increase as the benzylic position of thiiranium ion derivatives became more electrophilic (ρ = +1.69; R 2 = 0.974). The more reactive isomeric sulfonium ion 22 was discounted as being responsible for the observed reactivity with infrared spectroscopy and DFT calculations suggesting little possibility for isomerization. To further explore the differences in reactivity, thiiranium ion 25 and sulfonium ion 27 were formed independently, with the latter ion reacting over 260 times faster toward cis-cyclooctene than the thiiranium ion rationalized by calculations suggesting a barrierless pathway for sulfonium ion 27 to react with the cycloalkene.

show abstract

Section: Methodsmentioning

confidence: 99%

Reactions of Thiiranium and Sulfonium Ions with Alkenes in the Gas Phase

et al. 2019

View full text Add to dashboard Cite

show abstract

“…While the Pummerer strategy provided an effective alternative to the alkylation strategy for the synthesis of 16 , the subsequent chlorination was problematic, as predicted by literature precedent . The conversion of 16 to 1 was effected by sulfuryl chloride in dichloromethane at −20 °C.…”

Section: Discussionmentioning

confidence: 94%

“…We next turned to an indirect approach from an aryl- or alkylthiomethyl ester (Scheme ). There is good precedent for the conversion of thioaryl esters ( 15 ) and thiomethyl esters ( 16 ) into the corresponding chloromethyl esters by treatment with electrophilic chlorinating reagents such as chlorine gas or sulfuryl chloride (SO 2 Cl 2 ). The chlorination of methylthiomethyl esters (e.g., 16 ) is typically less efficient due to competitive chlorination of the methyl group (e.g., 19 in Scheme ) .…”

Section: Discussionmentioning

confidence: 99%

“…There is good precedent for the conversion of thioaryl esters ( 15 ) and thiomethyl esters ( 16 ) into the corresponding chloromethyl esters by treatment with electrophilic chlorinating reagents such as chlorine gas or sulfuryl chloride (SO 2 Cl 2 ). The chlorination of methylthiomethyl esters (e.g., 16 ) is typically less efficient due to competitive chlorination of the methyl group (e.g., 19 in Scheme ) . Our initial approach was based on alkylation with chloromethyl phenyl sulfide or chloromethyl methyl sulfide to generate 15 and 16 , respectively.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a Practical and Efficient Synthesis of Chloromethyl 2-Ethoxy-2-methylpropanoate

Ragan

Ide

Cai

et al. 2010

Org. Process Res. Dev.

View full text Add to dashboard Cite

An efficient synthesis of chloromethyl 2-ethoxy-2-methylpropanoate from 2-bromoisobutyric acid is reported. Four developments were key to this route: (i) a mild, base-mediated ethanolysis of a tertiary alkyl bromide, (ii) a sodium bisulfite purge of 2-methylacrylic acid, (iii) preparation of a thiomethyl ester via a formal Pummerer process with DMSO, and (iv) improved conversion of a thiomethyl ester to a chloromethyl ester through suppression of a competing chlorination pathway.

show abstract

“…We reasoned that if the trapping agent for 8 contained a double bond plus a water-solublizing group, then the addition product could be removed by an aqueous wash. A number of such trapping agents were tested (including trans -cinnamic acid and 3-cyclohexenecarboxylic acid), but cis -4-cyclohexene-1,2-dicarboxylic acid ( 9 ) was found to be by far the most useful (eq 3). This procedure is recommended as an attractive variation on the published theme …”

Section: Synthesismentioning

confidence: 99%

Synthesis and Reactivity of 5-Fluorouracil/Cytarabine Mutual Prodrugs

Menger

Rourk

1997

J. Org. Chem.

View full text Add to dashboard Cite

Two mutual prodrugs, in which two different anti-cancer drugs are attached to the same molecule via labile linkages, are synthesized and examined kinetically. One of the mutual prodrugs loses a drug component under physiological conditions within an hour, but the other mutual prodrug (having a longer spacer between the two drugs) is stable to chemical degradation even at higher pH values. Thus, enzymatic hydrolysis alone will release the two anti-cancer drugs. The potential value of anti-cancer mutual prodrugs is discussed.

show abstract

Synthesis of alpha-Haloalkyl Esters from alpha-Arylthioalkyl Esters.

Cited by 14 publications

References 0 publications

Reactions of Thiiranium and Sulfonium Ions with Alkenes in the Gas Phase

Reactions of Thiiranium and Sulfonium Ions with Alkenes in the Gas Phase

Development of a Practical and Efficient Synthesis of Chloromethyl 2-Ethoxy-2-methylpropanoate

Synthesis and Reactivity of 5-Fluorouracil/Cytarabine Mutual Prodrugs

Contact Info

Product

Resources

About