One-pot synthesis of 1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-lithiophenyl isothiocyanates with aldehydes or ketones

Kobayashi, Kazuhiro; Yokoi, Yuki; Komatsu, Toshihide; Konishi, Hisatoshi

doi:10.1016/j.tet.2010.10.010

Cited by 20 publications

(14 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1a,b,d Therefore, we have recently reported a facile method for the preparation of 4-monosubstituted and 4,4-disubstituted derivatives by the reaction of 2-lithiophenyl isothiocyanates with aldehydes, ketones, or butanolide. 2 Literature searching revealed that there have been no reports on the synthesis of derivatives carrying an alkoxy substituent at the 4-position. In this paper, we wish to describe the results of our study on the reaction of 2-isothiocyanatobenzoates 1 with organolithiums including lithium enolates of acetates and tertiary acetamides, which provide facile access to 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones 3.…”

Section: Introductionmentioning

confidence: 99%

One-pot synthesis of 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-isothiocyanatobenzoates with organolithiums

Kobayashi¹,

Hashimoto²,

Kanbe³

et al. 2011

Tetrahedron

Self Cite

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

One-pot synthesis of 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-isothiocyanatobenzoates with organolithiums

Kobayashi¹,

Hashimoto²,

Kanbe³

et al. 2011

Tetrahedron

Self Cite

View full text Add to dashboard Cite

“…[12] However, it was reported that the microfluidic device allowed the reaction of an aryllithium intermediate, generated by Br-Li exchange, with electrophiles at much higher temperature due to excellent control of the reaction time at a time scale that is within the decomposition time scale of reactive intermediates. In flask, the Br-Li exchange reaction was generally conducted at low temperature, such as À78 8C.…”

mentioning

confidence: 99%

Integrated One‐Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates

Kim

Lee

2014

Angew Chem Int Ed

View full text Add to dashboard Cite

The synthesis of pharmaceutical compounds via short-lived intermediates in a microreactor is attractive, because of the fast flow and high throughput. Additionally, intermediates can be utilized sequentially to efficiently build up a library in a short time. Here we present an integrated microfluidic synthesis of biologically active thioquinazolinone libraries. Generation of o-lithiophenyl isothiocyanate and subsequent reaction with aryl isocyanate is optimized by controlling the residence time in the microreactor to 16 ms at room temperature. Various S-benzylic thioquinazolinone derivatives are synthesized within 10 s in high yields (75-98%) at room temperature. These three-step reactions involve two organolithium intermediates, an isothiocyanate-functionalized aryllithium intermediate, and a subsequent lithium thiolate intermediate. We also demonstrate the gram-scale synthesis of a multifunctionalized thioquinazolinone in the microfluidic device with a high yield (91%) and productivity (1.25 g in 5 min).

show abstract

“…The reaction time for the generation of NCS-substituted aryllithium was kept within 1 min to avoid decomposition of the intermediate. [12] However, it was reported that the microfluidic device allowed the reaction of an aryllithium intermediate, generated by Br-Li exchange, with electrophiles at much higher temperature due to excellent control of the reaction time at a time scale that is within the decomposition time scale of reactive intermediates. [11] Therefore, we conducted the Br-Li exchange reaction of o-bromophenyl isothiocyanate at mild temperature in a microfluidic device consisting of two Tshaped micromixers (M1 and M2) and two microtube reactors (R1 and R2) as shown in Table 1.…”

mentioning

confidence: 99%

Integrated One‐Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates

2014

View full text Add to dashboard Cite

The synthesis of pharmaceutical compounds via short‐lived intermediates in a microreactor is attractive, because of the fast flow and high throughput. Additionally, intermediates can be utilized sequentially to efficiently build up a library in a short time. Here we present an integrated microfluidic synthesis of biologically active thioquinazolinone libraries. Generation of o‐lithiophenyl isothiocyanate and subsequent reaction with aryl isocyanate is optimized by controlling the residence time in the microreactor to 16 ms at room temperature. Various S‐benzylic thioquinazolinone derivatives are synthesized within 10 s in high yields (75–98 %) at room temperature. These three‐step reactions involve two organolithium intermediates, an isothiocyanate‐functionalized aryllithium intermediate, and a subsequent lithium thiolate intermediate. We also demonstrate the gram‐scale synthesis of a multifunctionalized thioquinazolinone in the microfluidic device with a high yield (91 %) and productivity (1.25 g in 5 min).

show abstract

One-pot synthesis of 1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-lithiophenyl isothiocyanates with aldehydes or ketones

Cited by 20 publications

References 10 publications

One-pot synthesis of 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-isothiocyanatobenzoates with organolithiums

One-pot synthesis of 4-substituted 4-alkoxy-1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-isothiocyanatobenzoates with organolithiums

Integrated One‐Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates

Integrated One‐Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates

Contact Info

Product

Resources

About