Four-component tandem protocol for the stereoselective synthesis of highly functionalized [1,4]-thiazines

Isomorphous diethyl 1-(4-chlorobenzyl)-4-(4-chlorophenyl)-2,2-dioxo-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]thiazine-1,3-dicarboxylate and its 1-(4-methylbenzyl)-4-(4-methylphenyl)-substituted analogue obeying the chloro–methyl exchange rule

“…A search in the Cambridge Structural Database (CSD Version 5.39, update November 2017; Groom et al, 2016) for the skeleton of the title compound without chlorine or methyl substitution for which 3D coordinates were determined with no disorder, no ions and no other errors, with R factors less than 0.05 revealed only one structure, with refcode EXIYAM (Chitradevi, et al, 2011). A search on 4-thiomorpholine-1,1dione gave five hits with refcodes EXIYAM, IDOGIT (Chitradevi et al, 2013), IJULAB (Sugumar et al, 2011), NEVCUN (Indumathi et al,2007) and ZEXYEG (Krishnaiah et al, 1995).…”

“…A mixture of ethyl 2-[(2-ethoxy-2-oxo-ethyl)sulfonyl]acetate (1.6 mmol), aromatic aldehyde (3.2 mmol) and pyrrolidine (1.6mmol) was dissolved in ethanol (10 mL), heated until the solution turned yellow and stirred at room temperature for 2-5 days. After completion of the reaction, the crude product was purified using flash column chromatography on silica gel (230-400 mesh) with petroleum ether and ethyl acetate mixture (95:5 v/v) as eluent (Indumathi et al, 2007). Computer programs: APEX2 and SAINT (Bruker, 2009), SHELXS2013 (Sheldrick, 2008), SHELXL2018 (Sheldrick, 2015), PLUTON (Spek, 2009) and publCIF (Westrip, 2010).…”

Crystal structure and Hirshfeld surface analysis of a pyrrolo-thiazine complex

“…was further restricted to fused pyrrolo-thiazine ring structures, the number of hits reduced to five, viz. EXIYAM (Chitradevi et al, 2011), IDOGIT (Chitradevi et al, 2013), NEVCUN (Indumathi et al, 2007), VOKHAG (Gao, et al, 2005) and SINSAM (Sribala, et al, 2018) while a search for pyrrolothiazine ring combined with the other substituents in skeleton of the title compound, gave zero hits.…”

“…A mixture of ethyl 2-[(2-ethoxy-2-oxoethyl)sulfonyl]acetate (1.6 mmol), thiophene-2-carboxaldehyde (3.2 mmol) and pyrrolidine (1.6 mmol) was dissolved in ethanol (10 mL), heated until the solution turned yellow and stirred at room temperature for 2-5 days. After completion of the reaction, the crude product was purified using flash column chromatography on silica gel (230-400 mesh) with petroleum ether and ethyl acetate mixture (95:5 v/v) as eluent (Indumathi et al, 2007).…”

Photocatalytic Oxidative Bromination of 2,6-Dichlorotoluene to 2,6-Dichlorobenzyl Bromide in a Microchannel Reactor

“…2,6-Dichlorobenzyl bromide (DCBB) is an important intermediate in the synthesis of bioactive molecules such as functionalized [1,4]-thiazines, 4,6-diarylpyrimidin-2­(1 H )-ones, and 2-benzyloxybenzamides (Figure ). − DCBB is commonly obtained by benzylic bromination of 2,6-dichlorotoluene (DCT) with bromine in the presence of the free radical initiator or under light irradiation. , The benzylic bromination with bromine suffers from the disadvantages of the low utilization rate of bromine due to transformation of half bromine to hydrogen bromide as a byproduct and dangers in transport and storage of bromine due to its toxicity and high vapor pressure . Therefore, many reagents and protocols instead of bromine have been developed for the selectively benzylic bromination, such as H 2 O 2 /HBr/NBS, BBr 3 , and NBS/SiCl 4 , and various oxidative bromination systems including NaBrO 3 /NaHSO 3 , NaBrO 3 /KBr – /H + , KBr/Oxone, NaNO 2 /KBr/HCl, and HBr/H 2 O 2 . − Among them, the oxidative bromination with HBr/H 2 O 2 is the most recommended because of low cost of both hydrobromic acid (HBr) and H 2 O 2 , 100% utilization of bromine source, and water as the only byproduct avoiding the environmental problems being frequently involved with other oxidants …”