Efficient chemical fixation and defixation cycle of carbon dioxide under ambient conditions

Chemical fixation of CO2 as a C1 feedstock for producing value-added products is an important post-combustion technology reducing the CO2 emission. As it is an irreversible process, not considered for the CO2 capture and release. Overall, these chemical transformations also do not help to mitigate global warming, as the energy consumed in different forms is much higher than the amount of CO2 fixed by chemical reactions. Here we describe the development of re-generable chemical fixation of CO2 by spiroaziridine oxindole, where CO2 is captured (chemical fixation) under catalyst-free condition at room temperature both in aqueous and non-aqueous medium even directly from the slow stream of flue gas producing regioselectively spirooxazolidinyl oxindoles, a potential drug. The CO2-adduct is reversed back to the spiroaziridine releasing CO2 under mild conditions. Further both the fixation-defixation of CO2 can be repeated under near ambient conditions for several cycles in a single loop using a recyclable reagent.

Means of viable development, typically relying on more sensible resource management, is a conceit challenge in front of modern human society. Sustainability level in recent economic growth requires a massive improvement as it is far from an adequate level. According to the data released by Intergovernmental Panel on Climate Change (IPPC 2018), global surface temperature has mounted by approximately 1.5 °C from 1880 to 2018, which is a phenomenon caused by anthropogenic activities, predominantly greenhouse gases like CO 2 emissions from fossil carbon to accomplish the escalating energy demand. Under this circumstances, melting of thousand years old glaciers, desertification of fertile land, rise in ocean water level and acidification of ocean water had caused enormous detriment to diverse ecological environment 1 . Scientific and technical advancements to curve atmospheric CO 2 concentration via limiting industrial emission and use CO 2 as an alternative fuel source in the renewable energy sector, had been a recurrent course of study for past few years [2][3][4][5] . The reduction of CO 2 can be considered as a typical cohesive technology to rise artificial efficiency in producing various valuable hydrocarbons like formic acid, methanol, methane, and C2-C4 olefins [6][7][8][9][10][11][12] . Several fascinating integrated protocols have freshly been reported for hydrothermal and photochemical CO 2 reduction, e.g., metal/metal oxide redox reaction based solar two-step water-splitting thermochemical cycle for CO 2 reduction via hydrogen generation [13][14][15][16][17][18][19][20][21][22] . Alongside, chemical fixation of CO 2 has gained substantial importance in synthetic chemistry because CO 2 could be used as a benign, abundant, inexpensive, and renewable C1 reserve to yield a variety of value-added chemicals e.g. esters, amides, aldehydes, carboxylic acids, alcohols, organic carbonates and 2-oxazolidinones, etc [23][24][25][26] . In particular, synthesis of therapeutically cherished and synthetically convenient five-membered cyclic urethanes such as oxazolidinones via cycloaddition of CO 2 with aziridines has become one of the most promising approaches in this area, because this process possess 100% atom efficiency, which exactly matches one of the most substantial criteria of green chemistry [27][28][29][30][31] . Despite being an admirable strategy to chemically capture and recycle CO 2 , most of these protocols suffer from high energy demand and utilize costly catalysts/ionic liquids to achieve ambient or near ambient condition for CO 2 fixation, even from highly enriched CO 2 source 32-40 . However, emissions from thermal power plants contain numerous gaseous components like SO 2 , NO 2 along with CO 2 41 . In these context, post-combustion CO 2 capture, release, and storage (CCS) had been the most abundantly used protocols for CO 2 purification from industrial exhausts. Various strategies are being industrialized for capture, release and storage (CCS) of CO 2 from gas streams, where gas-solid adsorption by metal-organic frameworks, gas-liquid chemiabsorption by amines and carbonation by quick/slacked lime are notable [42][43][44][45][46] . However, chemical fixation of CO 2 from contaminated sources under mild conditions to produce industrially vibrant chemicals and products faces great defies because of two main reasons: (1) the high ionization potential (IP), and (2) the negative adiabatic electron affinity (EA) of carbon dioxide. Therefore, most of the reports use harsh reaction conditions to overcome the high thermodynamic stability and chemical inertness of carbon dioxide. Hence, the development of a costeffective and robust protocol for CO 2 capture, storage, and release in ambient conditions along with utility is highly desirable. Further, the chemical fixation is an irreversible process producing stable covalent compounds and thus, till now it could not be utilized for CO 2 capture and release. It might be a potential CCS protocol as it would produce valuable chemicals, provided the chemical fixation and the defixation (release) done under ambient conditions, the latter is an unmet challenge. Herein, we report the first regenerable chemical fixation, where CO 2 fixation by spiroaziridine oxindole under atmospheric pressure at rt (30 °C) without any catalyst producing stable spirooxazolidinone, a potential drug candidate [47][48][49] , further reversed back (defixation) to the spiroaziridine releasing CO 2 under mild conditions. This fixation and defixation cycle can be repeated in a single loop for several times using a recyclable reagent.

Results and discussion
Uniqueness of spiroaziridine-and spirooxazolidinone oxindoles. CO 2 is an overall non-polar molecule, but the presence of net partial charges [O −δ -C +2δ -O δ ] makes its susceptibility to nucleophilic as well as electrophilic attack at carbon and oxygen, respectively. As a consequence, substrate such as epoxide and aziridine with both reactivity centres are suitable for the fixation of CO 2 20, [36][37][38][39][40] . However, all these require high pressure, -temperature and/or catalyst/additive. Designing substrate with tuned reactivity may lower the pressure and temperature for the chemical fixation of CO 2 and may further facilitate the CO 2 release. We envision that NHfree spiroaziridine oxindole 1 could be a suitable substrate with desired reactivity as the presence of oxindole unit may enhance the nucleophilicity of aziridine-nitrogen via an electron-donating resonance effect of nitrogen of oxindole unit and/or its anchimeric assistance (Fig. 1), simultaneously these may increase the electrophilicity of the C3 center of oxindole via resonance structure 1A and/or the formation of intermediate 1B under neutral or mild basic condition [50][51][52] . It is further envisioned that the presence of oxindole unit in spirooxazolidinone similarly will enable the release of CO 2 under acidic conditions as shown in Fig. 1) 53,54 . More importantly, the spirooxazolidinoyl oxindole is a potential drug candidate [47][48][49] , so this CO 2 fixation could be excellent and cheap method for its production.
Optimization of auto-chemical fixation of CO 2 by NH-free spiroaziridine 1a under ambient conditions. According to the presumption, we started our studies initially on synthesis of NH-free spiroaziridne oxindole 1a and its reactivity towards CO 2 under different conditions. We have developed a new and efficient method for the synthesis of NH-free spiro aziridine 1a from easily available amino alcohol 3a on successive treatment with chlorosulfonic acid (ClSO 3 H) in dioxane and aqueous KOH. The exclusive formation of NH-free spiroaziridine 1a was detected by MS and NMR analysis. With great delight, when a slow stream of CO 2 was passed through an aqueous dioxane solution of in situ synthesized spiroaziridine 1a at rt, within 30 min it produced exclusively CO 2 adduct, spiro oxazolidione 2a in excellent yield ( Table 1, entry 1) without any catalyst. This might be the first report of catalyst-free spontaneous chemical fixation of CO 2 under ambient condition and also in aqueous medium. Instead of aqueous, solid KOH was also found to be suitable for the in situ synthesis of www.nature.com/scientificreports/ spiroaziridine 1a and subsequent fixation of CO 2 , but it took a bit more time than the aqueous-dioxane (entry 2). The dioxane was the optimized solvent for both in situ spiroaziridine formation and the chemical fixation of CO 2 . NaOH instead of KOH is also equally effective for the synthesis of spiroaziridine and subsequent CO 2 fixation (entries 3 and 4). Further, when in situ generated spiroaziridine was taken in ethyl acetate and treated with slow stream of CO 2 in absence of any base, it also gave the CO 2 -adduct within 1.5 h in 69% isolated yield (entry 5). Thus it can be concluded that the chemical fixation of CO 2 by spiroaziridine does not require base as a catalyst/promoter. Ultimately with our great delight, the auto-chemical fixation of CO 2 was successful with 12.5% CO 2 in N 2 as well as a stimulated coal flue gas (12.5% CO 2 , 7.5% O 2 and 80% N 2 ) without any appreciable loss in the yield of the adduct (entries 6-8). These took longer reaction time, may be due to low concentration and retention of CO 2 in solution.
Defixation of CO 2 at near ambient conditions. We next sought to explore the possibility to regenerate the spiroaziridine via decarboxylation, which is an unmet challenge in CO 2 -chemical fixation. As per the presumption, the decarboxylation (CO 2 release) was initiated with the reaction of spiroxazolidinone in the presence of different Brǿnsted acids and the subsequent treatment of base to regenerate the spiroaziridine and its regeneration was quantified with the further chemical fixation of CO 2 leading to spirooxazolidione again. Both the CO 2 defixation and the fixation were optimized in dioxane and briefly summarized in Table 2. The regeneration of spiroaziridine 1a was detected when a dioxane solution of spirooxazolidinone was heated with triflic acid at 100 °C. The extend of formation of spiroaziridine was confirmed by its chemical fixation of CO 2 and it gave only 24% yield of the resynthesized spirooxazolidinone 2a ( Table 2, entry 1). With our great delight, near quantitative formation of spiroaziridine 1a was achieved, when the compound 2a was heated only at 70 °C with HI followed by treatment with aqueous NaOH ( Table 2, entry 4). This was revealed with the re-synthesis of spirooxazolidinone 2a with 94% of isolated yield. HBr was also found to act on at 70 °C, but it took longer time with incomplete conversion (entry 6). Further, to avoid the cumbersome procedure for the preparation of dioxane-HX, we Table 1. Optimization of in situ synthesis of spiroaziridine 1a and fixation of CO 2 .
Chlorosulfonic acid (1.0 equiv.) was added slowly into the dioxane solution of 3a (100 mg, 0.521 mmol) and stirred at 70 °C. Reaction mixture was basified and a slow stream of carbon dioxide was passed through the solution until complete consumption of 1a. a GC-yield is determined using naphthalene as internal standard; the value in parenthesis referred to the isolated yield. b Spiroaziridine 1a was extracted with ethyl acetate and treated with slow stream of CO 2 . c 12.5% CO 2 gas in N 2 was used as CO 2 source. d Stimulated flue gas (12.5% CO 2 , 7.5% O 2 and 80% N 2 ) was used as CO 2 source.    A dioxane solution of spiro-oxazolidone 2a (100 mg, 0.46 mol) was heated under specified acidic conditions followed by treatment of base and then slow stream of CO 2 . a Conversion of 2a was determined by GC-MS analysis. b GC-yield is determined using naphthalene as internal standard; the value in parenthesis referred to the isolated yield.  Fig. 3). Further the CO 2 defixation (at 70 °C) and the fixation (at rt) were successfully continued for consecutive five cycles in one-pot by treating with NaI-H 3 PO 4 and solid NaOH. Excitingly the overall yield of spirooxazolidinone after five cycles was found to be excellent (overall GC yield 95% and isolated yield 90%). Again, if we deeply look into the chemical reactions involved during the release and capture of CO 2 of the process, NaI supposed to regenerate after the treatment of 4a′/1a′ with NaOH. So, in principle, NaI may be reused for the subsequent cycles. For the purpose, the first regeneration cycle with release of CO 2 was carried out as usual with the combination of NaI-H 3 PO 4 and NaOH and subsequent chemical fixation of CO 2 produced the spirooxazolidione. The subsequent cycles for the regeneration of spiroaziridine (CO 2 -release/defixation) and CO 2 -fixation were performed without further addition of NaI, only varying with the equivalent of H 3 PO 4 and NaOH (Fig. 4). Thrillingly these were smoothly continued for five cycles. It showed almost quantitative yield   In some of the developed technologies, the sorbent (liquid or solid) loaded with the captured CO 2 is transported to a different vessel, where it releases the CO 2 (regeneration) either after being heated or after a pressure decrease or after any other change of conditions around the sorbent. The sorbent resulting after the regeneration step is sent back to capture more CO 2 in a cycle. This makes additional cost of the process. It will be desirable to conduct both CO 2 capture and the release in a single vessel, this is possible when both are near similar conditions. In our case, 70 °C was found to be optimum temperature for the CO 2 defixation. So, we further studied the temperature effect on CO 2 fixation. Interestingly, it showed a near horizontal line for the fixation at 5 °C, 30 °C, 50 °C, 60 °C and 70 °C, respectively, with > 95% yield in each case (Fig. 5).
Inspired by the above findings of temperature effect on CO 2 fixation, we performed both CO 2 defixation and fixation at 70 °C and continued for five cycles. With our great delight, it showed almost quantitative yield of spirooxazolidinone 2a in each cycle and an excellent overall yield after five cycles. This chemical fixationdefixation (five) cycles at 70 °C are repeated for three times with a standard deviation of 0.47-1.70 (Fig. 6). The spirooxazolidonyl oxindoles are important bioactive compounds 21,22 . Thus further efforts are made to generalize the developed method for the synthesis of various spirooxazolidines by catalyst-free CO 2 fixation of in situ generated spiroaziridines (Fig. 7). Irrespective of N-protection-and substitution of arene moiety of the oxindole unit, all underwent smooth auto-chemical fixation of CO 2 providing the excellent isolated yields of the adducts 2, albeit N-benzyl and N-allyl substrates took longer time in comparison with others for the CO 2 fixation. Further, alike 1a, the spiroaziridines derived from 3b, 3e, 3f and 3j also efficiently produced the corresponding CO 2 -adducts 2b, 2e, 2f and 2j with the flue gas in similar yields as with pure CO 2 . The regioselectivity of the fixation and the structure of the compound 2 was confirmed from the single crystal X-ray analysis of the compounds 2g ( Fig. 7; CCDC 1898609). All the CO 2 -adducts 2 are solid compounds with melting point > 100 °C and bench stable for a couple of months under ambient conditions. Thus the developed regenerable chemical fixation protocol can be utilized for CO 2 capture, storage and release, if and when it needed.

Conclusion
In summary, the first regenerable chemical fixation by spiroaziridine oxindole proved to be an excellent protocol for spontaneous and reversible CO 2 fixation and defixation. We have demonstrated that the CCS [CO 2 fixation and defixation cycle (regeneration)] can work well in one-pot (single vessel) for several cycles with excellent recovery using recyclable reagent under near ambient conditions. More importantly, the process regioselectively produced bioactive spirooxazolidinoyl oxindole in quantitative yields under extremely mild conditions (no extra reagent/catalyst, 1 atm., and rt). The CO 2 -adducts are stable compounds with high melting points, these can be stored for months under ambient conditions and can be reversed back to the sorbent as and when it requires. So, these findings in the ongoing research can open up a new avenue of the chemical fixation for the development The values in parenthesis refer to the GC yield using stimulated flue gas as a source of CO 2 .

Methods
Auto-chemical fixation of CO 2 by in situ generated spiroaziridine 1a. Amino alcohol 3a (500 mg, 2.60 mmol) was dissolved in dry dioxane (8 ml) and cooled to 0 ºC. Chlorosulfonic acid (174 µl, 2.6 mmol) was added drop wise and the reaction mixture was stirred for 2 h at room temperature (rt). 14 ml of 1 M aqueous NaOH solution was added dropwise to quench the acid at 0 ºC and stirred at 70 °C for 16 h. The complete conversion to spiroaziridine was detected by MS analysis. Next, a slow stream of CO 2 was passed through the solution at rt for 30 min. After complete consumption of 1a (monitored with TLC and also by MS analysis) the dioxane was removed under reduced pressure and the residue was extracted with EtOAc (3 × 10 ml), washed with brine solution and dried over anhydrous Na 2 SO 4 . Combined organic layer was concentrated and purified by silica gel flash chromatography using EtOAc/hexanes (1:1) to afford the desired CO 2 -adduct 2a (528 mg, 93%). Note In case of stimulated flue gas (12.5% CO 2 , 80% N 2 and 7.5% O 2 ) or 12.5% CO 2 in N 2 , the stream of gas was passed through the solution for 18 h.  in dry dioxane (6 ml), sodium iodide (414 mg, 2.76 mmol) and o-phosphoric acid (144 μl, 2.76 mmol) were successively added at 70 °C and the reaction (consumption of 2a) was monitored by TLC. After complete consumption of 2a (5 h), it was brought to 0 °C and solid NaOH powder (390 mg, 9.75 mmol) was added to the reaction mixture. After attaining rt, it was stirred for additional 1 h. The stream of 100% CO 2 was passed through to the suspended mixture for 1 h at rt. The solid mass was filtered off and washed with dioxane (2 × 5 ml). The combined organic solvent was evaporated to dryness under reduced pressure. The crude compound was dissolved in dioxane (6 ml) and 150 μl of the solution was taken out for the GC-MS analysis with naphthalene (5 mg) as an internal standard. The analysis showed 97% yield of the spirooxazolidinone 2a. So the calculated amount of resynthesized 2a was found to be 148.5 mg and 150 μl of the solution contained 3.7 mg of 2a. The resynthesized compound 2a (148.5 − 3.7 = 144.8 mg) was used for the second cycle for the regeneration of spiroaziridine and the fixation of CO 2 using the same procedure as mentioned above i.e. the use of NaI-H 3 PO 4 , solid NaOH and the stream of CO 2 . The GC-yield of the second cycle was observed to be 96%. Similarly, another three cycles were carried and the GC-yields were found to be 99%, 97% and 95%, respectively.

Defixation of CO
One-pot CO 2 -defixation and fixation cycles without isolation of re-synthesized spirooxazolidinone. The one-pot CO 2 -defixation and fixation cycles were carried out following the similar procedure as above without separating out the solid by-products and isolation of re-synthesized spirooxazolidinone in the intermediate cycles.
To a stirred solution of spirooxazolidinone 2a (150 mg, 0.69 mmol) in dry dioxane (6 ml), sodium iodide (414 mg, 2.76 mmol) and o-phosphoric acid (144 μl, 2.76 mmol) were successively added at 70 °C and the reaction (consumption of 2a) was monitored by TLC. After complete consumption of 2a (5 h), it was brought to rt and solid NaOH powder (390 mg, 9.75 mmol) was added to the reaction mixture at 0 °C. After attaining to rt, it was stirred for additional 1 h. The stream of CO 2 was passed through to the suspended mixture for 1 h at rt. The complete consumption of in situ regenerated spiroaziridine and the formation of spirooxazolidinone 2a were monitored by TLC and MS analysis. Without separating out the solid mass and the isolation of spirooxazolidinone, another consecutive four cycles were repeated by adding the same amount of sodium iodide and o-phosphoric acid followed by solid NaOH and the stream of CO 2 for each cycle in the same pot. The consumption of the intermediate substrate and regeneration of the product were monitored during each cycles by TLC and MS analysis. At the end of 5 th cycles, the solid mass was filtered off and washed with dioxane (3 × 10 ml). The combined organic solvent was evaporated to dryness under reduced pressure. The crude compound was dissolved in dioxane (6 ml) and the GC-MS analysis with naphthalene as an internal standard showed 95% overall yield of the spirooxazolidinone 2a for the five cycles. The silica gel flash column chromatographic purification of the crude with hexanes-EtOAc (1:1) gave the spirooxazolidinone 2a (134.9 mg, 90% overall yield) as a white solid.
Recycling of spiroaziridine and NaI for the fixation-and defixation of CO 2 . To a stirred solution of spirooxazolidinone 2a (150 mg, 0.69 mmol) in dry dioxane (6 ml), sodium iodide (414 mg, 2.76 mmol) and o-phosphoric acid (144 μl, 2.76 mmol) were successively added at rt and the reaction (consumption of 2a) was monitored by TLC. After complete consumption of 2a (5 h), solid NaOH powder (342 mg, 8.6 mmol) was added to the reaction mixture at 0 °C. After attaining to rt, it was stirred for additional 1 h. The stream of CO 2

Scientific RepoRtS
| (2020) 10:15825 | https://doi.org/10.1038/s41598-020-71761-w www.nature.com/scientificreports/ was passed through to the suspended mixture for 1 h at rt. The complete consumption of in situ regenerated spiroaziridine and the formation of spirooxazolidinone 2a (97% GC yield) were monitored by TLC and MS analysis. For the next cycle, the reaction mixture was acidified with o-phosphoric acid (292 μl, 5.6 mmol) and stirred at 70 °C without further addition of sodium iodide. After complete consumption of the spirooxazolidinone (monitored with TLC), solid NaOH powder was added (694 mg, 17.36 mmol) and the stream of CO 2 was passed through for 1 h to reproduce the spirooxazolidinone 2a (98%, GC yield). This process was repeated for five consecutive cycles. GC-MS analysis showed almost quantitative yield of spirooxazolidinone in each stage and finally the spirooxazolidinone 2a (135.0 mg, 90%) was isolated after fifth cycle by flash chromatography using hexanes-EtOAc (1:1). Note (a) GC yield is determined by using naphthalene as internal standard; (b) the release of CO 2 from spiroxazolidinone and its subsequent regeneration using CO 2 fixation is considered as one complete cycle. (c) At constant temperature (70 °C) five consecutive cycles of CO 2 fixation and defixation was accomplished using above method (Supplementary material; General procedure 2). GC yield in resynthesis of spirooxazolidione 2a was monitored at each stage (Fig. 3).