Sustainable Production of Pyromellitic Acid with Pinacol and Diethyl Maleate

Home , Pinacol

Electronic Supplementary Material (ESI) for Green Chemistry. This journal is © The Royal Society of Chemistry 2017

Supporting Information

Yancheng Hu,a Ning Li,*a,b Guangyi Li,a Aiqin Wang,a,b Yu Cong,a Xiaodong Wanga

and Tao Zhang*a,b

aState Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of

Sciences, Dalian 116023, China.

biChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Dalian Institute of

Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

*E-mail: [email protected]; [email protected] 1. General information

Pinacol was purchased from Aladdin Industrial Inc. Diethyl maleate and ethyl acrylate were obtained from Tokyo Chemical Industry. Choline chloride and formic acid were supplied by Acros Organics. Other carboxylic acids were provided by Aladdin Industrial Inc. All chemicals were of analytical grade and were used without further purification.

Various deep eutectic solvents (DESs) were prepared according to literature1 by stirring choline chloride and the other component at 100 oC until a homogeneous liquid was formed (ca. 40 min).

Amberlyst-15 resin was purchased from Sigma-Aldrich company. The Raney Ni, Ni/C, Pd/C, Pt/C, Ru/C and Rh/C catalysts were purchased from Aladdin Industrial Inc. To facilitate the comparison, the metal contents in these catalysts were chosen as 5% by weight.

NMR spectra were recorded at room temperature in CDCl3 on 400 MHz spectrometers. The chemical shifts for 1H NMR were recorded in ppm downfield

6 using the peak of CDCl3 (7.26 ppm) or d -DMSO (2.50 ppm) as the internal standard. The chemical shifts for 13C NMR were recorded in ppm downfield using the central

6 peak of CDCl3 (77.16 ppm) or d -DMSO (39.52 ppm) as the internal standard. HRMS data was obtained with Micromass HPLC-Q-TOF mass spectrometer (ESI) or Agilent 6540 Accurate-MS spectrometer (Q-TOF).

2. Pinacol dehydration to 2,3-dimethylbutadiene

2.1 Pinacol dehydration using Amberlyst-15 resin as catalyst

1,2-Elimination

HO OH -2 H2O Amberlyst-15 2 solvent O Pinacol, 1 Pinacol rearrangement 3

Pinacol (8.5 mmol, 1.0 g), Amberlyst-15 resin (100 mg), and solvent (4.0 g or 0 g for the solvent-free test) were added to a sealed tube (35 mL) in sequence. The

S1 mixture was stirred at 120 oC for 12 h. Upon completion, the product was diluted with pentane and analyzed by an Agilent GC 7890A equipped with HP-5 column (30 m, 0.25 mm ID, 0.5 mm film) and a flame ionization detector (FID) using tridecane as the internal standard. Examples see Fig. S1 (no solvent, compound 3 in 88% carbon yield) and Fig. S2 (DMSO as solvent, compound 2 in 31% carbon yield, compound 3 in 15% carbon yield; NMP as solvent, compound 2 in 39% carbon yield, compound 3 in 21% carbon yield).

2.2 Pinacol dehydration in acidic deep eutectic solvents (DESs) 1,2-Elimination

HO OH -2 H2O acidic DES 2 O Pinacol, 1 Pinacol rearrangement 3

Pinacol (8.5 mmol, 1.0 g) and acidic DES (4-10 g) were added to a sealed tube (35 mL) in sequence. The reaction mixture was stirred at 100-150 oC for 12 h. Upon completion, the product was diluted with pentane and analyzed by an Agilent GC 7890A equipped with HP-5 column (30 m, 0.25 mm ID, 0.5 mm film) and a FID using tridecane as the internal standard. Example see Fig. S3 (8.0 g ChCl/HCOOH, 140 oC, compound 2 in 83% yield, compound 3 in 13% yield) and Fig. S4 (8.0 g ChCl/HCOOH, 150 oC, compound 2 in 71% yield, compound 3 in 16% yield).

The influence of ChCl/HCOOH dosage on the dehydration of pinacol was studied. According to Fig. S5, the carbon yield of compound 2 increased with the increment of ChCl/HCOOH dosage, reached the maximum (78%) when 8.0 g ChCl/HCOOH was used, then stabilized with further increasing the dosage. In contrast, it is noticed that the dosage of DES had no evident effect on the the carbon yield of compound 3.

We also investigated the effect of reaction temperature on the carbon yields of compounds 2 and 3. Taking into consideration that the thermal decomposition of formic acid is 160 oC, we set the maximum reaction temperature as 150 oC. As shown in Fig. S6, with the increasing of reaction temperature, the carbon yield of compound 2 slightly increased, reached the maximum (83%) when the pinacol dehydration was

S2 performed at 140 oC, then decreased with further increment of the temperature. This can be rationalized because too high temperature led to the self D-A reaction of compound 2 (Fig. S4), which decreased its carbon yield or selectivity.

2.3 Recycling performance of ChCl/HCOOH in pinacol dehydration

Pinacol (8.5 mmol, 1.0 g) and ChCl/HCOOH (molar ratio 2:1, 8.0 g) were added to a sealed tube (35 mL) in sequence. The reaction mixture was stirred at 140 oC for 12 h. Upon completion, the upper layer was removed by decantation, diluted with pentane and analyzed by an Agilent GC 7890A equipped with HP-5 column (30 m, 0.25 mm ID, 0.5 mm film) and a FID using tridecane as the internal standard. The lower layer ChCl/HCOOH was dried at room temperature under vacuum for 10 h prior to use in next cycle. The water content in the desiccated ChCl/HCOOH was determined as < 2% by a Mettler Toledo DL39 Karl Fischer Titrator. Examples see Fig. S7 (the photographs of the system during the reaction) and Fig. S8 (the carbon yield of compound 2 as a function of recycle time). To check the thermal stability of formic acid under the investigated conditions, we conducted a blank experiment. From the chromatograms which were illustrated in Fig. S9, we can see that the areas of formic acid were almost the same (15703.5 vs. 15322.9). This result indicates that the formic acid was stable under the investigated conditions. No decomposition of formic acid was noticed during the reaction. NMR and HRMS data of compounds 2 and 3

1 13 H NMR (400 MHz, CDCl3) δ 4.98 (s, 2H), 4.89 (s, 2H), 1.84 (s, 6H); C

2 NMR (100 MHz, CDCl3) δ 143.5, 113.1, 20.6. HRMS (ESI) calcd. for

+ C6H11 [M + H] 83.0855, found 83.0852.

1 13 O H NMR (400 MHz, CDCl3) δ 2.07 (s, 3H), 1.07 (s, 9H); C NMR (100

3 MHz, CDCl3) δ 214.4, 44.4, 26.5, 24.8. HRMS (ESI) calcd. for C6H13O [M + H]+ 101.0961, found 101.0960.

S3 3. D-A reaction, dehydrogenation, and hydrolysis 3.1 D-A reactions of 2,3-dimethylbutadiene with maleic anhydride, diethyl maleate, and diethyl fumarate

O O 60 oC + O O

O 2 4 O 5

Compound 2 (10 mmol, 1.1 mL) and maleic anhydride (10 mmol, 0.98 g) were added to a 35 mL sealed tube. The mixture was stirred at 60 oC for 1.5 h, then cooled down to room temperature and the white solid was formed. According to the NMR data (Fig. S24 and S25), D-A product (i.e. compound 5) was obtained in a nearly quantitative yield. H CO Et CO Et 2 120 oC 2 + CO Et CO Et 2 H 2 2 7 8

Compound 2 (10 mmol, 1.1 mL) and diethyl maleate (10 mmol, 1.6 mL) were added to a 35 mL sealed tube. The mixture was stirred at 120 oC for 6 h, then cooled down to room temperature and analyzed by the Agilent GC 7890A equipped with an HP-5 column and a FID (Fig. S10a, nearly quantitative yield). It is noteworthy that the temperature exerted a significant effect on the D-A reaction. For example, the reaction did not occur at 60 oC and the starting materials still remained unchanged. Diethyl maleate cannot be completely consumed when the D-A reaction was performed at 100 oC for 12 h (Fig. S10b). H EtO C CO Et 2 120 oC 2 + CO Et CO Et 2 H 2 2 10

For comparison, we also prepared compound 10 by the D-A reaction of compound 2 and diethyl fumarate. To do this, compound 2 (10 mmol, 1.1 mL) and diethyl fumarate (10 mmol, 1.6 mL) were added to a 35 mL sealed tube. The mixture was stirred at 120 oC for 6 h, then cooled down to room temperature and analyzed by the Agilent GC 7890A equipped with an HP-5 column and a FID. As shown in Fig. S11, compound 2 and diethyl fumarate were totally converted to compound 10 (nearly quantitative yield). S4 NMR and HRMS data of D-A adducts

1 O H NMR (400 MHz, CDCl3) δ 3.38 – 3.28 (m, 2H), 2.43 (d, J = 15.1 Hz, O 2H), 2.25 (d, J = 13.9 Hz, 2H), 1.68 (s, 6H); 13C NMR (100 MHz, 5 O CDCl3) δ 174.6, 127.4, 40.5, 30.5, 19.4. HRMS (ESI) calcd. for

+ C10H13O3 [M + H] 181.0859, found 181.0855.

1 H H NMR (400 MHz, CDCl3) δ 4.12 (qd, J = 7.1, 1.6 Hz, 4H), 3.08 – CO2Et

CO Et 2.88 (m, 2H), 2.53 – 2.32 (m, 2H), 2.30 – 2.15 (m, 2H), 1.61 (s, 6H), H 2 8 13 1.22 (t, J = 7.1 Hz, 6H). C NMR (100 MHz, CDCl3) δ 173.5, 124.0,

+ 60.5, 40.6, 32.0, 19.0, 14.2. HRMS (ESI) calcd. for C14H23O4 [M + H] 255.1591, found 255.1594.

1 H H NMR (400 MHz, CDCl3) δ 4.24 – 4.00 (m, 4H), 2.87 – 2.70 (m, CO2Et

CO Et 2H), 2.31 – 2.18 (m, 2H), 2.18 – 2.04 (m, 2H), 1.60 (s, 6H), 1.23 (t, J = H 2 10 13 7.1 Hz, 6H); C NMR (100 MHz, CDCl3) δ 175.0, 124.0, 60.6, 42.2,

+ 34.3, 18.7, 14.3. HRMS (ESI) calcd. for C14H23O4 [M + H] 255.1591, found 255.1599.

3.2 Dehydrogenation of the D-A adducts under solvent-free condition H H CO Et CO Et CO Et 2 Pd/C 2 2 + 220 oC CO2Et CO2Et CO Et H H 2 8 9 10

H CO Et CO Et 2 Pd/C 2 220 oC CO Et CO Et H 2 slow 2 10 9

The compounds 8 or 10 (10 mmol, 2.5 g) and Pd/C (250 mg) were added to a

100 mL stainless steel batch reactor. The reaction was conducted under argon atmosphere (1 atm) at 220 oC for 24 h. The product was analyzed by the Agilent GC 7890A equipped with an HP-5 column and a FID using p-xylene as the internal standard. Examples see Fig. S12 (dehydrogenation of compound 8, 100% conversion of compound 8, 80% carbon yield of compound 9, and 11% carbon yield of compound 10) and Fig. S13 (dehydrogenation of compound 10, 87% conversion of compound 10 and 66% carbon yield of compound 9). Because the dehydrogenation of compound 8 was faster than that of 10, the side product (i.e. compound 10) was still S5 observed when compound 8 was completely consumed (24 h). Gratifyingly, after prolonging the reaction time to 48 h, the carbon yield of compound 9 increased to 84% (Fig. S14). It is noteworthy that the effects of the temperature on the dehydrogenation process were also investigated (Fig. S15). The reaction at higher temperature (260 oC) led to a decreased yield of compound 9, due to the formation of other unknown impurities.

The pathway for the formation of side product (i.e. compound 10) in the course of dehydrogenation of compound 8:

Diels-Alder H CO Et CO Et CO2Et 2 cycloaddition 2 Pd/C + o Retro Diels-Alder 220 C CO2Et CO2Et CO2Et cycloaddition H 2 4 8 9

220 oC, Pd/C Isomerization Standard Fig. S16 conditions slower Fig. S13

H CO2Et CO2Et

EtO2C Diels-Alder cycloaddition CO Et H 2 Fig. S11 Diethyl fumarate 10

The isomerization of diethyl maleate under standard conditions: Diethyl maleate (10 mmol, 1.6 mL) and Pd/C (0.25 g) were added to a 100 mL stainless steel batch reactor. The mixture was stirred at 220 oC for 24 h, then cooled down to room temperature and analyzed by the Agilent GC 7890A equipped with an HP-5 column and a FID. From the result shown in Fig. S16, some diethyl maleate was isomerized to diethyl fumarate.

NMR and HRMS data of compound 9

1 H NMR (400 MHz, CDCl3) δ 7.38 (s, 2H), 4.25 (q, J = 7.1 Hz, 4H), CO2Et 13 CO2Et 2.20 (s, 6H), 1.26 (t, J = 7.2 Hz, 6H); C NMR (100 MHz, CDCl3) δ 9 167.8, 140.0, 129.9, 129.7, 61.3, 19.6, 14.1. HRMS (ESI) calcd. for

+ C14H19O4 [M + H] 251.1278, found 251.1274.

S6 3.3 One-step pinacol dehydration and D-A reaction in ChCl/HCOOH

HO OH CO2Et CO2Et ChCl/HCOOH + 140 oC CO2Et CO2Et One-step 1 4 8 + 10 (7.1 : 1) 89% yield

Pinacol (10 mmol, 1.2 g), ChCl/HCOOH (molar ratio 2:1, 9.6 g) and diethyl maleate (10 mmol, 1.6 mL) were added to a sealed tube (35 mL) in sequence. The reaction mixture was stirred at 140 oC for 12 h. Upon completion, the upper layer D-A adduct was isolated by decantation and analyzed by an Agilent GC 7890A equipped with HP-5 column (30 m, 0.25 mm ID, 0.5 mm film) and a FID using tridecane and p- xylene as the internal standards. Examples see Fig. S17 (89% carbon yield of D-A adduct, the ratio of compounds 8 and 10 is 7.1:1, and trace amount of pinacolone).

3.4 One-pot dehydrogenation/hydrolysis

CO Et CO H 2 1) Pd/C, 220 oC, 24 h 2 o 2) NaOH/H2O, 55 C CO2Et CO2H One-pot 11 73% yield

The resulting D-A products (10 mmol, 2.5 g) and Pd/C (250 mg) were added to a 100 mL stainless steel batch reactor. The reaction was conducted under argon atmosphere (1 atm) at 220 oC for 24 h. After that, a mixture of water (80 mL) and NaOH (25 mmol, 1.0 g) was directly added into the system, and stirred at 55 oC for 5 h. Then, Pd/C was filtered and the aqueous phase was acidified by diluted HCl solution until pH = 1. Subsequently, the aqueous solution was extracted with ethyl acetate (20 mL) for three times. The combined organic phase was dried with anhydrous MgSO4 and concentrated via rotary evaporation. Direct crystallization in ethanol afforded compound 11 as a white solid (1.42 g, 73% yield, m.p. 207‒208 oC).

NMR and HRMS data of compound 11

1 H NMR (400 MHz, DMSO-d6) δ 12.88 (s, 2H), 7.43 (s, 2H), 2.27 CO2H 13 (s, 6H); C NMR (100 MHz, DMSO-d6) δ 168.8, 139.4, 130.4, CO2H 11 + 129.4, 19.2. HRMS (ESI) calcd. for C10H11O4 [M + H] 195.0652, found 195.0644.

S7 4. Catalytic aerobic oxidation

CO2H HO2C CO2H Co(OAc)2/Mn(OAc)2 (4 mol%) NHPI (20 mol%) HO C CO H CO2H o 2 2 HOAc, O2, 120 C 11 PMA, 12 88% yield

Compound 11 (1.0 mmol, 0.19 g), N-hydroxyphthalimide (NHPI, 20 mol%, 32.6 mg), Co(OAc)2 (4 mol%, 7.0 mg), Mn(OAc)2•4H2O (4 mol%, 10 mg) and acetic acid (3 mL) were added to a 30 mL stainless steel reactor in sequence. The reaction was conducted under oxygen atmosphere (1 atm) at 120 oC for 14 h. Upon completion, acetic acid was removed via rotary evaporation. The crude residue was crystallized with ethanol/acetone to afford pyromellitic acid (PMA, compound 12) as a white solid (224.4 mg, 88% yield, m.p. 247‒248 oC).

NMR and HRMS data of compound 12

1 13 H NMR (400 MHz, DMSO-d6) δ 13.52 (s, 4H), 7.92 (s, 2H); C HO2C CO2H

NMR (100 MHz, DMSO-d6) δ 167.3, 134.6, 128.5. HRMS (ESI) HO2C CO2H 12 + calcd. for C10H6O8Na [M + Na] 276.9955, found 276.9953.

S8 5. Production of trimellitic acid using ethyl acrylate as the feedstock

CO2Et

OH HO C HO o 2 ChCl/HCOOH 1) Pd/C, 220 C Co/Mn/NHPI 140 oC 2) NaOH/H O HOAc, O2 CO Et 2 CO H HO2C CO2H 1 2 2 One-step 13 One-pot 15 TMA, 16 83% yield 78% yield 90% yield

One-step pinacol dehydration and D-A reaction with acrylate: Pinacol (10 mmol, 1.2 g), ChCl/HCOOH (molar ratio 2:1, 9.6 g) and ethyl acrylate (10 mmol, 1.0 mL) were added to a sealed tube (35 mL) in sequence. The reaction mixture was stirred at 140 oC for 12 h. Upon completion, the upper layer D-A adduct was isolated by decantation and analyzed by an Agilent GC 7890A equipped with HP-5 column (30 m, 0.25 mm ID, 0.5 mm film) and a FID using tridecane and toluene as the internal standards. Examples see Fig. S18 (83% carbon yield of D-A adduct 13).

One-pot dehydrogenation/hydrolysis: The resulting D-A adduct 13 (10 mmol, 1.8 g) and Pd/C (180 mg) were added to a 100 mL stainless steel batch reactor. The reaction was conducted under argon atmosphere (1 atm) at 220 oC for 24 h (the GC chromatogram of the dehydrogenation product was illustrated in Fig. S19). After that, a mixture of water (80 mL) and NaOH (12 mmol, 0.48 g) was directly added into the system, and stirred at 55 oC for 5 h. Then, Pd/C was filtered and the aqueous phase was acidified by diluted HCl solution until pH = 1. Subsequently, the aqueous solution was extracted with ethyl acetate (20 mL) for three times. The combined organic phases were dried with anhydrous MgSO4 and concentrated via rotary evaporation. Direct crystallization in ethanol afforded 3,4-dimethylbenzoic acid 15 as a white solid (1.17 g, 78% yield, m.p. 118‒119 oC). Catalytic aerobic oxidation: To a 30 mL stainless steel reactor were added 3,4- dimethylbenzoic acid 15 (1.0 mmol, 0.15 g), N-hydroxyphthalimide (NHPI, 20 mol%,

32.6 mg), Co(OAc)2 (4 mol%, 7.0 mg), Mn(OAc)2•4H2O (4 mol%, 10 mg) and acetic acid (3 mL) in sequence. The reaction was conducted under oxygen atmosphere (1 atm) at 120 oC for 14 h. Upon completion, acetic acid was removed via rotary

S9 evaporation. The crude residue was crystallized with ethanol/acetone to afford trimellitic acid (TMA) as a white solid (189.0 mg, 90% yield, m.p. 225‒226 oC). NMR and HRMS data of the products

1 H NMR (400 MHz, CDCl3) δ 4.12 (q, J = 7.1 Hz, 2H), 2.55 – 2.42 (m,

CO2Et 1H), 2.27 – 1.85 (m, 6H), 1.60 (d, J = 5.5 Hz, 6H), 1.25 (t, J = 7.1 Hz, 13 13 3H); C NMR (100 MHz, CDCl3) δ 176.2, 125.4, 124.1, 60.3, 40.4,

+ 33.9, 31.2, 26.0, 19.1, 19.0, 14.4. HRMS (ESI) calcd. for C11H19O2 [M + H] 183.1380, found 183.1373.

1 H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.77 (dd, J = 7.9, 1.9 Hz,

CO2Et 1H), 7.18 (d, J = 7.9 Hz, 1H), 4.36 (q, J = 7.1 Hz, 2H), 2.31 (s, 6H), 14

13 1.39 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3) δ 167.0, 142.2, 136.7, 130.7, 129.7, 128.2, 127.2, 60.8, 20.1, 19.8, 14.5. HRMS (ESI) calcd. for

+ C11H15O2 [M + H] 179.1067, found 179.1068.

1 H NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 7.71 (s, 1H), 7.66 (d, J

CO2H = 7.8 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 2.27 (s, 3H), 2.26 (s, 3H); 13C 15

NMR (100 MHz, DMSO-d6) δ 167.5, 141.8, 136.5, 130.3, 129.6, 128.5,

+ 126.9, 19.6, 19.3. HRMS (ESI) calcd. for C9H9O2 [M ‒ H] 149.0597, found 149.0617.

1 HO2C H NMR (400 MHz, DMSO-d6) δ 13.50 (s, 3H), 8.23 (s, 1H), 8.11 (d,

HO2C CO2H J = 7.5 Hz, 1H), 7.76 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, 16

DMSO-d6) δ 168.4, 167.5, 166.0, 137.4, 134.3, 132.4, 131.7, 129.4,

+ 128.7. HRMS (ESI) calcd. for C9H5O6 [M ‒ H] 209.0081, found 209.0102.

6. References

1. A. P. Abbott, D. Boothby, G. Capper, D. L. Davies and R. K. Rasheed, J. Am. Chem. Soc., 2004, 126, 9142-9147.

S10 7. Copies of GC chromatograms and NMR spectroscopy

OH O HO Amberlyst-15 Neat, 120 oC Pinacol, 1 3

(a) O

3 pinacolone, internal standard (tridecane)

Fig. S1. GC chromatogram of the dehydration product of pinacol over Amberlyst-15 resin under solvent-free condition. Reaction conditions: pinacol (8.5 mmol, 1.0 g), Amberlyst-15 (100 mg), 120 oC, 12 h.

S11 OH O HO Amberlyst-15 + DMSO or NMP, Pinacol, 1 120 oC 2 3

a) DMSO as solvent 2

3 internal standard (tridecane)

pinacol

2 b) NMP as solvent

pinacol

Fig. S2. GC chromatograms of the dehydration product of pinacol over Amberlyst-15 resin using DMSO or NMP as solvent. Reaction conditions: pinacol (8.5 mmol, 1.0 g), Amberlyst-15 (100 mg), DMSO or NMP (4.0 g), 120 oC, 12 h.

S12 O HO OH ChCl/HCOOH (2:1) + 140 oC Pinacol, 1 2 3

3 internal standard (tridecane)

Fig. S3. GC chromatogram of the dehydration product of pinacol in DES ChCl/HCOOH (2:1). Reaction conditions: pinacol (8.5 mmol, 1.0 g), ChCl/HCOOH (molar ratio 2:1, 8.0 g), 140 oC, 12 h.

S13 O HO OH ChCl/HCOOH (2:1) + + 150 oC 2 Pinacol, 1 3 Dimer of compound 2

2 internal standard

Dimer of (tridecane) O compound 2

Fig. S4. GC chromatogram of the dehydration product of pinacol in DES ChCl/HCOOH (2:1). Reaction conditions: pinacol (8.5 mmol, 1.0 g), ChCl/HCOOH (molar ratio 2:1, 8.0 g), 150 oC, 12 h.

S14 O HO OH ChCl/HCOOH (2:1) + 120 oC Pinacol, 1 2 3

100 Carbon yield of compound 2 Carbon yield of compound 3 80 ) % ( 60 d l e i y

o 40 b r a C 20

0 4 6 8 10 Dosage of DES (ChCl:HCOOH = 2:1) (g)

Fig. S5. Carbon yields of compounds 2 and 3 as a function of DES ChCl/HCOOH (2:1) dosage. Reaction conditions: pinacol (1.0 g), 120 oC, 12 h.

S15 OH O HO ChCl/HCOOH (2:1) + 8 g Pinacol, 1 2 3

100 Carbon yield of compound 2 Carbon yield of compound 3 80 ) % (

l 60 e i y

n o

b 40 r a C 20

0 100 110 120 130 140 150 Reaction temperature (oC)

Fig. S6. Carbon yields of compounds 2 and 3 as a function of reaction temperature. Reaction conditions: pinacol (1.0 g), ChCl/HCOOH (2:1) 8.0 g, 12 h.

S16 (a) (b) (c)

Fig. S7. Photographs of the mixture during the reaction. (a) A homogeneous liquid between pinacol (8.5 mmol, 1.0 g) and ChCl/HCOOH (molar ratio 2:1, 8.0 g) at 140 oC before reaction; (b) A biphasic system was obtained upon completion of the reaction; (c) After being cooled down to 0 oC, the lower layer became solid.

S17 O HO OH ChCl/HCOOH (2:1) + 140 oC Pinacol, 1 2 3

100 Carbon yield of 2 Carbon yield of 3 80 ) % (

l 60 e i y

n o

b 40 r a C 20

0 0 1 2 3 4 Recycle time

Fig. S8. Carbon yields of compounds 2 and 3 as a function of recycle time. Reaction conditions: pinacol (8.5 mmol, 1.0 g), ChCl/HCOOH (molar ratio 2:1) 8.0 g, 140 oC, 12 h. After each usage, the ChCl/HCOOH was dried at room temperature under vacuum for 10 h.

S18 (a) Formic acid

(b) Formic acid

Fig. S9. HPLC chromatograms of a) the solution prepared by the dilution of ChCl/HCOOH (molar ratio 2:1, 8.0 g) with 30 mL H2O and b) the solution prepared by diluting the mixture of pinacol (1.0 g), o ChCl/HCOOH (molar ratio 2:1, 8.0 g) which has been heated at 140 C for 12 h with 30 mL H2O. Column: Rezex ROA-Organic Acid H+, eluent: 5 mmol/L sulfuric acid, flow rate: 0.5 mL/min, detection wavelength: 210 nm, column temperature: 45 oC. The area of formic acid was comparable, indicating that HCOOH did not decompose in the course of the reaction.

S19 120 oC H CO Et CO Et 2 or 100 oC 2 + Neat CO Et CO Et 2 H 2 2 8

a) 120 oC, neat

H CO2Et

CO Et H 2 8

H CO2Et o CO Et b) 100 C, neat H 2 8

Diethyl maleate Compound 2

Fig. S10. GC chromatograms of the D-A reaction product of compound 2 and diethyl maleate. Reaction conditions: a) compound 2 (10.0 mmol, 1.1 mL), diethyl maleate (10.0 mmol, 1.6 mL), 120 oC, 6 h; b) compound 2 (10.0 mmol, 1.1 mL), diethyl maleate (10.0 mmol, 1.6 mL), 100 oC, 12 h.

S20 H EtO2C CO2Et 120 oC + CO Et CO Et 2 H 2 2 10

H CO2Et

CO Et H 2 10

Fig. S11. GC chromatogram of the D-A reaction product of compound 2 and diethyl fumarate. Reaction conditions: compound 2 (10.0 mmol, 1.1 mL), diethyl fumarate (10.0 mmol, 1.6 mL), 120 oC, 6 h.

S21 H H CO Et CO Et CO Et 2 Pd/C 2 2 + o CO Et 220 C CO Et CO Et H 2 2 H 2 8 9 10

CO2Et

H CO Et CO2Et 2 9 CO Et internal standard H 2 (p-xylene) 10

Fig. S12. GC chromatogram of the dehydrogenation of compound 8 at 220 oC under solvent-free condition. Reaction conditions: compound 8 (10.0 mmol, 2.5 g), Pd/C (250 mg), 220 oC for 24 h.

S22 H CO Et CO Et 2 Pd/C 2 220 oC CO2Et CO Et H slow 2 10 9

H CO2Et CO2Et CO Et H 2 CO2Et 10 9 internal standard (p-xylene)

Fig. S13. GC chromatogram of the dehydrogenation of compound 10 at 220 oC under solvent-free condition. Reaction conditions: compound 10 (10.0 mmol, 2.5 g), Pd/C (250 mg), 220 oC for 24 h.

S23 H H CO Et CO Et CO Et 2 Pd/C 2 2 + 220 oC CO2Et CO Et CO2Et H 48 h 2 H 8 9 10

H CO2Et

CO Et H 2 10 CO2Et

CO Et internal standard 2 (p-xylene) 6

Fig. S14. GC chromatogram of the dehydrogenation of compound 8 at 220 oC under solvent-free condition. Reaction conditions: compound 8 (10.0 mmol, 2.5 g), Pd/C (250 mg), 220 oC for 48 h.

S24 H H CO Et CO Et CO Et 2 Pd/C 2 2 + CO Et CO Et CO Et H 2 2 H 2 8 9 10

Conversion of compound 8 Carbon yield of compound 9 Carbon yield of compound 10

) 100 % (

d l e

i 80 y

n o b

a 60 c

r o

n 40 o i s r e v

n 20 o C 0 200 220 240 260 Reaction temperature (oC)

Fig. S15. Effect of dehydrogenation temperature on the conversion of compound 8 and carbon yields of compounds 9 and 10 from the solvent-free dehydrogenation. Reaction conditions: compound 8 (10.0 mmol, 2.5 g), Pd/C (250 mg), 24 h.

S25 CO2Et CO2Et Isomerization

EtO2C CO2Et Diethyl maleate Diethyl fumarate

CO2Et CO2Et

CO2Et EtO2C

Fig. S16. GC chromatogram of the isomerization of diethyl maleate. Reaction conditions: diethyl maleate (10.0 mmol, 1.6 mL), Pd/C (250 mg), 220 oC, 24 h.

S26 HO OH CO2Et CO2Et ChCl/HCOOH + 140 oC CO2Et CO2Et One-step 1 4 8 + 10 (7.1 : 1) 89% yield

H CO2Et

CO Et H 2 8

internal standard (tridecane)

pinacolone H CO2Et internal standard CO Et (p-xylene) H 2 10

Fig. S17. GC chromatogram of the one-step reaction of pinacol and diethyl maleate. Reaction conditions: pinacol (10.0 mmol, 1.2 g), ChCl/HCOOH (2:1, 9.6 g), diethyl maleate (10.0 mmol, 1.6 mL), 140 oC, 12 h.

S27 HO OH CO2Et ChCl/HCOOH + 140 oC CO Et 1 2 One-step 13 83% yield

CO Et internal standard 2 (toluene) pinacolone internal standard (tridecane)

Fig. S18. GC chromatogram of the one-step reaction of pinacol and ethyl acrylate. Reaction conditions: pinacol (10.0 mmol, 1.2 g), ChCl/HCOOH (2:1, 9.6 g), ethyl acrylate (10.0 mmol, 1.0 mL), 140 oC, 12 h.

S28 Pd/C, 220 oC CO Et 2 CO2Et 13 14

internal standard toluene

unknown impurities

CO2Et

Fig. S19. GC chromatogram of the dehydrogenation of the D-A adduct. Reaction conditions: the D-A adduct 13 (10.0 mmol, 1.8 g), Pd/C (180 mg), 220 oC for 24 h.

S29 4.98 4.89 1.84

1 H NMR (400 MHz, CDCl3) 2.00 1.96 6.04

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S20. 1H NMR of compound 2 143.50 113.11 77.48 77.16 76.84 20.67

13 C NMR (100 MHz, CDCl3)

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S21. 13C NMR of compound 2.

S30 2.07 1.07 0.00

1 H NMR (400 MHz, CDCl3) 3.00 9.05

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S22. 1H NMR of compound 3. 214.39 77.48 77.16 76.84 44.39 26.46 24.78

13 C NMR (100 MHz, CDCl3)

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 f1 (ppm) Fig. S23. 13C NMR of compound 3.

S31 HYC-222D.10.fid 7.26 3.34 3.33 3.33 3.33 3.32 3.32 3.31 2.45 2.41 2.27 2.24 1.69

5 O

1 H NMR (400 MHz, CDCl3) 1.95 1.98 2.02 6.00

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S24. 1H NMR of compound 5.

HYC-222D.11.fid 174.64 127.40 77.48 77.16 76.84 40.47 30.53 19.36

5 O

13 C NMR (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S25. 13C NMR of compound 5.

S32

7.26 4.16 4.15 4.14 4.14 4.13 4.13 4.11 4.11 4.10 4.09 4.09 4.08 2.98 2.98 2.97 2.97 2.96 2.96 2.95 2.45 2.44 2.41 2.40 2.25 2.24 2.21 2.21 2.20 1.61 1.24 1.23 1.22 1.20

H CO2Et

CO Et H 2 8

1 H NMR (400 MHz, CDCl3 ) 3.98 1.95 1.98 2.04 6.00 6.00

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S26. 1H NMR of compound 8.

173.52 124.01 77.48 77.16 76.84 60.53 40.59 31.95 19.02 14.25

H CO2Et

CO Et H 2 8

13 C NMR (100 MHz, CDCl3 )

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S27. 13C NMR of compound 8.

S33 7.38 4.27 4.25 4.24 4.22 2.20 1.28 1.26 1.24 0.00

CO2Et

CO2Et 9

1 H NMR (400 MHz, CDCl3) 2.00 4.08 6.09 6.05

8 7 6 5 4 3 2 1 0 ppm Fig. S28. 1H NMR of compound 9. 167.77 139.97 129.94 129.70 77.47 77.16 76.84 61.31 19.57 14.09

CO2Et

CO2Et 9

13 C NMR (100 MHz, CDCl3)

180 160 140 120 100 80 60 40 20 0 ppm Fig. S29. 13C NMR of compound 9.

S34 7.26 4.15 4.15 4.14 4.13 4.12 4.11 4.10 4.09 4.08 4.07 2.82 2.80 2.79 2.78 2.76 2.76 2.74 2.26 2.22 2.14 2.13 2.12 2.10 2.08 1.60 1.24 1.23 1.21

H CO2Et

CO Et H 2 10

1 H NMR (400 MHz, CDCl3 ) 4.00 1.98 1.99 2.07 6.03 6.02

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S30. 1H NMR of compound 10. 175.04 123.98 77.48 77.16 76.84 60.57 42.22 34.31 18.69 14.27

H CO2Et

CO Et H 2 10

13 C NMR (100 MHz, CDCl3 )

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S31. 13C NMR of compound 10.

S35 12.88 7.43 2.50 2.50 2.49 2.27

CO2H

CO2H 11

1H NMR (400 MHz, d6-DMSO) 2.01 2.00 6.06

15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm Fig. S32. 1H NMR of compound 11. 168.78 139.44 130.41 129.37 40.15 39.94 39.73 39.52 39.31 39.10 38.89 19.16

CO2H

CO2H 11

13C NMR (100 MHz, d6-DMSO)

180 160 140 120 100 80 60 40 20 0 ppm Fig. S33. 13C NMR of compound 11.

S36 13.52 7.92 2.51 2.50 2.50 2.50 2.49

HO2C CO2H

HO2C CO2H 12

1H NMR (400 MHz, d6-DMSO) 4.00 2.03

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 f1 (ppm) Fig. S34. 1H NMR of compound 12. 167.34 134.65 128.50 40.15 39.94 39.73 39.52 39.31 39.10 38.89

HO2C CO2H

HO2C CO2H 12

13C NMR (100 MHz, d6-DMSO)

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S35. 13C NMR of compound 12.

S37 7.26 4.15 4.13 4.12 4.10 2.53 2.52 2.51 2.50 2.49 2.49 2.47 2.47 2.46 2.45 2.23 2.18 2.16 2.12 2.10 2.07 2.03 1.98 1.97 1.97 1.94 1.91 1.61 1.60 1.26 1.25 1.23

CO2Et 13 1 H NMR (400 MHz, CDCl3) 2.04 1.00 5.90 6.39 3.01

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S36. 1H NMR of compound 13. 176.17 125.36 124.06 77.48 77.16 76.84 60.29 40.37 33.86 31.15 25.99 19.10 18.96 14.38

CO2Et 13 13 C NMR (100 MHz, CDCl3)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S37. 13C NMR of compound 13.

S38 7.81 7.79 7.78 7.77 7.76 7.26 7.19 7.17 4.38 4.37 4.35 4.33 2.31 1.41 1.39 1.37

CO2Et 14 1 H NMR (400 MHz, CDCl3) 1.01 0.98 1.00 2.06 6.09 3.09

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) Fig. S38. 1H NMR of compound 14. 167.00 142.19 136.73 130.69 129.71 128.20 127.22 77.48 77.16 76.84 60.80 20.10 19.78 14.49

CO2Et 14 13 C NMR (100 MHz, CDCl3)

180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 f1 (ppm) Fig. S39. 13C NMR of compound 14.

S39 12.71 7.71 7.67 7.65 7.25 7.23 2.50 2.27 2.26

CO2H 15

1H NMR (400 MHz, d6-DMSO) 1.09 0.94 0.90 1.08 6.00

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm Fig. S40. 1H NMR of compound 15. 167.52 141.76 136.52 130.26 129.62 128.46 126.92 40.15 39.94 39.73 39.52 39.31 39.10 38.89 19.56 19.32

CO2H 15

13C NMR (100 MHz, d6-DMSO)

180 160 140 120 100 80 60 40 20 0 ppm Fig. S41. 13C NMR of compound 15.

S40 13.50 8.23 8.12 8.10 7.77 7.75 2.50

HO2C

HO2C CO2H 16

1H NMR (400 MHz, d6-DMSO) 3.08 1.04 1.00 0.93

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 f1 (ppm) Fig. S42. 1H NMR of compound 16. 168.41 167.50 165.98 137.42 134.30 132.42 131.75 129.43 128.71 40.15 39.94 39.73 39.52 39.31 39.10 38.90

HO2C

HO2C CO2H 16

13C NMR (100 MHz, d6-DMSO)

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) Fig. S43. 13C NMR of compound 16.

S41