contentskolbe-schmitt type reaction under ambient conditions mediated by organic base yuta...

S1

Supporting Information

Kolbe-Schmitt Type Reaction under Ambient Conditions Mediated by Organic Base

Yuta Sadamitsu, Akira Okumura, Kodai Saito, and Tohru Yamada*

Contents

1. General S2

2. Supporting results & discussion

2.1 Confirmation of decarboxylation of 2n S2

2.2 Molecular orbital of HOMO of resorcinol dianion 1a’-1q’ (B3LYP/6-311++G**) S3

2.3 Examination and consideration of the site-selectivity of 1q S6

3. General procedure & characterization data

3.1 Procedure for the preparation of resorcinols S7

3.2 Procedure for Kolbe-Schmitt reaction on resorcinols S13

4. NMR Spectra S20

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2019

S2

1. General

1H and 13C NMR spectra were recorded with a JEOL model AL-400, alpha-400 or ECX-400 spectrometer using CD3CN, Acetone-d6 or DMSO-d6 as the solvent. IR spectra were measured with a Thermo Electron Corporation model NICOLET 6700 FT-IR spectrometer. Melting points were measured with a Stanford Research Systems MPA100. ESI high resolution mass spectra were obtained using a Waters LCT Premier XE mass spectrometer. Column chromatography was conducted on silica gel (CHROMATOREX PSQ 100B Fuji Silysia). DBU was purchased from Tokyo Chemical Industry Co., Ltd., and used without further purification. Dehydrated CH3CN was purchased from FUJIFILM Wako Pure Chemical Co..

2. Supporting results & discussion

2.1 Confirmation of decarboxylation of 2n

When the resorcinol 1n was treated with 3 equiv of DBU in CH3CN under 2 MPa of CO2 atmosphere at 30 °C, the carboxylated product 2n was not observed. On the other hand, when the salicylic acid 2n was employed for this reaction condition under Ar atmosphere, the decarboxylation proceeded to afford the resorcinol 1n (20% conversion, detected by 1H NMR). It suggested that the reaction rate of decarboxylation of 2n was faster than that of carboxylation of 1n.

6.0

DFI E 20180831 ex.2000.alsC auto DA I Fri Aug 31 20:45:18 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 24.5 c

DE EF 2.49 ppmBF 0.12 HzGAI 13

1.0

0

0.5

5

0.2

6

1.0

2

6.1

46

6.1

39

6.0

67

6.0

63

5.9

31

5.9

26

5.9

21

5.7

99

5.7

93

Ha Hb

Ha’ Hb’

OH

HO Br

COOHHa

Hb

OH

HO Br

Ha’

Hb’

Hb’Ar (balloon)DBU (3.0 equiv)

CH3CN, 30 °C, 24 h

2n 1n

S3

2.2 Molecular orbital of HOMO of resorcinol dianion 1a’-1q’ (B3LYP/6-311++G**)

The HOMO of dianions of resorcinols 1a’-1q’ were calculated at the level of B3LYP/ 6-311++G**.

1a’

O

O

O

O

Me

1b’

O

O

Et

1c’

O

O

Me Me

O

O Me1e’

O

O

MeO

1d’

1f’

OH

HO R

OH

HO R

COOH

CO2

1a-1n 2a-2n

DBU 2

S4

O

OOMe

1g’

O

OOH

1h’

1i’ 1j’

O

OMe

O

1k’

O

O

Br

1l’

O

OBr

1m’ 1n’

O

O Br

O

O

HNMe

O

O

O

Me

O

S5

O

O

OMe

1o’

O

O O

OMe

1p’

O

O OMe

1q’

The carboxylation site of 1q was not matched with the site predicted by the theoretical caluculation. Please see the detail at the next section (S6).

OH

HO R

OH

HO RCO2

1o-1q 3o-3q

DBU HOOC 6

S6

2.3 Examination and consideration of the site-selectivity of 1q

According to the HOMO of dianion 1q’ computed by theoretical calculation, the carboxylation should occur at the 2-position of resorcinol 1q. However, when 1q was employed for this reaction, only 6-carboxylated product 3q was obtained. In order to elucidate this reason, time course experiment of the carboxylation reaction of 1q using 1H NMR was conducted. When 3 equiv of DBU was added to 1q, Hb was observed in the lowest chemical shift. It suggested that the Hb (2-position) is the most reactive site. After 2 MPa of CO2 was purged and the reaction was stirred for 1 h, the two doublet peaks appeared. Those could be signals of 2-carboxylated product 2q. Thus, it indicated that carboxylation at Cb was faster than that of Ca. After furthermore reaction, one singlet peak area was increased and former two doublet peaks were diminished. The singlet peak was assigned as the signal of 6-carboxylated product 3q. It indicated that 2-carboxylated product 2q is not thermodynamically stable and decarboxylation proceeded. Therefore, 3q was finally obtained.

PPM

5.707

OX

XO

Ha Hb

HbOMe

(X = H or H-DBU+)

OX

XO

Ha’ COOX

Hb’OMe

(X = H or H-DBU+)

OX

XO

XOOC Hb’’

Hb’’OMe

(X = H or H-DBU+)

1q + DBU (3 equiv) 0 h

1 h

3 h

6 h

24 h

1q’

2q’

3q’

Ha Hb

Ha’ and Hb’

Hb’’

1q + DBU (3 equiv) + CO2

S7

3. General procedure & characterization data

3.1 Procedure for the preparation of resorcinols

3.1.1 The preparation of 1c1

Resorcinol 1c was prepared by the following procedure1. Under N2 atmosphere, 2’,6’-dihydroxyacetophenone (304.3 mg, 2.0 mmol) was dissolved into TFA (6.7 mL). To the solution, triethylsilane (0.92 mL, 5.8 mmol) was added dropwise. After being stirred for 3 h at room temperature, the reaction was neutralized by sat. NaHCO3 aq., and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the desired resorcinol 1c (224.6 mg, 81%).

2-ethylbenzene-1,3-diol (1c)2

Pale brown solid; 1H NMR (400 MHz, CD3CN): d = 1.05 (t, J = 7.2 Hz, 3H), 2.56 (q, J = 7.2 Hz, 2H), 6.32 (d, J = 7.6 Hz, 2H), 6.65-6.69 (m, 2H), 6.82 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d = 13.8, 16.1, 106.2, 116.6,

125.9, 156.0. 3.1.2 The preparation of 1d1,3,4

OH

HO

O

MeEt3SiH (2.9 equiv)

TFA (0.3 M), r.t., 3 h81%

OH

HO

Me

1c

OH

HO

O Me

K2CO3 (3.0 equiv)MeI (2.5 equiv)

DMF (1.6 M), r.t., 16 h92%

OMe

MeO

O

MeMgBr (1.5 equiv)THF (0.5 M), 0 °C to r.t.

90%

OMe

MeO

HO MeMe

Me

S1 S2

Et3SiH (2.9 equiv)TFA (0.3 M), r.t., 3 h

74%

OMe

MeO

Me Me

S3

BBr3 (2.4 equiv)DCM (1.0 M), 0 °C to r.t.

59%

OH

HO

Me Me

1d

OH

HO

Me

S8

Resorcinol 1d was prepared by the following procedure1,3,4. Under N2 atmosphere, 2’,4’-dihydroxy acetophenone (760.8 mg, 5.0 mmol), and K2CO3 (2.07 g, 15 mmol) were dissolved into DMF (3.1 mL). To the solution, iodomethane (0.78 mL, 12.5 mmol) was added. After being stirred for 16 h at room temperature, the reaction was diluted by water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=20:1) to afford the acetophenone S1 (826.7 mg, 92%).

Under N2 atmosphere, the acetophenone S1 (826.7 mg, 4.6 mmol) was dissolved into THF (9.2 mL). After cooling at 0 °C, MeMgBr (6.9 mL, 6.9 mmol, 1.0 M solution in THF) was added dropwise, and the reaction was warmed to room temperature. The reaction was quenched by sat. NH4Cl aq., and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=5:1) to afford the benzyl alcohol S2 (806.8 mg, 90%).

Under N2 atmosphere, the benzyl alcohol S2 (392.5 mg, 2.0 mmol) was dissolved into TFA (6.7 mL). To the solution, triethylsilane (0.92 mL, 5.8 mmol) was added dropwise. After being stirred for 3 h at room temperature, the reaction was neutralized by sat. NaHCO3 aq., and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=50:1) to afford the desired dimethoxybenzene S3 (266.6 mg, 74%).

Under N2 atmosphere, dimethoxybenzene S3 (855.3 mg, 4.7 mmol) was dissolved into DCM (4.7 mL). After cooling at 0 °C, BBr3 (11.3 mL, 11.3 mmol, 1.0 M solution in DCM) was added dropwise, and the reaction was warmed to room temperature. The reaction was quenched by water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the resorcinol 1d (424.1 mg, 59%).

4-isopropylbenzene-1,3-diol (1d)5

Pale brown solid; 1H NMR (400 MHz, DMSO-d6): d = 1.08 (d, J = 6.8 Hz, 6H), 3.05 (sept, J = 6.8 Hz, 1H), 6.13 (dd, J = 2.4, 8.4 Hz, 1H), 6.24 (d, J = 2.4 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 8.89 (bs, 1H), 9.01 (s, 1H); 13C NMR (100 MHz, DMSO-d6): d = 22.9, 25.8, 102.4, 105.9, 124.8, 126.1, 155.0, 155.8.

OH

HO

MeMe

S9

3.1.3 The preparation of 1f6

Resorcinol 1f was prepared by the following procedure6. Under N2 atmosphere, pyrogallol (630.6 mg, 5.0 mmol), and Li2CO3 (923.6 mg, 12.5 mmol) were dissolved into DMF (19 mL). To the solution, iodomethane (0.78 mL, 12.5 mmol) was added and the reaction mixture was stirred at 50 °C overnight. The reaction was diluted by water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=5:1 to 3:1) to afford the resorcinol 1f (138.9 mg, 20%).

2-methoxybenzene-1,3-diol (1f)6

White solid; 1H NMR (400 MHz, DMSO-d6): d = 3.65 (s, 3H), 6.26 (d, J = 8.4 Hz, 2H), 6.65 (t, J = 8.4 Hz, 1H), 8.99 (s, 2H); 13C NMR (100 MHz, DMSO-d6): d = 59.8, 107.4, 123.5, 135.7, 151.0.

3.1.4 The preparation of 1g7,8

Resorcinol 1g was prepared by the following procedure7,8. Under N2 atmosphere, isovanillin (1.52 g, 10 mmol), DMAP (2 pieces, cat.), and pyridine (1.6 mL, 20 mmol) were dissolved into DCM (20 mL). After cooling at 0 °C, AcCl (0.71 mL, 12.5 mmol) was added

OHHO

HO

OHMeO

HO

Li2CO3 (2.5 equiv)MeI (2.5 equiv)

DMF (0.26 M), r.t. to 50 °Covernight, 20%

1f

OMe

H O

HO

DMAP (cat.)Pyridine (2.0 equiv)AcCl (1.0 equiv)DCM (0.5 M), 0 °C

86%OMe

H O

AcO

S4

mCPBA (2.0 equiv)DCM (0.3 M), reflux

74%

OMe

O

AcO

O

H

MeOH (0.5 M), r.t.72%

OMe

OH

HO

1g

S5

NaHCO3 (2.0 equiv)

OH

HO

MeO

S10

dropwise. The reaction was quenched by water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the benzaldehyde S4 (1.66 g, 86%).

Under N2 atmosphere, the benzaldehyde S4 (918.6 g, 4.7 mmol) and mCPBA (2.33 g, 9.5 mmol, contains ca. 30% water) were dissolved into DCM (16 mL), and the reaction was refluxed. The reaction was quenched by sat. NaHSO3 aq., and extracted three times with DCM, and washed with sat. NaHCO3 aq.. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=5:1) to afford the methoxybenzene S5 (732.3 mg, 74%).

The methoxybenzene S5 (732.3 mg, 3.5 mmol) and NaHCO3 (588.1 mg, 7.0 mmol) were dissolved into MeOH (7 mL), and the reaction was stirred at room temperature. The reaction was diluted with water and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the resorcinol 1g (348.8 g, 72%).

4-methoxybenzene-1,3-diol (1g)9

White solid; 1H NMR (400 MHz, DMSO-d6): d = 3.63 (s, 3H), 6.10 (dd, J =2.8 Hz, 8.4 Hz, 1H), 6.26 (d, J = 2.8 Hz, 1H) , 6.67 (d, J = 8.4 Hz, 1H), 8.76 (s, 1H), 8.81 (s, 1H); 13C NMR (100 MHz, DMSO-d6): d = 55.6, 103.8, 104.9, 114.2, 140.7, 147.5, 151.9.

3.1.5 The preparation of 1i10,11

OMe

MeO

nBuLi (1.25 equiv)B(OMe)3 (2.0 equiv)

THF (0.17 M), 0 °C to -78 °C81%

OMe

MeO

(HO)2BNaOH (5.0 equiv)HSA (1.5 equiv)

MeCN/H2O (1:1), µW100 °C, 80%

OMe

MeO

H2N

S6 S7

AcCl (1.0 equiv)DCM (1.0 M), 0 °C to r.t.

93%

OMe

MeO

HNMe

O


83%

OH

HO

HNMe

O

S8 1i

OH

HOOMe

S11

Resorcinol 1i was prepared by the following procedure10,11. Under N2 atmosphere, 1,3-dimethoxybenzene (1.3 mL, 10 mmol) was dissolved into THF (59 mL). The reaction was cooled at 0 °C, and nBuLi (0.92 mL, 8.0 mmol, 1.57 M solution in n-hexane) was added, dropwise. After being stirred for 4 h at 0 °C, the reaction was cooled at -78 °C, and B(OMe)3 (2.2 mL, 20 mmol) was added. After stirred overnight at room temperature, the reaction was quenched with 1 N HCl aq., and stirred for 1 h. The reaction mixture was extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the desired phenyl boronic acid S6 (1.48 g, 81%).

To the vial, the aryl boronic acid S6 (364.0 mg, 2.0 mmol), Hydroxylamine-O-sulfonic acid (339.3 mg, 3.0 mmol), MeCN (10 mL), and NaOH (10 mmol, 10 mL, 1 N solution in H2O) were added. The vial tube was sealed and heated with microwave at 100 °C for 1 h. After the reaction was cooled to room temperature, the reaction mixture was extracted three times with Et2O. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=5:1) to afford the desired aniline S7 (244.7 mg, 80%).

Under N2 atmosphere, the aniline S7 (408.6 mg, 2.7 mmol) was dissolved into DCM (3 mL). The reaction was cooled at 0 °C, and AcCl (0.19 mL, 2.7 mmol) was added, dropwise. After stirred overnight at room temperature, the reaction was quenched with water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=1:1) to afford the desired amide S8 (484.3 mg, 93%).

Under N2 atmosphere, amide S3 (484.3 mg, 2.5 mmol) was dissolved into DCM (25 mL). After cooling at 0 °C, BBr3 (6.0 mL, 6.0 mmol, 1.0 M solution in DCM) was added dropwise, and the reaction was warmed at room temperature. The reaction was quenched by water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=2:1) to afford the resorcinol 1i (344.1 mg, 83%)

N-(2,6-dihydroxyphenyl)acetamide (1i)12

Pale brown solid; 1H NMR (400 MHz, DMSO-d6): d = 2.10 (s, 3H), 6.34 (d, J = 7.6 Hz, 2H), 6.86 (d, J = 7.6 Hz, 1H) , 9.24-9.51 (m, 3H); 13C NMR (100 MHz, DMSO-d6): d = 22.8, 107.6, 114.1, 126.7, 152.1, 170.4.

OH

HO

HNMe

O

S12

3.1.6 The preparation of 1l13

Resorcinol 1l was prepared by the following literature13. Under N2 atmosphere, resorcinol (220.2 mg, 2.0 mmol) was dissolved into CHCl3 (2.0 mL). After cooling at 0 °C, Br2 (0.36 mL, 7.0 mmol) was added dropwise, and the reaction was warmed at room temperature. After being stirred, the solvent was removed, and the crude was dissolved into MeOH (0.8 mL). To the reaction, NaOH (160.0 mg, 4.0 mmol), Na2SO3 (504.2 mg, 4.0 mmol), and water (4 mL) was added and stirred for 1 h. The reaction was quenched by 1 N HCl aq., and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the resorcinol 1l (325.0 mg, 86%)

2-bromobenzene-1,3-diol (1l)14

White solid; 1H NMR (400 MHz, DMSO-d6): d = 6.39 (d, J = 8.4 Hz, 2H), 6.91 (t, J = 8.4 Hz, 1H), 9.96 (s, 2H); 13C NMR (100 MHz, DMSO-d6): d = 98.0, 106.8, 128.0, 155.5.

3.1.7 The preparation of 1n4

Resorcinol 1n was prepared by the following procedure4. Under N2 atmosphere, 5-bromo-1,3-dimethoxybenzene (1.09 g, 5.0 mmol) was dissolved into DCM (5 mL). After cooling at 0 °C, BBr3 (12 mL, 12 mmol, 1.0 M solution in DCM) was added dropwise, and the reaction was warmed at room temperature. The reaction was quenched by water, and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=3:1) to afford the resorcinol 1n (562.8 mg, 60%)

OH

HO

Br2 (3.5 equiv)CHCl3 (1.0 M), 0 °C to r.t.

NaOH (2.0 equiv)Na2SO3 (2.0 equiv)H2O/MeOH (5:1)

86% (over 2 steps)

OH

HO

Br

1l

OMe

MeO Br


60%

OH

HO Br

1n

OH

HO

Br

S13

5-bromobenzene-1,3-diol (1n)4

Pale brown solid; 1H NMR (400 MHz, DMSO-d6): d = 6.19 (t, J = 2.0 Hz, 1H), 6.38 (d, J = 2.0 Hz, 2H) , 9.69 (s, 2H); 13C NMR (100 MHz, DMSO-d6): d = 101.8, 109.4, 121.8, 159.3.

3.1.8 The preparation of 1q15

Resorcinol 1q was prepared by the following literature15. Under N2 atmosphere, phloroglucinol (630.6 mg, 5.0 mmol) was dissolved into MeOH (7 mL). To the reaction, H2SO4 (1.0 mL, 19.5 mmol) was added dropwise, and the reaction was refluxed for 3 h. The reaction was quenched by sat. NaHCO3 aq., and extracted three times with EtOAc. The combined organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=4:1 to 2:1) to afford the resorcinol 1n (442.7 mg, 63%)

5-methoxybenzene-1,3-diol (1q)16

White solid; 1H NMR (400 MHz, DMSO-d6): d = 3.60 (s, 3H), 5.78 (s, 2H), 5.81 (s, 1H), 9.19 (s, 2H); 13C NMR (100 MHz, DMSO-d6): d = 54.7, 92.6, 95.5, 159.1, 161.2.

3.2 Procedure for Kolbe-Schmitt reaction on resorcinols

The reaction was performed using a pressure test tube equipped with a stirring bar in a 30 mL autoclave. To a solution of resorcinol 1a (11.0 mg, 0.100 mmol) in dry CH3CN (1.0 mL) in a pressure test tube was added DBU (44.9 μL, 0.300 mmol). The pressure test tube containing the reaction mixture was placed in the autoclave. CO2 (2.0 MPa) was charged and the reaction mixture was stirred at 30 °C for 24 h. After the CO2 was carefully vented, 1 M HCl aq. (ca. 3.0 mL) was added to the mixture. The resulting mixture was extracted with ethyl acetate three times and volatile materials were removed under reduced pressure. The residue was purified by flash silica-gel column chromatography (eluent: EtOAc:AcOH=99:1, v/v) to afford 2a (15.4 mg, 0.999 mmol) in >99% as a white solid. The larger scale reaction was carried out as follows. The reaction was performed using

OH

HO OH

H2SO4 (3.9 equiv)MeOH (0.69 M), reflux, 3 h

63%

OH

HO OMe

1q

OH

HO Br

OH

HO OMe

S14

a 1 L three necked round bottom flask. To a solution of resorcinol 1a (11.0 g, 0.100 mol) in dry CH3CN (500 mL) in a flask was added DBU (44.9 mL, 0.300 mol). CO2 (balloon) was charged and the reaction mixture was stirred at room temperature for 28 h. After the CO2 balloon was removed, 1 M HCl aq. (ca. 500 mL) was added to the mixture. The resulting mixture was extracted with ethyl acetate several times (checked by TLC) and volatile materials were removed under reduced pressure. The residue was purified by recrystallization (hexane/EtOAc) to afford 2a (12.9 g, 0.838 mol) in 84% as a white solid.

2,4-dihydroxybenzoic acid (2a)17

White solid; 1H NMR (400 MHz, DMSO-d6): d = 6.25 (d, J = 2.4 Hz, 1H), 6.33 (dd, J = 2.4 Hz, 8.8 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 10.42 (bs, 1H), 11.40 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 102.4, 104.5, 108.1,

132.1, 163.5, 164.2, 172.1. 2,4-dihydroxy-3-methylbenzoic acid (2b)

The reaction was carried out with 1b (12.4 mg, 0.1 mmol), DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (16.0 mg, 95%); mp 182 °C (decomp.)(lit.18, 213-214 °C, decomp); 1H NMR (400 MHz,

DMSO-d6): d = 1.95 (s, 3H), 6.39 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 10.29 (s, 1H), 11.72 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 7.9, 103.9, 107.0, 110.2, 128.5, 161.4, 161.6, 172.6.; IR (KBr): 3426, 1645, 1622, 1504, 1420, 1300, 1084, 781; HRMS (ESI): [M+H]+ calcd for C8H9O4+, 169.0495; found, m/z 169.0498. 3-ethyl-2,4-dihydroxybenzoic acid (2c)

The reaction was carried out with 1c (13.8 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (18.2 mg, quant); mp 167 °C (decomp.); 1H NMR (400 MHz, DMSO-d6): d = 1.01 (t, J = 7.2 Hz, 3H), 2.52 (q, J = 7.2 Hz, 2H), 6.39 (d, J = 8.8 Hz, 1H), 7.48 (d, J

= 8.8 Hz, 1H), 10.22 (s, 1H), 11.71 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 13.3,15.6, 104.0, 107.2, 116.5, 128.7, 161.2, 161.3, 172.6 ; IR (KBr): 3415, 1621, 1423, 1278, 1098, 792 ; HRMS (ESI): [M+H]+ calcd for C9H11O4+, 183.0652; found, m/z 183.0657. 2,4-dihydroxy-5-isopropylbenzoic acid (2d)19

The reaction was carried out with 1d (15.2 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (16.6 mg, 85%); 1H NMR (400 MHz, DMSO-d6): d = 1.11 (d, J = 7.2 Hz, 6H), 3.06 (sept, J = 7.2 Hz, 1H), 6.31 (s, 1H), 7.48 (s, 1H), 10.34 (s, 1H), 11.30 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 22.5, 25.8, 102.0, 103.8, 126.7, 127.4,

OH

HO

COOH

OH

HO

COOHMe

OH

HO

COOHMe

OH

HO

COOH

Me Me

S15

161.3, 161.4, 172.1. 2,4-dihydroxy-6-methylbenzoic acid (2e)20

The reaction was carried out with 1e (12.4 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 40 ºC for 24 h; White solid (16.0 mg, 95%); ; 1H NMR (400 MHz, DMSO-d6): d = 2.46 (s, 3H), 6.16 (d, J = 2.4 Hz, 1H),

6.21 (d, J = 2.4 Hz, 1H), 10.10 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 23.5, 100.5, 104.9, 111.1, 143.0, 162.0, 164.5, 173.4. 2,4-dihydroxy-3-methoxybenzoic acid (2f)21

The reaction was carried out with 1f (14.0 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (15.2 mg, 83%);1H NMR (400 MHz, DMSO-d6): d = 3.69 (s, 3H), 6.33 (d, J = 9.2 Hz, 1H),

7.36 (d, J = 9.2 Hz, 1H), 9.91 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 59.8, 105.3, 107.8, 125.7, 134.8, 156.2, 156.4, 172.3. 2,4-dihydroxy-5-methoxybenzoic acid (2g)

The reaction was carried out with 1g (14.0 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (17.9 mg, 97%); mp 174 °C (decomp.)(lit.22, 201 °C, decomp.); 1H NMR (400 MHz, DMSO-d6): d = 3.69 (s, 3H), 6.32 (s, 1H), 7.14 (s, 1H), 10.31 (bs, 1H); 13C NMR

(100 MHz, DMSO-d6): d = 56.3, 102.8, 103.5, 112.2, 141.4, 154.5, 158.0, 172.1 ; IR (KBr): 3488, 1654, 1624, 1259, 1171, 1025, 868; HRMS (ESI): [M+H]+ calcd for C8H9O5+, 185.0444; found, m/z 185.0458. 5,7-dihydroxyisobenzofuran-1(3H)-one (2h)

The reaction was carried out with 1h (14.0 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; Pale purple solid (15.2 mg, 92%); mp 221 °C (decomp.)(lit., 253-260, decomp.); 1H NMR (400 MHz, DMSO-d6):

d = 5.10 (s, 2H), 6.28 (d, J = 1.2 Hz, 1H), 6.33 (d, J = 1.2 Hz, 1H), 10.30-10.59 (m, 2H); 13C NMR (100 MHz, DMSO-d6): d = 68.1, 100.2, 102.2, 102.9, 151.5, 158.2, 164.6, 168.5; IR (KBr): 3358, 3213, 1717, 1617, 1487, 1351, 1217, 1167, 1053; HRMS (ESI): [M+H]+ calcd for C7H7O4+, 167.3339; found, m/z 167.3338.

OH

HO

COOH

Me

OH

HO

COOHMeO

OH

HO

COOH

OMe

OH

HOO

O

S16

3-acetamido-2,4-dihydroxybenzoic acid (2i) The reaction was carried out with 1i (16.7 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (18.9 mg, 90%); mp 169 °C; 1H NMR (400 MHz, DMSO-d6): d = 2.01 (s, 3H),

6.42 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 9.04 (s, 1H), 10.21 (s, 1H), 11.81 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 22.8, 104.5, 107.9, 112.8, 129.0, 159.0, 159.3, 169.2, 172.3; IR (KBr): 3385, 1660, 1617, 1426, 1267, 1241, 756 ; HRMS (ESI): [M+H]+ calcd for C9H10O5N+, 212.0553; found, m/z 212.0555. 3-acetyl-2,4-dihydroxybenzoic acid (2j)

The reaction was carried out with 1j (15.2 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 40 ºC for 24 h; White solid (14.5 mg, 74%); mp 159 °C (decomp.); 1H NMR (400 MHz, DMSO-d6): d = 2.62 (s, 3H),

6.44 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 12.88 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 32.3, 104.1, 108.3, 111.4, 135.8, 164.1, 166.2, 171.9, 203.5; IR (KBr): 3437, 2843, 1629, 1585, 1480, 1451, 1261, 1235; HRMS (ESI): [M+H]+ calcd for C9H9O5+, 197.0444; found, m/z 197.0446. 2-acetyl-4,6-dihydroxybenzoic acid (2k)

The reaction was carried out with 1k (15.2 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 40 ºC for 24 h; White solid (13.7 mg, 70%); mp 153 °C (decomp.); 1H NMR (400 MHz, DMSO-d6): d = 1.59 (s, 3H), 6.31 (s, 1H), 6.32 (s, 1H), 7.43 (bs, 1H), 10.47-10.55 (m, 2H); 13C NMR (100

MHz, DMSO-d6): d = 26.5, 100.5, 103.3, 103.4, 103.6, 155.1, 157.8, 164.8, 166.0; IR (KBr): 3458, 3251, 1726, 1618, 1268, 1216, 1167, 1154; HRMS (ESI): [M+H]+ calcd for C9H9O5+,197.0444; found, m/z 197.0446. 3-bromo-2,4-dihydroxybenzoic acid (2l)24

The reaction was carried out with 1l (18.9 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (21.5 mg, 92%); 1H NMR (400 MHz, DMSO-d6): d = 6.54 (d, J = 8.8 Hz, 1H), 7.63 (d, J = 8.8 Hz, 1H), 11.22 (bs, 1H), 12.28 (bs, 1H); 13C NMR (100 MHz, DMSO-d6):

d = 97.2, 105.2, 107.5, 130.2, 160.2, 160.7, 172.0.

OH

HO

COOHHN

O

Me

OH

HO

COOHO

Me

OH

HO

COOH

O

Me

OH

HO

COOHBr

S17

5-bromo-2,4-dihydroxybenzoic acid (2m)25

The reaction was carried out with 1m (18.9 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (21.9 mg, 94%);1H NMR (400 MHz, DMSO-d6): d = 6.47 (s, 1H), 7.81 (s, 1H), 10.58-11.94 (m, 2H); 13C NMR (100 MHz, DMSO-d6): d = 99.8, 103.4, 106.2, 134.1, 160.2, 162.3, 170.9.

2-bromo-4,6-dihydroxybenzoic acid (2n)

The reaction was carried out with 1n (18.9 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 40 ºC for 24 h; White solid (4.6 mg, 20%); mp 131 °C (decomp.); 1H NMR (400 MHz, DMSO-d6): d = 6.29 (d, J = 2.4 Hz, 1H), 6.47 (d, J = 2.4 Hz, 1H), 10.01 (s, 1H); 13C NMR (100 MHz, DMSO-

d6): d = 102.0, 111.0, 114.6, 119.9, 158.1, 159.8, 168.3; IR (KBr): 3855, 3646, 1644, 1595, 1454, 1269, 1169, 854; HRMS (ESI): [M+H]+ calcd for C7H6O4Br+, 232.9444; found, m/z 232.9453.

3-acetyl-2,6-dihydroxybenzoic acid (3o)

The reaction was carried out with 1o (15.2 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in DMF at 100 ºC for 48 h. The residue was purified by column chromatography (SiO2, eluent: hexane:EtOAc=1:1 to EtOAc:AcOH=99:1); White solid (8.4 mg, 43%); mp 185 °C (decomp.)(lit.26, 245-246, decomp.); 1H NMR (400 MHz, DMSO-d6): d = 2.46 (s, 3H), 6.15 (d, J = 9.2 Hz, 1H),

7.60 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d = 31.6, 103.4, 106.5, 115.7, 133.6, 165.6, 167.8, 175.6, 195.4; IR (KBr): 3245, 3439, 1650, 1610, 1408, 1368, 1256, 604; HRMS (ESI): [M+H]+ calcd for C9H9O5+, 197.0444; found, m/z 197.0437.

5,7-dihydroxy-4-methyl-2-oxo-2H-chromene-6-carboxylic acid (3p) The reaction was carried out with 1p (19.2 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 50 ºC for 24 h. The residue was purified by column chromatography (SiO2, eluent: EtOAc:AcOH=50:1); Pale yellow solid (19.3 mg, 82%); mp 103 °C; 1H NMR (400 MHz, DMSO-d6): d = 2.48 (s, 3H), 5.78 (s, 1H), 6.00-6.03 (m, 1H); 13C NMR (100 MHz,

DMSO-d6): d = 23.3, 93.0, 99.7, 101.3, 107.9, 155.8, 158.1, 160.0, 164.4, 165.4, 175.0; IR (KBr): 3408, 2933, 1686, 1604, 1391, 1369, 1263, 559; HRMS (ESI): [M+H]+ calcd for C11H9O6+, 237.0394; found, m/z 237.0373.

OH

HO

COOH

Br

OH

HO

COOH

Br

OH

HO

HOOC

O Me

OH

HO

HOOC

O

OMe

S18

2,6-dihydroxy-4-methoxybenzoic acid (3q)

The reaction was carried out with 1q (14.0 mg, 0.1 mmol) , DBU (44.9 μL, 0.3 mmol) in CH3CN at 30 ºC for 24 h; White solid (18.4 mg, quant); mp 132 °C (decomp.); 1H NMR (400 MHz, Acetone-d6): d = 3.72 (s, 3H), 5.80 (s, 2H), 12.69 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d = 54.7,

91.0, 92.7, 95.5, 159.0, 161.1; IR (KBr): 3555, 3493, 3442, 1655, 1591, 1372, 1159; HRMS (ESI): [M+H]+ calcd for C8H9O5+, 185.0444; found, m/z 185.0469.

References 1) J. R. Moran, J. L. Ericson, E. Dalcanale, J. A. Bryant, C. B. Knobler, D. J. Cram, J. Am. Chem. Soc. 1991, 113, 5707-5714.

2) R. Robinson, R. C. Shah, J. Chem. Soc. 1934, 1491-1498.

3) G.-H. Zheng, J.-J. Shen, Y.-C. Zhan, H. Yi, S.-T. Xue, Z. Wang, X.-Y. Ji, Z.-R. Li, Eur. J. Med. Chem. 2014, 81, 277-288.

4) K. Maeda, K. Morioka, E. Yashima, Macromolecules 2007, 40, 1349-1352.

5) P. A. Brough, W. Aherne, X. Barril, J. Borgognoni, K. Boxall, J. E. Cansfield, K.-M. J. Cheung, I. Collins, N. G. M. Davies, M. J. Drysdale, B. Dymock, S. A. Eccles, H. Finch, A. Fink, A. Hayes, R. Howes, R. E. Hubbard, K. James, A. M. Jordan, A. Lockie, V. Martins, A. Massey, T. P. Matthews, E. McDonald, C. J. Northfield, L. H. Pearl, C. Prodromou, S. Ray, F. I. Raynaud, S. D. Roughley, S. Y. Sharp, A. Surgenor, D. L. Walmsley, P. Webb, M. Wood, P. Workman, L. Wright, J. Med. Chem. 2008, 51, 196-218.

6) A. C. Donnelly, J. R. Mays, J. A. Burlison, J. T. Nelson, G. Vielhauer, J. Holzbeierlein, B. S. J. Blagg, J. Org. Chem. 2008, 73, 8901-8920.

7) A. B. Naidu, D. Ganapathy, G. Sekar, Synthesis 2010, 2010, 3509-3519.

8) X. Sun, J. Qiu, J. Wasley, U.S. Patent 20120295966 A1, 2012.

9) M. C. Foti, C. Daquino, I. D. Mackie, G. A. DiLabio, K. U. Ingold, J. Org. Chem. 2008, 73, 9270-9282.

10) T. Tu, Z. Sun, W. Fang, M. Xu, Y. Zhou, Org. Lett. 2012, 14, 4250-4253.

11) D. Kuik, J. A. McCubbin, G. K. Tranmer, Synthesis 2017, 49, 2555-2561.

12) J. Kalisiak, E. Kalisiak, J. Jurczak, Tetrahedron 2006, 62, 5905-5914.

13) T. Ikawa, S. Masuda, A. Takagi, S. Akai, Chem. Sci. 2016, 7, 5206-5211.

14) M. Weimar, G. Dürner, J. W. Bats, M. W. Göbel, J. Org. Chem. 2010, 75, 2718-2721.

15) M. Hayashi, L. E. Brown, J. A. Porco, Jr. Eur. J. Org. Chem. 2016, 4800-4804.

OH

HO

HOOC

OMe

S19

16) I. Thomsen, K. B. G. Torssell, Acta. Chem. Scand. 1991, 45, 539-542.

17) R. Das, D. Chakraborty, Appl. Organometal. Chem. 2011, 25, 437.

18) C. A. Townsend, S. B. Christensen, S. G. Davis, J. Chem. Soc. Perkin Trans. 1 1988, 839-861.

19) J. H. Jeong, Y. J. Oh, Y. Lho, S. Y. Park, K.-H. Liu, E. Ha, Y. H. Seo, Eur. J. Med. Chem. 2016, 124, 1069-1080.

20) M. Vansteelandt, E. Blanchet, M. Egorov, F. Petit, L. Toupet, A. Bondon, F. Monteau, B. L. Bizec, O. P. Thomas, Y. F. Pouchus, R. L. Bot, O. Grovel, J. Nat. Prod. 2013, 76, 297-301.

21) N. Guo, J. Liu, L. Qin, D. Jiang, X. You, K. Lu, Y.-O. Teng, P. Yu, J. Asian Nat. Prod. Res. 2015, 17, 377-383.

22) A. Ueno, Yakugaku Zasshi 1962, 82, 486-488.

23) W. R. Allison, G. T. Newbold, J. Chem. Soc. 1959, 3335-3340.

24) M. Saifuzzaman, R. Morrison, Z. Zheng, S. Orive, J. Hamilton, P. E. Thompson, J. M.A. Al-rawi, Bioorg. Med. Chem. 2017, 25, 5531-5536.

25) G. Shen, M. Wang, T. R. Welch, B. S. J. Blagg, J. Org. Chem. 2006, 71, 7618-7631.

26) M. Nakajima, H. Fukami, K. Konishi, J. Oda, Agr. Biol. Chem. 1963, 27, 700-705.

1c

OH

HO

Me

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,2,3_Et_CD3C .C auto DA I on ar 26 14:12:01 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 24.5 c

CD3CE EF 1.93 ppmBF 0.12 HzGAI 12

1.0

01.8

2

1.8

9 2.1

1

3.1

5

6.8

37

6.8

18

6.7

97

6.6

92

6.6

50

6.3

32

6.3

13

2.5

95

2.5

75

2.5

57

2.5

39

1.9

30

1.0

66

1.0

48

1.0

30

S20

1c

OH

HO

Me

S21

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,2,3_Et_bcm_DC auto DA I on ar 26 11:15:10 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 128

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 17.1 c


155.9

84

125.8

94

116.5

91

106.2

10

39.9

20

39.7

14

39.5

00

39.2

94

39.0

80

16.0

53

13.7

89

1d

OH

HO

MeMe

S22

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,2,4_i r_D .aC auto DA I on ar 26 14:29:59 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E -13.4 c


1.0

60.9

7

1.0

0

0.9

81.0

2

1.0

9

6.3

5

9.0

07

8.8

90

6.8

39

6.8

18

6.2

42

6.2

36

6.1

54

6.1

48

6.1

33

6.1

27

3.4

20

3.1

04

3.0

87

3.0

70

3.0

52

3.0

35

3.0

18

3.0

01

2.4

90

1.0

90

1.0

73

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,2,4_i r_bcm_DC auto DA I on ar 26 14:39:21 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 64

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E -19.8 c


155.8

36

155.0

38

126.1

24

124.8

40

105.9

38

102.3

73

39.9

12

39.7

06

39.5

00

39.2

86

39.0

80

38.8

74

25.7

84

22.8

86

1d

OH

HO

MeMe

S23

1f

OH

HO

MeO

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,2,3_ e.alsC auto DA I on ar 26 14:44:31 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E -34.5 c


2.0

1

1.0

0

1.9

9

2.9

3

8.9

85

6.6

67

6.6

46

6.6

26

6.2

82

6.2

61

3.6

53

3.4

78

2.4

90

S24

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,2,3_ e_bcm.aC auto DA I on ar 26 14:50:56 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 32

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 18.1 c


150.9

95

135.6

58

123.5

15

107.4

28

59.7

69

40.1

50

39.9

28

39.7

14

39.5

08

39.2

94

39.0

97

38.8

74

1f

OH

HO

MeO

S25

1g

OH

HOOMe

S26

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,2,4_ e.alsC auto DA I on ar 26 14:57:58 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 23.4 c


1.0

01.0

3

1.0

0

0.9

80.9

9

2.9

9

8.8

14

8.7

63

6.6

80

6.6

59

6.2

61

6.2

54

6.1

19

6.1

11

6.0

98

6.0

91

3.6

33

3.4

55

3.4

47

2.4

90

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,2,4_ e_bcm.aC auto DA I on ar 26 15:06:33 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 64

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 17.4 c


151.9

26

147.5

21

140.7

46

114.1

87

104.9

17

103.7

56

56.6

49

40.1

26

39.9

12

39.7

06

39.5

00

39.2

86

39.0

80

1g

OH

HOOMe

S27

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,2,3_amide.alsC auto DA I on ar 26 17:25:38 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 23.4 c


3.0

9

1.0

0

2.0

7

2.9

4

9.5

12

9.2

44

6.8

80

6.8

61

6.8

40

6.3

49

6.3

30

3.4

15

2.4

90

2.0

95

1i

OH

HO

HNMe

O

S28

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,2,3_amide_bcm.aC auto DA I on ar 26 17:34:02 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 64

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 13.0 c


170.4

00

152.0

74

126.6

76

114.1

13

107.6

01

40.1

26

39.9

20

39.7

06

39.5

00

39.2

94

39.0

80

38.8

74

22.7

96

1i

OH

HO

HNMe

O

S29

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,2,3_Br.alsC auto DA I on ar 26 13:07:53 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 23.4 c


2.0

5

1.0

0

2.0

2

9.9

60

6.9

33

6.9

12

6.8

91

6.4

03

6.3

82

3.6

04

3.5

93

3.5

78

2.4

90

1l

OH

HO

Br

S30

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,2,3_Br_bcm.alsC auto DA I on ar 26 13:15:24 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 64

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 17.4 c


155.5

07

128.0

18

106.8

35

97.9

52

40.1

34

39.9

20

39.7

14

39.5

00

39.2

94

39.0

88

38.8

74

1l

OH

HO

Br

S31

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180326 1,3,5_Br.alsC auto DA I on ar 26 13:20:17 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 23.4 c


2.1

4

1.9

21.0

0

9.6

94

6.3

81

6.3

76

6.1

94

6.1

88

6.1

83

3.6

00

3.5

98

2.4

90

1n

OH

HO Br

S32

200.0 150.0 100.0 50.0 0.0

DFI E 20180326 1,3,5_Br_bcm.alsC auto DA I on ar 26 13:24:57 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 16

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 17.0 c


159.3

43

121.7

94

109.3

96

101.7

64

39.9

53

39.7

47

39.5

41

39.3

27

39.1

21

38.9

15

38.7

01

1n

OH

HO Br

S33

11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180406 1,3,5_ e.alsC auto DA I Fri Apr 06 16:06:31 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 22.1 c


2.0

0

1.0

01.9

1

3.0

0

9.1

89

5.8

14

5.7

75

3.6

00

3.4

38

2.4

90

1q

OH

HO OMe

S34

200.0 150.0 100.0 50.0 0.0

DFI E 20180406 1,3,5_ e_bcm.aC auto DA I Fri Apr 06 16:15:46 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 64

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 6.8 c


161.1

63

159.0

80

95.4

99

92.6

42

54.7

30

40.1

26

39.9

20

39.7

06

39.5

00

39.2

94

39.0

80

38.8

66

1q

OH

HO OMe

S35

2a

OH

HO

COOH

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

20180628 olbe_pro_model_n

hu un 28 10:47:52 20181

399.65 z 124.00 z 10500.00 z 16384 7992.01 z 8 2.0500 sec 2.0000 sec

1 6.60 usec1 6348.8 c

2.49 ppm 0.12 z 12

0.7

0

0.8

8

1.0

0

1.0

01.0

0

11.3

96

10.4

23

7.6

15

7.5

93

6.3

41

6.3

35

6.3

19

6.3

13

6.2

55

6.2

49

4.1

58

2.4

90

S36

200.0 150.0 100.0 50.0 0.0

20180628 olbe_pro_model_b

hu un 28 10:56:36 201813

100.40 z 125.00 z 10500.00 z 32768 27118.64 z 32 1.2083 sec 3.0000 sec

1 4.70 usec1 6348.8 c

39.50 ppm 0.12 z 23

172.0

88

164.1

68

163.5

42

132.0

77

108.1

36

104.4

72

102.3

98

40.1

26

39.9

20

39.7

06

39.5

00

39.2

94

39.0

80

38.8

74

2a

OH

HO

COOH

S37

2b

OH

HO

COOHMe

S38

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

20180628 olbe_pro_2 e_no

hu un 28 11:04:58 20181

399.65 z 124.00 z 10500.00 z 16384 7992.01 z 8 2.0500 sec 2.0000 sec

1 6.60 usec1 6348.8 c

2.49 ppm 0.12 z 12

0.9

4

0.9

7

1.0

0

1.0

3

3.1

4

11.7

22

10.2

93

7.4

87

7.4

66

6.4

07

6.3

86

3.6

03

2.4

90

2.4

88

1.9

51

200.0 150.0 100.0 50.0 0.0

20180628 olbe_pro_2 e_bc

hu un 28 11:13:20 201813

100.40 z 125.00 z 10500.00 z 32768 27118.64 z 64 1.2083 sec 3.0000 sec

1 4.70 usec1 6348.8 c

39.50 ppm 0.12 z 23

172.5

90

161.6

32

161.4

34

128.4

87

110.1

86

107.0

25

103.9

21

40.1

26

39.9

20

39.7

06

39.5

00

39.2

86

39.0

80

38.8

66

7.9

03

2b

OH

HO

COOHMe

S39

2c

OH

HO

COOHMe

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180517 pro-2Et.alsC auto DA I hu ay 17 21:39:15 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E -39.9 c


0.9

5

0.9

7

0.9

6

1.0

0

2.0

9

3.0

8

11.7

09

10.2

15

7.4

89

7.4

67

6.4

04

6.3

82

3.5

05

2.5

53

2.5

35

2.5

17

2.4

90

1.0

27

1.0

09

0.9

90

S40

200.0 150.0 100.0 50.0 0.0

DFI E 20180517 pro-2Et_bcm.alsC auto DA I hu ay 17 21:47:55 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 32

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E -19.8 c


172.6

14

161.3

27

161.2

04

128.6

60

116.4

76

107.2

14

103.9

95

40.1

26

39.9

20

39.7

06

39.5

00

39.2

86

39.0

80

38.8

66

15.6

09

13.3

36

2c

OH

HO

COOHMe

S41

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180331 4-ipr-prod(ao277C single_pulseDA I 2018-03-31 18:25:53

B C 1HE D single_pulse.ex2

BF 391.78 HzB E 8.51 HzBFI 3.34 HzI 26214

F E 5882.26 HzCA 16

AC 4.4564 secD 3.0000 sec

1 5.55 usecI C 1HC E 21.0 c


0.3

7 0.9

4

1.0

0

1.0

0

1.1

4

5.8

6

11.3

01

10.3

41

7.4

80

6.3

06

3.3

61

3.1

08

3.0

90

3.0

73

3.0

55

3.0

38

3.0

20

3.0

03

2.4

90

1.9

73

1.1

21

1.1

03

2d

OH

HO

COOH

Me Me

S42

200.0 150.0 100.0 50.0 0.0

DFI E 20180331 4-ipr-prod(ao277C single pulse decoupled gatedDA I 2018-03-31 18:36:48

B C 13CE D single_pulse_dec

BF 98.52 HzB E 4.64 HzBFI 8.74 HzI 26214

F E 24630.17 HzCA 128

AC 1.0643 secD 2.0000 sec

1 3.00 usecI C 1HC E 21.3 c


172.0

52

161.3

98

161.2

74

127.3

97

126.7

20

103.8

30

101.9

80

40.1

39

39.9

29

39.7

19

39.5

00

39.2

90

39.0

80

38.8

61

25.8

42

22.4

85

2d

OH

HO

COOH

Me Me

S43

2e

OH

HO

COOH

Me

S44

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180404 5-methyl-prod(aoC single_pulseDA I 2018-04-04 17:58:35


BF 391.78 HzB E 8.51 HzBFI 3.34 HzI 26214

F E 5882.26 HzCA 16

AC 4.4564 secD 3.0000 sec

1 5.55 usecI C 1HC E 21.4 c


0.6

8 1.0

21.0

0

3.0

1

10.1

04

6.2

09

6.2

03

6.1

59

6.1

53

3.4

23

2.5

65

2.4

61

200.0 150.0 100.0 50.0 0.0

DFI E 20180421 5-methyl-prod(aoC single pulse decoupled gatedDA I 2018-04-21 15:35:21


BF 98.52 HzB E 4.64 HzBFI 8.74 HzI 26214

F E 24630.17 HzCA 256

AC 1.0643 secD 2.0000 sec

1 3.00 usecI C 1HC E 21.4 c


173.3

58

164.5

46

162.0

18

142.9

91

111.0

50

104.8

70

100.5

49

40.1

39

39.9

29

39.7

19

39.5

00

39.2

90

39.0

80

38.8

61

23.5

44

2e

OH

HO

COOH

Me

S45

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

DFI E 20180404 2-methoxy-prod(aC single_pulseDA I 2018-04-04 17:33:02


BF 391.78 HzB E 8.51 HzBFI 3.34 HzI 26214

F E 5882.26 HzCA 16

AC 4.4564 secD 3.0000 sec

1 5.55 usecI C 1HC E 21.2 c


0.5

5

1.0

0

1.0

1

2.9

4

9.9

07

7.3

69

7.3

46

6.3

46

6.3

23

3.6

85

2.4

91

2f

OH

HO

COOHMeO

S46

200.0 150.0 100.0 50.0 0.0

DFI E 20180404 2-methoxy-prod(aC single pulse decoupled gatedDA I 2018-04-14 17:08:10


BF 98.52 HzB E 4.64 HzBFI 8.74 HzI 26214

F E 24630.17 HzCA 1024

AC 1.0643 secD 2.0000 sec

1 3.00 usecI C 1HC E 21.7 c


172.2

61

156.3

81

156.2

19

134.7

60

125.7

38

107.7

98

105.3

47

59.7

67

40.1

39

39.9

20

39.7

10

39.5

00

39.2

81

39.0

71

38.8

61

2f

OH

HO

COOHMeO

S47

2g

OH

HO

COOH

OMe

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20181108 4 e_pro_non.alsC auto DA I hu ov 08 17:21:31 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 6348.8 c


0.9

6

1.0

0

0.9

8

3.0

5

10.3

05

7.1

41

6.3

21

3.9

35

3.6

88

2.4

90

S48

200.0 150.0 100.0 50.0 0.0

DFI E 20181108 4 e_pro_bcm.alC auto DA I hu ov 08 17:36:55 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 100

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 6348.8 c


172.1

29

158.0

43

154.5

19

141.4

04

112.1

70

103.4

76

102.7

60

56.3

19

40.1

34

39.9

20

39.7

06

39.5

00

39.2

86

39.0

80

38.8

74

2g

OH

HO

COOH

OMe

S49

2h

OH

HOO

O

S50

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20181108 5hydroxymethyl_pC auto DA I Fri ov 09 20:17:03 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 6348.8 c


2.0

7

1.0

01.0

3

2.0

9

10.5

94

10.3

03

6.3

29

6.3

26

6.2

83

6.2

80

5.0

99

3.3

78

2.4

90

200.0 150.0 100.0 50.0 0.0

DFI E 20181108 5hydroxymethyl_pC auto DA I Fri ov 09 20:26:50 2018

B C 13CE D BC

BF 100.40 HzB E 125.00 HzBFI 10500.00 HzI 32768

F E 27118.64 HzCA 64

AC 1.2083 secD 3.0000 sec

1 4.70 usecI C 1HC E 6348.8 c


168.5

23

164.5

55

158.1

50

151.4

98

102.8

59

102.2

25

100.1

59

68.1

33

40.1

26

39.9

12

39.7

06

39.5

00

39.2

86

39.0

80

38.8

66

2h

OH

HOO

O

S51

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20190426 kolbe_pro_amide_nC single_pulseDA I 2019-04-26 17:17:25


BF 391.78 HzB E 8.51 HzBFI 3.34 HzI 32768

F E 7352.94 HzCA 8

AC 4.4564 secD 3.0000 sec

1 5.90 usecI C 1HC E 21.1 c


0.8

9

0.9

1

0.8

9 1.0

0

1.0

2

2.7

7

11.8

06

10.2

07

9.0

38

7.5

57

7.5

35

6.4

30

6.4

08

3.3

74

2.4

95

2.4

90

2.4

85

2.0

05

2i

OH

HO

COOHHN

O

Me

S52

200 150 100 50 0

DFI E 20190426 kolbe_pro_2amide_CDA I Fri Apr 26 20:20:27 2019

B C 13CE D I G

BF 100.50 HzB E 0.00 HzBFI 135159.00 HzI 32768

F E 27100.27 HzCA 128

AC 1.2091 secD 1.0000 sec

1 4.80 usecI C 1HC E 23.1 c


172.2

69

169.2

20

159.2

59

159.0

12

129.0

13

112.8

38

107.8

82

104.4

71

40.1

25

39.9

19

39.7

14

39.5

00

39.2

95

39.0

89

38.8

75

22.7

58

2i

OH

HO

COOHHN

O

Me

S53

13.0 12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

DFI E 20190427 kolbe_pro_2Ac_nonCDA I at Apr 27 13:34:53 2019

B C 1HE D I G

BF 400.05 HzB E 0.00 HzBFI 130800.00 HzI 16384

F E 8000.00 HzCA 8

AC 2.0480 secD 2.0000 sec

1 5.30 usecI C 1HC E 69.7 c


0.8

1 1.0

0

1.2

5

2.7

6

12.8

78

7.8

50

7.8

28

6.4

54

6.4

32

2.6

23

2.4

94

2.4

90

2.4

85

2j

OH

HO

COOHO

Me

S54

200.0 150.0 100.0 50.0 0.0

DFI E 20190427 kolbe_pro_2Ac_bcmCDA I at Apr 27 14:40:41 2019

B C 13CE D I G

BF 100.50 HzB E 0.00 HzBFI 135159.00 HzI 32768

F E 27100.27 HzCA 200

AC 1.2091 secD 1.0000 sec

1 4.80 usecI C 1HC E 69.7 c


203.4

60

171.8

75

166.2

28

164.1

16

135.7

93

111.3

67

108.2

68

104.1

34

40.1

25

39.9

19

39.7

14

39.5

00

39.2

95

39.0

81

38.8

75

32.3

41

2j

OH

HO

COOHO

Me

S55

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

20180628 olbe_pro_5 c_no

hu un 28 11:19:36 20181

399.65 z 124.00 z 10500.00 z 16384 7992.01 z 8 2.0500 sec 2.0000 sec

1 6.60 usec1 6348.8 c

2.49 ppm 0.12 z 11

2.1

8

0.9

2

1.0

0 1.1

9

3.2

3

10.5

54

10.4

65

7.4

28

6.3

21

6.3

05

3.4

95

2.4

90

2.4

85

1.5

86

2k

OH

HO

COOH

O

Me

S56

200.0 150.0 100.0 50.0 0.0

DFI E 201805015 pro_5_Ac_bcm-1.C single pulse decoupled gatedDA I 2018-05-15 16:03:24


BF 98.52 HzB E 4.64 HzBFI 8.74 HzI 32768

F E 30788.18 HzCA 1024

AC 1.0643 secD 2.0000 sec

1 3.83 usecI C 1HC E 21.8 c


165.9

67

164.8

03

157.8

03

155.0

65

103.6

30

103.3

53

103.2

86

100.5

11

40.1

39

39.9

29

39.7

10

39.5

00

39.2

81

39.0

71

38.8

61

26.5

20

2k

OH

HO

COOH

O

Me

S57

13.0 12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20190426 kolbe_pro_2Br_nonCDA I Fri Apr 26 20:30:41 2019

B C 1HE D I G

BF 400.05 HzB E 0.00 HzBFI 130800.00 HzI 16384

F E 8000.00 HzCA 8

AC 2.0480 secD 2.0000 sec

1 5.30 usecI C 1HC E 22.9 c


0.8

0

0.9

5

1.0

0

1.0

3

12.2

81

11.2

17

7.6

44

7.6

22

6.5

48

6.5

26

2.4

90

2l

OH

HO

COOHBr

S58

200.0 150.0 100.0 50.0 0.0

DFI E 20190426 kolbe_pro_2Br_bcmCDA I Fri Apr 26 20:29:15 2019

B C 13CE D I G

BF 100.50 HzB E 0.00 HzBFI 135159.00 HzI 32768

F E 27100.27 HzCA 64

AC 1.2091 secD 1.0000 sec

1 4.80 usecI C 1HC E 23.0 c


171.9

57

160.7

13

160.2

04

130.1

88

107.5

20

105.2

19

97.1

81

40.1

33

39.9

19

39.7

14

39.5

00

39.2

95

39.0

89

38.8

75

2l

OH

HO

COOHBr

S59

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20190423 kolbe_pro_4Br.alsC auto DA I on Apr 22 19:58:14 2019

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 6348.8 c


1.6

9

1.0

0

1.0

5

11.9

36

10.5

80

7.8

10

6.4

69

2.4

90

2m

OH

HO

COOH

Br

S60

200 150 100 50 0

DFI E 20190427 kolbe_pro_4Br_bcmCDA I at Apr 27 13:11:56 2019

B C 13CE D I G

BF 100.50 HzB E 0.00 HzBFI 135159.00 HzI 32768

F E 27100.27 HzCA 64

AC 1.2091 secD 1.0000 sec

1 4.80 usecI C 1HC E 22.6 c


170.9

38

162.2

75

160.2

45

134.0

92

106.1

81

103.4

11

99.8

03

39.9

19

39.7

14

39.5

00

39.2

95

39.0

81

2m

OH

HO

COOH

Br

S61

2n

OH

HO

COOH

Br

S62

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180904 5Br_pro_recry.alsC auto DA I ue ep 04 15:36:56 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 25.7 c


0.9

8

1.0

01.0

2

10.0

79

6.4

76

6.4

70

6.2

97

6.2

91

3.3

55

2.4

90

200 150 100 50 0

DFI E 20190426 kolbe_pro_5Br_bcmCDA I Fri Apr 26 19:47:37 2019

B C 13CE D I G

BF 100.50 HzB E 0.00 HzBFI 135159.00 HzI 32768

F E 27100.27 HzCA 128

AC 1.2091 secD 1.0000 sec

1 4.80 usecI C 1HC E 22.8 c


168.2

91

159.7

85

158.1

00

119.9

23

114.6

46

110.9

89

101.9

89

40.1

25

39.9

11

39.7

14

39.5

00

39.2

86

39.0

81

38.8

84

2n

OH

HO

COOH

Br

S63

3o

OH

HO

HOOC

O Me

S64

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20190427 resorcinol-4- AcC auto DA I at Apr 27 15:57:16 2019

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E 6348.8 c


1.0

0

0.9

8

3.7

6

7.6

12

7.5

89

6.1

60

6.1

37

3.3

71

2.4

90

2.4

64

200.0 150.0 100.0 50.0 0.0

DFI E 20180507 4-acetyl-prod(ao2C single pulse decoupled gatedDA I 2018-05-07 20:12:18


BF 98.52 HzB E 4.64 HzBFI 8.74 HzI 26214

F E 24630.17 HzCA 512

AC 1.0643 secD 2.0000 sec

1 3.00 usecI C 1HC E 21.4 c


195.4

47

175.5

71

167.7

50

165.6

14

133.5

97

115.6

95

106.4

82

103.3

63

40.1

39

39.9

20

39.7

10

39.5

00

39.2

81

39.0

71

38.8

61

31.6

41

3o

OH

HO

HOOC

O Me

S65

3p

OH

HO

HOOC

O

OMe

S66

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

20180724 coumarin_pro.als

ue ul 24 14:27:55 20181

399.65 z 124.00 z 10500.00 z 16384 7992.01 z 8 2.0500 sec 2.0000 sec

1 6.60 usec1 -59.5 c

2.49 ppm 0.12 z 14

1.0

00.9

6

2.7

2

6.0

27

5.9

89

5.7

75

2.4

90

2.4

81

200.0 150.0 100.0 50.0 0.0

20180724 coumarin_pro_bcm

ue ul 24 14:40:37 201813

100.40 z 125.00 z 10500.00 z 32768 27118.64 z 128 1.2083 sec 3.0000 sec

1 4.70 usec1 -81.8 c

39.50 ppm 0.12 z 22

175.0

02

165.3

78

164.4

06

159.9

86

158.0

67

155.7

79

107.9

30

101.3

19

99.6

65

93.0

13

40.1

26

39.9

12

39.7

06

39.5

00

39.2

86

39.0

80

38.8

74

23.2

65

3p

OH

HO

HOOC

O

OMe

S67

3q

OH

HO

HOOC

OMe

S68

13.0 12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 -1.0

DFI E 20180515 pro_5_ e.alsC auto DA I ue ay 15 13:58:43 2018

B C 1HE D

BF 399.65 HzB E 124.00 HzBFI 10500.00 HzI 16384

F E 7992.01 HzCA 8

AC 2.0500 secD 2.0000 sec

1 6.60 usecI C 1HC E -9.4 c

ACEE EF 2.04 ppmBF 0.12 HzGAI 18

1.4

2

2.0

0

3.0

9

12.6

86

5.8

02

3.7

16

3.1

34

2.0

51

2.0

46

2.0

40

2.0

35

200 150 100 50 0

DFI E 20190427 kolbe_pro_5 e_bCDA I at Apr 27 15:25:33 2019

B C 13CE D I G

BF 100.50 HzB E 0.00 HzBFI 135159.00 HzI 32768

F E 27100.27 HzCA 736

AC 1.2091 secD 1.0000 sec

1 4.80 usecI C 1HC E 39.8 c


161.0

91

158.9

63

95.5

12

92.6

69

90.9

75

54.6

80

40.1

25

39.9

19

39.7

05

39.5

00

39.2

86

39.0

81

38.8

75

3q

OH

HO

HOOC

OMe

S69

contentskolbe-schmitt type reaction under ambient conditions mediated by organic base yuta...

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