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Synlett 2024; 35(20): 2515-2519
DOI: 10.1055/a-2384-6807
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Special Issue to Celebrate the 75th Birthday of Prof. B. C. Ranu

Nickel-Catalyzed O-Methylation of Cinnamic Acid Using DMSO as Methyl Surrogate

Hrishikesh Talukdar
,
Prodeep Phukan  ∗

Financial support from the University Grants Commission (UGC), India (Grant No. F.19-255/2021(BSR) and the Department of Science and Technology (DST), Ministry of Science and Technology, India under the PURSE Programme (Grant No. SR/PURSE/2022/116) is gratefully acknowledged.
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Abstract

A new method for the O-methylation of cinnamic acid employing DMSO as the methylating agent has been devised, employing a Ni-DMAP complex as catalyst along with Ag2O and dimethylamine as additives. This protocol demonstrates broad substrate compatibility and good tolerance towards various functional groups. The key advantages of this approach include the utilization of cost-effective catalysts, moderate to high yield of the products, and short reaction time.


#

Key words

cinnamic acid - methylation - DMSO - Ag2O - diethylamine - Ni-DMAP catalyst

Throughout human history, cinnamic acid derivatives have stood out as a prominent class of compounds derived from plants, finding extensive use as both scents and flavorings.[1] It belongs to the class of auxin which is recognized as plant hormone responsible for cell growth and differentiation.[2] Cinnamic acid esters find widespread application in the food industry for their flavor-enhancing properties, as well as in the pharmaceutical, perfumery, and cosmetic sectors.[3] The classical approach for the esterification of cinnamic acid is the Fischer esterification method which involves the treatment of an alcohol in the presence of a strong mineral acid.[4] Apart from the traditional methods, alternative procedures for esterification using metal catalysts have also been emerged in recent years. Recently, the group of Mao reported the O-methylation of benzoic acid using tert-butyl hydroperoxide as a methyl source in the presence of a copper catalyst.[5] They achieved the methyl esterification by treating the corresponding acid with tert-butyl hydroperoxide at 120 ℃ in DMSO for 24 h. Parallelly, Chen also developed a similar protocol for a Cu-catalyzed method for the methylation of amides and benzoic acids.[6] This process also rely on the use of di-tert-butyl peroxide as methyl surrogate where the corresponding acid was treated at 130 ℃ in chlorobenzene for 12 h. Although this reaction is successful for benzoic acid, the reaction gives poor yield of the methyl ester when cinnamic acid was subjected for esterification.

Dimethyl sulfoxide (DMSO) has been widely used as a solvent as well as a reagent for organic reactions because of its high stability, low toxicity, and low cost. The importance of DMSO has already been established in classical organic transformations such as Swern oxidation, Pfitzner–Moffatt oxidations, Parikh–Doering and Kornblum oxidation, etc.[7] In recent years, the scope of DMSO has also been further diversified for applications such as hydroxylation,[8] carbonylation,[9] sulfonylation,[10] formylation,[11] and cyanation reactions.[12] Moreover, DMSO is also served as a source of sulfur providing the MeSMe,[13] SMe,[14] and SOMe groups[15] and as a methylating agent.

The multiple application potential of DMSO as a source of oxygen and sulfur atoms or one-carbon units is only possible because of the presence of electrophilic sulfur and nucleophilic oxygen in the molecule. Literature reports on the application of DMSO reveals that there are a very few instances where DMSO is used as a methylating agent. In early 1966 Russell and Weiner reported the methylation of hydrocarbons through a carbanion intermediate.[16] Recently, the group of Tiwari reported several methods utilizing DMSO as a carbon synthon. They reported the use of DMSO as a dual methyl source for synthesizing N-alkylated quinazolinones.[17a] In another approach, the same group reported using DMSO as a methine source for the synthesis of pyrazolo[3,4-b]quinolone.[17b] The group of Xiao used DMSO for the methylation of amines and nitro compounds in the presence of formic acid.[18] Recently Jia et al. reported O-methylation of benzoic acid by DMSO. In this work they are using CuCl2·2H2O as a catalyst in the presence of CaCl2, H2O2, and K2CO3.[19]

However, this method produces poor yield in the case of the synthesis of methyl cinnamate. Although there are few efficient methods for methyl esterification of benzoic acid under catalytic conditions using alternative methyl source, none could successfully be applied in the case of cinnamic acids. We are reporting herein an efficient method for the O-methylation of cinnamic acid through an intermolecular cascade reductive protocol using DMSO as a methylating reagent in the presence of a nickel catalyst (Scheme [1]).

Zoom Image
Scheme 1 Esterification of cinnamic acid

Recently, we have developed an octahedral Ni(DMAP)4Cl2·2H2O complex by treating NiCl2·6H2O with DMAP and studied the catalytic activity for the Chan–Lam C–N cross-coupling reaction.[20] The nickel complex was synthesized by mixing 1 equivalent of NiCl2·6H2O with 4 equivalents of DMAP in DMF at room temperature. The structure of the complex was fully optimized by DFT calculation using B3LYP, and LANL2DZ was used as the basis set using the program Gaussian 09 (Figure [1]).[21]

Zoom Image
Figure 1 (a) DFT-optimized structure of the Ni(DMAP)4Cl2·2H2O complex; (b) HOMO and (c) LUMO of the complex.

We conducted calculations on the HOMO and LUMO energies of the complex to assess its stability. The HOMO energy was determined to be –0.625 kcal/mol, while the LUMO energy was found to be –4.360 kcal/mol, signifying a stable complex. Moreover, the HOMO–LUMO energy difference for the complex was calculated to be 3.735 kcal/mol.

In the recent past, there has been considerable interest in the esterification of cinnamic acid and benzoic acid to produce methyl ester derivatives under catalytic conditions using alternative methyl sources. We are reporting herein an efficient method for the O-methylation of cinnamic acid through an intermolecular cascade reductive protocol using DMSO as a methylating reagent (Scheme [1]).

Initial experiments for the standardization of our method were conducted using cinnamic acid as our model substrate. The very first experiment by treating cinnamic acid (1 mmol) with K2CO3 (1 mmol) in the presence of the Ni-DMAP complex (3 mol%) at 120 °C in DMSO (2 mL) for 12 h failed to produce the corresponding methyl cinnamate (Table [1], entry 1). Surprisingly, when 2 mmol of Ag2O was added as an additive under the same reaction conditions, we achieved a 32% yield of the desired product (Table [1], entry 2). Changing the base to NaOt-Bu, KF, and DBU resulted in the formation of the product with similar yields of 20%, 35%, and 37%, respectively (Table [1], entries 3–5). Interestingly, the use of diethylamine as the base produced the desired methyl cinnamate in 53% yield (Table [1], entry 6). Increasing the amount of diethylamine to 2 mmol improved the product yield to 62% (Table [1], entry 7). Further increasing the amount to 4 mmol resulted in a 79% yield of the product (Table [1], entry 8). Increasing the amount of Et2NH to 6 mmol resulted in a similar yield of 79% for the desired product (Table [1], entry 9). Reducing the reaction temperature to 90 °C lowered the product yield to 66% (Table [1], entry 10). Similarly, when the reaction was heated at 120 °C for only 6 h, the yield decreased to 71% (Table [1], entry 11). Using NiCl2·6H2O as a catalyst resulted in 30% yield of the product (Table [1], entry 12). Without the additive or the base, no product was formed (Table [1], entries 13, 14).

Table 1 Optimization of Reaction Conditionsa

Entry

Base (mmol)

Catalyst

Additive

Temp (°C)

Time (h)

Yield (%)

 1

K2CO3 (1)

Ni-DMAP

–

120

12

–

 2

K2CO3 (1)

Ni-DMAP

Ag2O

120

12

32

 3

Nat-OBu (1)

Ni-DMAP

Ag2O

120

12

20

 4

KF (1)

Ni-DMAP

Ag2O

120

12

35

 5

DBU (1)

Ni-DMAP

Ag2O

120

12

37

 6

Et2N (1)

Ni-DMAP

Ag2O

120

12

53

 7

Et2NH (2)

Ni-DMAP

Ag2O

120

12

62

 8

Et2NH (4)

Ni-DMAP

Ag2O

120

12

79

 9

Et2NH (6)

Ni-DMAP

Ag2O

120

12

79

10

Et2NH (4)

Ni-DMAP

Ag2O

 90

12

66

11

Et2NH (4)

Ni-DMAP

Ag2O

120

 6

71

12

Et2NH (4)

NiCl2·6H2O

Ag2O

120

12

30

13

Et2NH (4)

Ni-DMAP

–

120

12

–

14

–

Ni-DMAP

Ag2O

120

12

–

a Reaction conditions: cinnamic acid (1 mmol), base, Ag2O (2 mmol), DMSO (2 mL), catalyst (3 mol%).

From Table [1] it is clear that entry 8 provides the best conditions for synthesizing methyl cinnamate from cinnamic acid. This involves adding 2 mmol of Ag2O in the presence of 3 mol% Ni-DMAP catalyst and 4 mmol of Et2NH and stirring the reaction at 120 °C for 12 h.

After establishing the standard reaction conditions for the best yield of methyl cinnamate, the scope of the reaction was expanded for different cinnamic acids. A variety of cinnamic acids were well tolerated by this method, producing moderate to high yields of the corresponding products. Cinnamic acid with an electron-donating group gives a comparatively high yield of the products (2, 3, and 7), whereas the presence of halogen in the phenyl ring lowers the yield of the corresponding products. A decreasing trend in yield was observed when the position of the MeO group changes from para to meta and then to ortho (Table [2], substrates 3, 7, and 12). In this specific case, although the yields decrease slightly, the margin is too small to consider the effect of the steric hindrance on the reaction yield. However, in the presence of more than one electron-withdrawing group, the yields of the products decreased significantly (13, 15).

When the reaction was attempted with benzoic acid under the optimized reaction conditions, the desired methyl benzoate formed only in trace amount (Scheme [2]). To further testify the selectivity of the process, a mixture benzoic acid and cinnamic acid (in 1:1 molar ratio) was subjected O-methylation under the same reaction conditions. The reaction selectively produced methyl cinnamate in high yield (Scheme [3]).

Zoom Image
Scheme 2 Reaction of benzoic acid
Zoom Image
Scheme 3 Selective methylation of cinnamic acid

To confirm that the methyl group originated from DMSO, we repeated the identical reaction using DMSO-d 6 instead of DMSO (Scheme [4]). The absence of the methyl peak in the aliphatic region in the 1H NMR spectrum confirms that DMSO is the source of the CH3 group in the esterification reaction.

Zoom Image
Scheme 4 Reaction of cinnamic acid with deuterated DMSO

To investigate the mechanistic pathway, we conducted the reaction of cinnamic acid in the presence of four equivalents of TEMPO, maintaining consistent reaction conditions throughout. After 12 h, only trace amount of methyl cinnamate was obtained (Scheme [5]).

Zoom Image
Scheme 5 Reaction of cinnamic acid in the presence of TEMPO

On the basis of the results of the controlled experiment and literature reports, a plausible reaction mechanism can be outlined (Scheme [6]). Initially, the catalyst coordinates with the oxygen atom of cinnamic acid, displacing the hydrogen atom in the presence of the base (Scheme [6], eq. 1). Subsequently, DMSO generates a methyl radical and a sulfoxide radical in the presence of Ag2O and the catalyst (Scheme [6], eq. 2). The methyl radical then engages with the Ni-cinnamic acid complex to yield methyl cinnamate (Scheme [6], eq. 3) as the final product.

Zoom Image
Scheme 6 Plausible mechanism

Table 2 Substrate Scopea

a Reaction conditions: cinnamic acid (1 mmol), catalyst (3 mol%), Ag2O (2 mmol), DMSO (3 mL), diethylamine (4 mmol), 120 °C, 12 h.

In summary, a new protocol for O-methylation of cinnamic acid has been devised showcasing the suitability of DMSO as methyl surrogate.[22] A wide range of cinnamic acid derivatives could be transformed into the corresponding methyl cinnamates with high yields. This process promotes O-methylation of cinnamic acids selectively in the presence of benzoic acid. Utilization of cost-effective and low-toxic DMSO and inexpensive nickel catalyst make this protocol an attractive alternative of existing methods for esterification reactions for the production of methyl cinnamates.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We acknowledge IIT, Guwahati for NMR instrumentation facility.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2384-6807.
  • Supporting Information

  • References and Notes

  • 1 Baltas P, Bedos-Belval M. Curr. Med. Chem. 2011; 18: 1672
    CrossrefPubMedSearch in Google Scholar
  • 2 Ruwizhi N, Aderibigbe B. Int. J. Mol. Sci. 2020; 21: 5712
    CrossrefPubMedSearch in Google Scholar
  • 4 Fischer E, Speier A. Ber. Dtsch. Chem. Ges. 1895; 28: 3252
    CrossrefSearch in Google Scholar
  • 5 Zhu Y, Yan H, Lu L, Liu D, Rong G, Mao J. J. Org. Chem. 2013; 78: 9898
    CrossrefPubMedSearch in Google Scholar
  • 6 Xia Q, Liu X, Zhang Y, Chen C, Chen W. Org. Lett. 2013; 15: 3326
    CrossrefPubMedSearch in Google Scholar
  • 9 Tomita R, Yasu Y, Koike T, Akita M. Angew. Chem. Int. Ed. 2014; 53: 7144
    CrossrefPubMedSearch in Google Scholar
  • 11 Zhang Z, Tian Q, Qian J, Liu Q, Liu T, Shi L, Zhang G. J. Org. Chem. 2014; 79: 8182
    CrossrefPubMedSearch in Google Scholar
  • 12 Ren X, Chen J, Chen F, Cheng J. Chem. Commun. 2011; 47: 6725
    CrossrefPubMedSearch in Google Scholar
  • 13 Liu J, Wang X, Guo H, Shi X, Ren X, Huang G. Tetrahedron 2012; 68: 1560
    CrossrefSearch in Google Scholar
  • 15 Pramanik M, Rastogi N. Chem. Commun. 2016; 52: 8557
    CrossrefPubMedSearch in Google Scholar
  • 16 Russell GA, Weiner SA. J. Org. Chem. 1966; 31: 248
    CrossrefSearch in Google Scholar
  • 18 Jiang X, Wang C, Wei Y, Xue D, Liu Z, Xiao J. Chem. Eur. J. 2013; 20: 58
    CrossrefPubMedSearch in Google Scholar
  • 19 Guo C, Jia J, Jiang Q, Zhao A, Xu B, Liu Q, Luo W. Synthesis 2015; 48: 421
    Thieme ConnectSearch in Google Scholar
  • 20 Talukdar H, Gogoi D, Phukan P. Tetrahedron 2023; 132: 133251
    CrossrefSearch in Google Scholar
  • 21 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA. Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision D.01. Gaussian, Inc; Wallingford: 2013
    Search in Google Scholar
  • 22 Representative Procedure for the O-Methylation of Cinnamic Acid In a Schlenk tube containing 2 mL of DMSO, cinnamic acid (148 mg, 1 mmol), diethylamine (414 mL, 4 mmol), Ag2O (460 mg, 2 mmol), and catalyst (3 mol%) were added with constant stirring. The tube containing the reaction mixture was then kept under heating in an oil bath at 120 °C for 12 h. The reaction mixture was quenched by 30 mL of water and extracted by using ethyl acetate (3 × 20 mL). The combined organic phase was then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography over silica gel using a mixture of ethyl acetate (10%) and petroleum ether (90%) to furnish the pure methyl cinnamate. (E)-Methyl 3-(3-Chloro-4-methoxyphenyl)acrylate White solid; 0.161 g (72%) yield; mp 84–86 °C. 1H NMR (400 MHz, CDCl3): δ = 7.59 (s, 1 H), 7.55 (s, 1 H), 7.39–7.36 (m, 1 H), 6.91 (d, J = 12.0 Hz, 1 H), 6.30 (d, J = 16.0 Hz, 1 H), 3.92 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.3, 156.4, 143.1, 129.3, 128.1, 127.8, 123.8, 123.1, 116.6, 111.9, 56.1, 51.6. HRMS (ESI): m/z calcd for C11H12ClO3 +: 227.0470 [M + H]+; found: 227.047. (E)-Methyl 3-(5-Bromo-2-fluorophenyl)acrylate White solid; 0.174 g (68%) yield, mp 70–72 °C. 1H NMR (400 MHz, CDCl3): δ = 7.72–7.68 (m, 1 H), 7.63–7.62 (m, 1 H), 7.44–7.42 (m, 1 H), 7.00–6.96 (m, 1 H), 6.52–6.49 (m, 1 H), 3.8 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 166.6, 160.9, 135.7, 134.1 (JCF = 8.8 Hz), 131.3 (JCF = 1.4 Hz), 124.3 (J CF = 8.8 Hz), 121.5 (J CF = 4.3 Hz), 117.9 (J CF = 15.4 Hz), 116.9 (J CF = 2.2 Hz), 51.8. HRMS (ESI): m/z calcd for C10H9BrFO2 +: 258.9765 [M + H]+; found: 258.9757. (E)-Methyl 3-(Benzo[d][1,3]dioxol-5-yl)acrylate White solid; 0.164 g (80%) yield; mp 66–68 °C. 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 12.0 Hz, 1 H), 7.03–6.99 (m, 2 H), 6.81 (d, J = 5.6 Hz, 1 H), 6.26 (d, J = 10.8 Hz, 1 H), 6.00 (s, 2 H), 3.79 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.5, 149.5, 148.3, 144.5, 128.7, 124.4, 115.6, 108.5, 106.4, 101.5, 51.6.

Corresponding Author

Prodeep Phukan
Department of Chemistry
Gauhati University, Guwahati, Assam, 781014
India   

Publication History

Received: 10 July 2024

Accepted after revision: 12 August 2024

Accepted Manuscript online:
12 August 2024

Article published online:
16 September 2024

© 2024. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References and Notes

  • 1 Baltas P, Bedos-Belval M. Curr. Med. Chem. 2011; 18: 1672
    CrossrefPubMedSearch in Google Scholar
  • 2 Ruwizhi N, Aderibigbe B. Int. J. Mol. Sci. 2020; 21: 5712
    CrossrefPubMedSearch in Google Scholar
  • 4 Fischer E, Speier A. Ber. Dtsch. Chem. Ges. 1895; 28: 3252
    CrossrefSearch in Google Scholar
  • 5 Zhu Y, Yan H, Lu L, Liu D, Rong G, Mao J. J. Org. Chem. 2013; 78: 9898
    CrossrefPubMedSearch in Google Scholar
  • 6 Xia Q, Liu X, Zhang Y, Chen C, Chen W. Org. Lett. 2013; 15: 3326
    CrossrefPubMedSearch in Google Scholar
  • 9 Tomita R, Yasu Y, Koike T, Akita M. Angew. Chem. Int. Ed. 2014; 53: 7144
    CrossrefPubMedSearch in Google Scholar
  • 11 Zhang Z, Tian Q, Qian J, Liu Q, Liu T, Shi L, Zhang G. J. Org. Chem. 2014; 79: 8182
    CrossrefPubMedSearch in Google Scholar
  • 12 Ren X, Chen J, Chen F, Cheng J. Chem. Commun. 2011; 47: 6725
    CrossrefPubMedSearch in Google Scholar
  • 13 Liu J, Wang X, Guo H, Shi X, Ren X, Huang G. Tetrahedron 2012; 68: 1560
    CrossrefSearch in Google Scholar
  • 15 Pramanik M, Rastogi N. Chem. Commun. 2016; 52: 8557
    CrossrefPubMedSearch in Google Scholar
  • 16 Russell GA, Weiner SA. J. Org. Chem. 1966; 31: 248
    CrossrefSearch in Google Scholar
  • 18 Jiang X, Wang C, Wei Y, Xue D, Liu Z, Xiao J. Chem. Eur. J. 2013; 20: 58
    CrossrefPubMedSearch in Google Scholar
  • 19 Guo C, Jia J, Jiang Q, Zhao A, Xu B, Liu Q, Luo W. Synthesis 2015; 48: 421
    Thieme ConnectSearch in Google Scholar
  • 20 Talukdar H, Gogoi D, Phukan P. Tetrahedron 2023; 132: 133251
    CrossrefSearch in Google Scholar
  • 21 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA. Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision D.01. Gaussian, Inc; Wallingford: 2013
    Search in Google Scholar
  • 22 Representative Procedure for the O-Methylation of Cinnamic Acid In a Schlenk tube containing 2 mL of DMSO, cinnamic acid (148 mg, 1 mmol), diethylamine (414 mL, 4 mmol), Ag2O (460 mg, 2 mmol), and catalyst (3 mol%) were added with constant stirring. The tube containing the reaction mixture was then kept under heating in an oil bath at 120 °C for 12 h. The reaction mixture was quenched by 30 mL of water and extracted by using ethyl acetate (3 × 20 mL). The combined organic phase was then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography over silica gel using a mixture of ethyl acetate (10%) and petroleum ether (90%) to furnish the pure methyl cinnamate. (E)-Methyl 3-(3-Chloro-4-methoxyphenyl)acrylate White solid; 0.161 g (72%) yield; mp 84–86 °C. 1H NMR (400 MHz, CDCl3): δ = 7.59 (s, 1 H), 7.55 (s, 1 H), 7.39–7.36 (m, 1 H), 6.91 (d, J = 12.0 Hz, 1 H), 6.30 (d, J = 16.0 Hz, 1 H), 3.92 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.3, 156.4, 143.1, 129.3, 128.1, 127.8, 123.8, 123.1, 116.6, 111.9, 56.1, 51.6. HRMS (ESI): m/z calcd for C11H12ClO3 +: 227.0470 [M + H]+; found: 227.047. (E)-Methyl 3-(5-Bromo-2-fluorophenyl)acrylate White solid; 0.174 g (68%) yield, mp 70–72 °C. 1H NMR (400 MHz, CDCl3): δ = 7.72–7.68 (m, 1 H), 7.63–7.62 (m, 1 H), 7.44–7.42 (m, 1 H), 7.00–6.96 (m, 1 H), 6.52–6.49 (m, 1 H), 3.8 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 166.6, 160.9, 135.7, 134.1 (JCF = 8.8 Hz), 131.3 (JCF = 1.4 Hz), 124.3 (J CF = 8.8 Hz), 121.5 (J CF = 4.3 Hz), 117.9 (J CF = 15.4 Hz), 116.9 (J CF = 2.2 Hz), 51.8. HRMS (ESI): m/z calcd for C10H9BrFO2 +: 258.9765 [M + H]+; found: 258.9757. (E)-Methyl 3-(Benzo[d][1,3]dioxol-5-yl)acrylate White solid; 0.164 g (80%) yield; mp 66–68 °C. 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 12.0 Hz, 1 H), 7.03–6.99 (m, 2 H), 6.81 (d, J = 5.6 Hz, 1 H), 6.26 (d, J = 10.8 Hz, 1 H), 6.00 (s, 2 H), 3.79 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.5, 149.5, 148.3, 144.5, 128.7, 124.4, 115.6, 108.5, 106.4, 101.5, 51.6.

   Permissions and Reprints All articles of this category
Zoom Image
Scheme 1 Esterification of cinnamic acid
Zoom Image
Figure 1 (a) DFT-optimized structure of the Ni(DMAP)4Cl2·2H2O complex; (b) HOMO and (c) LUMO of the complex.
Zoom Image
Scheme 2 Reaction of benzoic acid
Zoom Image
Scheme 3 Selective methylation of cinnamic acid
Zoom Image
Scheme 4 Reaction of cinnamic acid with deuterated DMSO
Zoom Image
Scheme 5 Reaction of cinnamic acid in the presence of TEMPO
Zoom Image
Scheme 6 Plausible mechanism