Next Article in Journal
Green Photocatalysis: A Comprehensive Review of Plant-Based Materials for Sustainable Water Purification
Previous Article in Journal
Decolorization and Detoxification of Synthetic Dyes by Trametes versicolor Laccase Under Salt Stress Conditions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Reactions
Volume 6
Issue 4
10.3390/reactions6040054
reactions-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Regioselectivity of the Claisen Rearrangement of Meta- and Para-Substituted Allyl Aryl Ethers

by
William Thomas Möller
†,
Svava Dögg Hreinsdóttir
†,
Luis Antonio Arana
and
Benjamín Ragnar Sveinbjörnsson
*
Science Institute, University of Iceland, 107 Reykjavik, Iceland
*
Author to whom correspondence should be addressed.
†
Current address: Alvotech, Sæmtundargata 15-19, 102 Reykjavik, Iceland.
Reactions 2025, 6(4), 54; https://doi.org/10.3390/reactions6040054
Submission received: 8 July 2025 / Revised: 29 September 2025 / Accepted: 3 October 2025 / Published: 5 October 2025
Browse Figures
Versions Notes

Abstract

The regioselectivity of the Claisen rearrangement with different meta-substituted and meta- and para-substituted allyl phenyl ethers was investigated. The main results were that in meta-substituted Claisen rearrangements the regioselectivity depends roughly on the electronic nature of the substituent, with electron-donating groups favoring migration further from the meta-substituent while electron-withdrawing groups favor migration towards the meta-substituent. Different para-substituents were tested with two meta-substituents, Me, and Cl. Most of the para-substituent tested had a clear effect on the product ratio, in all but one case enhancing the proportion of the major product favored by the meta-substituent. Population analysis was performed with Mulliken, Löwdin, Hirshfeld, and natural population analysis to analyze the influence of the substituents on the atomic charges on the reaction sites. It was observed that the atomic charge on the carbon that forms the major isomer is of higher negativity than the atomic charge on the carbon that forms the minor isomer.

1. Introduction

When it comes to organic synthesis, it is important to understand the regioselectivity of the reactions to be used. This enables us to better utilize the reactions in the process of synthesizing target compounds. Many regioselective reactions are well understood and can be explained or rationalized using the stability of transition states, intermediates (e.g., Markovnikov’s rule for electrophilic addition reactions) or the stability of the products (e.g., Zaitsev’s rule for elimination reactions). It is also well known that substituents can influence regioselectivity and reaction pathways. Examples include the electrophilic aromatic substitutions [1] as well as substitution reactions where the electronic nature of the substituents (donating vs. withdrawing) can shift the mechanism pathway between SN1 and SN2 mechanism [2]. Steric factors are also known to affect the directing ability of the substituent.
The Claisen rearrangement is an established carbon-carbon bond-forming reaction discovered by Rainer Ludwig Claisen in 1912 [3,4,5]. Claisen first described the thermal [3,3]-sigmatropic rearrangement of allyl vinyl ethers and allyl aryl ethers before then proposing the mechanism of this rearrangement [6]. Normally the aromatic Claisen rearrangement requires very high temperature, 180–225 °C, which can lead to formation of several by-products through undesired side reactions. There are two major side reactions in the aromatic Claisen rearrangement: the first one is the rearrangement of the allylic moiety to the para position and the other one is the abnormal Claisen rearrangement [7,8]. The first one can be avoided by having a para-substituent.
The mechanism and regioselectivity of the Claisen rearrangement and the aromatic Claisen rearrangement have been the subject of many studies [4,5,9,10,11,12,13,14,15,16]. In 2002, Gozzo et al. studied the regioselectivity of allyl aryl ethers with different substituents via analysis of product distributions along with theoretical calculations of the transition state energies, which helped to explain the observed regioselectivity [9]. Comparison of two pairs of the allyl aryl ethers that were studied raises a question (Figure 1). Primarily, how the presence or absence of a para-substituent affects the regioselectivity of this Claisen rearrangement.
For non-substituted allyl-aryl ethers, the regioselectivity is not a significant issue as the allyl group migrates mostly to the neighboring ortho positions, and due to the symmetry of the starting material, both products are equivalent. A similar observation can be found for the symmetric starting materials of para-substituted allyl aryl ethers. If one of the ortho-positions is occupied, the allyl group is expected to migrate primarily to the other ortho position and can also result in the allyl group migrating to a vacant para-position. The meta-positions are expected to influence the regioselectivity of the reaction as Gozzo et al. discussed, but it was interesting to see the drastic effect that the additional para-substituents had on the regioselectivity.[9] Herein we explore further the results of the Claisen rearrangement of several meta- and para-substituted allyl aryl ethers, looking specifically at the para-substituents effect.

2. Materials and Methods

2.1. Materials

3-Fluorophenol (98%), 3-chlorophenol (98%), 3-bromophenol (98%), 3-iodophenol (98%), m-cresol (99%), 3-ethylphenol (99%), 3-tert-butylphenol (99%), [1,1′-biphenyl]-3-ol (85%), 3-(trifluoromethyl)phenol (99%), 3-acetamidophenol (97%), resorcinol (99%), 4-fluoro-3-methylphenol (98%), 4-chloro-3-methylphenol (98%), 3,4-dimethylphenol (98%), 4-isopropyl-3-methylphenol (99%), 3-methyl-4-(methylthio)phenol (97%), 3-chloro-4-fluorophenol (98%), 3,4-dichlorophenol (99%), 3-chloro-4-methylphenol (97%), 2-chloro-4-hydroxybenzonitrile (98%), allyl bromide, potassium carbonate (99.99%), sodium sulfate (≥99.0%) anhydrous, potassium iodide (≥99.0%), hexane (95%), and ethyl acetate (99.8%) were all bought from Sigma Aldrich. Acetone (≥99.8%) was bought from Honeywell. The silica gel for the chromatography (40–63 μm, 0.060–0.300 m, F60) and silica TLC plates (250 μm, F-255) were obtained from Silicycle. The nitrogen gas is from Isaga hf. The deuterated chloroform was obtained from Cambridge Isotope laboratories.

2.2. Instruments

1H- and 13C-NMR spectra were recorded on Bruker Avance 400 MHz spectrometer in deuterated chloroform as solvent, at 400.12 and 100.61 MHz, respectively. Chemical shifts (δ) are quoted in parts per million (ppm) and the coupling constants (J) in Hertz (Hz). The following abbreviations are used to describe the multiplicity: s, singlet; d, doublet; t, triplet; q: quartet; quin.: quintet; dd, doublet of doublets; dt, doublet of tripets; dq, doublet of quartets; m, multiplet.

2.3. General Procedure for the Synthesis of Substituted Allyl Aryl Ethers

A general procedure was used for the synthesis of all of the substituted allyl aryl ethers (Figure 2), only varying in substituents, scale, and purification method.
0.5–3 g of the substituted phenol was dissolved in 75 mL of acetone in a 100 mL round bottom flask. Approximately 1.3 equivalents of K2CO3 (potassium carbonate) and 0.1 equivalents of KI (potassium iodide) were added to the solution as well as 1.5 equivalents of allyl bromide. This mixture was refluxed for 3 h. After that the solution was filtered and the solvent evaporated off via rotary evaporator.
The products were purified by one of three methods:
  • Via silica gel chromatography where the mobile phase was 9:1 hexane–ethyl acetate.
  • By dissolving it in ethyl acetate and washing with a solution of KH2PO4, Na2CO3, and water. Then, it was dried over sodium sulfate, filtered, and solvent evaporated off.
  • Recrystallization from ethyl acetate (EtOAc) for m = NHCOCH3.
In all purification methods the product was dried under high vacuum at the end.

2.4. Characterization of Meta-Substituted Allyl Aryl Ethers

The majority of the allyl aryl ethers have been synthesized before and references are provided for those. For those compounds the 1H NMR was compared to the literature spectra to confirm the product identity. The remaining products were prepared solely as derivatives for analytical purposes.
  • 1-(allyloxy)-3-fluorobenzene [17,18]
1H NMR (400 MHz, CDCl3) δ 7.22 (td, J = 8.3, 6.9 Hz, 1H), 6.75–6.59 (m, 3H), 6.04 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.42 (dq, J = 17.3, 1.6 Hz, 1H), 5.31 (dq, J = 10.5, 1.4 Hz, 1H), 4.53 (dt, J = 5.3, 1.5 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 163.75 (d, J = 245.2 Hz), 160.09 (d, J = 10.7 Hz), 132.94, 130.30 (d, J = 10.2 Hz), 118.09, 110.67 (d, J = 2.9 Hz), 107.77 (d, J = 21.4 Hz), 102.59 (d, J = 24.9 Hz), 69.16.
  • 1-(allyloxy)-3-chlorobenzene [19]
1H NMR (400 MHz, CDCl3) δ 7.19 (t, J = 7.6 Hz, 1H), 6.96–6.90 (m, 2H), 6.86–6.75 (m, 1H), 6.04 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.42 (dqd, J = 17.3, 1.7, 0.6 Hz, 1H), 5.31 (ddd, J = 10.5, 1.5, 0.5 Hz, 1H), 4.52 (dt, J = 5.3, 1.6 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 159.50, 135.00, 132.92, 130.33, 121.18, 118.10, 115.33, 113.45, 69.15.
  • 1-(allyloxy)-3-bromobenzene [18,20]
1H NMR (400 MHz, CDCl3) δ 7.14 (t, J = 8.3 Hz, 1H), 7.11–7.05 (m, 2H), 6.85 (ddd, J = 8.1, 2.4, 1.3 Hz, 1H), 6.03 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.3, 1.6 Hz, 1H), 5.30 (dq, J = 10.4, 1.4 Hz, 1H), 4.52 (dt, J = 5.3, 1.6 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 159.49, 132.86, 130.66, 124.09, 122.91, 118.16, 118.13, 113.92, 69.12.
  • 1-(allyloxy)-3-iodobenzene [21]
1H NMR (400 MHz, CDCl3) δ 7.31–7.26 (m, 2H), 6.99 (t, J = 8.1 Hz, 1H), 6.88 (ddd, J = 8.4, 2.3, 1.1 Hz, 1H), 6.03 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.3, 1.6 Hz, 1H), 5.30 (dq, J = 10.6, 1.4 Hz, 1H), 4.51 (dt, J = 5.3, 1.6 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 159.26, 132.87, 130.89, 130.13, 124.04, 118.11, 114.59, 94.43, 69.05.
  • 1-(allyloxy)-3-methylbenzene [19]
1H NMR (400 MHz, CDCl3) δ 7.17 (td, J = 7.8, 1.6 Hz, 1H), 6.81–6.71 (m, 3H), 6.07 (ddtd, J = 17.2, 10.5, 5.3, 1.4 Hz, 1H), 5.42 (dt, J = 17.3, 1.6 Hz, 1H), 5.29 (dt, J = 10.5, 1.4 Hz, 1H), 4.53 (dq, J = 5.3, 1.4 Hz, 2H), 2.34 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 158.75, 139.61, 133.60, 129.30, 121.81, 117.63, 115.74, 111.71, 68.82, 21.67.
  • 1-(allyloxy)-3-ethylbenzene [18]
1H NMR (400 MHz, CDCl3) δ 7.20 (ddt, J = 8.8, 7.3, 1.1 Hz, 1H), 6.84–6.77 (m, 2H), 6.75 (dd, J = 8.1, 1.4 Hz, 1H), 6.07 (ddtd, J = 17.3, 10.6, 5.4, 1.5 Hz, 1H), 5.42 (dp, J = 17.2, 1.6 Hz, 1H), 5.29 (dq, J = 10.5, 1.5 Hz, 1H), 4.54 (dp, J = 5.3, 1.4 Hz, 2H), 2.63 (qd, J = 7.7, 1.6 Hz, 2H), 1.24 (td, J = 7.6, 1.7 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 158.83, 146.07, 133.63, 129.36, 120.63, 117.68, 114.67, 111.77, 68.85, 29.05, 15.61.
  • 1-(allyloxy)-3-(tert-butyl)benzene [22]
1H NMR (400 MHz, CDCl3) δ 7.22 (td, J = 7.9, 0.6 Hz, 1H), 7.04–6.93 (m, 2H), 6.73 (ddt, J = 8.2, 2.4, 0.9 Hz, 1H), 6.08 (ddtd, J = 17.3, 10.6, 5.4, 0.6 Hz, 1H), 5.43 (dqd, J = 17.3, 1.6, 0.6 Hz, 1H), 5.29 (dqd, J = 10.5, 1.4, 0.6 Hz, 1H), 4.54 (dtd, J = 5.4, 1.5, 0.6 Hz, 2H), 1.31 (s, 9H).
13C NMR (101 MHz, CDCl3) δ 158.58, 153.13, 133.67, 129.05, 118.16, 117.80, 112.98, 110.93, 68.93, 34.88, 31.45.
  • 3-(allyloxy)-1,1’-biphenyl [23]
1H NMR (400 MHz, CDCl3) δ 7.63–7.55 (m, 2H), 7.44 (tq, J = 6.9, 0.7 Hz, 2H), 7.39–7.32 (m, 2H), 7.19 (ddd, J = 7.6, 1.7, 0.9 Hz, 1H), 7.17–7.14 (m, 1H), 6.92 (ddt, J = 8.3, 2.6, 0.8 Hz, 1H), 6.10 (ddt, J = 17.0, 10.6, 5.3 Hz, 1H), 5.46 (dtd, J = 17.2, 1.9, 1.3 Hz, 1H), 5.32 (ddd, J = 10.5, 1.5, 0.6 Hz, 1H), 4.61 (dt, J = 5.3, 1.6 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 159.11, 142.89, 141.20, 133.45, 129.87, 128.87, 127.55, 127.32, 119.98, 117.88, 113.90, 113.63, 69.02.
  • 1-(allyloxy)-3-(trifluoromethyl)benzene [17,24,25]
1H NMR (400 MHz, CDCl3) δ 7.38 (tdd, J = 8.3, 1.3, 0.7 Hz, 1H), 7.21 (ddt, J = 7.7, 1.6, 0.8 Hz, 1H), 7.15 (t, J = 2.1 Hz, 1H), 7.11–7.06 (m, 1H), 6.05 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.43 (dq, J = 17.3, 1.6 Hz, 1H), 5.32 (dq, J = 10.5, 1.4 Hz, 1H), 4.58 (dt, J = 5.3, 1.6 Hz, 2H).
  • N-(3-(allyloxy)phenyl)acetamide [26]
1H NMR (400 MHz, CDCl3) δ 7.30 (t, J = 2.2 Hz, 1H), 7.20 (t, J = 8.1 Hz, 1H), 7.14 (broad s, 1H), 6.95 (dt, J = 8.0, 1.4 Hz, 1H), 6.67 (dd, J = 8.3, 2.5 Hz, 1H), 6.05 (ddt, J = 17.2, 10.6, 5.3 Hz, 1H), 5.41 (dq, J = 17.3, 1.6 Hz, 1H), 5.28 (dp, J = 10.5, 1.4 Hz, 1H), 4.54 (dt, J = 5.3, 1.5 Hz, 2H), 2.17 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 168.36, 159.31, 139.19, 133.28, 129.80, 117.88, 112.14, 111.02, 106.53, 69.00, 24.88.
  • 3-(allyloxy)-benzaldehyde [27]
1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 7.47–7.35 (m, 3H), 7.17 (dt, J = 6.9, 2.5 Hz, 1H), 6.03 (ddt, J = 17.4, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.3, 1.6 Hz, 1H), 5.29 (dq, J = 10.6, 1.5 Hz, 1H), 4.57 (dt, J = 5.3, 1.6 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 192.27, 159.29, 137.93, 132.78, 130.21, 123.76, 122.28, 118.25, 113.25, 69.12.
  • allyl 3-(allyloxy)benzoate [28]
1H NMR (400 MHz, CDCl3) δ 7.66 (dt, J = 7.7, 1.3 Hz, 1H), 7.60 (dd, J = 2.7, 1.5 Hz, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.12 (ddd, J = 8.3, 2.7, 1.0 Hz, 1H), 6.13–5.97 (m, 2H), 5.42 (ddq, J = 17.2, 8.6, 1.6 Hz, 2H), 5.30 (ddq, J = 10.6, 6.4, 1.4 Hz, 2H), 4.82 (dt, J = 5.6, 1.5 Hz, 2H), 4.59 (dt, J = 5.3, 1.5 Hz, 2H).
13C NMR (101 MHz, CDCl3) δ 166.24, 158.71, 133.02, 132.36, 131.61, 129.56, 122.36, 120.32, 118.39, 118.10, 115.22, 69.11, 65.77.
  • 1-(allyloxy)-3-nitrobenzene [9]
1H NMR (400 MHz, CDCl3) δ 7.82 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.74 (t, J = 2.3 Hz, 1H), 7.42 (t, J = 8.2 Hz, 1H), 7.24 (ddd, J = 8.3, 2.6, 1.0 Hz, 1H), 6.05 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.45 (dq, J = 17.3, 1.6 Hz, 1H), 5.34 (dq, J = 10.5, 1.4 Hz, 1H), 4.62 (dt, J = 5.3, 1.5 Hz, 2H).

2.5. Characterization of Meta- and Para-Substituted Allyl Aryl Ethers

  • 4-(allyloxy)-1-fluoro-2-methylbenzene
1H NMR (400 MHz, CDCl3) δ 6.90 (t, J = 9.0 Hz, 1H), 6.75–6.71 (m, 1H), 6.67 (dt, J = 8.9, 3.6 Hz, 1H), 6.11–5.97 (m, 1H), 5.45–5.35 (m, 1H), 5.33–5.24 (m, 1H), 4.48 (dt, J = 5.2, 1.6 Hz, 2H), 2.25 (d, J = 1.9 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 156.07 (d, J = 237.3 Hz), 154.50 (d, J = 2.1 Hz), 133.47, 125.69 (d, J = 18.9 Hz), 117.75, 117.60 (d, J = 4.6 Hz), 115.38 (d, J = 23.9 Hz), 112.90 (d, J = 8.0 Hz), 69.51, 14.95 (d, J = 3.4 Hz).
  • 4.-(allyloxy)-1-chloro-2-methylbenzene [9]
1H NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.7 Hz, 1H), 6.79 (dd, J = 2.9, 0.8 Hz, 1H), 6.69 (dd, J = 8.7, 3.0 Hz, 1H), 6.03 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.2, 1.6 Hz, 1H), 5.29 (dq, J = 10.5, 1.4 Hz, 1H), 4.50 (dt, J = 5.3, 1.5 Hz, 2H), 2.34 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 157.26, 137.12, 133.21, 129.70, 126.11, 117.88, 117.48, 113.47, 69.15, 20.46.
  • 4-(allyloxy)-1-bromo-2-methylbenzene [29]
1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.7 Hz, 1H), 6.81 (d, J = 3.0 Hz, 1H), 6.63 (dd, J = 8.7, 3.0 Hz, 1H), 6.03 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.29 (dq, J = 10.6, 1.5 Hz, 1H), 4.50 (dt, J = 5.3, 1.6 Hz, 2H), 2.36 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 157.93, 138.97, 133.15, 132.93, 117.93, 117.51, 115.73, 113.87, 69.08, 23.28.
  • 4-(allyloxy)-1,2-dimethylbenzene [30]
1H NMR (400 MHz, CDCl3) δ 7.04 (dd, J = 8.3, 3.6 Hz, 1H), 6.76 (t, J = 3.6 Hz, 1H), 6.73–6.62 (m, 1H), 6.15–6.00 (m, 1H), 5.48–5.37 (m, 1H), 5.28 (ddt, J = 10.5, 2.8, 1.5 Hz, 1H), 4.52 (ddt, J = 5.1, 3.1, 1.5 Hz, 2H), 2.25 (d, J = 3.7 Hz, 3H), 2.21 (d, J = 3.8 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 156.87, 137.82, 133.77, 130.39, 128.90, 117.51, 116.51, 111.77, 68.97, 20.17, 18.93.
  • 4-(allyloxy)-1-isopropyl-2-methylbenzene [31]
1H NMR (400 MHz, CDCl3) δ 7.15 (d, J = 8.4 Hz, 1H), 6.79–6.70 (m, 2H), 6.07 (ddtd, J = 17.3, 10.5, 5.3, 0.8 Hz, 1H), 5.41 (dqd, J = 17.2, 1.7, 0.9 Hz, 1H), 5.32–5.23 (m, 1H), 4.51 (dtd, J = 5.4, 1.6, 0.8 Hz, 2H), 3.08 (sept, J = 6.9 Hz, 1H), 2.32 (d, J = 0.9 Hz, 3H), 1.21 (dd, J = 6.9, 1.0 Hz, 6H).
13C NMR (101 MHz, CDCl3) δ 156.41, 139.42, 136.45, 133.82, 125.72, 117.54, 116.76, 112.17, 68.92, 28.77, 23.57, 19.64.
  • (4-(allyloxy)-2-methylphenyl)(methyl)sulfane [17]
1H NMR (400 MHz, CDCl3) δ 7.19 (d, J = 8.4 Hz, 1H), 6.78 (d, J = 2.9 Hz, 1H), 6.75 (dd, J = 8.4, 2.9 Hz, 1H), 6.05 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.2, 1.6 Hz, 1H), 5.28 (dq, J = 10.5, 1.5 Hz, 1H), 4.51 (dt, J = 5.3, 1.6 Hz, 2H), 2.40 (s, 3H), 2.37 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 157.15, 139.14, 133.44, 129.34, 128.45, 117.77, 117.00, 112.89, 69.02, 20.62, 17.26.
  • 4-(allyloxy)-2-chloro-1-fluorobenzene
1H NMR (400 MHz, CDCl3) δ 7.04 (t, J = 8.8 Hz, 1H), 6.94 (dd, J = 6.0, 3.0 Hz, 1H), 6.76 (dt, J = 9.1, 3.4 Hz, 1H), 6.02 (ddt, J = 17.4, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.30 (dq, J = 10.6, 1.5 Hz, 1H), 4.49 (dt, J = 5.3, 1.6 Hz, 2H).
  • 4-(allyloxy)-1,2-dichlorobenzene [32]
1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.9 Hz, 1H), 7.01 (d, J = 2.9 Hz, 1H), 6.77 (dd, J = 8.9, 2.9 Hz, 1H), 6.01 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.31 (dq, J = 10.6, 1.4 Hz, 1H), 4.51 (dt, J = 5.3, 1.5 Hz, 2H).
  • 4-(allyloxy)-2-chloro-1-methylbenzene
1H NMR (400 MHz, CDCl3) δ 7.10 (dd, J = 8.4, 0.8 Hz, 1H), 6.93 (d, J = 2.6 Hz, 1H), 6.73 (dd, J = 8.4, 2.6 Hz, 1H), 6.03 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.2, 1.6 Hz, 1H), 5.29 (dq, J = 10.5, 1.4 Hz, 1H), 4.50 (dt, J = 5.3, 1.6 Hz, 2H), 2.29 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 157.40, 134.69, 133.11, 131.34, 128.22, 117.97, 115.52, 113.63, 69.22, 19.20.
  • 4-(allyloxy)-2-chlorobenzonitrile
1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.7 Hz, 1H), 7.02 (d, J = 2.4 Hz, 1H), 6.87 (dd, J = 8.7, 2.5 Hz, 1H), 6.01 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.42 (dq, J = 17.2, 1.6 Hz, 1H), 5.35 (dq, J = 10.5, 1.3 Hz, 1H), 4.59 (dt, J = 5.3, 1.5 Hz, 2H).

2.6. General Protocol for the Claisen Rearrangement

A general procedure was used for all of the Claisen rearrangments (Figure 3), only varying in substituents and scale.
0.1–1 g of the substituted allyl aryl ether was put into a 25–100 mL Schlenk flask. The Schlenk flask was then connected to a vacuum inert gas line and three vacuum-nitrogen cycles performed. The Schlenk flask was then placed in an aluminum block that had been pre-heated to 200 °C. The reaction was allowed to run for approximately 4 h before being taken out of the aluminum block and allowed to cool to room temperature. A 1H NMR sample was then prepared from the crude product in order to obtain the product ratio.

2.7. NMR Analysis of the Claisen Rearrangement Products of Meta-Substituted Allyl Aryl Ethers

Due to challenges in product separation and peak overlap, a detailed 1H NMR analysis is omitted for some Claisen rearrangement product mixtures. All 1H NMR spectra are available in the Supplementary Information. When it says “overlapping peaks” it refers to overlapping peaks between separate products within the product mixture.
  • Claisen rearrangement of 1-(allyloxy)-3-chlorobenzene [19]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.03 (d, J = 8.2 Hz, 1H), 6.87 (dd, J = 8.1, 2.1 Hz, 1H), 6.84 (d, J = 2.1 Hz, 1H), 6.06–5.90 (m, 1H), 5.22–5.02 (m, 2H), 3.37 (dt, J = 6.3, 1.7 Hz, 2H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.05 (t, J = 8.0 Hz, 1H), 6.99 (dd, J = 8.1, 1.4 Hz, 1H), 6.73 (dd, J = 7.9, 1.4 Hz, 1H), 6.06–5.90 (m, 1H), 5.22–5.02 (m, 2H), 3.60 (dt, J = 6.0, 1.7 Hz, 2H).
  • Claisen rearrangement of 1-(allyloxy)-3-bromobenzene [20,33]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.02 (dd, J = 8.0, 1.9 Hz, 1H), 6.99 (d, J = 1.9 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.10–5.90 (m, 1H), 5.21–5.09 (m, 2H), 5.07 (br s, 1H) 3.36 (dt, J = 6.3, 1.7 Hz, 2H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.17 (dd, J = 8.1, 1.2 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.77 (dd, J = 8.1, 1.2 Hz, 1H), 6.10–5.90 (m, 1H), 5.20–5.09 (m, 2H), 5.07 (br s, 1H) 3.63 (dt, J = 6.0, 1.7 Hz, 2H).
  • Claisen rearrangement of 1-(allyloxy)-3-iodobenzene
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.22 (dd, J = 7.9, 1.7 Hz, 1H), 7.18 (d, J = 1.8 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.06–5.89 (m, 1H), 5.19–5.01 (m, 2H), 4.99 (s, 1H), 3.35 (dt, J = 6.3, 1.7 Hz, 2H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.44 (dd, J = 7.4, 1.7 Hz, 1H), 6.82 (t, J = 7.6 Hz, 1H), 6.79 (dd, J = 8.1, 1.7 Hz, 1H), 6.06–5.89 (m, 1H), 5.19–5.01 (m, 2H), 5.01 (s, 1H), 3.64 (dt, J = 5.9, 1.7 Hz, 2H).
  • Claisen rearrangement of 1-(allyloxy)-3-methylbenzene [9]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 6.99 (d, J = 8.2 Hz, 1H), 6.63 (ddd, J = 7.6, 1.7, 0.8 Hz, 1H), 6.57 (d, J = 1.6 Hz, 1H), 6.01–5.82 (m, 1H), 5.12–5.05 (m, 2H), 4.80 (broad s, 1H), 3.30 (dd, J = 6.3, 1.7 Hz, 2H), 2.21 (s, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.02 (t, J = 7.7 Hz, 1H), 6.70 (d, J = 7.6 Hz, 1H), 6.60 (d, J = 8.0 Hz, 1H), 6.01–5.82 (m, 1H), 5.02–4.92 (m, 2H), 4.80 (broad s, 1H), 3.36 (dt, J = 5.8, 1.8 Hz, 2H), 2.22 (s, 3H).
  • Claisen rearrangement of 1-(allyloxy)-3-ethylbenzene [34]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.02 (d, J = 7.6 Hz, 1H), 6.82–6.66 (overlapping peaks, 2H), 6.13–5.95 (m, 1H), 5.18 (dq, J = 11.2, 1.7 Hz, 1H), 5.14 (dt, J = 4.4, 1.7 Hz, 1H), 4.85 (broad s, 1H), 3.39 (dt, J = 6.4, 1.7 Hz, 2H), 2.70–2.54 (overlapping q, 2H), 1.34–1.14 (overlapping t, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.07 (t, J = 7.8 Hz, 1H), 6.82–6.66 (overlapping peaks, 2H) 6.13–5.95 (m, 1H), 5.12–5.08 (m, 1H), 5.05 (dq, J = 17.2, 1.8 Hz, 1H), 4.85 (broad s, 1H), 3.46 (dt, J = 5.7, 1.8 Hz, 2H), 2.70–2.54 (overlapping q, 2H), 1.34–1.14 (overlapping t, 3H).
  • Claisen rearrangement of N-(3-(allyloxy)phenyl)acetamide [35]
Isomer A: 1H NMR (400 MHz, Acetone) δ 7.48 (d, J = 2.1 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.76 (dd, J = 8.1, 2.1 Hz, 1H), 6.04–5.75 (overlapping m, 1H), 5.01–4.84 (overlapping m, 2H), 3.25 (dt, J = 6.6, 1.6 Hz, 2H), 2.01 (s, 3H).
Isomer B: 1H NMR (400 MHz, Acetone) δ 7.11 (d, J = 7.8 Hz, 1H), 6.92 (t, J = 8.1 Hz, 1H), 6.64 (d, J = 8.1 Hz, 1H), 6.04–5.75 (overlapping m, 1H), 5.01–4.84 (overlapping m, 2H), 3.40 (dt, J = 6.2, 1.7 Hz, 2H), 2.01 (s, 3H).
There are several peaks that might be the amide proton, but the specific peak can not be identified with confidence here.
  • Claisen rearrangement of 3-(allyloxy)-benzaldehyde [36]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 9.88 (s, 1H), 7.50–7.20 (overlapping peaks, 3H) 6.10–5.91 (m, 1H), 5.19–5.07 (m, 2H), 3.45 (dt, J = 6.4, 1.7 Hz, 2H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 10.16 (s, 1H), 7.50–7.35 (overlapping peaks, 1H) 7.27 (t, J = 7.7 Hz, 1H), 7.06 (dt, J = 8.0, 1.3 Hz, 1H), 6.10–5.91 (m, 1H), 5.11–5.06 (m, 1H), 5.01 (dq, J = 17.2, 1.7 Hz, 1H), 3.88 (dt, J = 5.8, 1.8 Hz, 2H).
  • Claisen rearrangement of allyl 3-(allyloxy)benzoate
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 1.7 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 6.13–5.93 (m, 2H), 5.47–5.37 (m, 1H), 5.33–5.26 (m, 1H), 5.21–5.06 (m, 2H), 4.78 (t, J = 1.4 Hz, 2H), 3.46 (dt, J = 6.3, 1.7 Hz, 2H). 1H peak missing in the description of the aromatic region due to overlap with starting material and other Claisen rearrangement product.
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.47 (dd, J = 7.8, 1.3 Hz, 1H), 7.18 (t, J = 7.9 Hz, 1H), 7.00 (dd, J = 8.1, 1.3 Hz, 1H), 6.13–5.93 (m, 2H), 5.48–5.35 (m, 1H), 5.33–5.26 (m, 1H), 5.21–5.06 (m, 2H), 4.80 (t, J = 1.4 Hz, 2H), 3.77 (dt, J = 6.0, 1.7 Hz, 2H).
  • Claisen rearrangement of 4-(allyloxy)-1-fluoro-2-methylbenzene
Isomer A: 1H NMR (400 MHz, CDCl3) δ 6.76 (d, J = 10.4 Hz, 1H), 6.63–6.59 (unclear multiplicity due to overlap, 1H), 6.02–5.87 (m, 1H), 5.17 (t, J = 1.8 Hz, 1H), 5.14 (dq, J = 8.6, 1.6 Hz, 1H), 4.60 (broad s, 1H), 3.34 (dt, J = 6.5, 1.7 Hz, 2H), 2.20 (d, 2 Hz, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 6.80 (t, J = 9.1 Hz, 1H), 6.63–6.59 (unclear multiplicity due to overlap, 1H), 6.02–5.87 (m, 1H), 5.08 (dq, J = 10.1, 1.7 Hz, 1H), 5.00 (dq, J = 17.2, 1.8 Hz, 1H), 4.60 (broad s, 1H), 3.42 (dt, J = 5.8, 1.9 Hz, 2H), 2.19 (d, J = 2–3 Hz, 3H).
  • Claisen rearrangement of 4-(allyloxy)-1-chloro-2-methylbenzene [9]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.09 (s, 1H), 6.71 (d, J = 0.8 Hz, 1H), 6.07–5.89 (m, 1H), 5.20 (t, J = 1.6 Hz, 1H), 5.17 (dq, J = 8.0, 1.6 Hz, 1H), 4.88 (s, 1H), 3.36 (dt, J = 6.3, 1.7 Hz, 2H), 2.32 (s, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.15 (d, J = 8.6 Hz, 1H), 6.65 (d, J = 8.6 Hz, 1H), 6.07–5.89 (m, 1H), 5.10 (dq, J = 10.1, 1.6 Hz, 1H), 5.01 (dq, J = 17.2, 1.8 Hz, 1H), 4.81 (s, 1H), 3.48 (dt, J = 5.7, 1.8 Hz, 2H), 2.36 (s, 3H).
  • Claisen rearrangement of 4-(allyloxy)-1-bromo-2-methylbenzene
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.25 (s, 1H), 6.70 (s, 1H), 6.00–5.87 (m, 1H), 5.19 (t, J = 1.6 Hz, 1H), 5.15 (dq, J = 7.5, 1.6 Hz, 1H), 3.35 (dt, J = 6.4, 1.7 Hz, 2H), 2.32 (s, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.6 Hz, 1H), 6.56 (d, J = 8.6 Hz, 1H), 6.00–5.87 (m, 1H), 5.09 (dq, J = 10.1, 1.7 Hz, 1H), 4.99 (dq, J = 17.2, 1.8 Hz, 1H), 3.49 (dt, J = 5.7, 1.8 Hz, 2H), 2.38 (s, 3H).
The hydroxyl peak seems to be around 5.0 ppm, overlapping with some of the other peaks.
  • Claisen rearrangement of 4-(allyloxy)-1,2-dimethylbenzene [37]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 6.86 (s, 1H), 6.63 (s, 1H), 6.13–5.90 (m, 1H), 5.21–5.10 (m, 2H), 4.64 (broad s, 1H) 3.35 (dt, J = 6.4, 1.7 Hz, 2H), 2.19 (s, 3H), 2.17 (s, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 6.92 (d, J = 8.1 Hz, 1H), 6.59 (d, J = 8.1 Hz, 1H), 6.13–5.90 (m, 1H), 5.10–4.95 (m, 2H), 4.64 (broad s, 1H), 3.47 (dt, J = 5.7, 1.8 Hz, 2H), 2.22 (s, 3H), 2.19 (s, 3H).
  • Claisen rearrangement of 4-(allyloxy)-1-isopropyl-2-methylbenzene
Isomer A: 1H NMR (400 MHz, CDCl3) δ 6.87 (s, 1H), 6.53 (s, 1H), 6.03–5.83 (m, 1H), 5.09 (dq, J = 25.0, 1.7 Hz, 1H), 5.08 (p, J = 1.6 Hz, 1H), 3.31 (dt, J = 6.4, 1.8 Hz, 2H), 2.96 (hept, J = 6.8 Hz, 1H), 2.19 (s, 3H), 1.12 (d, J = 6.9 Hz, 6H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 6.95 (d, J = 8.3 Hz, 1H), 6.59 (d, J = 8.3 Hz, 1H), 6.03–5.83 (m, 1H), 4.96 (dq, J = 6.3, 1.8 Hz, 1H), 4.95 (dq, J = 33.5, 1.8 Hz, 1H), 3.40 (dt, J = 5.8, 1.8 Hz, 2H), 3.06 (hept, J = 6.8 Hz, 1H), 2.18 (s, 3H), 1.12 (d, J = 6.8 Hz, 6H).
  • Claisen rearrangement of (4-(allyloxy)-2-methylphenyl)(methyl)sulfane
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.06 (s, 1H), 6.70 (s, 1H), 6.13–5.90 (m, 1H), 5.20 (dq, J = 6.4, 1.7 Hz, 1H), 5.17 (t, J = 1.6 Hz, 1H), 3.40 (dt, J = 6.3, 1.7 Hz, 2H), 2.41 (s, 3H), 2.36 (s, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 8.4 Hz, 1H), 6.70 (d, J = 8.7 Hz, 1H), 6.13–5.90 (m, 1H), 5.09 (dq, J = 10.1, 1.7 Hz, 1H), 5.02 (dq, J = 17.2, 1.8 Hz, 1H), 3.49 (dt, J = 5.8, 1.8 Hz, 2H), 2.41 (s, 3H), 2.40 (s, 3H).
  • Claisen rearrangement of 4-(allyloxy)-2-chloro-1-fluorobenzene
Isomer A: 1H NMR (400 MHz, CDCl3) δ 6.93 (d, J = 9.3 Hz, 1H), 6.88 (d, J = 6.2 Hz, 1H), 6.05–5.90 (m, 1H), 5.27–5.09 (m, 2H), 3.37 (dt, J = 6.3, 1.7 Hz, 2H)
Isomer B: 1H NMR (400 MHz, CDCl3) δ 6.96 (t, J = 8.7 Hz, 1H), 6.72 (dd, J = 8.8, 4.3 Hz, 1H), 6.05–5.90 (m, 1H), 5.27–5.09 (m, 2H), 3.62 (dt, J = 6.1, 1.8 Hz, 2H).
  • Claisen rearrangement of 4-(allyloxy)-1,2-dichlorobenzene [38]
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.17 (s, 1H), 6.93 (s, 1H), 6.08–5.87 (m, 1H), 5.22–5.08 (unclear exact peak location and multiplicity due to overlap, 2H), 5.04 (broad s, 1H), 3.35 (dt, J = 6.4, 1.8 Hz, 2H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.7 Hz, 1H), 6.71 (d, J = 8.7 Hz, 1H), 6.08–5.87 (m, 1H), 5.22–5.08 (unclear exact peak location and multiplicity due to overlap, 2H), 5.04 (broad s, 1H), 3.63 (dt, J = 6.1, 1.7 Hz, 2H).
  • Claisen rearrangement of 4-(allyloxy)-2-chloro-1-methylbenzene
Isomer A: 1H NMR (400 MHz, CDCl3) δ 6.94 (d, J = 0.8 Hz, 1H), 6.84 (s, 1H), 6.10–5.89 (m, 1H), 5.09 (dp, J = 7.2, 1.8 Hz, 2H), 3.34 (dt, J = 6.3, 1.7 Hz, 2H), 2.27 (d, J = 0.7 Hz, 3H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 6.99 (dd, J = 8.2, 0.8 Hz, 1H), 6.66 (d, J = 8.2 Hz, 1H), 6.04–5.91 (m, 1H), 5.18–5.11 (m, 2H), 3.62 (dt, J = 6.0, 1.7 Hz, 2H), 2.31 (d, J = 0.7 Hz, 3H).
  • Claisen rearrangement of 4-(allyloxy)-2-chloro-benzonitrile
Isomer A: 1H NMR (400 MHz, CDCl3) δ 7.41 (s, 1H), 6.98 (s, 1H), 6.21 (s, 1H), 6.08–5.85 (m, 1H), 5.25–5.15 (m, 2H), 3.38 (dd, J = 6.5, 1.7 Hz, 2H).
Isomer B: 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.5 Hz, 1H), 6.84 (d, J = 8.5 Hz, 1H), 6.17 (s, 1H), 6.08–5.85 (m, 1H), 5.17–5.08 (m, 2H), 3.61 (dt, J = 6.1, 1.7 Hz, 2H).

3. Results and Discussion

In this study, Claisen rearrangements were performed at 200 °C on allyl aryl ethers containing 13 different meta-substituents and 10 combinations of meta- and para-substituents (see Figure 4).
The ratios between constitutional isomers A and B were determined by analyzing the crude 1H NMR spectra of the product mixture. This was carried out to prevent the separation and purification process to affect the product ratio and because some of the products were inseparable. The crude NMR was therefore deemed to have the most reliable product ratio for the reaction itself. The splitting patterns in the aromatic region were sufficiently distinct to provide a basis for identification of the different isomers, with the integration being used to calculate the product ratio. The two alkyl protons on the allyl group provided the best peaks for this integration, as the aromatic and alkene peaks overlapped more often between products, but wherever possible, other peaks were also taken into consideration.

3.1. Meta-Substituted Allyl Aryl Ethers

The results for the meta-substituted allyl phenyl ethers are summarized in Table 1. While the substituents did have a clear effect on the product distribution, the effect was not high under the reaction conditions used. Two of the substituents were the same as those Gozzo et al. had used, Me and NO2. Their results showed a product ratio of 1.0:1.0 when the meta-substituent was Me, whereas our results showed a product ratio of 1.0:1.2. Similarly, our results for NO2 as the meta-substituent gave a different product ratio of 1:1.6 compared to 1.0:1.8 in the previous study [9].
White et al. studied the ortho-Claisen rearrangement extensively in the 1960s [15,39,40,41]. When investigating the topic, they found that in all cases except for the electron-donating methoxy-substituent, rearrangement occurs primarily towards the substituted meta-position [39]. Among the meta-substituents they tried were methoxy-, methyl-, chlorine-, and cyano-substituents. The proposed explanation was that the ratio between the isomers depended roughly on the electronic nature of the meta substituent. Thus, electron-donating favored migration to the unhindered position (isomer A) while electron-withdrawing substituents favored migration towards the substituted meta position (isomer B) [40].
The original conclusion seems to hold up for most of the Claisen rearrangements performed on meta-substituted allyl aryl ethers in this study. There are three main exceptions to point out however. First, the fluorine is expected to be electron withdrawing but more of isomer A forms rather than isomer B. Second, the methyl group was expected to be electron donating but more of isomer B was formed rather than isomer A. Third, the ethyl group gave approximately equal proportions of both isomers, whereas it was expected to be electron donating like the methyl group. These two cases might imply that it is not as straight forward as just saying electron-donating groups favor migration to the unhindered position while electron-withdrawing group favor migration towards the substituted meta position.
Looking at the halogens, there is a clear trend that as the halogen size increases, more of isomer B is formed. The halogens are electron withdrawing via induction but can be electron donating through resonance. The electron-donating resonance is, however, not as good compared to if the substituent were hydroxide or amine instead of halogens. When chlorine, bromine, or iodine are the substituents, the problem is size. The 2p orbital of the carbon does not overlap well with the 2p orbital of the halogens (3p for Cl, 4p for Br, and 5p for I). Fluorine has 2p orbitals that are a better fit in size for overlap with the carbon 2p orbitals, but fluorine is nevertheless so electronegative that the 2p orbitals are expected to be much lower in energy than the 2p orbitals of carbon. Conjugation in the halobenzenes was therefore expected to be weak and the inductive electron withdrawal ability was expected to be the dominant factor [42]. The case of fluorine here could suggest that, for the Claisen rearrangement, the electron-donating resonance of fluorine has a more significant effect than for the other halogens.
When the meta-substituent was a methyl group, isomer B was favored over isomer A. This agrees with previous results by White et al. [39]. However, the result found by Gozzo et al. showed a ratio of 1:1 [9]. White et al. had shown that temperature can affect the product ratio, so this difference in results might be due to slight differences in the reaction set-up, e.g., how quickly the reaction temperature reached 200 °C [39]. Similarly, the ethyl gave approximately the same ratio, although the integration showed slightly more of product B (A:B ratio of 1:0.95 if one more significant figure is included).
When looking at the larger alkyl substituent, steric effect may also play a larger role in the product distribution than the electronic effect, especially for the bulky t-butyl group. This applies especially to the case where the substituent is t-butyl and the allyl group migrates preferentially to the less hindered site.
Finally, a Hammett plot was drawn to see if the electronic nature of the substituent could help rationalize not only which isomer was likely to be more prevalent, but also to what extent. The substituent parameters used were σmeta, σinduction, and Taft size parameters. None of the plots showed a clear trend, and trendlines that were drawn gave an R2 ≤ 0.25 (see Supplementary Information). This suggests that there is something more at play than just the electronic nature of the substituents.

3.2. Meta- and Para-Substited Allyl Aryl Ethers

Of main interest in this study were the results for the meta- and para-substituted allyl aryl ethers. These results are summarized in Table 2. In this part of the study, the main emphasis was on observing how the different para-substituents affected the product ratio.
The first thing to note in Table 2 is that the para-substituents have a clear effect on the product ratio. In all these reactions, isomer B was favored over isomer A. This on its own is synthetically interesting as it produces the more sterically crowded 1,2,3,4-tetrasubstituted aromatic ring compared to the sterically less crowded 1,2,4,5-tetrasubstituted alternative product. Secondly, there is not a clear pattern that arises by looking at the electron-donating/withdrawing effect of the para-substituents. Attempts at Hammett plot supported this as they did not give a good trendline (see Supplementary information).
The effect of the para-substituent also seems to depend significantly on the meta-substituent. This can, e.g., be seen when comparing the fluoro and methyl groups as para-substituents. When the meta-substituent is methyl, neither the fluoro nor methyl para-substituents changed the product ratio. However, when the meta-substituent was a chlorine atom, both the methyl and fluoro substituents altered the product ratio with the methyl para-substituent having much more effect on the product ratio than the fluoro para-substituent. Out of all the para-substituents tested, chlorine had the most effect on the product ratios for both methyl and chlorine as meta-substituents.
In most cases, the para-substituent led to increased proportion of the isomer that the meta-substituent on its own favored, if it had any effect on the product ratio to begin with. There was only one deviation from this observation, i.e., -SMe in para position with Me in meta position led to slightly less of isomer B compared to when there was a H in the para position. It would be interesting to explore a larger sample size, and especially meta-substituents where isomer A was produced to a greater extent than isomer B. There it would be interesting to see if the para-substituents continue to enhance the proportion of the isomer favored by the meta-substituent on its own, or if the para-substituent would have opposing directing effect to the meta-substituent.

3.3. Population Analysis

Population analysis was performed for the molecules to find out the effective atomic charges. To study the electrostatic arguments that could explain possible differences in the potential of the reaction sides in the Claisen rearrangement, the atomic charges of reactants were determined with Mulliken population analysis (MPA), the Hirshfeld population analysis (HPA), the Löwdin population analysis (LPA), and the natural population analysis (NPA) at HF/def2-SV(P) level of theory [43,44,45,46]. Here, the aim is not to compare the different population analysis methods or to find the exact atomic charges of the molecule, but much rather to see if they show similar trends. It needs to be pointed out that results from atomic charge calculation need to be carefully interpreted, as equating electrostatic potential with atomic charges is not always a valid procedure [47].
Herein, we will concentrate on the effective atomic charges on the two carbons in the aromatic ring that connect to the allyl group. We will use A and B to designate the carbons that connect to the allyl group in isomer A and B, respectively. The approach that gave the best corresponding trend was HPA. Those results are shown in Table 3.
These calculations suggest that it may be possible to estimate which of the isomeric products will be the major product using effective atomic charges. The carbon atom with the greater negative charge seems to react to a greater extent in this Claisen rearrangement. All four methods used (MPA, HPA, LPA, and NPA) agreed with which carbon had the greater negative charge, except for one allyl aryl ether. When fluorine was the meta-substituent, the MPA and NPA approaches gave the opposite results. Detailed results of these calculations can be found in the Supplementary Materials.
While this method seems to have some predictive power for what the major product will be, there are too many significant deviations between the charge ratios and experimental product ratios to consider this a viable method to predict product ratios. For improved predictive power it may be necessary to use a linear combination of several factors, including, e.g., steric factors. Further studies will be needed to explore such linear combination approaches to predicting the regioselectivity of the Claisen rearrangement.

4. Conclusions

This study further supports the results of previous studies, indicating that electron-donating meta-substituents lead to the allyl group migrating to a greater extent to the less hindered position further away from meta-substituent (isomer A). Electron-withdrawing meta-substituents lead to the allyl group migrating more towards the meta-substituent to form isomer B. A couple of meta-substituents, in particular fluorine and methyl, did not however conform to this trend, suggesting further analysis is still warranted.
The main results for the meta- and para-substituted aromatic Claisen rearrangements were that most of the para-substituents tested had either little effect on the regioselectivity or amplified the regioselectivity promoted by the meta-substituents. There was no clear trend however in how these para-substituents affected the product distribution, and it was also clear that the para-effect could vary significantly based on the meta-substituent. This provides an interesting avenue for further analysis.
Population analysis suggested that it may be of use to indicate in what direction the regioselectivity will be, using the effective atomic charge ratios of the aromatic carbons that will be connected to the allyl groups.
For what appears to be just a simple rearrangement, it seems further investigation on the aromatic Claisen rearrangement is required. Meta- and para-substituted aromatic Claisen rearrangement could be studied further with more variation in the meta- and para-substituents. Similarly, there is still room to advance theoretical calculations even further in relation to this reaction.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/reactions6040054/s1, Claisen experimental section (PDF), Claisen Computational methods (PDF).

Author Contributions

Conceptualization, B.R.S.; methodology, B.R.S. and W.T.M.; formal analysis, W.T.M. and B.R.S.; investigation, W.T.M., S.D.H., L.A.A. and B.R.S.; validation, B.R.S.; software, W.T.M.; resources, B.R.S.; data curation, W.T.M.; writing—original draft preparation, W.T.M. and B.R.S.; writing—review and editing, B.R.S.; supervision, B.R.S.; project administration, B.R.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

The data underlying in this study are available in the published article and its Supplementary Materials. Raw data files relating to this study are available from the corresponding author upon request.

Acknowledgments

The authors would like to thank Sigríður Jónsdóttir and Gunnar Widtefeldt Reginsson for help with NMR measurements. The authors would also like to thank Vilhjálmur Ásgeirsson for his help with the computational aspect of the study.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
EtOAcEthyl acetate
HPAHirshfeld population analysis
K2CO3Potassium carbonate
KIPotassium Iodide
LPALöwdin population analysis
MPAMulliken population analysis
NMRNuclear Magnetic Resonance
NPANatural population analysis

References

  1. Olah Vol, G.A. Mechanism of Electrophilic Aromatic Substitutions. Acc. Chem. Res. 1971, 4, 240–248. [Google Scholar] [CrossRef]
  2. Richard, J.P.; Jencks, W.P. A Simple Relationship between Carbocation Lifetime and Reactivity-Selectivity Relationships for the Solvolysis of Ring-Substituted 1-Phenylethyl Derivatives. J. Am. Chem. Soc. 1982, 104, 4689–4691. [Google Scholar] [CrossRef]
  3. Claisen, L. Über Umlagerung von Phenol-Allyl-Äthern in C-Allyl-Phenole. Ber. Dtsch. Chem. Ges. 1912, 45, 3157–3166. [Google Scholar] [CrossRef]
  4. Castro, A.M.M. Claisen Rearrangement over the Past Nine Decades. Chem. Rev. 2004, 104, 2939–3002. [Google Scholar] [CrossRef]
  5. Ganem, B. The Mechanism of the Claisen Rearrangement: Déja Vu All Over Again. Angew. Chem. Int. Ed. Engl. 1996, 35, 936–945. [Google Scholar] [CrossRef]
  6. Claisen, L.; Tietze, E. Über Den Mechanismus Der Umlagerung Der Phenol-Allyläther. Ber. Dtsch. Chem. Ges. 1925, 58, 275–281. [Google Scholar] [CrossRef]
  7. Jefferson, A.; Scheinmann, F. Molecular Rearrangements Related to the Claisen Rearrangement. Q. Rev. Chem. Soc. 1968, 22, 391–421. [Google Scholar] [CrossRef]
  8. Hiersemann, M.; Nubbemeyer, U. (Eds.) The Claisen Rearrangement; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2007; ISBN 9783527308255. [Google Scholar]
  9. Gozzo, F.C.; Fernandes, S.A.; Rodrigues, D.C.; Eberlin, M.N.; Marsaioli, A.J. Regioselectivity in Aromatic Claisen Rearrangements. J. Org. Chem. 2003, 68, 5493–5499. [Google Scholar] [CrossRef] [PubMed]
  10. Krenske, E.H.; Burns, J.M.; McGeary, R.P. Claisen Rearrangements of Benzyl Vinyl Ethers: Theoretical Investigation of Mechanism, Substituent Effects, and Regioselectivity. Org. Biomol. Chem. 2017, 15, 7887–7893. [Google Scholar] [CrossRef] [PubMed]
  11. Ito, F.; Fusegi, K.; Kumamoto, T.; Ishikawa, T. Boron Trichloride Mediated Regioselective Claisen Rearrangement of Resorcinol Derivatives: Application to Resorcinol Carvonyl Ethers. Synthesis 2007, 2007, 1785–1796. [Google Scholar] [CrossRef]
  12. Meyer, M.P.; DelMonte, A.J.; Singleton, D.A. Reinvestigation of the Isotope Effects for the Claisen and Aromatic Claisen Rearrangements: The Nature of the Claisen Transition States. J. Am. Chem. Soc. 1999, 121, 10865–10874. [Google Scholar] [CrossRef]
  13. Lto, H.; Sato, A.; Taguchi, T. Enantioselective Aromatic Claisen Rearrangement. Tetrahedron Lett. 1997, 38, 4815–4818. [Google Scholar] [CrossRef]
  14. Pincock, A.L.; Pincock, J.A.; Stefanova, R. Substituent Effects on the Rate Constants for the Photo-Claisen Rearrangement of Allyl Aryl Ethers. J. Am. Chem. Soc. 2002, 124, 9768–9778. [Google Scholar] [CrossRef]
  15. White, W.N.; Gwynn, D.; Schlitt, R.; Girard, C.; Fife, W. The Ortho-Claisen Rearrangement. I. The Effect of Substituents on the Rearrangement of Allyl p-X-Phenyl Ethers. J. Am. Chem. Soc. 1958, 80, 3271–3277. [Google Scholar] [CrossRef]
  16. Kirsten, M.; Rehbein, J.; Hiersemann, M.; Strassner, T. Organocatalytic Claisen Rearrangement: Theory and Experiment. J. Org. Chem. 2007, 72, 4001–4011. [Google Scholar] [CrossRef]
  17. Pan, W.; Li, C.; Zhu, H.; Li, F.; Li, T.; Zhao, W. A Mild and Practical Method for Deprotection of Aryl Methyl/Benzyl/Allyl Ethers with HPPh 2 and t BuOK. Org. Biomol. Chem. 2021, 19, 7633–7640. [Google Scholar] [CrossRef]
  18. Kathe, P.M.; Berkefeld, A.; Fleischer, I. Nickel Hydride Catalyzed Cleavage of Allyl Ethers Induced by Isomerization. Synlett 2021, 32, 1629–1632. [Google Scholar] [CrossRef]
  19. Lin, Y.L.; Cheng, J.Y.; Chu, Y.H. Microwave-Accelerated Claisen Rearrangement in Bicyclic Imidazolium [b-3C-Im][NTf2] Ionic Liquid. Tetrahedron 2007, 63, 10949–10957. [Google Scholar] [CrossRef]
  20. Minutolo, F.; Bellini, R.; Bertini, S.; Carboni, I.; Lapucci, A.; Pistolesi, L.; Prota, G.; Rapposelli, S.; Solati, F.; Tuccinardi, T.; et al. Monoaryl-Substituted Salicylaldoximes as Ligands for Estrogen Receptor β. J. Med. Chem. 2008, 51, 1344–1351. [Google Scholar] [CrossRef]
  21. Verhasselt, S.; Roman, B.I.; De Wever, O.; Van Hecke, K.; Van Deun, R.; Bracke, M.E.; Stevens, C.V. Discovery of (S)-3′-Hydroxyblebbistatin and (S)-3′-Aminoblebbistatin: Polar Myosin II Inhibitors with Superior Research Tool Properties. Org. Biomol. Chem. 2017, 15, 2104–2118. [Google Scholar] [CrossRef]
  22. Maity, S.; Kancherla, R.; Dhawa, U.; Hoque, E.; Pimparkar, S.; Maiti, D. Switch to Allylic Selectivity in Cobalt Catalyzed Dehydrogenative Heck Reaction with Unbiased Aliphatic Olefins Supporting Information. ACS Catal. 2016, 6, 5493–5499. [Google Scholar] [CrossRef]
  23. Sánchez-Peris, M.; Murga, J.; Falomir, E.; Carda, M.; Marco, J.A. Synthesis of Honokiol Analogues and Evaluation of Their Modulating Action on VEGF Protein Secretion and Telomerase-Related Gene Expressions. Chem. Biol. Drug Des. 2017, 89, 577–584. [Google Scholar] [CrossRef]
  24. Khan, A.; Komejan, S.; Patel, A.; Lombardi, C.; Lough, A.J.; Foucher, D.A. Reduction of C,O-Chelated Organotin(IV) Dichlorides and Dihydrides Leading to Protected Polystannanes. J. Organomet. Chem. 2015, 776, 180–191. [Google Scholar] [CrossRef]
  25. Han, X.; Armstrong, D.W. Using Geminal Dicationic Ionic Liquids as Solvents for High-Temperature Organic Reactions. Org. Lett. 2005, 7, 4205–4208. [Google Scholar] [CrossRef]
  26. Kisiel-Nawrot, E.; Pindjakova, D.; Latocha, M.; Bak, A.; Kozik, V.; Suwinska, K.; Sochanik, A.; Cizek, A.; Jampilek, J.; Zięba, A. Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives. Int. J. Mol. Sci. 2022, 23, 15078. [Google Scholar] [CrossRef]
  27. Thiruvengetam, P.; Chakravarthy, R.D.; Chand, D.K. A Molybdenum Based Metallomicellar Catalyst for Controlled and Chemoselective Oxidation of Activated Alcohols in Aqueous Medium. J. Catal. 2019, 376, 123–133. [Google Scholar] [CrossRef]
  28. Brown, D.P.; Duong, H.Q. Synthesis of Novel Aromatic Macrolactones via Ring Closing Metathesis of Substituted Phenylalkanoic Acid Allylic Esters. J. Heterocycl. Chem. 2008, 45, 435–443. [Google Scholar] [CrossRef]
  29. Kölbel, M.; Beyersdorff, T.; Tschierske, C.; Diele, S.; Kain, J. Thermotropic and Lyotropic Liquid Crystalline Phases of Rigid Aromatic Amphiphiles. Chem. Eur. J. 2000, 6, 3821–3837. [Google Scholar] [CrossRef]
  30. Bredikhina, Z.A.; Kurenkov, A.V.; Bredikhin, A.A. Nonracemic Dimethylphenyl Glycerol Ethers in the Synthesis of Physiologically Active Aminopropanols. Russ. J. Org. Chem. 2019, 55, 837–844. [Google Scholar] [CrossRef]
  31. Hsieh, C.E.; Jiang, Y.M.; Chou, C.M. Functionalized Allyl Aryl Ether Synthesis from Benzoic Acids Using a Dearomatization and Decarboxylative Allylation Approach. J. Org. Chem. 2019, 84, 653–665. [Google Scholar] [CrossRef] [PubMed]
  32. Kumaraswamy, B.; Ranjith Kumar, T.; Narsimha, S.; Vasudeva Reddy, N. Synthesis, Characterization and in Vitro Microbial Evaluation of Regioisomers of Allyl Phenyl Ethers Derived 1,2,4-Triazoles. Int. J. Pharm. Pharm. Sci. 2014, 6, 572–575. [Google Scholar]
  33. Chen, P.; Chen, C.; Zheng, Y.; Chen, F.; Liu, Z.; Ren, S.; Song, H.; Liu, T.; Lu, Z.; Sun, H.; et al. Discovery of 2,3-Dihydro[1,4]Dioxino[2,3-g]Benzofuran Derivatives as Protease Activated Receptor 4 (PAR4) Antagonists with Potent Antiplatelet Aggregation Activity and Low Bleeding Tendency. J. Med. Chem. 2024, 67, 5502–5537. [Google Scholar] [CrossRef]
  34. Geresh, S.; Markovits, Y.; Shani, A. On the Mechanism of Intramolecular Photocycloaddition of Substituted O-Allylphenols to Cyclic Ethers. Tetrahedron 1975, 31, 2803–2807. [Google Scholar] [CrossRef]
  35. Sakamuri, S.; Kozikowski, A.P. Synthesis of 7-Methoxybenzolactam-V8 Using a Diastereoselective Strecker Synthesis. Chem. Commun. 2001, 32, 475–476. [Google Scholar] [CrossRef]
  36. Vargas, D.F.; Larghi, E.L.; Kaufman, T.S. Synthesis of Polysubstituted 3-Methylisoquinolines through the 6π-Electron Cyclization/Elimination of 1-Azatrienes Derived from 1,1-Dimethylhydrazine. Eur. J. Org. Chem. 2018, 2018, 5605–5614. [Google Scholar] [CrossRef]
  37. Wang, B.; Ren, M.; Iqbal, N.; Mu, X.; Yang, B. Environmentally Friendly Synthesis of Highly Substituted Phenols Using Enallenoates and Grignard Reagents. Org. Lett. 2024, 26, 3361–3365. [Google Scholar] [CrossRef] [PubMed]
  38. Marín-Ramos, N.I.; Piñar, C.; Vázquez-Villa, H.; Martín-Fontecha, M.; González, Á.; Canales, Á.; Algar, S.; Mayo, P.P.; Jiménez-Barbero, J.; Gajate, C.; et al. Development of a Nucleotide Exchange Inhibitor That Impairs Ras Oncogenic Signaling. Chem. A Eur. J. 2017, 23, 1676–1685. [Google Scholar] [CrossRef] [PubMed]
  39. White, W.N.; Slater, C.D. The Ortho-Claisen Rearrangement. V. The Products of Rearrangement of Allyl m-X-Phenyl Ethers. J. Org. Chem. 1961, 26, 3631–3638. [Google Scholar] [CrossRef]
  40. White, W.N.; Slater, C.D. The Ortho-Claisen Rearrangement. VI. The Rates of Rearrangement of Allyl m-X-Phenyl Ethers to 2-Allyl-5-X-Phenols. J. Org. Chem. 1962, 27, 2908–2914. [Google Scholar] [CrossRef]
  41. White, W.N.; Slater, C.D.; Fife, W. The Electronic Nature of the Transition State of the Claisen Rearrangement. J. Org. Chem. 1961, 26, 627–628. [Google Scholar] [CrossRef]
  42. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press Inc.: New York, NY, USA, 2012; ISBN 978-0-19-927029-3. [Google Scholar]
  43. Contreras, R.; Domingo, L.R.; Silvi, B. Electron Densities: Population Analysis and Beyond. In Encyclopedia of Physical Organic Chemistry; Wang, Z., Wille, U., Juaristi, E., Eds.; John Wiley & Sons Inc.: Hoboken, NJ, USA, 2016; ISBN 9781118468586. [Google Scholar]
  44. Neese, F. The ORCA Program System. WIREs Comput. Mol. Sci. 2012, 2, 73–78. [Google Scholar] [CrossRef]
  45. Nikolaienko, T.Y.; Bulavin, L.A.; Hovorun, D.M. JANPA: An Open Source Cross-Platform Implementation of the Natural Population Analysis on the Java Platform. Comput. Theor. Chem. 2014, 1050, 15–22. [Google Scholar] [CrossRef]
  46. Nikolaienko, T.Y.; Bulavin, L.A. Localized Orbitals for Optimal Decomposition of Molecular Properties. Int. J. Quantum Chem. 2019, 119, e25798. [Google Scholar] [CrossRef]
  47. Shusterman, A.J.; Hoistad, L.M. Teaching Chemistry with Electron Density Models. 2. Can Atomic Charges Adequately Explain Electrostatic Potential Maps? Chem. Educ. 2001, 6, 36–40. [Google Scholar] [CrossRef]
Reactions 06 00054 g001
Figure 1. Ratio of products when H as para-substituent is switched for two different groups. This experiment was performed by Gozzo and co-workers [9].
Figure 1. Ratio of products when H as para-substituent is switched for two different groups. This experiment was performed by Gozzo and co-workers [9].
Reactions 06 00054 g001
Reactions 06 00054 g002
Figure 2. Reaction scheme for the general synthesis of substituted allyl aryl ethers.
Figure 2. Reaction scheme for the general synthesis of substituted allyl aryl ethers.
Reactions 06 00054 g002
Reactions 06 00054 g003
Figure 3. A general reaction scheme for the Claisen rearrangement of the substituted allyl aryl ethers.
Figure 3. A general reaction scheme for the Claisen rearrangement of the substituted allyl aryl ethers.
Reactions 06 00054 g003
Reactions 06 00054 g004
Figure 4. Reaction scheme for the Claisen rearrangement of allyl aryl ethers with intermediates and isomers A and B defined.
Figure 4. Reaction scheme for the Claisen rearrangement of allyl aryl ethers with intermediates and isomers A and B defined.
Reactions 06 00054 g004
Table 1. The A:B ratio for the Claisen rearrangement of meta-substituted allyl phenyl ethers, where R2 = H for all samples.
Table 1. The A:B ratio for the Claisen rearrangement of meta-substituted allyl phenyl ethers, where R2 = H for all samples.
R1 (Meta)A:B
F1:0.6
Cl1:1.4
Br1:1.6
I1:1.7
Me1:1.2
Et1:1.0
tBu1:0.5
Ph1:0.8
NHCOCH31:0.8
CHO1:3.0
CO2CH2CH=CH21:1.8
CF31:1.3
NO21:1.6
Table 2. The A:B ratio for the Claisen rearrangement of meta- and para-substituted allyl phenyl ethers.
Table 2. The A:B ratio for the Claisen rearrangement of meta- and para-substituted allyl phenyl ethers.
Reactions 06 00054 i001
R1 (Meta)R2 (Para)A:B
MeH1:1.2
F1:1.2
Cl1:2.3
Br1:1.7
Me1:1.2
iPr1:1.3
SMe1:1.1
ClH1:1.4
F1:1.7
Cl1:2.4
Me1:2.1
CN1:1.6
Table 3. Hirshfeld population analysis for the carbons that connect to the allyl group in isomers A and B for select allyl aryl ethers. Columns A and B show the calculated charge, whereas the last two columns show comparison between the HPA calculated charge ratios and the experimental product ratios.
Table 3. Hirshfeld population analysis for the carbons that connect to the allyl group in isomers A and B for select allyl aryl ethers. Columns A and B show the calculated charge, whereas the last two columns show comparison between the HPA calculated charge ratios and the experimental product ratios.
Reactions 06 00054 i002
R1 (Meta)R2 (Para)ABB/A (HPA)B/A (Experiment)
FH−0.132672−0.0999270.750.6
Cl−0.048462−0.0692991.431.4
Br−0.045385−0.0661081.461.6
Me−0.055549−0.0748391.351.2
Et−0.070555−0.057930.821.0
CF3−0.035212−0.0577431.641.3
MeF−0.042287−0.0599521.421.2
Cl−0.045936−0.0675381.472.3
Me−0.055732−0.0724691.301.2
ClF−0.035107−0.0588321.681.7
Cl−0.039825−0.0642151.612.4
Me−0.047678−0.0679951.432.1
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Möller, W.T.; Hreinsdóttir, S.D.; Arana, L.A.; Sveinbjörnsson, B.R. Regioselectivity of the Claisen Rearrangement of Meta- and Para-Substituted Allyl Aryl Ethers. Reactions 2025, 6, 54. https://doi.org/10.3390/reactions6040054

AMA Style

Möller WT, Hreinsdóttir SD, Arana LA, Sveinbjörnsson BR. Regioselectivity of the Claisen Rearrangement of Meta- and Para-Substituted Allyl Aryl Ethers. Reactions. 2025; 6(4):54. https://doi.org/10.3390/reactions6040054

Chicago/Turabian Style

Möller, William Thomas, Svava Dögg Hreinsdóttir, Luis Antonio Arana, and Benjamín Ragnar Sveinbjörnsson. 2025. "Regioselectivity of the Claisen Rearrangement of Meta- and Para-Substituted Allyl Aryl Ethers" Reactions 6, no. 4: 54. https://doi.org/10.3390/reactions6040054

APA Style

Möller, W. T., Hreinsdóttir, S. D., Arana, L. A., & Sveinbjörnsson, B. R. (2025). Regioselectivity of the Claisen Rearrangement of Meta- and Para-Substituted Allyl Aryl Ethers. Reactions, 6(4), 54. https://doi.org/10.3390/reactions6040054

Article Metrics

Back to TopTop