Using 13C NMR Spectroscopy for Assessing Regioselectivity of Hydrochlorination

Chemo- and regioselective reactions are vital in order to make multistep syntheses efficient, high-yielding, and atom economic. Core selectivity concepts, such as Markovnikov’s Rule for hydrohalogenation of carbon double bonds, are an introductory topic in organic chemistry lectures.[1]

This article will emphasize the importance of 13C NMR spectroscopy, used alongside the DEPT experiment, for resolving the identity of the product of addition reactions by means of a simple and rapid experimental procedure[2] adapted from a J. Chem. Educ. article published by M. W. Pelter and N. W. Walker. [3]

This experiment is an ideal teaching tool for undergraduate students within the organic chemistry practical course and will increase the familiarity of the students with analyzing and interpreting 13C NMR spectra.


To properly assign a 13C NMR spectrum, especially when identifying an unknown species, it is advantageous to gain definitive information of the CH3, CH2, CH or quaternary (Cq) carbon atoms present. The Distortionless Enhancement by Polarization Transfer (DEPT) is a particularly well-suited NMR spectroscopic method for extracting this information. Figure 1 depicts its pulse sequence.

Pulse sequence of the different DEPT experiments (DEPT-45, -90, -135).[4]

Figure 1. Pulse sequence of the different DEPT experiments (DEPT-45, -90, -135).[4]

In the proton channel a spin echo sequence (90°x’-τ-180°x’-τ) is followed by a θ = 45°, 90° or 135° pulse in the y’ direction, respectively. The angle θ determines which of the different signal intensities for the different carbon atoms (CH3/CH2/CH/Cq) are observed in the resulting spectrum (Figure 2). It should be noted that in all the DEPT experiments quaternary carbons are not observed (herein DEPTq is not discussed), but by comparing with the 13C{1H}NMR spectrum these may be revealed.

Signal intensities of CH3 (blue), CH2 (red) and CH (black) groups as a function of the pulse angle in the DEPT experiment.[5]

Figure 2. Signal intensities of CH3 (blue), CH2 (red) and CH (black) groups as a function of the pulse angle in the DEPT experiment.[5]

In the DEPT-45 experiment all carbon atoms have positive intensities, whereas DEPT-135 outputs a negative peak for the CH2 signals, and positive for the CH and CH3 resonances. In DEPT-90 spectra all carbon signals are absent with the exception of positive CH signals.

At this point it may be noted that, by comparing the 13C{1H}, DEPT-135 and DEPT-90 NMR spectra, all the different carbon atoms can be distinguished.

It can be said that the DEPT experiment shares features with the J modulated spin echo (Attached Proton Test, APT). The advantage of DEPT over APT is the sensitivity enhancement afforded by the polarization transfer from 1H to 13C.[5]

Synthetic Route

The hydrochlorination of carvone 1 may be achieved via in situ generation of HCl employing oxalyl chloride and alumina or TMS-Cl in water.[6,7] In the article by M. W. Pelter and N. W. Walker, it is reported that treatment with inexpensive acetyl chloride in ethanol improves the regio- and chemoselectivity with high yields (scheme 1).

Possible products of the hydrochlorination of (R)-(−)-Carvone (1).[3]

Scheme 1. Possible products of the hydrochlorination of (R)-(−)-Carvone (1).[3]


In accordance with a literature procedure[1,3], monoterpene 1 was dissolved in absolute EtOH and stirred in a round-bottom flask with an attached air condenser. The flask was heated to 45 °C in a fume hood. Acetyl chloride was added dropwise to the reaction mixture, resulting in an increasingly darkened mixture. The progress of the reaction was monitored via TLC until the carvone was fully consumed (less than 90 min).

Once the reaction was completed, the reaction mixture was allowed to cool to room temperature and the solvent was removed under reduced pressure. Compound 2a was obtained as a colorless oil in 75% yield. The 13C{1H} (5 min), DEPT-135 and DEPT-90 (2.5 min each) NMR spectra were recorded on an NMReady-60PRO.

Results and Discussion

The signals with low intensities, such as at 130.29 and 23.78 ppm (greyed out), can be attributed to impurities, and were therefore not characterized any further. By comparing the stacked spectra and following the previously discussed rules, all other observed 13C NMR signals can be assigned to the different types of chemically distinct carbons:

Cq (not seen in DEPT): δ [ppm] = 198.15, 134.58, 72.03

CH3 (positive in DEPT-135, not seen in DEPT-90): δ [ppm] = 29.93 (2x), 15.15

CH2 (negative in DEPT-135): δ [ppm] = 39.62, 27.54

CH (positive in DEPT-90): δ [ppm] = 144.05, 46.81

By matching the intensities with the expected chemical shifts of components, all 13C NMR signals can be assigned to the molecular structure of the Markovnikov product 2a (figure 4).

Stacked 13C{1H}, DEPT-135 and DEPT-90 NMR spectra of compound 2a in CDCl3

Figure 3. Stacked 13C{1H}, DEPT-135 and DEPT-90 NMR spectra of compound 2a in CDCl3.

13C NMR signal assignment for carvone*HCl (2a)

Figure 4. 13C NMR signal assignment for carvone*HCl (2a).

A final item of note is that the number of the different carbon types extracted from the NMR spectra alone, leads solely to the Markovnikov product 2a (see table 1)

Table 1. Number of chemically distinct carbons in possible hydrochlorination products 2a-d.

Carbon type 2a 2b 2c 2d
Cq 3 2 3 2
CH3 3 2 2 2
CH2 2 3 4 3
CH 2 3 1 3


This experiment demonstrated a method of utilizing 13C and DEPT NMR spectroscopy in order to determine which of the regioisomer products 2a-d was obtained from the hydrochlorination of (R)-(-)-Carvone (1) with acetyl chloride in ethanol.

Through logical interpretation, the correct isomer 2a was unambiguously characterized and all observed carbon resonances were assigned to its molecular structure.


[1] J. Clayden, N. Greeves, S. Warren and P. Wothers, Organic Chemisry, 2nd edition, Oxford University Press Inc., New York, 2012, p. 434.

[2] K. Yadav, K. G. Babu, Eur. J. org. Chem. 2005, 425-456.

[3] M. W. Pelter, N. W. Walker, J. Chem. Educ 2012, 89, 1183-1185.

[4] Riegel, S. D.; Leskowitz, G. L. TAC, 2016, 83A, 27-38; 1 /19/dept-a-tool-for-13c-peak-assignments (accessed December 2018).

[5] H. Friebolin, Ein- Und zweidimensionale NMR-Spektroskopie, 5th edition, Wiley-VCH Verlag GmbH, Weinheim, 2013, p. 233.

Data Accessibility

The data can be processed directly on the NMReady-60 and printed and/or exported directly to a USB or networked file where it can be worked up using third party NMR processing software.

This information has been sourced, reviewed and adapted from materials provided by Nanalysis.

For more information on this source, please visit Nanalysis.

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