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. Author manuscript; available in PMC: 2013 Dec 2.
Published in final edited form as: Chem Pharm Bull (Tokyo). 2011;59(8):978–983. doi: 10.1248/cpb.59.978

Synthesis and Characterization of Two Homologous Series of Diastereomeric 2-Alkoxyphenylcarbamates

Fridrich Gregan a, Juraj Gregan b,*, Marek Skorsepa a
PMCID: PMC3845385  EMSID: EMS55797  PMID: 21804242

Abstract

Two homologous series of racemic diastereomeric cis- and trans-(2-dimethylaminomethylcycloheptyl)-2-alkoxyphenylcarbamates with alkyl chain lengths ranging from C1 to C8 were synthesized by stereoselective reactions. The chemical structures of these compounds were confirmed by 1H-NMR. 13C-NMR and IR spectroscopy and their physico-chemical properties were characterized. The two new series of diastereomeric compounds were tested for their local anesthetic activity and parabolic relationship between the local a nesthetic activity and lipophilicity was found for both cis- and trans-series. Interestingly, cis-stereoisomers exhibited higher local anesthetic activity.

Keywords: 2-alkoxyphenylcarbamate, local anesthetic activity, synthesis

Over the past century, the field of anesthesia has strongly benefited from advances in techniques employing local anesthetics. Local anesthetics have been widely used to prevent acute pain and to ameliorate pain associated with chronic painful conditions. Despite the remarkable efficacy of local anesthetics, the risk of toxicity associated with these drugs has been a recurring issue since their introduction.1,2) Therefore, there is a need for new local anesthetic compounds with the aim of maximizing analgesia and minimizing the adverse effects. In our current work, we report the synthesis of two homologous series of diastereomeric 2-alkoxyphenylcarbamates and characterization of their local anesthetic activity. The studied compounds belong to the class of local anesthetics with carbamate group. Many of local anesthetics have functional groups such as aromatic ester, amide, ether, ketone or carbamate that are linked via a short chain (2—3 carbon atoms) with a tertiary aminogroup in the form of hydrochloride.3—5) Previous studies have shown that anesthetic activity depends on the structure and molecular lipophilicity represented by log P and related parameters.6—14) Here, we analyzed the effect of stereoisomerism on the local anesthetic activity of two homologous series of diastereomeric 2-alkoxyphenylcarbamates. Stereochemistry of local anesthetic drugs may affect their potency by altering various characteristics of the drugs such as binding to the target molecules, rate of metabolism and lipophilicity. In this study, we synthesized two homologous series of 16 diastereomeric cis- and trans-(2-dimethylaminomethylcyclohexyl)-2-alkoxyphenylcarbamates in the form of their hydrochloride salts with one to eight carbon atoms in the alkoxy group and studied the relationship between local anesthetic activity and lipophilicity for both cis- and trans-isomers.

Chemistry

cis- and trans-2-Dimethylaminomethylcycloheptanols were prepared according to the literature (Chart 1). 11,15–18) 2-Dimethylaminomethylcycloheptanone (A, Chart 1) was prepared from cycloheptanone.19) 2-Alkoxyphenylisocyanates (C, Chart 2) were freshly prepared from 2-alkoxyphenylanilines by reaction with phosgene according to the published method.8,20) Finally, two homologous series of racemic cis- and trans-(2-dimethylaminomethylcycloheptyl)-2-alkoxyphenylcarbamates (P1 , Chart 2) were prepared by addition reaction of aminoalcohol (B, Chart 2) with alkoxyphenylisocynates (C, Chart 2) in toluene.21, 22) The number of carbon atoms in the alkyl group was from 1 to 8. The carbamates (P1 , Chart 2) were used in their hydrochlorid form (P2, Chart 2).

Chart 1.

Chart 1

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Preparation of cis- and trans-2-Dimethylaminomethylcycloheptanol

Chart 2.

Chart 2

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Preparation of Two Homologous Series of cis- and trans-Carbamates

R = alkyl chain with 1—8 carbons

Pharmacology

The surface local anesthetic activity indices (SLAA) of prepared compounds P2-1—P2-8 were determined on rabbit cornea according to the Vrba and Sekera method.22) Different concentrations of the compound were applied into the conjunctival sac for 30 min. Afterwards, corneal sensitivity was tested using a hair aesthesiometer repeatedly in 3-min intervals. The full anesthesia occurred if no response was elicited by 6 consecutive stimulations. Each compound was tested in 3—6 independent experiments using at least three different concentrations. The surface local anesthetic activity index (SLAA) was calculated as the ratio of equieffective concentrations of the standard and the compound and it is a dimensionless value.23) All biological tests were performed in compliance with regulations for biological testing on animals.

Results and Discussion

The 16 synthesized compounds—hydrochloride salts of cis- and trans-P2 (Chart 2) are listed in the Table 1. The yields ranged within the interval 40—63%. The purity of all compounds was checked by partition TLC. The Rf values decreased with the number of carbon atoms in the alkoxy group for both cis- and trans-diastereomers (Table 2). The difference in Rf values caused by one methylene group in the alkoxy group obtained by partition TLC was higher than the one obtained by adsorption TLC. The values obtained from elemental analysis (C, H, N) agreed with theoretical values within ±0.3%. Structure of all prepared compounds was confirmed by NMR and IR spectroscopy.

Table 1.

Summary of Prepared cis- and trans-N,N-Dimethyl-2-(2-alkoxyphenylcarbamoyloxy)cycloheptylmethylammonium Chlorides (cis-P2 and trans-P2) and Atoms Numbering for 1H-NMR and 13C-NMR

graphic file with name emss-55797-t0004.jpg

  Comp.     R     M.r.a)  
cis -P2-1 Methyl 356.91
trans -P2-l Methyl
cis -P2-2 Ethyl 370.94
trans -P2-2 Ethyl
cis -P2-3 Propyl 384.97
trans -P2-3 Propyl
cis -P2-4 Butyl 399.00
trans -P2-4 Butyl
cis -P2-5 Pentyl 413.03
trans -P2-5 Pentyl
cis -P2-6 Hexyl 427.06
trans -P2-6 Hexyl
cis -P2-7 Heptyl 441.09
trans -P2-7 Heptyl
cis -P2-8 Octyl 455.12
trans -P2-8 Octyl
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a)

M r. stands for relative molecular mass.

Table 2.

Indices of Relative Surface Local Anesthetic Activity (SLAA), Partition Coefficients (P) and Rf Values for cis- and trans-P2 Carbamates (See Chart 2)

Comp. log P SLAA log SLAA Rf
cis -P2-l 1.206 16.3 1.212 0.65
trans -P2-l 1.410 10.8 1.032 0.68
cis -P2-2 1.704 30.3 1.481 0.63
trans -P2-2 1.905 22.5 1.352 0.66
cis -P2-3 2.107 89.1 1.950 0.56
trans -P2-4 2.236 52.6 1.721 0.57
cis -P2-4 2.561 209.9 2.322 0.48
trans -P2-4 2.643 152.1 2.180 0.51
cis -P2-5 3.030 269.8 2.431 0.41
trans -P2-5 3.127 162.2 2.210 0.44
cis -P2-6 3.072 289.1 2.461 0.36
trans -P2-6 3.188 192.8 2.285 0.39
cis -P2-7 3.968 200.9 2.303 0.29
trans -P2-7 4.117 129.1 2.111 0.32
cis -P2-8 4.450 177.8 2.250 0.19
trans -P2-8 4.533 105.4 2.023 0.23
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The SLAA index was calculated as the ratio of equieffective concentrations of the standard and the compound.23)

All prepared P compounds had characteristic absorption bands in the IR spectra at 3432 cm−1 (N–H stretching), 2383 cm−1 (+NH stretching), 1732 cm−1 (C=O stretching), 1604 cm−1 (aromatic C=C stretching) and 1533 cm−1 (C–N–H deformation). There were three absorption bands in the UV spectra at 198, 228 and 260 nm. The εmax values of all three absorption bands for trans-isomers were higher than that of cis-isomers. The εmax values decreased with number of carbon atoms for both cis- and trans-isomers.

Starting 2-dimethylaminomethylcycloheptanone was reduced to 2-dimethylaminomethylcycloheptanol. cis- and trans-Aminoalcohols were prepared according to the literature15,16) (Charts 1, 2). Depending on the selective reducing agent the cis- or trans-2-dimethylaminomethylcycloheptanol was formed, respectively.

The steric arrangement of C1 hydrogen atoms was axial for both cis- and trans-isomers. δ (cis-isomers) = 2.21—2.23 ppm, δ (trans-isomers)=2.05—2.09 ppm. As expected, we found only a small difference (on average Δ=0. 15 ppm) in chemical shifts between these C1 axial hydrogen atoms in cis- and trans-isomers. However, the steric arrangement of C2 hydrogen atoms was different for cis- and trans-isomers. While hydrogen atoms in cis-isomers were equatorial (δ=5.13—5.15 ppm), in trans-isomers they had axial positions (δ=4.57—4.62 ppm). The differences in chemical shifts of C2 hydrogen atoms for cis- and trans-isomers were significantly higher (Δ=0.55 ppm) compared to C1 hydrogen atoms (Δ=0.15 ppm) where they were in axial positions for both of the isomers. These results are in agreement with the 1H-NMR data previously published for cyclic systems.

Differences were also found in 13C-NMR for cis- and trans-isomers. Chemical shifts of C1 carbons were in the interval of δ=37.0—37.2 ppm for cis-isomers and δ=39.4—39.5 ppm for trans-isomers. Chemical shifts of C2 carbons were δ=73.0—73.2 ppm for cis-isomers and δ=76.1—76.2 ppm for trans-isomers.

All physico-chemical properties and biological activity of prepared cis-isomers differed from those of trans-isomers. The mp values were higher for cis-isomers compared to corresponding trans-isomers. Differences were also found in Rf values and partition coefficients (Table 2).

Partition coefficients for both cis- and trans-isomers were measured in the octanol/phosphate buffer system. The relative concentration of the samples in each phase was determined spectrophotometrically in the 228 nm absorption band. The logP values of all trans-isomers were higher than that of cis-isomers (Table 2), presumably due to a higher lipophilicity of the trans-isomers. The log P values increased with the number of carbon atoms in the alkoxy group for both, cis- and trans-isomers.

The results of pharmacological evaluation of prepared cis-P2 and trans-P2 compounds are presented in Table 3. The local anesthetic activities (logSLAA) of both cis- and trans-series were plotted against n and logP values shown in Fig. 1. The activity increased gradually with the number of carbon atoms in the alkoxy group and reached a maximum for logP=3.3 which corresponds to the compound with 6 carbon atoms in alkoxy group (see Fig. 1). Indices of the SLAA were significantly higher compared to the reference cocaine compound for all tested compounds with the exception of the methyl homologues of cis-P2-1 and trans-P2-1. Regression analysis revealed that the data presented in Fig. 1 can best be fitted by a parabolic function. Regression coefficients for parabolic relationship between the log SLAA and the number of carbon atoms in the alkoxy group (n) as well as log P values are shown in Table 3.

Table 3.

Regression Coefficients for Parabolic Relationships between log SLAA and x (x=n or log P) for the cis- and trans-Series of Compounds P2-1—P2-8 and for the Equation: log SLAA=a0+a1x+a2x2

Series x a o a 1 a 2 Ra)
cis nb) 0.5521 0.6360 −0.0535 0.9871
cis log P −0.6698 1.7981 −0.2584 0.9821
trans n 0.3828 0.6368 −0.0543 0.9863
trans log P −1.3843 2.0681 −0.2919 0.9799
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a)

Correlation coefficient.

b)

Number of carbon atoms in the alkoxy group.

Fig. 1.

Fig. 1

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Log Values of Local Anesthetic Activity (SLAA) vs. n (Number of Carbon Atoms in Alkoxy Group) and log P (Partition Coefficient) for Compounds cis-P2-l to cis-P2-8 (○; Full Lines) and trans-P2-1 to trans-P2-8 (□; Dashed Lines)

Diastereoisomers often have different physical and chemical characteristics such as solubility which may result in different pharmacokinetic and pharmacodynamic properties.14,24) In this study, we synthesized eight isomeric pairs and compared anesthetic activity of the respective cis- and trans-isoforms. We observed that anesthetic activity of cis-isomers was higher than those of the trans-isomers (Table 2, Fig. 1). The potency of local anesthetic drugs is determined by many factors such as lipophilicity, ionization and the rate of metabolism. We observed that partition coefficients of trans-isomers were higher than that of the cis-isomers (Table 2). Therefore, one possible explanation is that the high anesthetic activity of cis-isomers was due to their lower lipophilicity as compared to the respective trans-isomers. However, there are other possible explanations which could account for differences in local anesthetic activity of cis- and trans-isomers (e.g. binding to the target molecule) and further experiments are needed to elucidate the underlying mechanism.

Concluding Remarks

Two homologous series of racemic diastereomeric cis- and trans-(2-dimethylaminomethylcycloheptyl)-2-alkoxyphenylcarbamates were synthesized and assayed for their local anesthetic activity. cis-Stereoisomers exhibited higher local anesthetic activity and parabolic relationship between the local anesthetic activity and lipophilicity was found for both cis- and trans-series. Further studies are required to explain differences in local anesthetic activity of the studied cis- and trans-isomers.

Experimental

General

1H-NMR spectra at 300 MHz and 13C-NMR spectra at 75 MHz were obtained on Varian Gemini spectrophotometer using tetramethyl silane as an internal standard. IR spectra were taken on M-80 spectrophotometer in chlorophorm. UV spectra were measured on Hewlett Packard 8452 A spectrophotometer.

Melting points were determined on Koflerblock and are uncorrected. Elemental analyses (C, H, N) were obtained on Elemental Analyser Carlo Erba Science Model 1106. The obtained results had a maximum deviation of 0.3% compared to the theoretical value.

The purity of all compounds were checked by partition TLC on Merck silica gel 60 F254 plates impregnated with 5% solution of silicon oil in heptane and using 1 m HCl–acetone (1 : 1) as the mobile phase. The detection was performed by the Dragendorff’s spray reagent and UV light at 254 nm.

Octanol/water partition coefficients (P) were measured in the system of n-Octanol and 10−2 M potassium phosphate buffer. The relative concentration of the measured compound in each phase was determined spectrophotometrically from the absorption band at 232 nm.

General Procedure for Preparation of cis- and trans-2-(2-Alkoxyphenylcarbamoloyloxy)cycloheptylmethylammonium Chlorides (cis-P2 and trans-P2, Chart 2)

Solution of freshly prepared 2-alkoxyphenylisocyanate (0.01 mol) in anhydrous toluene (15 ml) was mixed with the corresponding cis- or trans-dimethylaminomethylcycloheptanol (1.7 g, 0,01 mol) and the stirring mixture was heated under reflux for 6 h in argon atmosphere. After cooling, hexane was added (15 ml) and the mixture was allowed to stand for 12 h at −5°C in a refrigerator. The solid by-product, bis-(2-alkoxyphenyl) urea that formed in a small amount, was filtered off and the toluene filtrate was extracted with 5% hydrochloric acid (3×10ml). The aqueous layer was extracted with chloroform (3×10 ml). The combined chloroform extracts were dried over anhydrous sodium sulfate. After filtration, chloroform was evaporated using a vacuum rotary evaporator. The residue was mixed with 2×5 ml of anhydrous ether. The solid product was filtered and dried. The obtained colorless solids were finally purified by crystallization: compounds P2-1—P2-3 from butanone, compounds P2-4—P2-6 from ethylacetate and compounds P2-7—P2-8 from heptane: ethylacetate (1 :1). The yields and physico-chemical characteristics of prepared compounds are presented below.

±cis-N,N-Dimethyl-2-(2-methoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (cis-P2-1)

Colourless solid. Yield: 53%. mp 202—203°C (butanone). IR cm−1: 3428 (N–Hstretching), 2383 (+N–Hstretching), 1726 ( C=Ostretching), 1602 (aromatic C=Cstretching), 1533 (C–N–Hdeformation), 1034 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (3101), 218 (886), 260 (319). 1H-NMR (CDCl3) δ (ppm): 6.87 (d, 1H, H-3′, J=8.00 Hz), 7.02 (t, 1H, H-4′, J=8.00, 8.02 Hz), 6.93 (t, 1H, H-5′, J=8.02, 7.68 Hz), 8.03 (d, 1H, H-6′, J=7.68 Hz), 2.82 (s, 6H, H-10, H-11), 7.35 (s, 1H, H-7′), 12.02 (s, 1H, H-9), 3.91 (s, 3H, H-1″), 2.21 (m, 1H, H-1), 3.07 (m, 2H, H-8), 5.13 (ddd. 1H, H-2), 1.99 (m, 2H, H-3), 2.12 (m, 2H, H-7), 1.26—1.32 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.0 (C-1), 73.0 (C-2), 30.4 (C-3), 20.6 (C-4), 24.5 (C-5), 25.5 (C-6), 26.5 (C-7), 61.3 (C-8), 42.8 (C-10), 46.4 (C-11), 129.3 (C-1′), 150.2 (C-2′), 113.1 (C-3′), 125.3 (C-4′), 123.0 (C-5′), 120.3 (C-6′), 155.3 (C-8′), 56.2 (C-1″). Element Analysis for C18H29N2O3Cl: (i) Calcd: C=60.57%, H=8.19%, N=7.85%. (ii) Found: C=60.75%, H=8.09%, N=7.74%.

±cis-N-N-Dimethyl-2-(2-ethoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (cis-P2-2)

Colourless solid. Yield: 63%. mp 134—136°C (butanone). IR cm−1: 3428 (N–Hstretching), 2383 (+N–Hstretching), 1726 (C = Ostretching), 1602 (aromatic C=Cstretching). 1533 (C–N–Hdeformation), 1034 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (2092), 218 (850), 260 (295). 1H-NMR (CDCl3) δ (ppm): 6.87 (d, 1H, H-3′, J=8.00 Hz), 7.03 (t, 1H, H-4′, J=8.00, 8.02 Hz), 6.94 (t, 1H, H-5′, J=8.02, 7.68 Hz), 8.03 (d, 1H, H-6′, J=7.68 Hz), 2.82 (s, 6H, H-10, H-11), 7.32 (s, 1H, H-7′), 12.04 (s, 1H, H-9), 4.15 (q, 2H, H-1″, J=6.96 Hz), 1.48 (t, 3H, H-2″, J=6.96 Hz), 2.21 (m, 1H, H-1), 3.08 (m, 2H, H-8), 5.13 (ddd, 1H, H-2), 2.00 (m, 2H, H-3), 2.12 (m, 2H, H-7), 1.25–1.33 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.1 (C-1), 73.2 (C-2), 30.5 (C-3), 20.7 (C-4), 24.5 (C-5), 25.5 (C-6), 26.5 (C-7), 61.3 (C-8), 42.8 (C-10), 46.5 (C-11), 129.4 (C-1′), 149.7 (C-2′), 113.2 (C-3′), 125.4 (C-4′), 123.0 (C-5′), 120.4 (C-6′), 155.4 (C-8′), 64.9 (C-1″), 15.1 (C-2″). Element Analysis for C19H31N2O3Cl: (i) Calcd: C=61.52%, H=8.42%, N=7.55%. (ii) Found: C=61.38%, H=8.53%, N=7.67%.

±cis-N,N-Dimethyl-2-(2-propoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (cis-P2-3)

Colourless solid. Yield: 60%. mp 150–151°C (butanone). IR cm−1: 3429 (N–Hstretching), 2384 (+N–Hstretching), 1726 (C = Ostretching). 1602 (aromatic C = Cstretching). 1532 (C–N–Hdeformation), 1034 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (2902), 218 (816), 260 (287). 1H-NMR (CDCl3) δ (ppm): 6.88 (d, 1H, H-3′, J=8.03 Hz), 7.03 (t, 1H, H-4′, J=8.03, 8.04 Hz), 6.93 (t, 1H, H-5′, J=8.04, 7.69 Hz), 8.03 (d, 1H, H-6′, J=7.69 Hz). 2.83 (s, 6H, H-10, H-11), 7.32 (s, 1H, H-7′), 12.21 (s, 1H, H-9), 4.03 (t, 2H, H-1″, J=7.11 Hz), 1.88 (sext, 2H, H-2″, J=7.11, 7.36 Hz), 1.05 (t, 3H, H-3″, J=7.36 Hz), 2.22 (m, 1H, H-1), 3.08 (m, 2H, H-8), 5.14 (ddd, 1H, H-2), 2.00 (m, 2H, H-3), 2.13 (m, 2H, H-7), 1.26—1.33 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.2 (C-1), 73.1 (C-2), 30.4 (C-3), 20.6 (C-4), 24.6 (C-5), 25.6 (C-6), 26.6 (C-7), 61.4 (C-8), 42.7 (C-10), 46.5 (C-11), 129.4 (C-1′), 150.1 (C-2′), 113.2 (C-3′), 125.4 (C-4′), 122.9 (C-5′), 120.3 (C-6′), 155.4 (C-8′), 70.9 (C-1″), 22.7 (C-2″), 10.6 (C-3″). Element Analysis for C20H33N2O3Cl: (i) Calcd: C=62.40%, H=8.64%, N=7.28%. (ii) Found: C=62.66%, H=8.51%, N=7.11%.

±cis-N,N-Dimethyl-2-(2-butoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (cis-P2-4)

Colourless solid. Yield: 57%. mp 131—133°C (ethyl acetate). IR cm−1: 3429 (N–H stretching), 2384 (+N–Hstretching), 1725 (C = Ostretching), 1603 (aromatic C = Cstretching), 1531 (C–N–Hdeformation), 1035 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol −1): 198 (2887), 218 (811), 260 (275). 1H-NMR (CDCl3) δ (ppm): 6.88 (d, 1H, H-3′, J=8.05 Hz), 7.03 (t, 1H, H-4′, J=8,05, 8.06 Hz), 6.93 (t, 1H, H-5′, J=8.06, 7.70 Hz), 8.04 (d, 1H, H-6′, J=7.70 Hz), 2.83 (s, 6H, H-10, H-11), 7.31 (s, 1H, H-7′), 12.15 (s, 1H, H-9), 4.05 (t, 2H, H-1″, J=6.75 Hz). 1.84 (m, 2H, H-2″, J=6.75, 7.00 Hz), 1.48 (m, 2H, H-3″, J=7.00, 6.9 Hz), 1.00 (t, 3H, H-4″, J=6.99 Hz), 2.22 (m, 1H, H-1), 3.07 (m, 2H, H-8), 5.14 (ddd, 1H, H-2), 2.01 (m, 2H, H-3), 2.13 (m, 2H, H-7), 1.26—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.1 (C-1), 73.2 (C-2), 30.4 (C-3), 20.6 (C-4), 24.6 (C-5), 25.6 (C-6), 26.6 (C-7), 61.4 (C-8), 42.7 (C-10), 46.4 (C-11), 129.4 (C-1′), 149.8 (C-2′), 113.1 (C-3′), 125.4 (C-4′), 123.0 (C-5′), 120.2 (C-6′), 155.4 (C-8′). 69.3 (C-1″), 31.4 (C-2″), 19.5 (C-3″), 14.1 (C-4″). Element Analysis for C21H35N2O3Cl: (i) Calcd: C=63.22%, H=8.84%, N=7.02%. (ii) Found: C=63.48%, H=8.95%, N=6.88%.

±cis-N,N-Dimethyl-2-(2-pentyloxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (cis-P2-5)

Colourless solid. Yield: 55%. mp 132—134°C (ethyl acetate). IR cm −1: 3430 (N–Hstretching), 2385 (+N–Hstretching), 1725 (C=Ostretching), 1602 (aromatic C=Cstretching), 1531 (C–N–Hdeformation), 1035 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (2803), 218 (798), 260 (266). 1H-NMR (CDCl3) δ (ppm): 6.87 (d, 1H, H-3′, J=8.07 Hz), 7.03 (t, 1H, H-4′ J=8.07, 8.06 Hz), 6.93 (t, 1H, H-5′, J=8.06, 7.70 Hz), 8.04 (d, 1H, H-6′, J=7 .70 Hz), 2.84 (s, 6H, H-10, H-11), 7.30 (s, 1H, H-7′), 12.08 (s, 1H, H-9), 4.04 (t, 2H, H-1″, J=6.47 Hz), 1.84 (m, 2H, H-2″, J=6.47, 7.00 Hz), 1.46 (m, 2H, H-3″, J=7.00, 7.30 Hz), 1.40 (m, 2H, H-4″, J=7.30,6.78 Hz), 0.93 (t, 3H, H-5″, J=6.78 Hz), 2.22 (m, 1H, H-1), 3.07 (m, 2H, H-8), 5.14 (ddd, 1H, H-2), 2.01 (m, 2H, H-3), 2.14 (m, 2H, H-7), 1.25—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.1 (C-1), 73.1 (C-2), 30.4 (C-3), 20.6 (C-4), 24.6 (C-5), 25.6 (C-6), 26.6 (C-7), 61.5 (C-8), 42.7 (C-10), 46.4 (C-11), 129.4 (C-1′), 149.8 (C-2′), 113.0 (C-3′), 125.4 (C-4′), 123.0 (C-5′), 120.2 (C-6′), 155.4 (C-8′), 69.5 (C-1″), 29.1 (C-2″), 28.5 (C-3″), 22.6 (C-4″), 14.3 (C-5″). Element Analysis for C22H37N2O3Cl: (i) Calcd: C=63.98%, H=9.03%, N=6.78%. (ii) Found: C=63.71%, H=9.22%, N=6.81%.

±cis-N,N-Dimethy-2-(2-heptyphenylcarbamoyloxy)cyclohepthlymethylammonium chloride(cis Chloride (cis-P2-6)

Colourless solid. Yield: 54%. mp 127—128°C (ethyl acetate). IR cm−1: 3431 (N–Hstretching), 2385 (+N–Hstretching) , 1725 (C = Ostretching), 1603 (aromatic C = Cstretching ), 1530 (C–N–Hdeformation), 1035 ( CO–Nstretching) . UV–VIS λmaxnm (ε, m2·mol−1): 198 (2682), 218 (770), 260 (260). 1H-NMR (CDCl3) δ (ppm): 6.87 (d, 1H, H-3′, J=8.08 Hz), 7.03 (t, 1H, H-4′, J=8.08, 8.07 Hz), 6.94 (t, 1H, H-5′, J=8.07, 7.70 Hz), 8.04 (d, 1H, H-6′, J=7.70 Hz), 2.84 (s, 6H, H-10, H-11), 7.31 (s, 1H, H-7′), 12.18 (s, 1H, H-9), 4.05 (t, 2H, H-1″, J=6.47 Hz), 1.85 (m, 2H, H-2″, J=6.47, 6.76 Hz), 1.44 (m, 2H, H-3″, J=6.76, 7.24 Hz), 1.35 (m, 2H, H-4″, J=7.24, 7.40 Hz), 1.34 (m, 2H, H-5″, J=7.40, 6.78 Hz), 0.90 (t, 3H, H-6″, J=6.78 Hz), 2.23 (m, 1H, H-1), 3.07 (m, 2H, H-8), 5.15 (ddd, 1H, H-2), 2.00 (m, 2H, H-3), 2.14 (m, 2H, H-7), 1.25—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.1 (C-1), 73.1 (C-2), 30.4 (C-3), 20.6 (C-4), 24.6 (C-5), 25.6 (C-6), 26.6 (C-7), 61.5 (C-8), 42.7 (C-10), 46.4 (C-11), 129.4 (C-1′), 149.8 (C-2′), 113.0 (C-3′), 125.4 (C-4′), 123.0 (C-5′), 120.2 (C-6′), 155.4 (C-8′), 69.6 (C-1″), 29.3 (C-2″), 26.0 (C-3″), 31.8 (C-4″), 22.8 (C-5″), 14.2 (C-6″). Element Analysis for C23H39N2O3Cl: (i) Calcd: C=64.69%, H=9.21%, N=6.56%. (ii) Found: C=64.93%, H=9.37%, N=6.35%.

±cis-N, N-Dimethyl-2-(2-heptyloxyphenylcarbaiiioyloxy)cyclohepthylmethylammonium Chloride (cis-P2-7)

Colourless solid. Yield: 52%. mp 136–138°C (heptane: ethyl acetate, 1 : 1). IR cm−1: 3431 (N–Hstreching), 2386 (+N–Hstreching), 1603 (aromatic C=Cstretching), 1529 (C–N–Hdeformation), 1036 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (1838), 218 (508), 260 (185). 1H-NMR (CDCl3) δ (ppm): 6.88 (d, 1H, H-3′, J=8.10 Hz), 7.03 (t, 1H, H-4′, J=8.10, 8.09 Hz), 6.94 (t, 1H, H-5′, J=8.09, 7.70 Hz), 8.04 (d, 1H, H-6′, J=7.70 Hz), 2.84 (s, 6H, H-10, H-11), 7.32 (s, 1H, H-7′), 12.18 (s, 1H, H-9), 4.05 (t, 2H, H-1″, J=6.47 Hz), 1.84 (m, 2H, H-2″, J=6.47, 6.76 Hz), 1.43 (m, 2H, H-3″, J=6.76, 7.00 Hz), 1.37 (m, 2H, H-4″, J=7.00, 7.40 Hz), 1.32 (m, 2H, H-5″, J=7.40, 7.40 Hz), 1.30 (m, 2H, H-6″, J=7.40, 6.78 Hz), 0.89 (t, 3H, H-7″, J=6.78 Hz), 2,23 (m, 1H, H-1), 3.07 (m, 2H, H-8), 5.15 (ddd, 1H, H-2), 1.99 (m, 2H, H-3), 2.14 (m, 2H, H-7), 1.26–1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.1 (C-1), 73.1 (C-2), 30.4 (C-3), 20.6 (C-4), 24.6 (C-5), 25.6 (C-6), 26.6 (C-7), 61.5 (C-8), 42.7 (C-10), 46.4 (C-11), 129.4 (C-1′), 149.8 (C-2′), 113.0 (C-3′), 125.4 (C-4′), 123.0 (C-5′), 120.2 (C-6′), 155.4 (C-8′), 69.6 (C-1″), 29.4 (C-2″), 26.3 (C-3″), 29.3 (C-4″), 32.1 (C-5″), 22.8 (C-6″), 14.3 (C-7″). Element Analysis for C24H41N2O3Cl: (i) Calcd: C=65.35%, H=9.37%, N=6.35%. (ii) Found: C=65.54%, H=9.16%, N=6.52%.

±cis-N,N-Dimethyl-2-(2-octyloxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (cis-P2-8)

Colourless solid. Yield: 50%. mp 127—129°C (heptane:ethyl acetate, 1:1). IR cm−1: 3432 (N–Hstretching), 2386 (+N–Hstretching), 1724 (C=Ostretching), 1603 (aromatic C=Cstretching), 1529 (C–N–Hdeformation), 1036 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (1272), 218 (343), 260 (227). 1H-NMR (CDCl3) δ (ppm): 6.88 (d, 1H, H-3′, J=8.11 Hz), 7.03 (t, 1H, H-4′, J=8.11, 8.09 Hz), 6.94 (t, 1H, H-5′, J=8.09, 7.70 Hz), 8.04 (d, 1H, H-6′, J=7.70 Hz), 2.83 (s, 6H, H-10, H-11), 7.31 (s, 1H, H-7′), 12.22 (s, 1H, H-9), 4.06 (t, 2H, H-1″, J=6.47 Hz), 1.85 (m, 2H, H-2″, J=6.47, 6.76 Hz), 1.43 (m, 2H, H-3″, J=6.76, 7.00 Hz), 1.37 (m, 2H, H-4″, J=7.00, 7.50 Hz), 1.31 (m, 2H, H-5″, J=7.50, 7.40 Hz), 1.29 (m, 2H, H-6″, J=7.40, 7.40 Hz), 1.28 (m, 2H, H-7″, J=7.40, 6.78 Hz), 0.87 (t, 3H, H-8″, J=6.78 Hz), 2,22 (m, 1H, H-1), 3.08 (m, 2H, H-8), 5.15 (ddd, 1H, H-2), 2.00 (m, 2H, H-3), 2.14 (m, 2H, H-7), 1.26—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 37.1 (C-1), 73.1 (C-2), 30.4 (C-3), 20.6 (C-4), 24.6 (C-5), 25.6 (C-6), 26.6 (C-7), 61.5 (C-8), 42.7 (C-10), 46.4 (C-11), 129.4 (C-1′), 149.8 (C-2′), 113.0 (C-3′), 125.4 (C-4′), 123.0 (C-5′), 120.2 (C-6′), 155.4 (C-8′), 69.6 (C-1″), 29.6 (C-2″), 26.3 (C-3″), 29.4 (C-4″), 29.6 (C-5″), 32.1 (C-6″), 22.8 (C-7″), 14.4 (C-8″). Element Analysis for C25H43N2O3Cl: (i) Calcd: C=65.98%, H=9.52%, N=6.16%. (ii) Found: C=66.24%, H=9.65%, N=6.07%.

±trans-N,N-Dimethyl-2-(2-methoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-P2-1)

Colourless solid. Yield: 46%. mp 150–151°C (butanone). IR cm−1: 3428 (N–Hstretching), 2383 (+N–Hstretching), 1726 ( C = Ostretching), 1602 (aromatic C=Cstretching), 1533 (C–N–Hdeformation), 1034 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (3305), 218 (946), 260 (325). 1H-NMR (CDCl3) δ (ppm): 7.00 (d, 1H, H-3′, J=8.00 Hz), 7.15 (t, 1H, H-4′, J=8.00, 8.02 Hz), 7.08 (t, 1H, H-5′, J=8.02, 7.68 Hz), 8.16 (d, 1H, H-6′, J=7.68 Hz), 2.91 (s, 6H, H-10, H-11), 7.62 (s, 1H, H-7′), 12.05 (s, 1H, H-9), 3.94 (s, 3H. H-1′), 2.05 (m, 1H, H-1), 2.96 (m, 2H, H-8). 4.57 (m, 1H, H-2), 2.18 (m, 2H, H-3), 2.52 (m, 2H, H-7), 1.26—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 39.5 (C-1), 76.2 (C-2), 32.4 (C-3), 24.4 (C-4), 24.8 (C-5), 25.0 (C-6), 30.9 (C-7), 62.1 (C-8), 43.2 (C-10), 46.3 (C-11), 129.2 (C-1′), 150.4 (C-2′), 112.0 (C-3′), 125.3 (C-4′), 123.0 (C-5′), 120.4 (C-6′), 155.2 (C-8′), 56.4 (C-1″). Element Analysis for C18H29N2O3Cl: (i) Calcd: C=60.57%, H=8.19%, N=7.85%. (ii) Found: C=60.41%, H=8.020%, N=7.91%.

±trans-N,N-Dimethyl-2-(2-ethoxyphenylcarbamoloxy)cyclohepthylmethylammonium Chloride (trans-P2-2)

Colourless solid. Yield: 44%. mp 119—120°C (butanone). IR cm−1: 3428 ( N–Hstretching), 2383 (+N–Hstretching), 1726 (C=Ostretching), 1602 (aromatic C=Cstretching), 1533 (C–N–Hdeformation), 1034 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (2100), 218 (913), 260 (299). 1H-NMR (CDCl3) δ (ppm): 6.99 (d, 1H, H-3′, J=8.00 Hz), 7.14 (t, 1H, H-4′, J=8.00, 8.02 Hz), 7.07 (t, 1H, H-5′, J=8.02, 7.68 Hz), 8.16 (d, 1H, H-6′, J=7.68 Hz), 2.92 (s, 6H, H-10, H-11); 7.62 (s, 1H, H-7′), 11.90 (s, 1H, H-9), 4.17 (q, 2H, H-1″, J=6.96 Hz), 1.49 (t, 3H, H-2″, J=6.96 Hz), 2.06 (m, 1H, H-1), 2.97 (m, 2H, H-8), 4.58 (m, 1H, H-2), 2.19 (m, 2H, H-3), 2.51 (m, 2H, H-7), 1.26—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 39.4 (C-1), 76.2 (C-2), 32.3 (C-3), 24.3 (C-4), 24.7 (C-5), 25.0 (C-6), 30.8 (C-7), 62.0 (C-8), 43.1 (C-10), 46.2 (C-11), 129.3 (C-1′), 149.7 (C-2′), 112.8 (C-3′), 125.2 (C-4′), 122.8 (C-5′), 120.5 (C-6′), 155.2 (C-8′), 64.9 (C-1″), 15.0 (C-2″). Element Analysis for C19H31N2O3Cl: (i) Calcd: C=61.52%, H=8.42%, N=7.55%. (ii) Found: C=61.44%, H=8.30%, N=7.45%.

±trans-N,N-Dimethyl-2-(2-propoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-p2-3)

Colourless soild yield: 43%. mp 143–144°c (butanone) IR cm−1: 3429 (N–Hstreching) , 2384(+N–Hstreching), 1726 (C=Ostreching), 1602 (aromatic C=Cstreching), 1532 (C–N–Hdeformation), 1034 (CO–Nstreching). UV–VIS λmax nm (ε, m2·mol−1): 198 (3112), 218 (870), 260 (293). 1H-NMR (CDCl3), δ (ppm): 6.99 (d, 1H, H-3′, J=8.03 Hz), 714 (t, 1H, H-4′, J=8.03, 8.04 Hz), 7.08 (t, 1H, H-5′, J=8.04, 7.69 Hz), 8.16 (d, 1H, H-6′, J=7.69 Hz), 2.87 (s, 6H, H-10, H-11), 7.55 (s, 1H, H-7′), 12.29 (s, 1H, H-9), 4.06 (t, 2H, H-1″, J=7.11 Hz), 1.90 (sext, 2H, H-2″, J=7.11, 7.36 Hz), 1.07 (t, 3H, H-3″, J=7.36 Hz), 2.08 (m, 1H, H-1), 2.95 (m, 2H, H-8), 4.60 (m, 1H, H-2), 2.19 (m, 2H, H-3), 2.60 (m, 2H, H-7), 1.25–1.34 (m. 6H. H-4–6). 13C-NMR (CDCl3) δ (ppm): 39.4 (C-1), 76.1 (C-2), 32.4 (C-3), 24.3 (C-4), 24.7 (C-5), 25.1 (C-6), 30.8 (C-7), 62.1 (C-8), 43.1 (C-10),46.3 (C-11), 129.2 (C-1′), 150.0 (C-2′), 112.7 (C-3′), 125.2(C-4′), 122.8 (C-5′), 120.4 (C-6′), 155.3 (C-8′), 70.9 (C-1″), 22.7 (C-2″), 10.7 (C-3″). Element Analysis for C20H33N2O3Cl: (i) Calcd: C=62.40%, H=8.64%, N=7.28%. (ii) Found: C=62.29%, H=8.72%, N=7.40%.

±trans-N,N-Dimethyl-2-(2-butoxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-P2-4)

Colourless solid. Yield: 42%. mp 130—132°C (ethyl acetate). IR cm−1: 3429 (N–Hstretching), 2384 (+N–Hstreching), 1725 (C=Ostreching), 1603 (aromatic C=Cstreching), 1531 (C–N–Hdeformation), 1035 (CO–Nstreching), UV–VIS λmax nm (ε m2·mol−1): 198(3047), 218 (835), 260 (280). 1H-NMR (CDCl3) δ (ppm): 7.00 (d, 1H, H-3′, J=8.05 Hz), 7.14 (t, 1H, H-4′, J=8.05, 8.06 Hz), 7.07 (t, 1H. H-5′, J=8.06, 7.70 Hz), 8.15 (d, 1H, H-6′, J=7.70 Hz), 2.88 (s, 6H, H-10, H-11), 7.55 (s, 1H, H-7′), 12.25 (s, 1H, H-9). 4.09 (t, 2H, H-1″, J=6.75 Hz), 1.85 (m, 2H, H-2″, J=6.75, 7.00 Hz), 1.52 (m, 2H, H-3″, J=7.00, 6.9 Hz), 1.01 (t, 3H, H-4″, J=6.99 Hz), 2.09 (m, 1H, H-1), 2.96 (M, 2H, H-8), 4.61 (m, 1H, H-2), 2.20 (m, 2H, H-3), 2.59 (m, 2H, H-7), 1.26—1.34 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 39.5 (C-1), 76.1 (C-2), 32.4 (C-3), 24.4 (C-4). 24.8 (C-5), 25.1 (C-6), 30.9 (C-7), 62.1 (C-8), 43.1 (C-10), 46.4 (C-11), 129.3 (C-1′), 150.1 (C-2′), 112.7 (C-3′), 125.3 (C-4′), 122.8 (C-5′), 120.4 (C-6′), 155.2 (C-8′), 69.0 (C-1″). 31.5 (C-2″), 19.0 (C-3″), 14.0 (C-4″). Element Analysis for C21H35N2O3Cl: (i) Calcd: C=63.22%. H=8.84%, N=7.02%. (ii) Found: C=63.19%, H=8.72%, N=7.10%.

±trans-N,N-Dimethyl-2-(2-pentyloxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-P2-5)

Colourless solid. Yield: 40%. mp 119—121°c (ethyl acetate), IR cm−1: 3430 (N-Hstretching), 2385 (+N–Hstretching), 1725 (C=Ostretching) 1602 (aromatic C=Cstretching), 1531 (C–N–Hdeformation), 1035 (CO–Nstretching), UV–VIS λmax nm (ε, m2·mol−1): 198 (2927), 218 (809), 260 (271). 1H-NMR (CDCl3,) δ (ppm): 7.00 (d, 1H, H-3′, J=8.07 Hz), 7.14 (t, 1H, H-4′, J=8.07, 8.06 Hz), 7.08 (t, 1H, H-5′, J=8.06, 7.70 Hz), 8.16 (t, 1H, H-6′, J=7.70 Hz), 2.87 (s, 6H, H-10, H-11), 7.56 (s, 1H, H-7′), 12.38 (s, 1H, H-9), 4.09 (t, 2H, H-1″, J=6.47 Hz), 1.87 (m, 2H, H-2″, J=6.47, 7.00 Hz), 1.50 (m, 2H, H-3″, J=7.00, 7.30 Hz), 1.44 (m, 2H, H-4″, J=7.30, 6.78 Hz), 0.96 (t, 3H, H-5″, J=6.78 Hz), 2.09 (m, 1H, H-2), 2.96 (m, 2H, H-8), 4.60 (m, 1H, H-2), 2.17 (m, 2H H-3), 2.62 (m, 2H, H-7), 1.26—1.33 (m, 6H, H4—6). 13C-NMR (CDCl3 δ (ppm): 39.5 (C-1), 76.2 (C-2), 32.4 (C-3), 24.4 (C-4), 24.8 (C-5), 24.9 (C-6), 31.0 (C-7), 62.1 (C-8), 43.2 (C-10), 46.4 (C-11), 129.2 (C-1′), 150.2 (C-2′), 112.8 (C-3′), 125.3 (C-4′), 122.8 (C-5′), 120.4 (C-6′), 155.2 (C-8′), 69.4 (C-1″), 29.1 (C-2″ ), 28.3 (C-3″), 22.6 (C-4″), 14.2 (C-5″). Element Analysis for C22H37N2O3Cl: (i) Calcd: C=63.98%, H=9.03% N=6.78%. (ii) Found: C=64.18%, H=8.89%, N=6.60%.

±trans-N,N-Dimethyl-2-(2-hexyloxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-P2-6)

Colourless solid. Yield: 42%. mp 107—109°C (ethyl acetate). IR cm−1: 3431 (N–Hstretching), 2385 (+N–Hstretching), 1725 (C=Ostretching), 1603 (aromatic C=Cstretching), 1530 (C–N–Hstretching), 1035 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (2831), 218 (783), 260 (263). 1H-NMR (CDCl3) δ (ppm): 6.99 (d, 1H, H-3′, J=8.08 Hz), 7.15 (t, 1H, H-4′, J=8.08, 8.07 Hz), 7.07 (t, 1H, H-5′, J=8.07, 7.70 Hz), 8.15 (d, 1H, H-6′, J=7.70 Hz), 2.90 (s, 6H, H-10, H-11), 7.56 (s, 1H, H-7′), 12.31 (s, 1H, H-9), 4.08 (t, 2H, H-1″, J=6.47 Hz), 1.86 (m, 2H, H-2″, J=6.47, 6.76 Hz), 1.47 (m, 2H, H-3″, J=6.76, 7.24 Hz), 1.38 (m, 2H, H-4″, J=7.24, 7.40 Hz), 1.38 (m, 2H, H-5″, J=7.40, 6.78 Hz), 0.93 (t, 3H, H-6″, J=6.78 Hz), 2.07 (m, 1H, H-1), 2.97 (m, 2H, H-8), 4.60 (m, 1H, H-2), 2.17 (m, 2H, H-3), 2.61 (m, 2H, H-7), 1.25—1.33 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 39.5 (C-1), 76.2 (C-2), 32.4 (C-3), 24.4 (C-4), 24.8 (C-5), 24.9 (C-6), 30.9 (C-7), 62.1 (C-8), 43.2 (C-10), 46.5 (C-11), 129.2 (C-1′), 150.2 (C-2′), 112.8 (C-3′), 125.3 (C-4′), 122.8 (C-5′), 120.4 (C-6′), 155.2 (C-8′), 69.4 (C-1″), 29.4 (C-2″), 26.0 (C-3″), 31.8 (C-4″), 22.2 (C-5″), 14.1 (C-6″). Element Analysis for C23H39N2O3Cl: (i) Calcd: C=64.69%, H=9.21%, N=6.56%. (ii) Found: C=64.41%, H=9.40%, N=6.72%.

±trans-N,N-Dimethyl-2-(2-heptyloxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-P2-7)

Colourless solid, Yield: 41%. mp 101—103°C (heptane:ethyl acetate, 1:1). IR cm−1; 3431 (N–Hstretching), 2386 (+N–Hstretching), 1724 (C=Ostretching), 1603 (aromatic C=Cstretching), 1529 (C–N–Hdeformation), 1036 (CO–Nstretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (2064), 218 (558), 260 (194). 1H-NMR (CDCl3) δ (ppm): 6.99 (d, 1H, H-3′, J=8.10 Hz), 7.15 (t, 1H, H-4′, J=8.10, 8.09 Hz), 7.07 (t, 1H, H-5′, J=8.09, 7.70 Hz), 8.15 (d, 1H, H-6′, J=7.70 Hz), 8.90 (s, 6H, H-10, H-11), 7.56 (s, 1H, H-7′), 12.35 (s, 1H, H-9), 4.08 (t, 2H, H-1″, J=6.47 Hz), 1.86 (m, 2H, H-2″, J=6.47, 6.76 Hz), 1.46 (m, 2H, H-3″, J=6.76, 7.00 Hz), 1.41 (m, 2H, H-4″, J=7.00, 7.40 Hz), 1.34 (m, 2H, H-5″, J=7.40, 7.40 Hz), 1.34 (m, 2H, H-6″, J=7.40, 6.78 Hz), 0.91 (t, 3H, H-7″, J=6.78 Hz), 2.06 (m, 1H, H-1), 2.98 (m, 2H, H-8), 4.62 (m, 1H, H-2), 2.16 (m, 2H, H-3), 2.62 (m, 2H, H-7), 1.26—1.32 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 39.5 (C-1), 76.2 (C-2), 32.3 (C-3), 24.4 (C-4), 24.8 (C-5), 24.9 (C-6), 30.9 (C-7), 62.1 (C-8), 43.2 (C-10), 46.5 (C-11), 129.2 (C-1′), 150.2 (C-2′), 112.8 (C-3′), 125.3 (C-4′), 122.8 (C-5′), 120.4 (C-6′), 155.2 (C-8′), 69.4 (C-1″), 29.4 (C-2″), 26.3 (C-3″), 29.3 (C-4″), 32.1 (C-5″), 22.8 (C-6″), 14.2 (C-7″). Element Analysis for C24H41N2O3Cl: (i) Calcd: C=65.35%, H=9.37%, N=6.35%. (ii) Found: C=65.17%, H=9.48%, N=6.19%.

±trans-N,N-Dimethyl-2-(2-octyloxyphenylcarbamoyloxy)cyclohepthylmethylammonium Chloride (trans-P2-8)

Colourless solid. Yield: 40%. mp 81—83°C (heptane:ethyl acetate, 1:1). IR cm−1: 3432 (N–HStretching), 2386 (+N–HStretching). 1724 (C = OStretching), 1603 (aromatic C=CStretching), 1529 (C–N–Hdeformation), 1036 (CO–NStretching). UV–VIS λmax nm (ε, m2·mol−1): 198 (1455), 218 (396), 260 (235). 1H-NMR (CDCl3) δ (ppm): 7.00 (d, 1H, H-3′, J=8.11 Hz), 7.15 (t, 1H, H-4′, J=8.11, 8.09 Hz), 7.09 (t, 1H, H-5′, J=8.09, 7.70 Hz), 8.15 (d, 1H, H-6′, J=7.70 Hz), 2.90 (s, 6H, H-10, H-11), 7.56 (s, 1H, H-7′), 12.36 (s, 1H, H-9), 4.08 (t, 2H, H-1″, J=6.47 Hz), 1.86 (m, 2H, H-2″, J=6.47, 6.76 Hz), 1.46 (m, 2H, H-3″, J=6.76, 7.00 Hz), 1.41 (m, 2H, H-4″, J=7.00, 7.50 Hz), 1.32 (m, 2H, H-5″, J=7.50, 7.40 Hz), 1.32 (m, 2H, H-6″, J=7.40, 7.40 Hz), 1.32 (m, 2H, H-7″, J=7.40, 6.78 Hz), 0.90 (t, 3H, H-8″, J=6.78 Hz), 2.06 (m, 1H, H-1), 3.01 (m, 2H, H-8), 4.60 (m, 1H, H-2), 2.16 (m, 2H, H-3), 2.62 (m, 2H, H-7), 1.26—1.32 (m, 6H, H-4—6). 13C-NMR (CDCl3) δ (ppm): 39.4 (C-1), 76.2 (C-2), 32.4 (C-3), 24.4 (C-4), 24.8 (C-5), 24.9 (C-6), 30.8 (C-7), 62.2 (C-8), 43.3 (C-10), 46.6 (C-11), 129.2 (C-1′), 150.3 (C-2′), 112.8 (C-3′), 125.3 (C-4′), 122.8 (C-5′), 120.5 (C-6′), 155.2 (C-8′), 69.5 (C-1″), 29.5 (C-2″), 26.3 (C-3″), 29.4 (C-4″), 29.6 (C-5″), 32.1 (C-6″), 22.9 (C-7″), 14.2 (C-8″). Element Analysis for C25H43N2O3Cl: (i) Calcd: C=65.98%, H=9.52%, N=6.16%. (ii) Found: C=65.92%, H=9.41%, N=6.13%.

Acknowledgements

We are indebted to Assoc. Prof. Dr. E. Racanska from Department of Pharmacology and Toxicology, Faculty of Pharmacy. Kalinciakova 8, 8332 32 Bratislava, for pharmaceutical testing and evaluation of the results. The work was supported by the Austrian Science Fund (FWF) Grant F3403.

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