Supporting Information:

Spontaneous Formation of Vesicles by Sodium 2-Dodecylnicotinate

in Water

Aparna Roy, Monali Maiti and Sumita Roy*

Department of Chemistry and Chemical Technology, Vidyasagar University,

Paschim Medinipur – 721 102, India.

E-mail: rsumita4@yahoo.co.in

Synthesis of 5-Bromo-2-dodecylpyridine1: A Grignard reagent was prepared from 1-

bromododecane (0.039, 9.79 g) and Mg turnings (0.047 mol, 1.13 g) in 50 ml of anhydrous THF.

This freshly prepared n-dodecylmagnesium bromide was added drop wise to a flask containing

ZnCl2 (0.05 mol, 6.85 g) in 40 ml of anhydrous THF (ice-water cooling bath) and a white

precipitate was obtained. The cooling bath was removed and the reaction mixture with a

considerable amount of white precipitate was stirred for 1 h. The resulting n-dodecylzinc

chloride (1.2 equiv.) was added drop wise to a solution of 2,5-dibromopyridine (0.02 mol, 5 g)

and Pd(PPh3)4 (0.5 mol%, 0.14 g) in 20 ml of freshly distilled THF. The reaction mixture was

stirred overnight at room temperature, poured into 40 ml of water, and 40 ml of CH2Cl2 was

added. The resulting solution was vacuum filtered to separate a small amount of insoluble white

solid, the organic phase was separated, and the aqueous phase was extracted with CH2Cl2. The

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organic phases were combined, washed with brine and then dried over MgSO4. The solvent was

removed by rotary evaporation and the product was purified by silica gel column

chromatography (eluent 20% ethyl acetate in hexane) to afford pure 2-n-dodecyl-5-

bromopyridine. Yield (4.3 g, 62 %.);1H NMR (400 MHz, DMSO-d6): δ 0.82-0.0.86 (t, J =6.96

Hz, 3H, CH3), 1.21-1.25 (m, 18H), 1.60-1.64 (m, 2H), 2.65-2.69 (t, J =7.64 Hz, 2H), 7.22-7.25

(d, J =8.32 Hz, 1H), 7.90-7.92 (dd, J =8.28 Hz, 2.36 Hz, 1H), 8.56-8.57 (d, J =2.2 Hz, 1H).MS

(ESI+) for C17H28BrN m/z 326 (M+H)+.

Synthesis of 2-dodecylnicotinic acid2: To a solution of 5-Bromo-2-dodecylpyridine (4 g, 12.27

mmol) in THF (40 mL) was added a hexane solution of n-butyllithium (1.8 M, 8.18 mL, 14.72

mmol) at -78 °C for 5 min. After 1 h of stirring the solution becomes dark brown, dry ice

(excess) was added slowly into the reaction mixture with a continuous flow of nitrogen. The

resulting yellow solution was stirred for 1 h. After evaporation of the solvent in vacuo, to the

pale yellow solid was added water (15 mL) and extracted with ether. The aqueous phase was

acidified with 3N hydrochloric solution until pH 4-5 at 0 °C to produce the white precipitate. The

solid was filtered and dried to afford the desired compound of a colorless solid having a melting

point 88 °C. Yield (1.5 g, 42.1%). 1H NMR (400 MHz, DMSO-d6) δ; δ 0.80-0.86 (t, J =6.16 Hz,

3H, CH3), 1.22-1.27 (m, 18H), 1.66 (m, 2H), 2.76-2.80 (t, J =7.76 Hz, 2H), 7.36-7.38 (d, J =8.16

Hz, 1H), 8.13-8.15 (dd, J =8.0 Hz, 2.0 Hz, 1H), 8.96 (s, 1H), 13.22 (brs, 1H); MS (ESI+) for

C18H29NO2 m/z 291 (M+H)+.

Synthesis of Sodium 2-dodecylnicotinate: To a solution of 2-dodecylnicotinic acid (3.4 ×10-3

mol, 1g) in freshly disttiled THF (20 ml), equimolar solution of NaOH in water was added drop

wise at room temperature. After stirring for 24 h, THF was evaporated in a rotary evaporator

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 and the remaining water solution was lypholized to obtain the sodium salt of the acid. 1H NMR

(400 MHz, DMSO-d6); δ 0.83-0.86 (t, J =6.3 Hz, 3H, CH3), 1.23-1.26 (m, 18H), 1.62 (m, 2H),

2.64-2.68 (m, 2H), 7.06 (d, J =7.60 Hz, 1H), 7.94 (d, J =7.68 Hz, 1H), 8.79 (s, 1H).

Br

R N Br Br
Mg, THF R ZnCl2, THF
Zn
R Br Mg Br rt , 14 h Br Pd(PPh3)4 N n *
Reflux , 4 h , THF
1 3 rt, 15 h 4 (n=11)
2
(R= C12H25)
1. nBuLi THF
CO2
2 . HCl -780C

+ -
Na OOC HOOC
NaOH
N n* THF-H2O N n*
5
6

Figure S1: Synthesis scheme of SDDNA.

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Figure S2. FT-IR spectra of 2-dodecylnicotinic acid.

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Figure S3. FT-IR spectra of Sodium 2-dodecylnicotinate.

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Figure S4. 1H NMR spectra of 5-Bromo-2-dodecylpyridine.

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Figure S5. LC-Ms of 5-Bromo-2-dodecylpyridine.

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Figure S6. 1H NMR spectra of 2-dodecylnicotinic acid.

Figure S7. LC-Ms of 2-dodecylnicotinic acid.

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 90
80
70

κ (µS cm )
60
-1
50
40
30
20
0.1 0.2 0.3 0.4 0.5 0.6
Surfactant (mM)

Figure S8. Plot of к vs. surfactant concentration.

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8
Volume(%)

6
4
2
0
0 300 600 900 1200
Size(nm)

Figure S9. Plot of volume (%) vs. size of SDDNA in aqueous solution.

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References

(1) Getmanenko, Yulia A.; Twieg, Robert J., J. Org. Chem. 2008, 73, 830-839.

(2) Ando, M.; Sato, N.; Nagase, T.; Nagai, K.; Ishikawa, S.; Takahashi, H.; Ohtake, N.; Ito, J.;

Hirayama, M.; Mitobe, Y.; Iwaasa, H.; Gomori, A.; Matsushita, H.; Tadano, K.; Fujino, N.;

Tanaka, S.; Ohe, T.; Ishihara, A.; Kanatani, A.; Fukami, T., Bio. Org. Med. Chem. 2009, 17,

6106–6122.

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