Introduction

1-Bromododecane (Figure 1) is an important intermediate for the synthesis of a new accelerator azone, and it is also an important raw material and common solvent for organic synthesis. The existing synthesis method of the product is to take dodecanol as the main raw material, and under the catalysis of concentrated sulfuric acid, react with hydrobromic acid to obtain Bromododecane. Although sulfuric acid has high activity and low price, it has large dosage, poor selectivity, difficult separation of products, serious equipment corrosion and environmental pollution. It has also been reported that 1-Bromododecane was synthesized from dodecanol and hydrobromic acid in the presence of concentrated sulfuric acid using quaternary ammonium salts such as tetrabutyl ammonium bromide as catalysts. Although high yield was obtained, sulfuric acid was still needed. Using solid superacid as catalyst can overcome the above shortcomings, and can be used repeatedly, with high selectivity, short reaction time and low cost.[1]

Synthesis of 1-bromododecane

1.Potassium bromide-concentrated sulfuric acid method

1-Bromododecane was synthesized from potassium bromide which is the by product of synthesizing 2-hydroxy-4-n-dodecyloxybenzophenone and n-dodecyl alcohol using concentrated sulfuric acid as catalyst . By investigating the reaction condition, the experimental result showed that the optimal conditions are potassium bromide 0. 1 mol, n-dodecyl alcohol 0. 08 mol, concentrated sulfuric acid 6 mL, H2O 2. 5 mL, refluxing for 4h, the separated yield is high up to 92.5%. Raw product was analyzed by GC and no by product was detected almost. Pure product was characterized by IR and index of refraction.[1]

2.Catalyzed by Solid Superacid SO₄^2-/TiO₂-ZrO₂

This paper reported the synthesis of 1-bromododecane catylyzed by solid superacid SO₄^2-/TiO₂-ZrO₂. The effect of these action factors such as amount of catalyst, reaction temperature 、reaction time and meterial ratio on yield ratio is discussed. The proper reaction conditions determined are as follow: amount of catalyst is 6.5%~9% of dodecanol, at 110℃, time 5h,dodecanol:hydro-bromic acid=0.1:0.14 (molar ratio). Under these conditions 1-bromododecane yield is more than 67.1%.[2]

Application research of 1-Bromododecane

Synthesis of (-)-muricatacin

The synthesis of (-)-muricatacin starting from 1-bromododecane and 2-pentyn-1-ol is described. 2-Pentadecyn-1-ol (4), which was prepared from 1-bromododecane (2) and 2-pentyn-1-ol (3), was converted to epoxy alcohol 6 through a two-step reaction sequence, 6 being successively submitted to tosylation, iodination, chain extension with tert-butyl lithioacetate, and acid-catalyzed cyclization to give (-)-muricatacin (1a). Recrystallization afforded optically pure 1a.[3]

Self-Assembly Nanoparticles based on 1-bromododecane

Different approaches have been reported to enhance penetration of small drugs through physiological barriers; among them is the self-assembly drug conjugates preparation that shows to be a promising approach to improve activity and penetration, as well as to reduce side effects. In recent years, the use of drug-conjugates, usually obtained by covalent coupling of a drug with biocompatible lipid moieties to form nanoparticles, has gained considerable attention. Natural products isolated from plants have been a successful source of potential drug leads with unique structural diversity. In the present work three molecules derived from natural products were employed as lead molecules for the synthesis of self-assembled nanoparticles. The first molecule is the cytotoxic royleanone 7α-acetoxy-6β-hydroxyroyleanone (Roy, 1) that has been isolated from hairy coleus (Plectranthus hadiensis (Forssk.) Schweinf). ex Sprenger leaves in a large amount. This royleanone, its hemisynthetic derivative 7α-acetoxy-6β-hydroxy-12-benzoyloxyroyleanone (12BzRoy, 2) and 6,7-dehydroroyleanone (DHR, 3), isolated from the essential oil of thicket coleus (P. madagascariensis (Pers.) Benth.) were employed in this study. The royleanones were conjugated with squalene (sq), oleic acid (OA), and/or 1-bromododecane (BD) self-assembly inducers. Roy-OA, DHR-sq, and 12BzRoy-sq conjugates were successfully synthesized and characterized. The cytotoxic effect of DHR-sq was previously assessed on three human cell lines: NCI-H460 (IC₅₀ 74.0±2.2 μM), NCI-H460/R (IC₅₀ 147.3±3.7 μM), and MRC-5 (IC₅₀ 127.3±7.3 μM), and in this work Roy-OA NPs was assayed against Vero-E6 cells at different concentrations (0.05, 0.1, and 0.2 mg/mL). The cytotoxicity of DHR-sq NPs was lower when compared with DHR alone in these cell lines: NCI-H460 (IC₅₀ 10.3±0.5 μM), NCI-H460/R (IC₅₀ 10.6±0.4 μM), and MRC-5 (IC₅₀ 16.9±0.5 μM). The same results were observed with Roy-OA NPs against Vero-E6 cells as was found to be less cytotoxic than Roy alone in all the concentrations tested. From the obtained DLS results, 12BzRoy-sq assemblies were not in the nano range, although Roy-OA NP assemblies show a promising size (509.33 nm), Pdl (0.249), zeta potential (-46.2 mV), and spherical morphology from SEM. In addition, these NPs had a low release of Roy at physiological pH 7.4 after 24 h. These results suggest the nano assemblies can act as prodrugs for the release of cytotoxic lead molecules.[4]

1-Bromododecane used in Furan-Based Non-Ionic Surfactants preparation

Two series of furan-based non-ionic surfactants (fbnios) were prepared by a combination of Williamson ether synthesis and anionic polymerization of ethylene oxide (EO). The reaction of 1-bromooctane and 1-bromododecane with 2,5-bis(hydroxymethyl)furan after deprotonation with potassium tert-butoxide yielded the corresponding alkane furfuryl alcohols (Cx-F-OH with x = 8 or 12). Deprotonation of Cx-F-OH with potassium tert-pentoxide enabled the anionic polymerization of EO, which yielded four C8-F-EOy samples with y=3, 6, 9, and 14 and four C12-F-EOy samples with y=9, 12, 18, and 23. The chemical composition of the fbnios was determined by NMR and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS) analysis, while their dispersity (?) was characterized by gel permeation chromatography (GPC) and MALDI-ToF MS. The purity of the Cx-F-EOy samples exceeded 92%, and they were produced with narrow molecular weight distributions (? ≤ 1.02, as determined by GPC analysis). The critical micelle concentration (CMC) of the Cx-F-EOy samples was determined by surface tension and pyrene fluorescence measurements. These showed that the CMC of the fbnios could be tuned by adjusting the molecular parameters x and y, with the CMC increasing for decreasing x and increasing y. In particular, the CMC of the C8-F-EOy and C12-F-EOy samples was significantly higher and lower, respectively, than for typical non-ionic surfactants (nios) like the Triton X and Brij surfactant families. The efficiency, effectiveness, and cross section of the EOy headgroup of the fbnios were also determined. Together, the CMC, efficiency, and effectiveness of the fbnios demonstrate that this new surfactant family displays tensioactive properties that match and even exceed those of traditional nios, suggesting that they could extend further the already broad range of applications for nios.[5] 

References

[1]Wang M, et al.Synthesis of 1-bromododecane using potassium bromide-concentrated sulfuric acid method[J].Science&Technology in chemical industry,2007,(06):33-35.DOI:10.16664/j.cnki.issn1008-0511.2007.06.007.

[2]Zhang Y, et al.A Study on the Synthesis of 1-Bromododecane catalyzed by Solid Superacid SO4/TiO2 -ZrO2[J].Inner Mongolia Petrochemical Industry,2001,(03):5-7.

[3]Makabe H, Tanaka A, Oritani T. Synthesis of (-)-muricatacin. Biosci Biotechnol Biochem. 1993;57(6):1028-1029. doi:10.1271/bbb.57.1028

[4]Ntungwe E, Domínguez-Martín EM, Bangay G, et al. Self-Assembly Nanoparticles of Natural Bioactive Abietane Diterpenes. Int J Mol Sci. 2021;22(19):10210. Published 2021 Sep 22. doi:10.3390/ijms221910210

[5]Liu D, Duhamel J, Gauthier M. Synthesis and Characterization of Furan-Based Non-Ionic Surfactants (fbnios). Langmuir. 2023;39(26):8974-8983. doi:10.1021/acs.langmuir.3c00344