Synthesis of Symmetrical Disubstituted Bridgehead Adamantane Derivatives†

doi:10.7503/cjcu20140051

Abstract

Abstract:

The symmetric bridge disubstituted adamantane derivatives are the key raw materials or interme-diates for preparing multisubstituted adamantane derivatives with admantane as the core. With 1-adamantane carboxylic acid that is more efficient and economical as an initial reactant, a series of synthesis technologies of symmetrical disubstituted bridgehead adamantane derivatives which have significant applications, were studied in this work. Those synthesis technologies include the following: 1,3-adamantane dicarboxylic acid(1) was synthesized by 1-adamantane carboxylic acid through Koch-Haaf carbonylation; compound 1 was reduced to get 1,3-adamantane dimethanol(2); compound 2 reacted by bromination in HBr-ZnBr₂ system to afford 1,3-dibromomethyl adamantane(3). Meanwhile, compound 2 converted to 1,3-dichloromethyl adamantane(4) through Apple-Lee reaction. The structures of prepared products were confirmed by IR spectra and ¹H NMR spectroscopy. The possible reaction mechanism was proposed, and the synthesis conditions were discussed and optimized for each technology respectively.

Key words: Adamantane, 1, 3-Adamantane dicarboxylic acid, 1, 3-Adamantane dimethanol, 1, 3-Dibromo-methyl adamantane, 1, 3-Dichloromethyl adamantane

CLC Number:

O621.3

TrendMD:

XU Xiaojian, GUO Jianwei, ZHU Dongyu, ZHONG Xing. Synthesis of Symmetrical Disubstituted Bridgehead Adamantane Derivatives^†[J]. Chem. J. Chinese Universities, 2014, 35(8): 1686.

Figures/Tables 6

Scheme 1 Synthesis routes of compounds 1—4

Scheme 2 Proposed mechanism for the formation of compound 1

Fig.1 Influences of temperature(A) and HCOOH adding rate(B) on yield of compound 1 (A) HCOOH adding rate is 0.23 mL/min; (B) reaction temperature is 0 ℃.

Fig.2 Influences of reaction time on yield of compound 2(A) and compound 3(B)

Scheme 3 Proposed mechanism for the formation of compound 4

Table 1 Influences of different feed molar ratio and reaction time on the yield of compound 4

n(compound 2)∶n(triphenylphosphine)	Time/h	Yield(%)
1∶2.0	12	48
1∶2.1	12	53
1∶2.2	12	55
1∶2.3	12	56
1∶2.2	15	58
1∶2.2	18	61
1∶2.2	21	62
1∶2.2	24	62

References 18

[1]	Jin J. C., Tong W. Q., Xie C. G., Chang W. G., Xu G. N., Wu J., Li L. G., Yan Z. Q., Wang Y. Y., J. Coord. Chem., 2013, 66, 3697—3705
[2]	Cai L., Guo J. W., Liu S., Zhu L. J., Guan N. Y., Chin. J. Org. Chem., 2011, 31(8), 1290—1294
	(蔡璐, 郭建维, 刘卅, 朱乐杰, 关念云. 有机化学, 2011, 31(8), 1290—1294)
[3]	Azzam W., Bashir A., Shekhah O., Appl. Surf. Sci., 2011, 257, 3739—3747
[4]	Guo J. W., Zhong X., Zhu H., Feng L. J., Cui Y. D., Chin. Chem. Lett., 2012, 23, 653—656
[5]	Liu M., Chen Y., Fu N., Synth. Commun., 2013, 43, 1055—1062
[6]	Xie B. Y., Guo J. W., Liu S., Peng J. P., Chin. J. Org. Chem.2011, 31(4), 486—489
	(谢炳玉, 郭建维, 刘卅, 彭进平. 有机化学2011, 31(4), 486—489)
[7]	Lee G. S., Bashara J. N., Sabih G., Oganesyan A., Godjoian G., Duong H. M., Marinez E. R., Gutiérrez C. G., Org. Lett., 2004, 6, 1705—1707
[8]	Rusanova J. A., Rusanov E. B., Domasevitch K. V., Acta Crystallogr. Sect. C: Cryst. Struct. Commun., 2010, 66, m207—m210
[9]	Haldar R., Maji T. K., CrystEngComm, 2013, 15, 9276—9295
[10]	Zhu H., Study on Synthesis and Properties of Oligomeric Surfactants Based on Adamantan, Guangdong University of Technology, Guangzhou, 2011
	(朱华. 金刚烷基低聚表面活性剂的合成与性能研究, 广州: 广东工业大学, 2011)
[11]	Rice K. D., Wang V. R., Gangloff A. R., Kuo E. Y. L., Dener J. M., Newcomb W. S., Young W. B., Putnam D., Cregar L., Wong M., Simpson P. J., Bioorg. Med. Chem. Lett., 2000, 10, 2361—2366
[12]	Fuji M., Akita M., Tanaka T., Polycarbonate Copolymer and Method of Producing the Same, US Patent 0257362, 2011-10-20
[13]	Teranishi T., He S., Umemoto K., Polyesters and Production Process Thereof, US Patent 6455666, 2002-09-24
[14]	fr Ghisaidoobe A., van der Marel G. A., Strijland A., Aerts J. M., Overkleeft H. S., Tetrahedron: Asymmetry, 2009, 20, 836—846
[15]	Klaiu-Majerski K., J. Phys. Org. Chem., 2008, 21, 299—305
[16]	Koch H., Haaf W., Justus Liebigs Ann. Chem., 1958, 1, 251—266
[17]	Shetty B. V., Anorectic Adamantane Derivatives and Method of Using the Same, US Patent 4100170, 1978-7-11
[18]	Huang D. X., Franzus B., Chemistry, 1983, 3, 49—54
	(黄道行, Franzus B. 化学通报, 1983, 3, 49—54)