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The application of ultrasound to N-methylation of diazacoronands
0040-4039/88 $3.00 + .oO Pergamon Journals Ltd.
Tetrahedron Letters,Vol.29,No.8,pp 959-960,1988 Printed in Great Britain
THE APPXCATION OF UT,TRASOUJ'JD TO A'-IIETXYLATIOM OF DIAZACORONANDS
Janusz Jurczak* and Syszard Ostaszewslci Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Flarszawa,Poland
Abstract - The application of ultrasound to N-methylation of variety of diazacoronands by methyl iodide under phase transfer conditions leads to N,N'-dimethyl diazacoronands in almost quantitative yields. N,N'-Diazacoronandsof type 2 are used as macrocyclic subunits forming binding sites for ammonium groups in synthetic mole&lar receptors such as cryptands and cylindrical macrotricycles.'N,N'-Diazacoronandsof this type serve also as key substrates in the high-pressure method of the synthesis of cryptands (Scheme l).'
methylotion
40
de
2
3
21’
Scheme I The high-pressure reaction of compound 2 with bis(2-iodoethyl)ether afforded bis-quaternary salt 3 which was then transformed into (l.l.l)cryptand4 by demethylation with triphenylphosphine.3 Compound 2 has been obtained by Eschweiler-Clark"N-methylation of the parent macrecycle 1.' This meth;d, widely used for N-methylation of diazacoronands,is not effective enough, &specially in case of highly elaborated substrates, e.g. chiral polyfunctionalized diazacoronands.The other methods such as methylation with formamide-cyanoborohydridereagent' or reductive carbonylation6are not of general character and require rather drastic conditions. Therefore, we take into account sonochemical approach' to this problem. Ultrasound has been found to be beneficial in reducing of reaction times and in increasing the reaction yields for the preparation of N-alkyl aromatic amines under phase transfer conditions.* These results prompted us to use this method for N-methylation of various diazacoronands. In this communication we wish to report the beneficial application of ultrasound to the N-methylation of five representative diazacoronandsand the simple cyclam with methyl iodide under phase transfer conditions (Scheme 2). Ultrasonic irradiation9 of a solid-liquid reaction mixture containing diazacoronand 5, methyl iodide, potassium hydroxide, and dry toluene, was carried out at room temperature &Iring 8 h to afford N,N'-dinethyl diazacoronand 6 in 92% yield. The results are summarized in the Table. It is obvious that diazacoronands serve in these reactions as phase transfer catalysts. The cyclam is not efficient enough as the catalyst, and addition of diazacoronand 7 (1%) improved the yield of compound 10 and reduced the reaction time (cf. entries 6 and 71. The above-presentedmeth;a of N-methylation offers very high yield of the desired N,N'dimethyl diazacoronands as result of mild conditions and convenient work-up. Namely, the postreaction mixture is filtered through a short pad of Celite and after evaporation, the product is destilled under reduced pressure. The presented results indicate that N-alkylation of many other non-activated secondary amines may benefit by the application of ultrasound under solid-liquid phase transfer conditioru 959
960
Me MeI,KOH.PhMe ultmsound,RT
5
6 Me
/a opYy ‘UN3
Me,
0
\
nNNMe
c)
Me/ /J\Me
Lie
tie
tie
7
6
10
6 Scheme 2
Table. Yield of E!-MethylatedProducts from the Reaction of Diazacoronandsand the Cyclam with Methyl Iodide in Toluene Solution in the Presence of Potassium Hydroxide Entry
Producta)
Reaction time (h)
1
2 . 6
8
95
110-115/0.2
2
a
92
150-155/0.2
3
7
4
97
160-170/0.3
4
;;
8
92
193-20510.3
210/0.4
11
5
9
12
95
170-180/0.3 (168-169)
(158-168)
11
6
10
12
60
130-135/0.2
120/0.1
12
7d)
;; __
4
98
Yieldb) (X1
B.P.C) (OC/Torr) (M.P. ("C))
Lit. B.P. (OC/Torr) (M.P. ("C))
Reference
7910.02
10
127-132/0.01
11
a) b)Yield of isolated product. ::~_~~~;1U~~~p~:~:~~~edd~~~~~~~n~7~%~n~a~~~d~~ctra. c) . . Acknowledgments- Financial support from the Polish Academy of Sciences (Grant CPBP 01. 13) is gratefully acknowledged. References and Notes 1 J.M.Lehn, Accounts Chem. Res., 11, 49 (1978); Pure Appl. Chem., 50, 871 (1978). 2 J.Jurczak and M.Pietrasz!
in UK 21 December
1987)
Tetrahedron Letters,Vol.29,No.8,pp 959-960,1988 Printed in Great Britain
THE APPXCATION OF UT,TRASOUJ'JD TO A'-IIETXYLATIOM OF DIAZACORONANDS
Janusz Jurczak* and Syszard Ostaszewslci Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Flarszawa,Poland
Abstract - The application of ultrasound to N-methylation of variety of diazacoronands by methyl iodide under phase transfer conditions leads to N,N'-dimethyl diazacoronands in almost quantitative yields. N,N'-Diazacoronandsof type 2 are used as macrocyclic subunits forming binding sites for ammonium groups in synthetic mole&lar receptors such as cryptands and cylindrical macrotricycles.'N,N'-Diazacoronandsof this type serve also as key substrates in the high-pressure method of the synthesis of cryptands (Scheme l).'
methylotion
40
de
2
3
21’
Scheme I The high-pressure reaction of compound 2 with bis(2-iodoethyl)ether afforded bis-quaternary salt 3 which was then transformed into (l.l.l)cryptand4 by demethylation with triphenylphosphine.3 Compound 2 has been obtained by Eschweiler-Clark"N-methylation of the parent macrecycle 1.' This meth;d, widely used for N-methylation of diazacoronands,is not effective enough, &specially in case of highly elaborated substrates, e.g. chiral polyfunctionalized diazacoronands.The other methods such as methylation with formamide-cyanoborohydridereagent' or reductive carbonylation6are not of general character and require rather drastic conditions. Therefore, we take into account sonochemical approach' to this problem. Ultrasound has been found to be beneficial in reducing of reaction times and in increasing the reaction yields for the preparation of N-alkyl aromatic amines under phase transfer conditions.* These results prompted us to use this method for N-methylation of various diazacoronands. In this communication we wish to report the beneficial application of ultrasound to the N-methylation of five representative diazacoronandsand the simple cyclam with methyl iodide under phase transfer conditions (Scheme 2). Ultrasonic irradiation9 of a solid-liquid reaction mixture containing diazacoronand 5, methyl iodide, potassium hydroxide, and dry toluene, was carried out at room temperature &Iring 8 h to afford N,N'-dinethyl diazacoronand 6 in 92% yield. The results are summarized in the Table. It is obvious that diazacoronands serve in these reactions as phase transfer catalysts. The cyclam is not efficient enough as the catalyst, and addition of diazacoronand 7 (1%) improved the yield of compound 10 and reduced the reaction time (cf. entries 6 and 71. The above-presentedmeth;a of N-methylation offers very high yield of the desired N,N'dimethyl diazacoronands as result of mild conditions and convenient work-up. Namely, the postreaction mixture is filtered through a short pad of Celite and after evaporation, the product is destilled under reduced pressure. The presented results indicate that N-alkylation of many other non-activated secondary amines may benefit by the application of ultrasound under solid-liquid phase transfer conditioru 959
960
Me MeI,KOH.PhMe ultmsound,RT
5
6 Me
/a opYy ‘UN3
Me,
0
\
nNNMe
c)
Me/ /J\Me
Lie
tie
tie
7
6
10
6 Scheme 2
Table. Yield of E!-MethylatedProducts from the Reaction of Diazacoronandsand the Cyclam with Methyl Iodide in Toluene Solution in the Presence of Potassium Hydroxide Entry
Producta)
Reaction time (h)
1
2 . 6
8
95
110-115/0.2
2
a
92
150-155/0.2
3
7
4
97
160-170/0.3
4
;;
8
92
193-20510.3
210/0.4
11
5
9
12
95
170-180/0.3 (168-169)
(158-168)
11
6
10
12
60
130-135/0.2
120/0.1
12
7d)
;; __
4
98
Yieldb) (X1
B.P.C) (OC/Torr) (M.P. ("C))
Lit. B.P. (OC/Torr) (M.P. ("C))
Reference
7910.02
10
127-132/0.01
11
a) b)Yield of isolated product. ::~_~~~;1U~~~p~:~:~~~edd~~~~~~~n~7~%~n~a~~~d~~ctra. c) . . Acknowledgments- Financial support from the Polish Academy of Sciences (Grant CPBP 01. 13) is gratefully acknowledged. References and Notes 1 J.M.Lehn, Accounts Chem. Res., 11, 49 (1978); Pure Appl. Chem., 50, 871 (1978). 2 J.Jurczak and M.Pietrasz!
in UK 21 December
1987)