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Investigations of the Statistical Syntheses of Rotaxanes
15 Investigations of the Statistical Syntheses of Rotaxanes
15.1.
Scheme 1
This scheme for the synthesis of rotaxanes has been investigated cursorily by Freudenberg and Cramer, 27 as well as by Stetter and Lihotzky,28 and more in depth by Harrison and Harrison. 29 Harrison and Harrison 29 reacted 2-hydroxycyclotriacontanone 550a with succinic anhydride and thus obtained the half ester 550b. The sodium salt of this compound was converted to the resin bond macrocycle 550c by reacting it with the chloromethylated copolymer from styrene and divinylbenzene. The latter was obtained by the method of Merrifield.198 The resin bound macrocycle was treated 70 times with 1,10-decanediol and triphenylmethyl chloride in a mixture of pyridine, dimethylformamide, and toluene. Unfortunately, the amounts of reaction materials used were not mentioned in the communication. After hydrolysis with sodium bicarbonate in refluxing methanol, a mixture containing 6 % of rotaxane 550d was obtained. Following chromatography, the rotaxane was isolated as an oil stable up to 200°. The compound showed the expected infrared absorption and when subjected to thin-layer chromatography was shown to be free of unbound molecular subunits. The structure of rotaxane 550d was verified by chemical degradation. Oxidation with silver oxide gave octacosane-l,28-dicarboxylic acid, which 145
146
15. STATISTICAL SYNTHESES OF ROTAXANES
was isolated as the dimethyl ester and the dumbbell-shaped molecule 550f. Cleavage of rotaxane 550d with BF3-etherate in benzene resulted in decane1,10-diol, triphenylmethanol, and acyloin 550a. OR O
OH O
-CH—C\
/CH—C\ (CH2)10 j - 0 - C ( C 6 H 5 ) 3 (H5C6)3C-0-f
I
II
I
^(CH2)2-T
^(ΟΗ2)2^
550a: R = H 550b: R = CO—(CH2)2—COOH 550c: R = CO—(CH2)2—COO—resin (H 5 C 6 ) 3 C-0
II
550d
(CH2)io 550f
0-C(C 6 H 5 ) 3
Freudenberg and Cramer 27 attempted to react inclusion compounds of cyclodextrins and long-chain dialdehydes with bulky hydrazine derivatives such as naphthylhydrazine. By inspecting a Stuart-Briegleb molecular model it can be seen, however, that naphthalin derivatives are not bulky enough to prevent the chain from slipping out of the cyclodextrin ring. If for no other reasons than this, the synthesis could not be successful. Stetter and Swincicki199 attempted to synthesize a rotaxane by reacting hexamethylene-l,6-diamine with diphenylketene in the presence of macrocycle 551. The reactions were carried out without solvent and in the presence of tetralin; here again, no rotaxane could be isolated. (CH2),
(CH2)6 551
The investigations of Stetter and Lihotzky28 were based on the observation that bis(7V,7V-tetramethylenebenzidine) 552 forms adducts with dioxane and benzene.138 In further investigations it was found that the tetraformyl compound 553 crystallizes with a molecule of solvent from pyridine. When compound 553 as well as the tetraacetyl compound 554 were dissolved in molten benzidine and washed free of excess solvent, they
147
1 5 . 1 . SCHEME 1
were found to retain a molecule of benzidine. By heating the adduct in a vacuum at 200° the benzidine could be recovered. The benzidine is also displaced by dissolving the adduct in diethylene glycol ; now a compound is obtained containing four molecules of solvent. In order to obtain a rotaxane, the 1:1 adducts of 553 and 554 with benzidine were reacted with triphenylpropyl isocyanate 555 in a molten state, as well as in the solvents benzene, dioxane, and anisole. Benzidine was also reacted with compound 555 in anisolç in the presence of 554. In all cases only the unchanged macrocycle 554 and the diurea compound 556 could be isolated. Likewise, when compound 554 was present in the reaction of hexamethylene-l,6-diamine with 555, or in the reaction of terephthalyl dichloride with triphenylpropylamine, only compounds 557 and 558 were (CH2).
552: R = H 553: R = CHO 554: R = COCH3 (C 6 H 5 ) 3 C—CH 2 —CH 2 —N=C=0 555 (C6H5)3C-(CH2)2-NH-CO-NH-/
\
/
Y-NH—CO—NH—(CH 2 ) 2 —C(C 6 H 5 ) 3
556 (C6H5)3C—(CH2)2—NH—CO—NH—(CH2)6—NH—CO—NH—(CH2)2—C(C6H5)3 557 (C6H5)3C-(CH2)2-NH—CO-/
\-CO—NH-(CH2)2—C(C6H5)3 558
(C6H5)3C—(CH2)2—NH—CO—NH—(CH2)2—C(C6H5)3 559
148
1 5 . STATISTICAL SYNTHESES OF ROTAXANES
obtained, respectively. Similarly, reaction of 555 and triphenylpropylamine in the presence of 554 only resulted in the urea derivative 559.
15.2. Scheme 2 Studies which can be schematically classified into this group were carried out by Schill and Tafelmair.126 Based on the work discussed in Section 8.5, 2,5-dibromohydroquinone was reacted with excess 1,10dibromodecane to diether 560. Alkylation of 3,4,5-triphenylphenol with this compound resulted in the dumbbell-shaped molecule 561. Treatment with cuprous cyanide in dimethylformamide according to Friedman and Shechter125 gave dinitrile 563. In a second procedure this compound was prepared by reacting 2,5-dicyanohydroquinone with excess 1,10-dibromodecane and subsequently treating compound 562 thus obtained, with 3,4,5triphenylphenol. Dinitrile 563 was reduced with LiAlH4 to diamine 564 and then reacted with 11-chloroundecanoyl chloride to give diamide 565. This compound could be reduced to diamine 566 with diisobutyl aluminum hydride, or better yet, with diborane in tetrahydrofuran. Diamine 566 was O—(CH2)10—Br
o—(CH2)10—OZ
O-(CH 2 ) 10 - Br 560
O-(CH 2 ) 10 - OZ 561
O—(CH2)10—Br
-OZ
O-(CH 2 ) 1 0 -Br 562
O—(CH2)10—OZ 563: R = CN 564: R = CH2—NH2 565: R = CH2—NH—CO—(CH2)10—Cl 566: R = CH2—NH—(CH2)U—Cl
O—(CH2),o—OZ O—(CH 2 ) 10 —OZ S^CHz—N (CH 2 ) n
(CH 2 )
N-CH2 O—(CH 2 ) 10 —OZ O—(CH2)10—OZ 567
568 -(CH,),
N
N
CH2 ^ ^ - ( C H 2 ) „ ^ ^ ^ .O—(CH2)10—OZ
CH2 A*C>—(CH2)10—OZ
Λ
ZO-(CH2)10-O^Y^
CH2
ZO-^CH2)iir-0X^p CH2 ^^_-(CH2)n__^^
N
N ^ ^ — (CH2)n
— - ^
569 O—(CH2)10—OZ AwCH2-OAc I
T
^ + CH3CO—N
AcO—CH2 O—(CH2)10—OZ 570
^(CH2)n^ CH3CO—N
N—COCH3
\cH 2 ),r 204
193
(CH2)n +
150
15. STATISTICAL SYNTHESES OF ROTAXANES
cyclized in isoamyl alcohol by the high-dilution method in the presence of potassium carbonate and sodium iodide. Acetylation with acetic anhydride in pyridine and chromatography gave, in 21 % yield, a mixture of three amines. From the Chromatographie behavior, inspection of the mass spectra, chemical degradation by acetolysis, and comparison with independently synthesized compound 567, structures 567, 568, and 569 were assigned to the three products. Since the separation of the mixture could not be carried out on a preparative scale, the cyclization products were cleaved with acetic anhydride. Compounds 570, 193, and 204 could be isolated by thin-layer chromatography. A rotaxane could not be detected. Of interest is the structure of the dimeric product 569. It differs from the dimer 206, obtained from the model compound 202 (see Section 8.5), in that both aromatic rings are now joined by four chains. The formation of this isomeric structure probably is caused by the bulky phenol substrates, which favor the formation of a structure in which the hydroquinone nuclei are separated as far as possible. To obtain compound 567, required for comparison, dinitrile 563 was hydrolyzed to the dicarboxylic acid 571 and subsequently esterified to 572. Reduction resulted in 573 and acetylation gave compound 574. For the preparation of the cyclization product 567, diol 573 was converted to dibromide 575 with triphenylphosphine dibromide193 and then reacted with cycloundecylamine. O-(CH 2 ) 1 0 -OZ
O—(CH2)10—OZ 571: 572: 573: 574: 575:
R = COOH R = COOC2H5 R = CH2—OH R = CH2—O—COCH3 R = CH2—Br
15.1.
Scheme 1
This scheme for the synthesis of rotaxanes has been investigated cursorily by Freudenberg and Cramer, 27 as well as by Stetter and Lihotzky,28 and more in depth by Harrison and Harrison. 29 Harrison and Harrison 29 reacted 2-hydroxycyclotriacontanone 550a with succinic anhydride and thus obtained the half ester 550b. The sodium salt of this compound was converted to the resin bond macrocycle 550c by reacting it with the chloromethylated copolymer from styrene and divinylbenzene. The latter was obtained by the method of Merrifield.198 The resin bound macrocycle was treated 70 times with 1,10-decanediol and triphenylmethyl chloride in a mixture of pyridine, dimethylformamide, and toluene. Unfortunately, the amounts of reaction materials used were not mentioned in the communication. After hydrolysis with sodium bicarbonate in refluxing methanol, a mixture containing 6 % of rotaxane 550d was obtained. Following chromatography, the rotaxane was isolated as an oil stable up to 200°. The compound showed the expected infrared absorption and when subjected to thin-layer chromatography was shown to be free of unbound molecular subunits. The structure of rotaxane 550d was verified by chemical degradation. Oxidation with silver oxide gave octacosane-l,28-dicarboxylic acid, which 145
146
15. STATISTICAL SYNTHESES OF ROTAXANES
was isolated as the dimethyl ester and the dumbbell-shaped molecule 550f. Cleavage of rotaxane 550d with BF3-etherate in benzene resulted in decane1,10-diol, triphenylmethanol, and acyloin 550a. OR O
OH O
-CH—C\
/CH—C\ (CH2)10 j - 0 - C ( C 6 H 5 ) 3 (H5C6)3C-0-f
I
II
I
^(CH2)2-T
^(ΟΗ2)2^
550a: R = H 550b: R = CO—(CH2)2—COOH 550c: R = CO—(CH2)2—COO—resin (H 5 C 6 ) 3 C-0
II
550d
(CH2)io 550f
0-C(C 6 H 5 ) 3
Freudenberg and Cramer 27 attempted to react inclusion compounds of cyclodextrins and long-chain dialdehydes with bulky hydrazine derivatives such as naphthylhydrazine. By inspecting a Stuart-Briegleb molecular model it can be seen, however, that naphthalin derivatives are not bulky enough to prevent the chain from slipping out of the cyclodextrin ring. If for no other reasons than this, the synthesis could not be successful. Stetter and Swincicki199 attempted to synthesize a rotaxane by reacting hexamethylene-l,6-diamine with diphenylketene in the presence of macrocycle 551. The reactions were carried out without solvent and in the presence of tetralin; here again, no rotaxane could be isolated. (CH2),
(CH2)6 551
The investigations of Stetter and Lihotzky28 were based on the observation that bis(7V,7V-tetramethylenebenzidine) 552 forms adducts with dioxane and benzene.138 In further investigations it was found that the tetraformyl compound 553 crystallizes with a molecule of solvent from pyridine. When compound 553 as well as the tetraacetyl compound 554 were dissolved in molten benzidine and washed free of excess solvent, they
147
1 5 . 1 . SCHEME 1
were found to retain a molecule of benzidine. By heating the adduct in a vacuum at 200° the benzidine could be recovered. The benzidine is also displaced by dissolving the adduct in diethylene glycol ; now a compound is obtained containing four molecules of solvent. In order to obtain a rotaxane, the 1:1 adducts of 553 and 554 with benzidine were reacted with triphenylpropyl isocyanate 555 in a molten state, as well as in the solvents benzene, dioxane, and anisole. Benzidine was also reacted with compound 555 in anisolç in the presence of 554. In all cases only the unchanged macrocycle 554 and the diurea compound 556 could be isolated. Likewise, when compound 554 was present in the reaction of hexamethylene-l,6-diamine with 555, or in the reaction of terephthalyl dichloride with triphenylpropylamine, only compounds 557 and 558 were (CH2).
552: R = H 553: R = CHO 554: R = COCH3 (C 6 H 5 ) 3 C—CH 2 —CH 2 —N=C=0 555 (C6H5)3C-(CH2)2-NH-CO-NH-/
\
/
Y-NH—CO—NH—(CH 2 ) 2 —C(C 6 H 5 ) 3
556 (C6H5)3C—(CH2)2—NH—CO—NH—(CH2)6—NH—CO—NH—(CH2)2—C(C6H5)3 557 (C6H5)3C-(CH2)2-NH—CO-/
\-CO—NH-(CH2)2—C(C6H5)3 558
(C6H5)3C—(CH2)2—NH—CO—NH—(CH2)2—C(C6H5)3 559
148
1 5 . STATISTICAL SYNTHESES OF ROTAXANES
obtained, respectively. Similarly, reaction of 555 and triphenylpropylamine in the presence of 554 only resulted in the urea derivative 559.
15.2. Scheme 2 Studies which can be schematically classified into this group were carried out by Schill and Tafelmair.126 Based on the work discussed in Section 8.5, 2,5-dibromohydroquinone was reacted with excess 1,10dibromodecane to diether 560. Alkylation of 3,4,5-triphenylphenol with this compound resulted in the dumbbell-shaped molecule 561. Treatment with cuprous cyanide in dimethylformamide according to Friedman and Shechter125 gave dinitrile 563. In a second procedure this compound was prepared by reacting 2,5-dicyanohydroquinone with excess 1,10-dibromodecane and subsequently treating compound 562 thus obtained, with 3,4,5triphenylphenol. Dinitrile 563 was reduced with LiAlH4 to diamine 564 and then reacted with 11-chloroundecanoyl chloride to give diamide 565. This compound could be reduced to diamine 566 with diisobutyl aluminum hydride, or better yet, with diborane in tetrahydrofuran. Diamine 566 was O—(CH2)10—Br
o—(CH2)10—OZ
O-(CH 2 ) 10 - Br 560
O-(CH 2 ) 10 - OZ 561
O—(CH2)10—Br
-OZ
O-(CH 2 ) 1 0 -Br 562
O—(CH2)10—OZ 563: R = CN 564: R = CH2—NH2 565: R = CH2—NH—CO—(CH2)10—Cl 566: R = CH2—NH—(CH2)U—Cl
O—(CH2),o—OZ O—(CH 2 ) 10 —OZ S^CHz—N (CH 2 ) n
(CH 2 )
N-CH2 O—(CH 2 ) 10 —OZ O—(CH2)10—OZ 567
568 -(CH,),
N
N
CH2 ^ ^ - ( C H 2 ) „ ^ ^ ^ .O—(CH2)10—OZ
CH2 A*C>—(CH2)10—OZ
Λ
ZO-(CH2)10-O^Y^
CH2
ZO-^CH2)iir-0X^p CH2 ^^_-(CH2)n__^^
N
N ^ ^ — (CH2)n
— - ^
569 O—(CH2)10—OZ AwCH2-OAc I
T
^ + CH3CO—N
AcO—CH2 O—(CH2)10—OZ 570
^(CH2)n^ CH3CO—N
N—COCH3
\cH 2 ),r 204
193
(CH2)n +
150
15. STATISTICAL SYNTHESES OF ROTAXANES
cyclized in isoamyl alcohol by the high-dilution method in the presence of potassium carbonate and sodium iodide. Acetylation with acetic anhydride in pyridine and chromatography gave, in 21 % yield, a mixture of three amines. From the Chromatographie behavior, inspection of the mass spectra, chemical degradation by acetolysis, and comparison with independently synthesized compound 567, structures 567, 568, and 569 were assigned to the three products. Since the separation of the mixture could not be carried out on a preparative scale, the cyclization products were cleaved with acetic anhydride. Compounds 570, 193, and 204 could be isolated by thin-layer chromatography. A rotaxane could not be detected. Of interest is the structure of the dimeric product 569. It differs from the dimer 206, obtained from the model compound 202 (see Section 8.5), in that both aromatic rings are now joined by four chains. The formation of this isomeric structure probably is caused by the bulky phenol substrates, which favor the formation of a structure in which the hydroquinone nuclei are separated as far as possible. To obtain compound 567, required for comparison, dinitrile 563 was hydrolyzed to the dicarboxylic acid 571 and subsequently esterified to 572. Reduction resulted in 573 and acetylation gave compound 574. For the preparation of the cyclization product 567, diol 573 was converted to dibromide 575 with triphenylphosphine dibromide193 and then reacted with cycloundecylamine. O-(CH 2 ) 1 0 -OZ
O—(CH2)10—OZ 571: 572: 573: 574: 575:
R = COOH R = COOC2H5 R = CH2—OH R = CH2—O—COCH3 R = CH2—Br