Ind. Eng. Chem. Res. 1995,34, 2825-2832
2826
Photochromic Polysulfones. 1. Synthesis of Polymeric Polysulfone Carrying Pendant Spiropyran and Spirooxazine Groups Abraham Warshawsky,*JNava Kahana, Frida Buchholtz, Alex Zelichonok, Judith Ratner, and Valeri Krongauz* Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Photochromic polysulfones were synthesized by condensation between carboxypolysulfone (degree of substitution DS = 0.74) and functional photochromes (spiropyrans SP and spirooxazines SO) carrying amino, spaced amino, or spaced hydroxy groups. The synthetic methods needed to find a n optimal path to satisfy the requirement of maximal photochrome concentration, maintaining sufficient chromophore mobility in the polymeric matrix, and avoiding polymer gelation, so that suitable membrane casting properties were maintained. The three-step strategy of (1)preblocking with auxiliary group (octylamide), (2) attachment of photochrome, and (3) postblocking is certainly cumbersome and suffers from partial removal of the attached groups, yet in essence provides material that satisfy the demands set out.
Introduction We have described chemical modification methods in several publications from this laboratory aimed at preparing functional polysulfones from polymeric polysulfone ethers (had-Yellin and Warshawsky, 1989;Warshawsky and Kedem, 1990;Warshawsky et al., 1990; Kahana et al., 1990;had-Yellin et al., 1993). Polysulfones (PS) are known to be outstanding membrane polymers with a Tgof 190 “C, amorphous glassy state, and thermal oxidative stability with excellent strength and flexibility (Kesting, 1985). The attempts to synthesize polysulfones carrying pendant photochromes of the spiropyran (SP)or spirooxazine (SO) type were borne of the realization of the potential of such pendant ligands to control the electric and ionic properties of membranes made from functional polysulfones, such as those made from bromomethylated polysulfones. The photochromic reaction may allow, in the membrane state, a change in ionic and molecular diffusion, as a result of the change from hydrophobic to ionic environment. Such “photoresponsive”changes are of great interest. In the present study, carboxypolysulfone, described by M. Guiver (Guiver et al., 1990), was used. The functional photochromes needed for the reaction with carboxypolysulfone include amine or hydroxy functionalities. Some of these photochromes are described here for the first time (compounds D and F, see Schemes 1-31; others were synthesized by procedures described in previous publications (Hinnen et al., 1968;Berman et al., 1959;Bercovici et al., 1969;Koelsch et al., 1952; Fox, 1961;Gale and Whilshire, 1974;Schvartsman and Krongauz, 1984;Zajtseva et al., 1973). Part 2 in this series (submitted for publication in Ind. Eng. Chem. Res.) includes the physical and photochromic properties of functional and blended photochromes.
Scheme 1. Structures of All Compounds for Which Photochromic Measurements Were Taken
I
I Hydroxyethylspmp H O C H I C H l (E) ~
(indoline-2,2’-[W-llbenzopyran), designated as H2N-RSP (D), was performed for this work as described in Scheme 2. The synthesis of aminospirooxazine (F) is shown in Scheme 3. Covalent Attachment of Functional PhotoResults and Discussion chromes to Carboxypolysulfone. The synthetic work described in this section involved finding condiSynthesis of Functional Spiropyran and Spirooxtions for attaching HzN-SP, H2N-R-SP,and HOCH2CH2azine Compounds. Scheme 1 describes the functional SP. Work in this direction showed limited and low spiropyrans and spirooxazines synthesized for the purdegrees of attachment. Consequently, there was a need pose of this work. to investigate the reactivity of the amino group in model The synthesis of the aminospiropyran with spacer 5-[(6-aminocaproyl)aminol-l,3,3-trimethyl-6‘-nitrospiro- compounds (primary amines, anilinic amines). The mode of polymer activation, by either DCC activation or NHS ester activation, required assessment (see * Author to whom correspondence should be addressed. + E-mail:
[email protected]. Scheme 4). The results are presented in Tables 1-3. ~~
~
0888-588519512634-2825$09.0010
0 1995 American Chemical Society
2826 Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995
-
Scheme 2. Synthesis of Spaced Aminospiropyran (Compound D) + (CH3)3COC02COzC(CH&
H,N(CH&COOH
DCC
NaOH __t (CH~)~COOCNH-(CHZ)SCOOH
HzN&Hz
DMAP
\
VI 11
6..
BOCNH(CH2)&0 H W
C
I.
2
- 0"
2. N@03
No,
VI1
1. TFA
BOCNH-(CHp)&O H
\
\
=
/
-
VI11
Spaced aminospiropyran(D)
Scheme 3. Synthesis of Aminospirooxazine (Compound F)
1
CH3 111
Scheme 4. Attachments of Functional Aminophotochromes to Polymeric Carboxypolysulfone PS-COzH NH2-q
NHz-Ra Direct coupling
f
WONHSactive Via
1
Y = m /
-RH/B
ester
Direct coupling with DCC was selected as the route of choice for reaction with alcohols, such as compound E. As for the attachment of amines, two routes were worked out: direct coupling with DCC or via the NHS ester. To overcome the problem of residual CO2H groups, we took advantage of the higher reactivity of aliphatic amines versus the anilinic amines and elaborated a three-step synthesis. This involved (a) a preblocking step, (b) insertion of spiropyran (or spiroox-
Aminospirooxazine (F)
H2N-B
azine), and (c) a postblocking step. This synthesis is demonstrated in Scheme 5. The first step allows blocking of most COzH sites with a hydrophobic amine spacer. Step b then incorporates the photochrome, and step c blocks the residual COzH sites. The need to block the free COzH sites became obvious from the photochromic measurements done on the first samples. The general strategy described in Scheme 5 was followed for both spiropyran SP and spirooxazines SO with no spacer (series a) or with a (CH2)&ONH spacer (series b), without considerable differences: varying reactant ratios (see Experimental Section) changed the ratio somewhat between the photochromes (SPor SO) and the hydrophobic ballast ( C ~ H I ~but ) , the overall incorporation was generally not higher than 15%. An alternative synthesis described in Scheme 6 provided a similar degree of photochrome incorporations, yet involved amidation of the methyl ester, and the final product contained excess methyl ester group and free carboxy inorganic groups. An attempt to condense hydroxyethylspiropyran is described in Table 3, and led to low incorporations and eventually to gelation. The incorporation of alcohols,
Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995 2827 Table 1. Reaction of Polysulfone Carboxylic Acid N-Hydroxysuccinimide Ester (PS-CONHS)with Model Amines and with Aminospiropyran H&SP (See Scheme 1) results %reactionc NKb amine (no. of equiv) solventkonditions INSR NHS gel 710 CHCl3, RT, 21 h 0 100 NH2CsH4COCH3 (2) 711 CHC13, RT, 21 h 20 80 N H ~ C ~ H ~ ( C H ~ (BOC) ) Z N H(1.5) 712 CHC13,50 "C, 21 h 50 50 N H Z C ~ H ~ ( C H ~ (BOC) ) ~ N H(1.5) CHCl3, RT, 2.5 h 100 0 713 NH2CsHi7 (2) THF, RT, 3 h low high 702 H2N-SP (1.5) 706 THF, RT, 20 h H2N-SP (1.5) CHC13, RT, 20 h 707 HzN-SP (1.5) 708 CHCl3, RT, 5 h H2N-SP (1.5) low high 709 CHCl3, 0 "C, 5 h HzN-SP 0 100 H2N-SP is compound A, Scheme 1. Notebook number. INSR = insertion.
Table 2. Reaction of PS-CONHS with Alcohols results ROH (no. of equiv)
NK
solvent/ conditions
715 HOCeH17 (3) CHC13, RT, 21 h 717 HOC4Hg (3) CHC13,60 "C, 17h 718 HOC4Hg (3) CHC13,60 "C, 17 h CHC13, 719 HOC~HR . . (3) 60 %, 17 h 720 HOC4Hg (3) CHC13, RT. 17 h 721 HOC4Hg (3) CHC13, 60 "C, 42 h 722 HOC4Hg (3) CHC13, RT, 21 h 725 HOQHg(3) THF,RT a
%
base
reaction
gel
(+/-I
0
-
0
-
NEt3
0
-
1,8-DMANa
0
-
NaH
0
Scheme 5. Three-Step Strategy: Synthesis of Spiropyran- or Spirooxazine-Polysulfone via NHS or DCC Methods pre-blocking step
cox
C8H17NH2,0.8 eq
*
X = OH, NHS
aCONHC8H17
1
1
photochrome insertion step 2
cox
H2N-•
+
CONH-
NEt3
0
-
NaH
0
-
3a
cox
+
NaH
+ means yes; - means no
+
H ~ N - R - ~ CONH-
I
1,8-DMAN = 1,8-bis(dimethylamino)naphthalene.
amine/alcohol (no. of equiv)
727 727 728
HOC4Hg (5) HOC4Hg (5) HOC4Hg (5)
734 735
H2N-SP (2) HOCH2CHz-SP (2)
solvent/ conditions PY, RT, 2 h PY,RT, 19 h THF, RT, 2 h (1,8-DMAN) PY, RT, 20 h py, RT, 17 h
%
reaction 53 74 65 -30
U
cox
Table 3. Coupling of PS-CO2H with AlcoholdAmines in Pyridine with DCC (1 equiv)" Results NK
R-m
3b
gel (+/-)
4
post-blockingstep
-
CONHC8H17
C8H17NH2
+ + +
3 or 4
5a
5b Y=
a For H2N-SP (compound A), see Scheme 1. For 1 , 8 - D W , see Table 2. For HOCH2CH2-SP (compound E),see Scheme 1.
although not relevant t o this study, is quite successful with DCC activation (see Table 3) and could be of interest for other purposes. In reviewing the results obtained for the two alternative routes, it is important t o emphasize that, besides the aim of introducing a maximal amount of photochromes bound to the polymer, there was a strong emphasis on achieving polymers that are suitable for the preparation of membranes, i.e., those photochromic polymers should not gel, and should be soluble in common organic solvents, particularly halogenated solvents, dimethylformamide, and N-methylpyrrolidone. Consequently, in the synthesis, attention was paid also to those listed requirements. Competitive reactions, such as concurrent replacement of octylamide groups (see synthesis of 5b),causes loss of octylamide groups. The need for the preblocking step is to avoid gelation problems, whereas the need for the hydrophobic ballast (octylamide) is to provide an "internal plasti-
~=a
6
R-•
Y=m
Scheme 6. Synthesis of Spiropyran-Polysulfone with Methyl Ester-BlockedGroups P.Sul-CO,H
-
P.Sul-CO,Na NK-828
CHI DMSO
P.*aI
-
/Co2Na
H , N m , DCCw
'COzCH, 80% NK-R3O
C02Na
NK-861
C02Na
NK-862
cizer" to ensure the photochromic effect. We found (part 2 in this series, submitted) that without a plasticizing effect no photochromism is recorded. In essence, changes in the degree of substitution (DS) and taking lower substituted (e.g., DS = 0.26) carboxypolysulfone would have required no octylamide blocking
2828 Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995
5-Amino-1,3,3-trimethyl-6'-nitrospiro(indoline-2,2'[2H-l]benzopyran) (5-aminospiropyran) (Compound A, see Scheme 1) was prepared following the procedure in Conclusion Schvartsman and Krongauz (1984)t o give dark cherryIn this work we have attempted to develop synthetic red crystals: mp 148-150 "C. Anal. Calcd for C1gH1gN303: C, 67.64; H, 5.86; N, 12.45%. Found: C, 67.75; methods for incorporation of the important photoH, 5.61; N, 12.52%. chromes, spiropyran and spirooxazine. The selection of carboxypolysulfone as the functional polymeric entity 5-/N-(tertbutyloxycarbonyl)aminol-l,3,3-trimethylspiroand amino-spaced photochrome as the functional pho(indoline-2,3'-[3Hlnaphtho[2,1-bl-1,4-oxazine) (BOCtochrome entity was justified by the lack of side reacaminospirooxazine) (ZV,)(see Scheme 3). BOC-aminotions. Yet the reactivity of the amide condensation step, Fischer's base (111) (2.35 g, 8.16 mmol) was dissolved by carbodiimide condensation, on N-hydroxysuccinimide in 40 mL of absolute methanol. l-Nitrosonaphthol(1.41 esters, is insufficient to lead to full blocking of the C02H g, 8.16 mmol) was added, and the solution was refluxed groups. Since these groups are detrimental for the for 35 min and then left in the refrigerator overnight. photochromic effect, a strategy of three-step reaction The precipitate obtained was filtered, dried, and reacted was developed. Although this reaction led to some in the next step without prior purification. unwanted displacement reactions, e.g., substitution of 5-Amino-l,3,3-trimethylspiro(indoline-2,3'-[3Hlnaphoctylamide by photochrome and the opposite, i.e., the th0[2,1 -bl-1,4-oxazine)N)(Compound F,see Scheme 3). photochrome by octylamide, the overall result was BOC-aminospirooxazine (W (1.78 g, 0.004 mol) was satisfactory. Photochromic polymeric materials suitable dissolved in 20 mL of trifluoroacetic acid. The solution to fabricate membranes were received and studied (part was stirred for 30 min. Methylene chloride was added 2 of this series, submitted). This is a first study and and the solution was cooled to -10 "C. A saturated more is needed to expand this study to various levels of solution of sodium carbonate was added until pH 9.5. functional group substitution, in order to obtain optimal The organic phase was separated, dried over sodium materials. Also full physical characterization using sulfate, and passed through a 3 cm column of basic NMR, thermogravimetric analysis (TGA), and other alumina. The solution obtained was concentrated and methods will be appropriate. slowly dropped into a beaker containing hexane, while stirring. A yellow powder was obtained in a yield of 0.95 Experimental Section g (69%). Materials and Methods. Polysulfone, Udel3500 P, 'H NMR (CDCl3) 6 1.31 (s,3H), 1.35 (s, 3H), 2.67 (5, was obtained from Union Carbide; carboxylated polysul3H), 6.56 (m, 2H), 7.01 (d, 2H), 7.35-7.70 (m, aromatic fone (DS = 0.06, 0.26, 0.74) was obtained from M. D. rings); 8.51 (d, 1H). Guiver, Institute of Enviromental Research, National 1-(P-Hydroxyethyl)-3,3-dimethyl-6'-nit~spi~(indolineResearch Council of Canada, Ottawa, Ontario, Canada. 2,2'-[2H-l]benzopyran) (compound E, see Scheme 1)was Spiropyran and spirooxazine were obtained from prepared following the procedure in Zajtseva et al. Aldrich. All organic solvents were A.R. grade or dis(1973) to give dark cherry-red crystals with mp 163tilled solvents. 165 "C [from benzene-hexane (1:2)1. Anal. Calcd for Thin-layer chromatography (TLC)was performed on C2oHzoN204: C, 68.2; H, 5.7; N, 8.0. Found: C, 68.4; Merck Kieselgel 60F 254 plates with ethyl acetateH, 5.7; N, 7.8. hexane as the eluent and basic aqueous 1%KMn04 BOC-aminocaproic acid N I ) (see Scheme 2) (Bodansolution as the dyeing agent. Flash chromatography szky and Bodanszky, 1984). A solution of aminocaproic was carried out on 0.040-0.063 mm silica gel 60 (Merck acid (10 mmol) in a mixture of tert-butyl alcohol (20 mL), No. 9835) with ethyl acetatehexane as the eluent. water (10 mL), and 1N sodium hydroxide (10 mL) was Melting points were determined on a Fisher-Johns stirred and cooled with an ice bath. Di-tert-butylpyroapparatus. carbonate (2.4 g, 11 mmol) was added and stirring lH NMR spectra were recorded on a Varian FT80A continued at room temperature for 30 min. The solution or Bruker 270 MHz Aspect 2000 spectrometer. was concentrated in vacuo to about 10-15 mL, cooled Atomic absorption analysis was determined on a in an ice bath, covered with a layer of ethyl acetate (30 Varian 1000 atomic absorption spectrophotometer. mL), and acidified with a dilute solution of potassium Syntheses of Low Molecular Weight Photohydrogen sulfate t o pH 2-3. The aqueous phase was chromes. The following starting compounds were extracted with ethyl acetate (2 x 15 mL). The ethyl resynthesized and their properties are presented. acetate extracts were separated, washed with water (2 5-Nitro-1,3,3-trimethyl-2-methyleneindoline (I) (see x 30 mL), dried, and evaporated: yield 70%; 'H NMR Scheme 3) was prepared following the procedure in Gale (400 MHz, CDC13) 6 1.44 (s, 9H, (CH2)3C), 1.24-1.70 and Whilshire (1974) and crystallized from hexane/ (m, 6H), 0.307 (m, 2H, CHzNH), 2.34 (t, 2H, CH2C02). methylene chloride, mp 89-91 "C. Yield 76%. 5-[[6-[(tert-Butyloxycarbonyl)aminolcaproyllaminol5-Amino-1,3,3-trimethy,l-2-methyleneindoline (II,) (see 1,3,3-trimethyl-2-methyleneindoline 0(see Scheme2). Scheme 3) was prepared following the procedure in Gale Amino-Fischer's base (11) was reacted with BOC-amiand Whilshire (1974) and crystallized from hexane to nocaproic acid (VI)in methylene chloride in the presgive 5-amino-1,3,3-trimethyl-2-methyleneindoline, mp ence of DCC and a catalytic amount of dimethylami98-100 "C, in 71% yield. 5-~N-(tert-Butyloxycarbonyl)aminol-1,3,3-trimethyl-2-nopyridine and left overnight at room temperature, according to Hassner's method (Hassner and Alexander, methyleneindoline (BOC-amino-Fischer's base) (III) (see 1978). The crude product was flash chromatographed Scheme 3) was prepared following the procedure in on silica. The eluent was ethyl acetatehexane (1:l). Schvartsman and Krongauz (1984)to give 93% of a very Yield 65%. viscous colorless oil of (111): TLC, Rf 0.3, plates DCAlufolien, Kieselgel 60F 254, eluent methanoymethyl5-[[6-~~tert-Butyloxycarbonyl)aminolcaproyllaminol1,3,3-trimethyl-~-nitrospiro(indoline-2,2'-[2H-l]benzopyene chloride 1:15. This product was used directly in the following step without further purification. ran) WIII) (see Scheme 2). 5-[[(tert-butyloxycarbonyl)step, but the polymers would have not shown photochromism.
Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995 2829
aminocaproyllaminol-1,3,3-trimethyl-2-methyleneindoline (VII) (4.228, 0.01 mol) and l-nitrosalicylaldehyde (1.82 g, 0.01 mol) were dissolved in 70 mL of absolute methanol. The solution was refluxed for 40 min. The crude product was flash chromatographed on silica. The eluent was ethyl acetatehexane (1:l):yield 40%; 'H NMR (400 MHz, C6D6) 6 1.0 (8,3H); 1.15 (m, 2H); 1.18 (s, 3H); 1.22 (m, 2H); 1.58 (m, 2H); 1.85 (t, 2H); 2.42 (s, 3H); 2.88 (t, 2H); 5.26 (d, 1H); 6.08-7.86 (m, 7H, aromatic rings). 5-[(Aminocaproyl)amino]-1,3,3-trimethyl-6'-nitrospiro(indoline-2,2'-[2H-l]benzopyran) (IX)(Compound D, see Scheme 2). This product was obtained similarly t o 5-aminospiropyran 0.The crude product was purified by passing the methylene chloride solution of the crude material through basic alumina and adding the purified solution dropwise into hexane. A yellow solid was obtained in 34% yield: lH NMR (CDC13) 6 1.18(s,3H), 1.26 (s, 3H), 1.57-1.80 (m, 8H), 2.28-2.45 (m, 4H), 2.70 (5, 3H), 5.78-5.91 (d, 2H), 6.41-7.97 (m, aromatic rings), 8.03 (m, 1H). Syntheses of Polymeric Photochromes. PS-CONHS (1, X = NHS, Scheme 5). N-Hydroxysuccinimide (0.269 g, 2.34 mmol) was added to a solution of carboxylated polysulfone (R = H) (DS = 0.74,l.OO g, 1.56 mmol CO2Wg) in THF (distilled over L a & , 10 mL). The reaction mixture was cooled to 0 "C in an ice-water bath and dicyclohexylcarbodiimide(DCC)(0.482 g, 2.34 mmol) was added. A few minutes later, a light suspension of dicyclohexylurea (DCU) was observed. After 2 h of stirring, the reaction mixture was refrigerated overnight. The mixture was then filtered over cotton and precipitated dropwise to ether. The white flakes obtained were filtered over sintered glass funnel, washed with ether, and air-flow dried. The polymer was precipitated twice by dissolving it in CHC4 (10% solution, w/v) and precipitating it dropwise to ether. The product polymer (white flakes) was soluble in DMSO, THF, and CHC13. Complete conversion of the carboxylic groups to the NHS ester groups was obtained (by NMR). 'H NMR 6 (CDCl3) 8.31 (O.llH, d, J = 8.7 Hz, H11.t Hiy), 8.11 (0.63H, d, J = 8.8 Hz, H110, 7.96 (1.26H, d, J =8.8 Hz, H13' +His.), 7.84 (1.26H, d, J =8.8 Hz, Hi0 Hi1 Hi3 H16), 7.50-6.80 (12H, m, H I Hg H12 Hi4 f His, H y , H I T ,Hg,HIT, Hip, Hiv), 2.84 (2.96H (4 x 0.74), S, OCCH2CH2CO), 1.69 (6H, S, 2cH3).
white flakes obtained were filtered over a sintered glass funnel, washed with ether, and air-flow dried. The polymer was reprecipitated twice by dissolving it in CHC13 (10% solution w/v) and precipitating it dropwise to ether to obtain white flakes. Complete conversion of the NHS groups to the amide groups was obtained (by NMR). 'H NMR 6 (CDCl3) = 8.10 (O.llH, d, H11.t Hiy), 7.99 (0.63H, d, J = 8.6 Hz, Hilt), 7.90 (1.26H, d, J=8.8H~,Hi3'+H~6'),7.84(1.26H,d, J=8.8H~,Hio H11 HI3 fHl6), 7.30-7.15 (4H, m, H2 H3 H5 HS),7.10-6.85 (8H, m, H1 H4 H6 H7 f Hg HO Hgt, Hi2 Hlz. H i 2 Hi4 H i p Hi5 f Hiy), 6.30,6.17 (0.74H, 2 bs, NH), 3.38-3.20 (1.48H, 2 q, J = 6.6 Hz, CONHCHz), 1.69 (6H, S, 2cH3); 1.55-1.70 (1.48H, m, NHCH~CHZ), 1.26 (7.4H,bs, (CH2)5CH3),0.86 (2.22 H, t, J = 6.7 Hz, NH(CH2)7CH3). Synthesis of 5b N = R-SP, R = (CHd&ONH, Scheme 5) via the NHS Method. Step 1. Preblocking: Synthesis of
+
+ +
+ +
+
+ + + + + + + + + +
+
,CONHS PS 'CONHCsH17 2 (X = NHS) (NK-737)
A sample of 0.8 eq of n-octylamine (0.01 mL, 0.06 mmol) was added to a solution of the NHS ester of polysulfone 1 (X= NHS) (NK-714, DS = 0.74, 50 mg, 1.35 mmol of NHS/g) in CHC13 (flashed over basic alumina, 0.75 mL). Following 17 h of stirring a t room temperature, half the amount of reaction mixture was precipitated dropwise to ether (dried over CaC12). The white flakes obtained were filtered over a sintered glass funnel, washed with ether, air-flow dried, reprecipitated twice (CHCl3 solution dripped to ether), and dried under high vacuum. The white flakes obtained contained 20% NHS groups and 80% octylamide groups (determined by NMR).
+
+
+
+
+
+
+
0
,COIN)
'H NMR 6 (CDC13) 8.20-7.65 (3.26H, m, H d Hd'), 7.45-6.60 (12H, m, Ha H b -tHc),6.10 (0.6H (0.74 x 0.80), bs, NH), 3.50-3.10 (1.18H (0.74 x 2 x 0.80), m, CONHCHz), 2.84 (0.6H (0.74 x 4.0.201, S, COCH2CH2CO), 2.10-1.80 (0.74 x 2 x 0.80, m, CONHCH~CHZ), 1.68 (6H, S, 2cH3 (PS)), 1.27 (5.9H (0.74 x 10 x 0.80), bs, CHz), 0.85 (1.8H (0.74 x 3 x 0.80), bt, NH(CHd7CH3). Step 2. Photochrome insertion: Synthesis (Scheme 5) of
+
,CONHS PS-CONH(CH&CONH-SP 'CONHCsH17 3b (X = NHS, R = (CH&CONH) (NK 738)
Synthesis of PS-CONHCSH17. Two equivalents of n-octylamine (0.013 mL, 0.08 mmol) were added to a solution of the NHS ester of polysulfone 1 (X = NHS) (NK-705, DS = 0.74, 30 mg, 1.35 mmol of NHS/g) in CHCl3 (dried over CaC12, 0.5 mL). Following 2.5 h of stirring a t room temperature, the clear solution was precipitated dropwise t o ether (dried over CaC12). The
[(6-Aminocaproyl)aminolspiropyran(H2N(CH&CONHSP (AZ-59,20 mg, 0.04 mmol) was added to the second portion of the reaction mixture NK-737. Following 22 h of stirring the solution was precipitated dropwise to ether (dried over CaC12). The flakes obtained were filtered over a sintered glass funnel, washed with ether, air-flow dried, reprecipitated twice (CHCls solution to ether), and dried under high vacuum. The product
2830 Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995
polymer contained 7% NHS groups, 34% spiropyran groups, and 59% octylamide groups. lH NMR 6 (CDC13) 8.30-7.70 (3.26H, m, f Hc), 7.45-6.65 (12H, m, Ha f Hb Hc),6.30-6.00 (m, NH), 3.50-3.10 (O.9H (0.74 x 2 x 0.591, m, CONHCHz), 2.79 (0.2H (0.74 x 4 x 0.07), bs, COCHZCH~CO), 2.66 (0.8H (0.74 x 3 x 0.341, bs, NCH3(SP)), 2.40-2.00 (1.8H (0.74 x 4 x 0.59), m, CH2CONH-SP CONHCHzCHz), 1.68 (6H, S, 2cH3 (PS)),1.26 (bs, (CH2)5 (CH2)2),0.85 (bt, CONH(CHz)7CH3). Step 3. Postblocking: Synthesis (Scheme 5) of
+
+
+
CONH(CH&CONH-SP
R = (CH&,CONH) (NK-739)
n-Octylamine (0.02 mL, 0.12 mmol) was added to a solution of the polymer NK-738 (15 mg) in CHCl3 (0.5 mL). Following 21 h of stirring the solution was precipitated dropwise to ether. The polymer was filtered over a sintered glass funnel, washed with ether, air-flow dried, reprecipitated twice (CHCl3 solution to ether), and dried under high vacuum. The polymer obtained contained 9% spiropyran groups and 91% octylamide groups. No residual NHS groups were detected (by NMR). lH NMR 6 (CDCl3) 8.20-7.65 (3.26H, In, Hd H c ) , 7.45-6.60 (12H, m, Ha H b Hc), 6.30-6.00 (0.7H (0.74 x 0.91), bs, NH), 3.55-3.10 (1.3H (0.74 x 2 x 0.911, m, CONHCHz),2.66 (0.2H (0.74 x 3 x 0.09), bs, NCH3(SP)),1.68 (6H, S, 2cH3 (PS)),1.27 (6.7H (0.74 x 10 x 0.911, S, (CH&CH3), 0.85 (2H (0.74 x 3 x 0.91), bt, CONH(CH2)7CH3). Synthesis of 5b N = R-SP, R = (CHd5CONH) (Scheme 5) via the DCC Method. Step 1. Synthesis of
+
+
+
/C02H PS 'CONHC8H17
+
+
,CONH(CHz)&ONH-SP PS 'CONHC8H17 5b (Y= R-SP,
R = (CH2)&ONH) (NK 744a)
n-Octylamine (0.05 mL, 0.3 mmol) followed by DCC (20 mg, 0.1 mmol) were added to the reaction mixture NK-744. Following 17 h of stirring the solution was precipitated dropwise to ether (dried over CaC12). The flakes obtained were filtered over a sintered glass funnel, washed with ether, air-flow dried, reprecipitated twice (CHC13solution dripped to ether), and dried under high vacuum. The pale yellow flakes obtained contained 14% SP groups and 86% octylamide groups (determined by NMR). 'H NMR 6 (CDCl3)8.20-7.65 (3.26H, m, H d Hc), 7.45-6.55 (12H, m, Ha -k Hc),6.40-6.00 (m, NH), 3.55-2.90 (1.5H, m, CONHCH2C7H15 CONHCHZ(CH>~CONH-SP), 2.66 (0.3H, bs, NHCH3(SP)),1.68 (6H, S, 2cH3 (PS)),1.26 (6.8H (6.8H = [0.74 (DS) x 10 (no. of H) x (86/100 (% C8H17))I 10.74 (DS) x 10 (no. of H) x (14/100 (% SP))])s, (cH2)5),0.85 (1.9H, bt, CONHC7H14CH3). Synthesis of 5a (Y = SP) (Scheme 5) via the DCC method. Step 1. Synthesis of
+
+
+
+
2 (X = OH) (NK-741)
A sample of 0.8 equiv of n-octylamine (0.021 mL, 0.125 mmol) was added to a solution of PS-COzH (1)(R = H) (DS = 0.74, 0.100 g, 1.56 mmol) in pyridine (dried over KOH, 1 mL), followed by DCC (0.026 g, 0.125 mmol). Following 20 h of stirring at room temperature, a sample of the solution was precipitated dropwise to ether (dried over CaC12). The flakes obtained were filtered over a sintered glass funnel, washed with ether, air-flow dried, reprecipitated twice (CHC13 solution dripped into ether), and dried under high vacuum to obtain a product that contained -80% of octylamide groups and -20% of carboxylic acid groups (determined by NMR). 'H NMR 6 (CDCl3)8.20-7.60 (3.26H, m, Hd f Ha,),7.35-6.70 (12H, m, Haf H b f Hc), 6.40-6.00 (0.6H m, NH), 3.50-3.10 (1.2H, m, CONHCHz), 3.053.65 (1.2H, m, CONHCH~CHZ), 1.68 (6H, s, 2cH3 (PSI), 1.25 (6H, S, (CHZ)~), 0.85 (1.8H, bt, CONHC7H14CH3). Step 2. Synthesis (Scheme 5) of
,COZH PS \CONHCeH17 2 (X = OH) (NK-749)
A sample of 0.8 equiv of n-octylamine (0.021 mL, 0.125 mmol) was added to a solution of carboxylated polysulfone (DS = 0.74, 0.100 g, 1.56 mmol of COzWg) in pyridine (dried over KOH, 1mL), followed by 0.8 equiv of DCC (0.026 g, 0.125 mmol). After 17 h of stirring at room temperature a sample was withdrawn for NMR analysis and purified by the method described in NK741. The product contained -80% octylamide groups and -20% carboxylic groups (determined by NMR). 'H NMR: as for NK-741. Step 2. Synthesis (Scheme 5) of /CW PS-CONH-SP
,Cod+ PS-CONH(CHp)&ONH
+
+
PS/ \CONHCp,H17 5b (Y= R-SP,
"01). The reaction mixture was stirred for 17 h at room temperature, ahd then a sample of the dark solution was removed and precipitated with ether (dried over CaClZ). The flakes obtained were filtered over a sintered glass funnel, washed with ether, and air-flow dried. The polymer was reprecipitated twice by dissolving it in CHC13, dripping it to ether, and drying it under high vacuum. The product polymer contained 18%spiropyran groups, 74% octylamide groups, and 8% carboxylic acid groups. lH NMR 6 (CDCl3) 8.15-7.65 (3.26H, m, Hd Hd), 7.45-6.75 (12H, m, Ha f H b + Hc), 6.35-6.00 (0.7H, m, CONHCHzCTH15 CONH(CH&CONH-SP), 3.55-3.10 (1.4H, m, CONHCHzC7H15 CONHCHZ(CH)~CONH-SP), 2.69 (0.4 H, bs, NCH3), 1.68 (6H, S, 2CH3 (PSI), 1.26 (6H, S, (CH& (CH2)2), 0.85 (1.6H, bt, CONHC7H14CH3). Step 3. Synthesis (Scheme 5) of
-SP
\CONHCsHl7
\CONHC8Hl, 3a (X = OH) (NK-749a)
3b (X =OH, R = (CHz)&ONH) (NK-744)
[(6-Aminocaproyl)aminolspiropyran(H*(CHz)&ONHSP)(AZ-59,22 mg, 0.05 mmol) was added to half of the reaction mixture NK-741, followed by DCC (3 mg, 0.015
Aminospiropyran (HzN-SP)(O.O42g, 0.125 mmol) was added to the reaction mixture, NK-749, followed by DCC (8 mg, 0.04 mmol). The reaction mixture was stirred for 23 h.
Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995 2831 Step 3. Synthesis (Scheme 5) of /CONH-SP PS \CONHC~H~, 5a (Y = SP) (NK-749b)
n-Octylamine (0.1 mL, 0.6 mmol) followed by DCC (40 mg) were added to the reaction mixture NK-749a. After 22 h of stirring, the solution was precipitated dropwise into ether (dried over CaC12). The resulting flakes were filtered over a sintered glass funnel, washed with ether, air-flow dried, reprecipitated twice (CHCl3 solution dripped to ether), and dried under high vacuum. The pale green flakes obtained contained 10%SP groups and 90% octylamide groups (determined by NMR). 'H NMR 6 (CDCl3) 8.15-7.75 (3.26H, m, H d f Hd),7.40-6.80 b Hc),6.30-6.10 (0.7H, bs, NH); 3.45(12H, m, Ha f H 3.30, 3.30-3.10 (1.5H, 2m, CONHCH2), 2.71 (0.2H, s, NCH3(SP)), 1.69 (6H, S, 2cH3 (PSI), 1.26 (6.7H, S, (CH2)5),0.85 (2.OH, bt, C7H14CH3). Synthesis via the DCC Method (NK-7536, Scheme 5)
+
of /CONHCsH17
PS 'CONH-SO
6 (Y = SO)
A sample of 0.85 equiv of n-octylamine (0.022 mL, 0.133 mmol) was added to a solution of carboxylated polysulfone 1 (DS = 0.74, 0.100 g, 1.56 mmol of C02W g) in pyridine (dried over KOH, 1mL), followed by 0.85 equiv of DCC (0.027 g, 0.133 "01). The reaction mixture was stirred for 21 h a t room temperature, and then aminospirooxazine (FB-223, 43 mg, 0.125 mmol) and DCC (13 mg, 0.062 mmol) were added. This was followed by stirring for 27 h and then adding noctylamine (0.1 mL, 0.6 mmol) and DCC (40 mg, 0.2 mmol). After further stirring for 20 h a t room temperature, the reaction mixture was precipitated dropwise into ether (dried over CaC12) and the resulting purple flakes were filtered over a sintered glass funnel, washed with ether, air-flow dried, dissolved in CHCl3, filtered over cotton, and reprecipitated twice t o ether. After a few hours of drying under high vacuum, 0.087 g of mauve flakes, containing 10% spirooxazine groups and 90% octylamide groups, was obtained. lH NMR 6 (CDC13)8.15-7.75 (3.26H,m, H d +&I, 7.30-6.80 (12H, m, Ha f Hb f Hc), 6.29-6.17 (0.7H, 2bs, NH), 3.453.10 (1.4H, 2m, CONHCH2), 2.73 (0.2H, s, NCH@P)), 1.69 (6H, s, 2CH3 (PSI),1.40-1.15 (m, (CH2)5), 0.86 (2H, bt, GHi4CH3). Synthesis of Carboxymethylpolysulfone: Procedure 1 (90% Conversion) (Scheme 6). (a) Preparation of PSCOzNa (NK-823 (825, 828)) (Scheme 6). Carboxylated polysulfone (1.00 g, 1.56 mmol of C02Wg) was stirred for 40 h at room temperature in 100 mL of 2.5 N NaOH (250 mmol), then filtered over a sintered glass funnel, washed with distilled water (300 mL), soaked for 10 min thrice with distilled water (100 mL), and dried under high vacuum with P2O5 for 6 h to yield 1.03 g of white flakes. (b) Preparation (NK-826) (Scheme 6) of /C02Na
PS \COzCH3
90%
A sample of 1 equiv of methyl iodide (0.05 mL, 0.75 mmol) was added to a solution of sodium carboxylate polymer (DS = 0.74,0.5 g, 0.75 "01) in DMSO (5 mL), which was stirred a t 80 "C. After 15 min a second equivalent of the methyl iodide was added and stirring was continued for 75 min. The hot, brown solution was precipitated dropwise into MeOH (200 mL), the solution was decanted, and the flakes obtained were washed with warm MeOH (200 mL), warm distilled water (2 x 200 mL), and finally with MeOH (100 mL). After drying for 16 h a t 37 "C under vacuum, 0.45 g of white flakes containing 90% methyl ester groups (determined by NMR) were obtained. lH NMR 6 (CDCl3) 8.10-7.70 (3.26H, m, H d &), 7.35-6.70 (12H, m, Ha H bf H J , 3.89, 3.85 (2H, 2s, co2cH3),1.68 (6H, S, 2cH3). Synthesis of Carboxymethylpolysulfone (PS-(202CH3): Procedure 2 (100% Conversion) (NK-836). Potassium carbonate (0.240 g, 1.72 mmol) followed by methyl iodide (0.2 ml, 3.12 mmol) were added t o a solution of carboxylated polysulfone (1.00 g, 1.56 mmol C02H) in NMP (10 mL). After 20 h of stirring the brown solution was precipitated dropwise into MeOH (600 mL), the solution was decanted, and the polymer flakes were washed with methanol (200 mL), then stirred with a fresh portion of warm methanol (400 mL), followed by a fresh portion of warm distilled H2O. After filteration over a sintered glass funnel, a second cycle of washing was applied and ended with methanol washing over the sintered glass funnel. The polymer was dissolved in CHCb (15 mL) and reprecipitated dropwise into MeOH (1L), filtered over a sintered glass funnel, air-dried for 2 days, and finally dried for 2 h in a vacuum oven at 47 "C. Off-white flakes (0.90 g) with 100% conversion t o the methyl ester group were obtained. lH NMR 6 (CDCl3)8.20-7.70 (3.26H, m, H d Hg),7.35-6.75 (12H, m, Ha f H b + Hc),3.90, 3.86 (2.2H, 2s, CO2CH3), 1.69 (6H, s, 2CH3). Preparation of NK-861 (Scheme 6).
+
+
+
POzNa PS-COZCH~ 'CONK-SP
65% 10%
A samplg of 4 equiv of aminospiropyran (31mg, 0.092 mmol) followed by 2 equiv of DCC (10 mg, 0.047 mmol) was added t o a solution of partially (80%)methyl ester blocked carboxylated (Na form) polysulfone (NK-830, prepared according to the procedure of NK-826, 0.50 g) in pyridine (0.5 mL, dried over KOH). After 18 h of stirring at room temperature, the deep green solution was precipitated dropwise into ether. The flakes were washed with ether, air-flow dried, and repreciptated three times (CHCl3solution dripped into ether) resulting in pale green flakes containing 10% SP and 65% C02CH3 groups (determined by NMR). 'H NMR 6 (CDCl3) 8.10-7.70 (3.26H, m, H d f Hc), 7.30-6.75 (12H, m, Ha f H b f Hc), 3.89, 3.85 (1.4H, 2S, co2cH3);2.70 (0.2H, bs, NCH3 (SP)),1.68 (6H, s, 2CH3). Preparation of NK-862 (Scheme 6). 70zNa PS-COzCH3 75% \coNH-sP
10%
Potassium carbonate (2 mg, 0.012 mmol) followed by methyl iodide (0.007 mL, 0.11 mmol) were added to a solution of the polymer NK-861 (25 mg) in NMP (0.35 mL). After 24 h of stirring at room temperature, the solution was precipitated dropwise into ether. The
2832 Ind. Eng. Chem. Res., Vol. 34, No. 8, 1995 resulting flakes were washed with ether, air-flow dried, and reprecipitated (CHCl3 solution dripped into ether) to obtain a product that contained 10% SP and 75% COaCH3 groups (determined by NMR). ‘H NMR 6 (CDC13) 8.10-7.70 (3.26H, m,Hd + H c ) , 7.35-6.75 (12H, m,H, 4-H b f HJ, 3.89, 3.85 (1.7H, 29, C02CH3); 2.70 (0.2H, S, NCH3 (SP)),1.69 (6H, 5, 2cH3).
Acknowledgment We wish to thank Dr. M. Guiver of NCRD, Ottawa, Canada, for generous samples of carboxypolysulfone. The support of the Ministry of Science and Arts, through Grant Gr 889 is also acknowledged.
Nomenclature DS = degree of substitution SP = spiropyran SO = spirooxazine PS = polysulfone (=P.Sul in Scheme 6) DCC = dicyclohexylcarbodiimide NHS = N-hydroxysuccinimide NMP = N-methylpyrrolidone BOC = tert-butyloxycarbonyl DMSO = dimethyl sulfoxide THF = tetrahydrofuran
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Bodanszky, M.; Bodanszky, A. The Practice of Peptides Synthesis; 1984;p 20. Fox, R. E. Research Reports and Test Items Pertaining to Eye Protection of Air Crew Personnel; Final Report on Contract AF 41(657)-215,AD 440226,April 1961. Gale, J. D.; Whilshire, J. F. K. Intramolecular Hydrogen Bonding in Some 0-nitrodiphenylamines and Related Compounds. J. SOC. Dyers Colour. 1974,90,97. Guiver, M. D.; Croteau, S.; Hazlett, J. D.; Kutowy, 0. The Modification of Polysulfone by Metalation. Br. Polym. J. 1990, 23,29-39. Hassner, A.; Alexander, V. Direct Room Temperature Esterification of CarboxylicAcids. Tetrahedron Lett. 1978,46,4475-4478. Hinnen, A.;Audic, C.; Gautron, R. Photohromisme des IndolinoChim. Fr. spiropyrannes. 1.-Synthese des F’roduits. Bull. SOC. 1968,2066-2074. Kahana, N.; Arad-Yellin, R.; Deshe, A.; Warshawsky, A. Functional Macrocyclic Polysulfones via Aminomethyl-Polysulfone. J. Polym. Sci., Polym. Chem. 1990,28,3303-3315. Kesting, R. E. Synthetic Polymeric Membranes; John Wiley & Sons: New York, 1985. Koelsch, G. F.; Workman, W. R. Some Thermochromic Spirans. J.Am. Chem. SOC. 1952,74,6288-6389. Schvartsman, F. P.; Krongauz, V. A. Quasi-Liquid Cristals of Thermochromic Spiropyrans. A Material Intermediate between Supercooled Liquid and Mesophases. J. Phys. Chem. 1984,88, 6448. Warshawsky, A,; Kedem, 0. Polysulfone-Based Interpolymer Anion Exchange Membrane. J. Membr. Sci. 1990,53,37. Warshawsky, A.; Kahana, N.; Deshe, A.; Gottlieb, H. E.; AradYellin, R. Halomethylated Polysulfone : Reactive Intermediates to Neutral and Ionic Film-Forming Polymers. J. Polym. Sci. Polym. Chem. 1990,28,2885-2905. Zajtseva, E.; Prohoda, A.; Kurkovskaya, L.; Shifrina, R.; Kardash, N.; Drapkina, D.; Krongauz, V. Preparation of N-methacryloxy Ethyl Derivatives of Spiropyrans of the Indoline Series. Chem. Heterocycl. Compd. 1973,9,1233-1239.
Received for review March 16, 1995 Accepted May 17, 1995 @
IE9501788
Abstract published in Advance A C S Abstracts, July 1, 1995.
