New Synthetic Approach to Aminosquarylium Cyanine Dyes

Abstract

A novel synthesis of aminosquarylium cyanine dyes, based on the methylation of readily available squarylium dyes with methyl triflate, followed by nucleophilic substitution with appropriate aliphatic amines, was disclosed. By this procedure several new aminosquarylium cyanine dyes bearing benzothiazole, benzoselen­azole and quinoline nuclei were prepared.

Key words

aminosquarylium dyes - squaraines - pentamethine­cyanines - dicarbocyanines - heterocycles

References and Notes

• 1 Sprenger HE. Ziegenbein W. Angew. Chem., Int. Ed. Engl.  1967,  6:  553 
• 2a Fabian J. Nakazumi H. Matsuoka M. Chem. Rev.  1992,  92:  1197 
• 2b Emmelius M. Pawlowski G. Vollmann HW. Angew. Chem., Int. Ed. Engl.  1989,  28:  1445 
• 3a Ikuo S, Hiroshi T, Yukiyoshi I, and Tsutomu S. inventors; Eur. Patent  568877.  ; Chem Abstr. 1993, 121, 46725
• 3b Tsutomu S, and Keiko I. inventors; US Patent  5260165.  ; Chem. Abstr. 1993, 121, 22657
• 3c Jipson VB. Jones CR. J. Vac. Sci. Technol.  1981,  18:  105 
• 4a Law K.-Y. Chem. Rev.  1993,  93:  449 
• 4b Kamat PV. Das S. Thomas KG. George MV. Chem. Phys. Lett.  1991,  178:  75 
• 4c Law K.-Y. J. Phys. Chem.  1988,  92:  4226 
• 5a Piechowski AP. Bird G R. Morel DL. Stogryn EL. Phys. Chem.  1984,  88:  934 
• 5b Morel DL. Ghosh AK. Feng T. Stogryn EL. Purwin PE. Shaw RF. Fishman C. Appl. Phys. Lett.  1978,  32:  495 
• 5c Merritt VY. Hovel HJ. Appl. Phys. Lett.  1976,  29:  414 
• 6a Kim SH. Hwang SH. Kim JJ. Yoon CM. Keum SR. Dyes Pigm.  1998,  37:  145 
• 6b Kim SH. Han SK. Color. Technol.  2001,  117:  61 
• 7 Morgan AR, Menes ME, and Wang R. inventors; W. Patent  44742.  ; Chem. Abstr. 2000, 133, 151988
• 8 Ramos SS. Santos PF. Reis LV. Almeida P. Dyes Pigm.  2002,  53:  143 
• 10 Bixian P. Tong L. Dyes Pigm.  1998,  39:  201 
• 11a

  General procedure for the preparation of aminosquarylium dyes 8: Crude 7, prepared as described above, was re-dissolved in anhyd CH₂Cl₂ (40 mL), under N₂ atmosphere, and a 4-fold excess of methylamine was added. After being stirred at r.t. for 30 min, the reaction mixture was washed with cold water and the organic layer was separated by decantation and dried over anhyd Na₂SO₄. The solvent was removed under reduced pressure and the resulting residue was recrystallized from CH₂Cl₂-MeOH-Et₂O

• 11b

  General procedure for the preparation of amino-squarylium dyes 9: To a untreated solution of 7 in dry CH₂Cl₂, prepared as described above, vigorously stirred under N₂ atmosphere at r.t., was added a 5-fold excess of N,N-diethylamine. After 3-5 h the reaction mixture was worked-up as described for the preparation of O-methylsquarylium dyes 7 and the resulting residue was recrystallized from CH₂Cl₂-MeOH-Et₂O (Table [1] ).

• 13 Bonett R. Chemical Aspects of Photodynamic Therapy   Gordon and Breach; Amsterdam: 2000. 

9

General procedure for the preparation of O-methylated squarylium dyes 7: To a solution of 6 (ca. 0.4 mmol) in anhyd CH₂Cl₂ (50 mL), vigorously stirred under N₂ atmosphere at r.t., was added a 4-fold excess of CF₃SO₃CH₃. After 3-5 h, the reaction mixture was quenched with cold 5% aq NaHCO₃. The organic layer, after separation by decantation, was dried over anhyd Na₂SO₄ and the solvent removed under reduced pressure. The resulting residue was recrystallized from CH₂Cl₂-MeOH-Et₂O.

12

General procedure for the replacement of counter-ion in dyes 8 and 9: To a solution of the dye, prepared as described, in MeOH, at r.t., was added an approximately equal volume of 14% aq KI. After 2 h, the precipitated dye was collected by filtration, washed with water and recrystallized from CH₂Cl₂-MeOH-Et₂O.

14

Selected data. Compound 7a: IR (KBr): 1648, 1506, 1427, 1396, 1361, 1311, 1247, 1218, 1157, 1118, 750 cm^-1;
¹H NMR (400.13 MHz, DMSO-CDCl₃): δ 1.36 (6 H, t, J = 7.2 Hz, CH₃), 4.44 (4 H, q, J = 7.2 Hz, CH₂), 4.51 (3 H, s, OCH₃), 5.99 (2 H, s, CH=), 7.36 (2 H, t, J = 8.0 Hz, ArH), 7.52 (2 H, t, J = 8.0 Hz, ArH), 7.64 (2 H, d, J = 8.0 Hz, ArH), 7.91 (2 H, d, J = 8.0 Hz, ArH); ¹³C NMR (100.62 MHz,

DMSO-CDCl₃): δ 12.3 (CH₃), 41.4 (CH₂), 60.3 (OCH₃), 84.6, 113.1, 122.5, 125.0, 127.4, 127.7, 139.8, 157.9, 161.5, 173.5, 176.7; HRMS (FAB): calcd for C₂₅H₂₃N₂O₂S₂ 447.120097, found 447.122165. Compound 8a: IR (KBr):

Table 1 The Yield, Melting Point, and UV Spectral Data of Squarylium Cyanine Dyes 6-9 (continued)

Dye	X	R	Yield (%)	Mp (ºC)	λmax c (nm)	Log ε
6a	S	Et	50	>300	650	5.24
6b	S	Hex	76	270b	650	5.41
6c	Se	Et	72	300b	665	5.49
6d	Se	Hex	74	262b	668	5.41
6e	CH=CH	Et	45	>300	707	5.39
6f	CH=CH	Hex	42	287b	710	5.37
7a	S	Et	81	274b	632	5.27
7b	S	Hex	87	234b	632	5.23
7c	Se	Et	76	274b	647	5.28
7d	Se	Hex	76	249b	650	5.32
7e	CH=CH	Et	95	289b	671	5.62
7f	CH=CH	Hex	86	259b	674	5.47
8a	S	Et	56a	291-292	659	5.23
8b	S	Hex	75 a	251-252	659	5.22
8c	Se	Et	44a	297b	674	5.26
8d	Se	Hex	69a	240b	677	5.23
8e	CH=CH	Et	76a	>300	707	5.43
8f	CH=CH	Hex	82a	260b	710	5.36
9a	S	Et	62a	283b	668	5.27
9b	S	Hex	75a	236-238	671	5.33
9c	Se	Et	56a	284b	686	5.22
9d	Se	Hex	88a	287b	689	5.26
9e	CH=CH	Et	89a	282b	719	5.55
9f	CH=CH	Hex	84a	242b	722	5.38
a From the corresponding squarylium dye 6. b With decomposition. c Measured in MeOH/CH2Cl2 (99:1).

3438, 1633, 1560, 1455, 1428, 1353, 1309, 1251, 1228, 1110, 746 cm^-1; ¹H NMR (250.13 MHz, DMSO-CDCl₃): δ 1.42-1.49 (6 H, m, CH₃), 3.36 (3 H, d, J = 5.0 Hz, NCH₃, collapses to s with D₂O), 4.31-4.41 (4 H, m, CH₂), 5.95 (1 H, s, CH=), 6.35 (1 H, s, CH=), 7.28-7.51 (6 H, m, ArH), 7.65-7.74 (2 H, m, ArH), 8.63 (1 H, br, NH, exchangeable with D₂O); ¹³C NMR (100.62 MHz, DMSO-CDCl₃): δ 10.7 (CH₃), 10.9 (CH₃), 28.8 (NCH₃), 39.5 (CH₂), 40.0 (CH₂), 84.5, 84.6, 110.8, 111.2, 120.7, 121.0, 122.8, 123.3, 125.9, 126.1, 126.3, 138.5, 138.6, 156.0, 159.4, 162.6, 171.9; HRMS (FAB): calcd for C₂₅H₂₄N₃OS₂ 446.136081, found 446.137251. Compound 9a: IR (KBr): 1621, 1544, 1421, 1357, 1313, 1214, 1149, 1116, 1008, 775 cm^-1; ¹H NMR (400.13 MHz, DMSO-CDCl₃): δ 1.00-1.04 (12 H, m, CH₃), 3.28 (4 H, q, J = 7.2 Hz, CH₂), 3.92 (4 H, q, J = 7.3 Hz, CH₂), 5.40 (2 H, s, CH=), 6.92 (2 H, t, J = 7.2 Hz, ArH), 7.03-7.10 (4 H, m, ArH), 7.26 (2 H, d, J = 7.6 Hz, ArH); ¹³C NMR (100.62 MHz, DMSO-CDCl₃): δ 11.4 (CH₃), 14.4 (CH₃), 40.8 (CH₂), 45.6 (CH₂), 84.9 (CH=), 111.7, 121.3, 124.3, 127.0, 127.2, 139.1, 155.4, 159.6, 160.9, 173.1; HRMS (FAB): calcd for C₂₈H₃₀N₃OS₂ 488,183031, found 488,185052.