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Статья Paper
Three-unit Products from Condensation of 3-Alkylsubstituted 2,5-Diamino-1,3,4-thiadiazoles with 1,1 -Dimethoxy-3-iminoisoindoline
Elena A. Danilova, Tat'yana V. Melenchuk, Ekaterina E. Melekhonova, Maria A. Tyutina, and Mikhail K. Islyaikin@
Ivanovo State University of Chemistry and Technology, Ivanovo, 153000, Russia @Corresponding author E-mail: [email protected]
New representatives of 3-alkyl-5-amino-2-imino-1,3,4-thiadiazolines (alkyl=C5Hn, C10H21, C15H31) were synthesized by alkylation of 2,5-diamino-1,3,4-thiadiazole with corresponding alkyl bromides. Their condensation with 1,1-dimethoxy-3-iminoisoindoline led to new three-units products of ABA-type - 1,3-bis[(3-alkyl-5-amino-1,3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindoles. These compounds were characterised by IR, UV-vis, and NMR spectroscopy, mass-spectromery, data of elemental analysis.
Keywords: S,N-Containing heterocycles, porhyrazine precursors, 3-alkyl-5-amino-2-imino-1,3,4-thiadiazolines, 2,5-diamino-1,3,4-thiadiazole, alkylation, condensation.
Introduction
2,6-Bis(1-imino-3-isoindolinylidenamino)pyridine (1) as the first representative of the compounds with new conjugated system was synthesized by Linstead and coworkers when they have studied condensation reaction of 1,3-diiminoisoindoline with 2,6-diaminopyridine.[1-3]
о н Ь
1
2
In the middle of the last century a new three-units system of ABA-type (2) containing two pyridine fragments (A) and one isoindoline-1,3 ring (B) was synthesized.[2-5] Its inner cavity holds three N-atoms and is able to coordinate a bivalent metal to give the correponding metallocomplexes.[5-6] Later the method for obtaining of ABA-type compounds was improved by the activation of nitrile groups of phthalonitrile by the salts of alkali-earth metals.[7] The influence of the catalyst, temperature, as well as the nature of amine and solvent on the condensation leading to formation of ABA products was examined.[8] It was shown that a substitution of imino groups in 1,3-diminoisoindoline molecule proceeds stepwise and suggested that using the corresponding molecular ratio of phthalonitrile and arylen-amine it is possible to obtain various products. However the used amines were limited by the compounds of aminopyri-dine and aminothiazole series.[8]
In 1996 the synthesis of unsymmetrically substituted triazoleporphyrazines was reported[9] in which the ABA-
type compound derived from 1-dodecyl-3,5-diamino-1,2,4-triazole was used as a precursor. To the best of our knowledge the similar products with 1,3,4-thiadiazole fragments were not yet described.
Experimental
Calculations
Quantum chemical calculations were carried out by means of software package GAMESS (PC)[10] by DFT B3LYP 6-31G(d,p) method with full optimization of geometrical parameters. The preparation of the input files and processing of output data of calculations were carried out by Chemcraft program.[11].
Measurements
Electronic absorption spectra in UV- and visible region (UV-vis spectra) were registered on HITACHI U-2001 spectrophotometer in quartz cuvettes having 1-10 mm thickness. MALDI-TOF mass-spectra were measured by Ultraflex Bruker Daltonics mass-spectrometer in a mode of positive ions with the use of reflectomodes with 20 mV target potential. The samples were prepared by dissolving of investigated compounds in chloroform (10-4 - 10-6 mol-l"1). 1H NMR spectra were registered in CDCl3 on AVANCE 500 MHz spectrometer and Bruker 300 MHz spectrometer. Chemical shifts (ppm) were measured at 295 K using hexamethyldisiloxane (8=0.037 ppm) or tetramethyl-silane (8=0.0 ppm) as internal standards. IR spectra were registered by AVATAR 360 FT-IR spectrometer for samples pressed in KBr or for solutions in СНCl3.
Synthesis
Previously described procedures were used for synthesis of 2,5-diamino-1,2,4-thiadiazole (3)[12] and 1,1-dimethoxy-3-iminoisoindoline (8).[13]
General procedure for the synthesis of 5-amino-2-imino-3-alkyl-1,3,4-thiadiazoline. The mixture of 2,5-diamino-1,3,4-thiadiazole (3) (2.32 g, 20 mmol), corresponding alkyl bromide (70 mmol) and MeOH (80 ml) was refluxed during 24 hours. Then the solvent was taken away under vacuum. The obtained precipitate was mixed with water and 30% aqueous ammonia solution and stirred two hours at room temperature. The target product was extracted by CHCl3 and solvent was distilled away.
5-Amino-2-imino-3-pentyl-1,3,4-thiadiazoline, 4. The product was purified by recrystallization from ethanol to obtain a white powder soluble in the majority of organic solvents, but not in water. Yield 2.64 g (71 %), m.p. = 175-177 °C. Found: C 45.07, H 6.42, N 30.96, S 17.28 %. C7H14N4S requires C 45.88, H 6.05, N 30.57, S 17.50 %. M 186.09. m/z: 185 [M+H]+. IR (KBr) v cm-1: 3312 and 3276 (NH2), 3099 (NH), 2956, 2932 and 2859 (alkyl CH), 2777, 1633, 1607, 1549 (C=N). UV-vis (EtOH, 1.2-10-4 M) Xmax nm (lge): 210 (3.71). 1H NMR (CDCl3, 200 MHz) SH ppm: 3.69 (2H, N-CH2-), 1.68 (2H, N-CH2-CH2-), 1.27 (2H,-CH2-CH3), 0.87 (3H,-CH3).
5-Amino-3-decyl-2-imino-1,3,4-thiadiazoline, 5. The product was washed by hexane, recrystallized from ethanol, and then from methanol to give a beige powder soluble in alcohols, dichloromethane, acetone, hexane, benzene and insoluble in water. Yield: 3.23 g (63 %), m.p. =182-184 °C. Found: C 56.13, H 9.77; N 22.45, S 12.63 %. C12H24N4S requires C 56.21, H 9.43, N 21.85, S 12.50 %. M 256.17. m/z: 257 [M+H]+. IR (KBr) v cm-1: 3425, 3270, 3147, 3054 (NH), 2949, 2920, 2850 (alkyl CH), 1609, 1541 (C=N). UV-vis (EtOH, 1.1-10-4 M) Xmax nm (lge): 271 (3.69). 1H NMR (CDCl3, 200 MHz) 5H ppm: 3.39 (2H, N-CH2-), 1.68 (2H, N-CH2-CH2-), 1.25 (14H, -CH2-), 0.86 (3H,-CH3).
5-Amino-3-dodecyl-2-imino-1,3,4-thiadiazoline, 6, was purified by recrystallization from ethanol and obtained as lightbeige wax-like mass, which is soluble in alcohols and CH2Cl2, moderately soluble in acetone, hexane and benzene and not soluble in water. Yield 4.66 g (82 %), m.p. 167-169 °C. Found: C 58.22, H 8.47, N 20.14, S 11.89 %. C14H28N4S requires C 59.11, H 9.93, N 19.44, S 10.95 %. M 284.20. m/z: 284 [M]+. IR (KBr) v cm-1: 3425, 3271, 3059 (NH), 2921, 2851 (alkyl CH), 1609, 1609, 1541 (C=N). UV-vis (EtOH, 1.2T0"4 M) Xmax nm (lge): 270 (3.72). 1H NMR (CDCl3, 500 MHz) SH ppm: 4.28(s., 2H, -NH2), 3.74 (t., 2H, N-CH2-), 1.87 (s., 2H, N-CH2-CH2-), 1.30 (m., 18H, -CH2-), 0.89 (-CH.).
5-Amino-3-pentadecyl-2-imino-1,3,4-thiadiazoline, 7. Gray wax-like product was received after evaporation of solvent and drying in vacuum at 60 - 70 °C. Compound 7 is soluble in acetone, hexane, benzene, moderately soluble in alcohols and dichloro-ethane. Yield 2.14 g (62.1 %), m.p. = 158-160 °C. Found: C 61.77, H 11.27, N 16.47, S 10.77 %. C17H34N4S requires C 62.53, H 10.49, N 17.16, S 9.82. M 362. m/z: 362 [M]+. IR (KBr) v cm-1: 3427, 3270, 3056 (NH), 2921, 2852 (alkyl CH), 1610, 1540 (C=N). UV-vis (EtOH, 0.8-10"4 M) Xmax nm (lge): 271 (3.70). 1H NMR (CDCl3, 500 MHz) 5H ppm: 4.50 (t,4H, N-CH2-), 1.9 (s., 4H, N-CH2-CH2-), 1.29 (m., 26H, -CH2-), 0.91 (t., 6H, -CH)).
General procedure for the synthesis of 1,3-bis[(3-alkyl-5-amino-1,3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindoles. The mixture of 3-alkyl-5-amino-2-imino-1,3,4-thiadiazoline and 1,1-dimethoxy-3-iminoisoindoline (8) in MeOH (50 ml) was stirred at 40-45 °C for 15 hours. After that the reaction mass was poured into 150 ml of water. The obtained precipitate was filtered off and dried at r.t. The product was purified by column chromatography on alumina, (CH2Cl2 : methanol : hexane = 10:1:3). The obtained crimson substance was not soluble in water but well soluble in organic solvents, exept hexane.
1,3-Bis[(5-amino-3-pentyl-1, 3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindole, 9, was synthesized from 5-amino-2-imino-3-penthyl-1,3,4-thiodiazoline (4) (1.138 g, 6 mmol) and 8 (0.58 g, 3 mmol). Yield: 166 mg (11.4 %). Found: C 53.86, H 6.57, N 25.05, S 12.34 %. C22H31N9S2 requires C 54.41, H 6.43,
N 25.96, S 13.20 %. M 485.2. m/z 484 [M-H]+. IR (KBr) v cm-1: 3394, 3288, 3120 (NH), 2954, 2924, 2852 (alkyl CH), 1699, 1608, 1548 (C=N). UV-vis (MeOH, 1.66-10"5 M) Xmax nm (lge): 384 (4.33), 404, 462, 495 (4.48), 527. 1H NMR (CDCl" 500 MHz) SH ppm: 7.59 - 7.89 (m., 4H arom.), 5.32 (b.s., 3H, NH, NH2), 4.70, 4.54 (t., 4H, N-CH2-), 1.58 (s., 4H, N-CH2-CH2-), 1.28 (m., 4H, -CH2-), 0.91 (t., 6H, -CH3).
1,3-Bis[(5-amino-3-decyl-1,3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindole, 10, was synthesized from 5-amino-2-imino-3-decyl-1,3,4-thiadiazoline (5) (0.0574 g, 0.11 mmol) and 8 (0.0106 g, 0.055 mmol). Yield: 172.3 mg (27.6 %). Found: C 60.13, H 8.77, N 20.45, S 9.83 %. C32H51N9S2 requires C 61.40, H 8.21, N 20.14, S 10.24 %. M 625.4. m/z 625 [M]+. IR (KBr) v cm-1: 3394, 3288, 3120 (NH), 2954, 2924, 2852 (alkyl CH), 1699, 1608, 1548 (C=N). UV-vis (MeOH, 5.50-10"4 M) nm Xmax (lge): 384 (3.8), 407, 461, 493 (3.96), 528. 1H NMR (CDCl3, 500 MHz) 5H ppm: 7.56 - 7.85 (m., 4H arom.), 7.24 (b.s., 3H, NH, NH2), 3.39 (t., 4H, N-CH2-), 1.68 (s., 4H, N-CH2-CH2-), 1.25 (m., 28H, -CH2-), 0.86 (t., 3H, -CH3).
1,3-Bis[(5-amino-3-dodecyl-1,3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindole, 11, was synthesized from 5-amino-2-imino-3-dodecyl-1,3,4-thiadiazoline (6) (0.0644 g, 0.23 mmol) and 8 (0.022 g, 0.12 mmol). Yield: 25.6 mg (31 %). Found: C 63.03, H 8.22, N 17.47, S 9.18 %. C36H59N9S2 requires C 63.40, H 8.72, N 18.48, S 9.40 %. M 682.04. m/z 682 [M]+. IR (KBr) v cm-1: 3390, 3285, 3120 (NH), 2955, 2922, 2854 (alkyl CH), 1698, 1610, 1545 (C=N). UV-vis (MeOH, 5.20-10"4 M) nm Xmax (lge): 384 (3.72), 410, 466, 498 (3.75), 536. 1H NMR (CDCl3, 50'0MHz) 5H ppm: 7.58 -7.90 (m., 4H arom.), 7.24 (b.s., 3H, NH, NH2), 4.28 (s., 2H, -NH2), 3.74 (t., 4H, N-CH2-), 1.87 (s., 4H, N-CH2-CH2-), 1.30 (m., 36H, -CH2-), 0.89 (t., 3H, -CH3).
1,3-Bis[(5-amino-3-pentadecyl-1,3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindole, 12, was synthesized from 5-amino-2-imino-3-pentadecyl-1,3,4-thiadiazoline (7) (1 g, 3 mmol) and 8 (0.27 g, 1.5 mmol). Yield: 0.413 g (36 %). Found C 65.03, H 8.56, N 15.77, S 6.92 %. C42H70N9S2 requires C 65.93, H 9.22, N 16.47, S 8.38 %. M 764.5. m/z 764 [M]+. IR (KBr) v cm-1: 3394, 3288, 3120 (NH), 2954, 2924, 2852 (alkyl CH), 1699, 1608, 1548 (C=N). UV-vis (MeOH, 1.0310-4 M) nm Xmax (lge): 295 (3.95), 301, 385 (3.89), 410, 466, 497 (4.06), 531. 1HNMR (CDCl3, 300 MHz) SH ppm: 7.58 - 7.90 (m., 4H arom.), 7.24 (b.s., 3H, NH, NH2), 4.50 (t., 4H, N-CH2-), 1.9 (s., 4H, N-CH2-CH2-), 1.29 (m., 48H, -CH2-), 0.91 (t., 6H, -CH3). 13C NMR (CDCl3, 75.5 MHz) 5C ppm: 172.4, 167.8, 164.4, 160.5, 139.5, 134.3, 132.7, 131.7, 123.6, 122.5, 51.1.
Results and Discussion
2,5-Diamino-1,3,4-thiadiazole (3) can exist in two forms, i.e. as thiadiazoline (3a) and thiadiazolinone (3b).[14]
H
/
N—N
N—N
H2N AX NH, H2N AX
NH
3a
3b
We succeeded in obtaining of thiadiazolinone tau-tomer by the substitution of the proton located in 1-position of 2,5-diamino-1,3,4-thiadiazole by alkyl group following the alkylation procedure by alkylbromide in boiling MeOH elaborated by us earlier.[15] As a result the compounds 4-7 were obtained following Scheme 1 and characterized by elemental analysis, UV-vis, IR, and 1H NMR spectra and mass-spectrometry.
Alk
®
Alk
N—N
N—N ©
JL JL
H2N—\ H2N----S y nh2 H2N^\ /^NH
4-7
4 - Alk = C5H1P 5 - Alk = C10H21, 6 - Alk = C12H25, 7 - Alk = C15H31 i - «-AlkBr, MeOH, 24 h, boil. ii - NH.OH.
Scheme 1.
H2N
Alk N-N*
NH
4 - 7
MeQ fOMe
NH
N'
Alk. JI
N^
NH2 h2n
9 - 12
.Alk
4, 9 - Alk = C5H„, 5, 10 -
i: MeOH, 40- 45 0C, 15 h.
Alk = C10H21, 6, 11 - Alk = C12H25,
7, 12
■ Alk = C15H31
Scheme 2.
Compounds 9-12 were synthesized for the first time by interaction of 4-7 with 1,1-dimethoxy-3-iminoisoindo-line in molar ratio 2:1 in MeOH at 40-45 °C for 15 hours (Scheme 2).
Compounds 9-12 were separated by pouring the reaction masses into water, a precipitate was filtered and then purified on column with alumina using a mixture of CH2Cl2:MeOH:hexane = 10:1:3. The obtained bright-red solids are soluble in the most of organic solvents and contain eventually a mixture of regio-isomeres, which we could not separate in this work. The introduction of dodecyl or pentadecyl fragments into the thia-diazole ring changes the aggregation state. The compounds 11 and 12 are wax-like substances which exhibit a strong fluorescence in organic solvents under UV light.
MALDI-TOF mass-spectrometry was applied to prove the structure of synthesized compounds. The massspectrum of 9 is shown in Figure 1. A good correlation of calculated and experimental m/z values with characteristic isotopic distribution for molecular ion proves the srtucture
6.00E+008
2.00E+008
0.00E+000
484
0 1000 2000 3000 4000 5000 ,_6000
nrVz
Figure 1. Mass-spectrum of compound 2.
of ABA-type product which contains two alkylthiadiazole (A) and one isoindole (B) fragments (Figure 2).
The characteristic bands (2954, 2924, 2852 cm-1) of stretching C-H vibrations of alkyl fragments are seen in the IR spectra of compounds 9-12. The absorption bands at 3411 and 3296 cm-1 can be assigned to the stretching vibrations of N-H bonds in amino- and iminogroups.
A series of signals located at 0.91, 1.29, 1.41, 1.97, 2.21 and 4.5 ppm in the 'H NMR spectra of 9-12 is assigned to protons of the alkyl groups and multiplet at 7.58 - 7.90 ppm to aromatic protons. Integral intensities of these signals confirm this assignment. These results are in agreement with the data reported [9] for the compounds of ABA-type with 1-dodecyl-1,2,4-triazole unit. Most probably the broad signal at 7.24 ppm can be induced by the resonance of protons of amino- and iminogroups. This signal disappears after a small amount of D2O was dropped into.
13C NMR spectrum of compound 12 is characterized by the presence of three series of signals assigned to carbon
1,20E-+009 ■
1,0()E+009 ■ 8.00E4008-6,00E-K)08 ■ 400E-+008 ■
2,00E-K)08 ■
A.
483 484 485 486 487 488
Figure 2. Calculated and experimental m/z magnitudes for 2.
3
8
D
0,4-
0,2-
0,0
400 500 600 700 800 900
A,nm
Figure 3. UV-vis spectrum of 9 in MeOH (c = 1.6610-5 M).
atoms of a thiadiazole ring (172.4, 167.8 ppm), isoindole rings (139.5, 134.3, 132.7, 131.7, 123.6, 122.5), and pentade-cyl groups (51.1, 31.9, 29.69, 29.65, 29.61, 29.5, 29.4, 29.3, 29.0, 28.6, 26.4, 22.7, 14.1 ppm). There are also two signals of C-atoms of pyrrole fragments located at 164.4, 160.5 ppm and their positions are in good agreement with the data for macroheterocyclic compounds sythesized earlier.[9]
UV-vis spectra of synthesized compounds 9-12 are quite similar. In the spectrum of pentyl substituted three-unit product 9 shown as an example (Figure 3) one can see two main absorption bands with maxima at 384 and 495 nm, and the bands of lower intensity which appear as inflexions at 404, 462 and 527 nm.
Quantum chemistry calculations of 1,3-bis[(5-amino-3-pentyl-1,3,4-thiadiazol-2(3H)-ylideneamino)]-2H-isoindole 9 having C2v symmetry were carried out with full geometry optimization by DFT B3LYP 6-31G(d,p) method implemented in GAMESS (PC) program package.[14] Figure 4
Figure 4. .The model of 1,3-bis[(5-amino-3-pentyl-1,3,4-thiadiazol-2(3H)-ylideneamino]-2H-isoindole 9, bond lengths (A), valence angles (degree). H-Atoms of C-H bonds are eliminated for the sake.
12 3 4 5 6
Figure 5. The experimental UV-vis spectrum of 9 in MeOH and spectrum, decomposed into several Gaussian functions.
shows the optimized molecular structure and bond lengths. The framework of the molecule having alkyl groups at N-atoms of the thiadiazole rings adjacent to the isoindole unit is planar. The sulfur atoms are separated by 4.301 A.
The results of TD DFT calculations of the first ten singlet-singlet electron transfers are given in Table 1.
Table 1. Calculated data of wave-length (nm), strength of oscillator (f) and the decomposition of experimental spectrum into several Gaussian functions.
Gaussian constituents of the experimental spectrum
Calculated data (TD DFT)
X, nm Height nm f
374 0.23
387 0.07 347 0.18
407 0.17
461 0.29 470 0.53
493 0.40
529 0.29
The experimental spectrum of 9 (black line) was decomposed into its Gaussian components (red line) (Figure 5). Hence a good correlation between quantum chemistry calculations and experimental UV-vis spectra of compound 9 can be another proof of structure of three-unit products of ABA-type.
References
1. Evidge J.A., Linstead R.P. J. Chem. Soc. 1952, 5008-5012.
2. Elvidge J.A., Linstead R.P. J.Chem.Soc. 1952, 5000-5007.
3. Elvidge J.A., Golden J.H. J. Chem. Soc. 1957, 700-709.
4. Linstead R.P. J .Org. Chem. 1953, 2873-2884.
5. Clark P.F., Elvidge J.A., Linstead R.P. J. Chem. Soc. 1954, 15, 2490-2497.
6. Scruggs J.A., Robinson M.A. Inorg. Chem. 1967, 6, 10061010.
7. Siegl W.O. Inorg. Chem. 1974, 10, 825-832.
8. Siegl W.O. J .Org. Chem. 1977, 42, 1872-1878.
9. Gema de la Torre, Torres T. J. Org. Chem. 1996, 61, 64466449.
10. Granovsky A.A. PC GAMESS version 7.1.E (Firefly), build number 5190, http://classic.chem.msu.su/gran/gamess/index. html
11. Zhurko G.A. http://www.chemcraftprog.com
12. Patent RF № 2313523. Danilova E.A., Islyaikin M.K., Ko-lesnikov N.A., Melenchuk T.V. B.I. № 36 from 27.12.07 (in Russ.).
13. Baumann F., Binert B., Röch G., Vollmann H., Wolf W. Angew. Chem. 1956, 68, 133-150.
14. Bambas L. Five-Membered Heterocyclic Compounds with Nitrogen and Sulfur or Nitrogen, Sulfer, and Oxygen. New York, London: Interscience publishers LTD, 1952, 124-142.
15. Danilova E.A., Melenchuk T.V., Stryapan M.G., Islyaikin M.K. Zh. Obsch. Khim. 2008, 78, 480-481 (in Russ.).
Received 21.04.2009 Accepted 03.07.2009
