A facile and highly chemoselective synthesis of 1-thia-3a,6-diaza-benzo[e]azulen-3-ones by 7-exo-dig/trig halocyclizations

Abstract

This manuscript describes a study on relatively unexplored halogen mediated 7-exo-dig/trig cyclization reactions of 2-(2-amino-aryl)-3-prop-2-ynyl/allyl-thiazolidin-4-ones for the formation of thiazole condensed 1,4-benzodiazepines in good yields. The reactions are facile, chemoselective and involve the use of simple substrates leading to synthesis of diversely functionalized 1,4-benzodiazepines. The synthesis of such condensed 1,4-benzodiazepines is important in terms of their usefulness as biological active agents.

---

Halogen mediated cyclizations are gaining increasing importance for the construction of cyclic compounds having variable complexity including medium and large ring sizes.¹ Iodocyclizations have been efficiently explored for the synthesis of biologically active heterocyclic molecules.² Significant progress has been made in recent years by application of 5-exo and 6-exo-dig/trig halocyclizations reactions for the synthesis of five or six membered heterocycles.^1–3 There are very limited examples in literature involving construction of seven-membered ring systems by 7-endo dig/trig cyclization^4,5 reactions. Recently, Miesch et al. explored a silver-catalyzed 7-exo-dig cyclization.^5a Hashmi et al. reported gold catalysed 7-exo-dig cyclizations.^5c However, the synthesis of seven membered carbo/heterocycles involving 7-exo dig/trig halocyclization received much less attention in past.⁵ Moreover, the bromoamination reaction for the synthesis of seven membered heterocycles is scarcely reported in literature. On the other hand, 1,4-benzodiazepine based structure class holds an important place in drug discovery because of their diverse pharmacological profiles.⁶ 1,4-Benzodiazepines are widely used as analgesic,⁸ anti depressive,⁸ anticonvulsant,⁸ anti-anxiety,⁸ sedative and hypnotic agents.^7,8 Olanzapine⁹ (I) is an atypical 1,4-benzodiazepines based anti-psychotic drug with a thieno-benzodiazepinyl structure. Olanzapine is approved for the treatment of schizophrenia. It is a selective monoaminergic antagonist with high affinity binding to serotonin 5HT2A/2C, dopamine D14, muscarinic M1–5 and adrenergic α1 receptors. Alprazolam (II) and estazolam (III) have found use as anxiolytic agents,^10a–c and triazolam (IV) is known as an antidepressant^10d (Fig. 1). In view of this diverse pharmacological profile of condensed 1,4-benzodiazepines, it was planned to explore a new synthetic route for the formation of 1,4-benzodiazepines having thiazole-benzodiazepinyl structure.

Fig. 1 Some clinically approved condensed 1,4-benzodiazepine based drugs.

As a part of our ongoing interest in heterocyclic chemistry,¹² we already reported a β-lactam mediated strategy for a facile, chemoselective, economical, as well as short synthetic route to 1,4-benzodiazepin-2-ones.¹¹ The present manuscript indicates a facile yet high yielding and chemoselective synthesis of functionalized thiazole condensed benzo[1,4]diazepines by relatively unexplored 7-exo-dig/trig halocyclization reactions of 2-(2-amino-aryl)-3-prop-2-ynyl/allyl-thiazolidin-4-ones using halogen and a mild base. The developed synthetic methodology can potentially play an important role in synthesis of structurally diverse fused benzo[1,4]diazepines having diverse pharmacological profile. Also, this methodology involves a study on relatively unexplored and unfavourable 7-exo-dig/trig iodo- and bromocyclization reactions for synthesis of condensed[1,4]diazepines.

Initially, we synthesized 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones 4a–d by three component cyclization reactions of corresponding N-allyl/propargyl imines generated in situ from 2-nitroaryl aldehydes 1a–b with allyl/propargyl amines 2a–b and thioglycolic acid 3.

The reactions resulted in the formation of 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones 4a–d in good yields (Scheme 1). During optimization studies, better reaction yield was observed employing dichloroethane (DCE) as a solvent at 80 °C temperature (Table 1, entry 4) compared to other solvents such as DCM, THF or toluene (Table 1, entry 5 to 7). Further, a high reaction yield was observed when higher equivalents of allyl/propargyl amines (Table 1, entry 3 and 4) were used. The use in higher amounts of corresponding amines probably compensate the loss in concentration of these volatile reagents during the course of reaction which lead to better reaction yields.

Scheme 1 3-Alkyl-2-(2-nitroaryl)thiazolidin-4-one 4a–d.

Table 1 Reaction conditions optimization for the synthesis of 4a

S. no.	R	1a : 2a	Solvent	Temp.	Product^a	Yields^b (%)
a Reaction performed for 18 h.b Isolated yields after purification.
1	1a	1 : 1	DCE	60 °C	4a	32
2	1a	1 : 1	DCE	80 °C	4a	55
3	1a	1 : 1.5	DCE	80 °C	4a	74
4	1a	1 : 2.5	DCE	80 °C	4a	92
5	1a	1 : 2.5	DCM	40 °C	4a	39
6	1a	1 : 2.5	THF	70 °C	4a	68
7	1a	1 : 2.5	Toluene	80 °C	4a	60

---

After optimization of initial reaction conditions as elaborated in Table 1, the cyclization reaction was further explored for the synthesis of diverse 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones 4a–d using corresponding 1a–b and allyl/propargyl amines (Table 2, entries 1 to 4).

Table 2 Synthesis of 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones (4a–d)

S. no.	Aldehyde	Amine	Product^a	Yields^b (%)
a Reaction conditions DCE was used at 80 °C.b Isolated yields after purifications.
1	1a	2a	4a	92
2	1a	2b	4b	81
3	1b	2a	4c	94
4	1b	2b	4d	83

---

The functionalized 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones 4a–d were further treated with Fe/NH₄Cl using a standard nitro reduction protocol to afford corresponding 3-allyl/propargyl-2-(2-aminoaryl)thiazolidin-4-ones 5a–d (Scheme 2) in good to excellent yields (Table 3, entries 1–4).

Scheme 2 Synthesis of 3-allyl/propargyl-2-(2-aminophenyl)thiazolidin-4-ones 5a–d.

Table 3 3-Alkyl-2-(2-aminoaryl) thiazolidin-4-ones 5a–d

S. no.	4a–d	Product^a	Yields^b (%)
a Reaction conditions ethanol was used at 60 °C.b Isolated yields after purifications.
1	4a	5a	88
2	4b	5b	90
3	4c	5c	85
4	4d	5d	86

---

All newly synthesized, functionalized 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones 4a–d and 3-allyl/propargyl-2-(2-aminoaryl)thiazolidin-4-ones 5a–d were characterized on the basis of analytical and spectral evidences.^13a,14 The compound 3-allyl-2-(2-nitrophenyl)thiazolidin-4-one 4a, for example, analyzed for C₁₂H₁₂N₂O₃S showed a molecular ion peak at m/z 265.1 in its mass spectrum. The ¹H NMR (300 MHz) spectrum showed a characteristic doublet (J = 1.2 Hz) at δ 6.13 corresponding to H⁵ of the thiazole ring, two triplet (J = 15.6 Hz) at δ 3.69 and δ 3.74 corresponds to two germinal H³ protons of the thiazole ring. Two doublet of triplet at δ 5.07 (J = 24, 0.6 Hz) assigned to H⁸ protons and a multiplet at δ 5.56–5.67 assigned to H⁷ proton of allyl group.

A ¹³C NMR analysis determined the presence of carbonyl carbon at δ 172 and two aliphatic CH₂ carbons at δ 31.7 and δ 45.7 corresponding to carbons C-3 and C-6 respectively. An aliphatic C-carbon at δ 57.9 corresponds to C-5. The ¹³C spectrum has also supported the presence of allylic methylene carbon C-8 and allylic CH carbon at δ 119.2 and δ 130.5 respectively (Fig. 2).

Fig. 2 3-Allyl-2-(2-nitrophenyl)thiazolidin-4-one 4a.

The 3-allyl/propargyl-2-(2-aminoaryl)thiazolidin-4-ones were then investigated for their respective intramolecular 7-exo-dig/trig ring closure haloamination reactions. All the reactions resulted in the formation of corresponding 6-(halomethyl/methylene)-5,6,7,11b-tetrahydrobenzo[f]thiazolo-[3,2-d][1,4]diazepin-3(2H)-ones in good yields. The reaction conditions were optimized further aiming for better yields as well as selectivity using molecular iodine/bromine in presence of different bases viz. Na₂CO₃, K₂CO₃, KO^tBu, Cs₂CO₃ using different solvent such as DCM, THF, DCE. No base or the use of a strong base provided low yield of the 1,4-benzodiazepines 7a (Table 4; entries 1 to 3 & 6 to 7). Comparatively better yields were observed using 1.1 eq. of iodine/bromine and 2.5 eq. of K₂CO₃ with DCM as solvent at room temperature stirring for these transformations. This optimized reaction condition was used further for the synthesis of structurally diverse thiazole condensed 1,4-benzodiazepines (Table 5). It is important to note that use of bromine as a halogen source also provide comparable results to iodine for these newly developed 7-exo dig/trig halocyclizations (Scheme 3).

Table 4 Reaction conditions optimization for intramolecular ring closure haloamination reactions

S. no.	R	X	Base	Solvent	Reaction time	Product^a	Yields^b (%)
a 1.1 equiv. iodine are used, at room temperature.b Isolated yields after purification.
1	5b	I	—	DCM	2 h	7a	45
2	5b	I	—	DCE	2 h	7a	35
3	5b	I	—	THF	3.5 h	7a	34
4	5b	I	K2CO3	DCM	2 h	7a	86
5	5b	I	Na2CO3	DCM	3 h	7a	72
6	5b	I	KO^tBu	DCM	4 h	7a	68
7	5b	I	Cs2CO3	DCM	4 h	7a	60

---

Table 5 Intramolecular 7-exo-dig/trig ring closure haloamination reactions 3-allyl/propargyl-2-(2-aminoaryl)thiazolidin-4-ones

S. no.	SM	X2	Product^a	Yields^b (%)
a 1.1 equiv. iodine/bromine and K2CO3 (2.5 equiv.) was used, DCM was used as a solvent, reaction time 1–2 h.b Isolated yields after purification.
1	5a	I2	6a	84
2	5a	Br2	6b	69
3	5b	Br2	7b	70
4	5c	I2	6c	80
5	5d	I2	7c	82
6	5d	Br2	7d	68

---

Scheme 3 Intramolecular 7-exo-dig/ring closure haloamination reactions 3-allyl/propargyl-2-(2-aminoaryl)thiazolidin-4-ones.

The functionalized novel 6-(halomethyl)-5,6,7,11b-tetrahydrobenzo[f]thiazolo[3,2-d][1,4]diazepin-3(2H)-one 6a–c, and 6-(halomethylene)-5,6,7,11b-tetrahydrobenzo[f]thiazolo[3,2-d][1,4]diazepin-3(2H)-one 7a–d thus obtained were characterized on the basis of analytical and spectral evidences.^13b,14 The compound, 6-(iodomethylene)-5,6,7,11b-tetrahydrobenzo[f]thiazolo[3,2-d][1,4]diazepin-3(2H)-one 7a for example, analyzed for C₁₂H₁₁IN₂OS showed a molecular ion peak at m/z 358.8 in its mass spectrum. The ¹H NMR (300 MHz) spectrum showed two characteristic singlet at δ 7.14 and at δ 5.79 corresponding to H⁷ and H⁵ respectively, a broad singlet at δ 4.03 corresponding to N–H¹ of the ring, two multiplets at δ 3.73–3.80 assigned to H⁶ protons. The ¹³C NMR has shown the presence of two aliphatic CH₂ carbons at δ 33.1 and 52.8 corresponding to C-6 and C-3 respectively. The ¹³C NMR has also shown the presence of carbonyl carbon at δ 171.1. Two methylene carbons were also observed at δ 83.9 and 96.8 corresponding to C-7 and C-2 respectively (Fig. 3).

Fig. 3 6-(Iodomethylene)-5,6,7,11b-tetrahydrobenzo[f]thiazolo[3,2-d][1,4]diazepin-3(2H)-one 7a.

A plausible mechanism involves the initial formation of halonium ion A. This intermediate A transformed by intramolecular 7-exo-dig ring closure aminocyclization to yield 1-thia-3a,6-diaza-benzo[e]azulen-3-ones in good yield. The possible 8-endo dig/trig cyclization is ruled out owing to unfavorable distant ring closure approach of the nitrogen during cyclization process (Scheme 4).

Scheme 4 A mechanistic approach for the formation of 1-thia-3a,6-diaza-benzo[e]azulen-3-ones by 7-exo-dig/trig halocyclizations.

Conclusions

In conclusion, we have explored 7-exo dig/trig halocyclizations reactions of 2-(2-amino-aryl)-3-prop-2-ynyl/allyl-thiazolidin-4-ones for the synthesis of biologically relevant benzodiazepines in good to excellent yields (68–86%). This reported synthetic methodology provides a new, economical, as well as short synthetic route to thiazole condensed 1,4-benzodiazepines, which can potentially have diverse biological profile.

Acknowledgements

The financial support from Department of Science and Technology (DST), New Delhi, under Scheme No. SB/FT/CS-079/2012 is highly acknowledged. I. K. Gujral Punjab Technical University (IKG PTU), Kapurthala is acknowledged for providing research facilities.

Notes and references

1. (a) P. T. Parvatkar, P. S. Parameswaran and S. G. Tilve, Chem.–Eur. J., 2012, 18, 5460; (b) T. Aggarwal, S. Kumar and A. K. Verma, Org. Biomol. Chem., 2016, 14, 7639; (c) A. K. Banerjee, M. S. Laya and E. V. Cabrera, Curr. Org. Chem., 2011, 15, 1058; (d) A. K. Mailyan, J. A. Eickhoff, A. S. Minakova, Z. Gu, P. Lu and A. Zakarian, Chem. Rev., 2016, 116, 4441–4557.
2. (a) S. Arimitsu, J. M. Jacobsen and G. B. Hammond, J. Org. Chem., 2008, 73, 2886; (b) M. Butters, M. C. Elliott, J. Hill-Cousins, J. S. Paine and J. K. E. Walker, Org. Lett., 2007, 9, 3635; (c) S. H. Kang, S. B. Lee and C. M. Park, J. Am. Chem. Soc., 2003, 125, 15748.
3. (a) K. C. Majumdar, A. Biswas and P. P. Mukhopadhyay, Synth. Commun., 2007, 37, 2881; (b) A. K. Yadav, B. K. Singh, N. Singh and R. P. Tripathi, Tetrahedron Lett., 2007, 48, 6628; (c) K. Kobayashi, K. Shikata, S. Fukamachi and H. Konishi, Heterocycles, 2008, 75, 599; (d) K.-G. Ji, H.-T. Zhu, F. Yang, X.-Z. Shu, S.-C. Zhao, X.-Y. Liu, A. Shaukat and Y. M. Liang, Chem.–Eur. J., 2010, 16, 6151; (e) A. Sniady, K. A. Wheeler and R. Dembinski, Org. Lett., 2005, 7, 1769; (f) D. W. Knight, A. L. Redfern and J. J. Gilmore, J. Chem. Soc., Perkin Trans. 1, 2001, 2874; (g) D. W. Knight, A. L. Redfern and J. J. Gilmore, J. Chem. Soc., Perkin Trans. 1, 2002, 622; (h) L. Miesch, T. Welsch, V. Rietsch and M. Miesch, Chem.–Eur. J., 2009, 15, 4394; (i) J. M. J. Nolsoee and T. V. Hansen, Eur. J. Org. Chem., 2014, 3051; (j) J. Chen and L. Zhou, Synthesis, 2014, 46, 586.
4. M. Ohtsuka, Y. Takekawa and K. Shishido, Tetrahedron Lett., 1998, 39, 5803.
5. (a) C. F. Heinrich, I. Fabre and L. Miesch, Angew. Chem., Int. Ed., 2016, 55, 5170; (b) K. C. Majumdar, B. Sinha, I. Ansary and S. Chakravorty, Synlett, 2010, 21, 1407; (c) D. Pflsterer, S. Schumacher, M. Rudolph and A. S. K. Hashmi, Chem.–Eur. J., 2015, 21, 11585; (d) D. Pflasterer, E. Rettenmeier, S. Schneider, E. de Las Heras Ruiz, M. Rudoplh and A. S. K. Hashmi, Chem.–Eur. J., 2014, 20, 6752; (e) H. Ito, H. Ohmiya and M. Sawamura, Org. Lett., 2010, 12, 4380; (f) C. Ferrer and A. M. Echavarren, Angew. Chem., Int. Ed., 2006, 45, 1105.
6. D. A. Horton, G. T. Bourne and M. L. Smythe, Chem. Rev., 2003, 103, 893.
7. (a) H. Schutz, Benzodiazepines, Springer, Heidelberg, 1982; (b) L. O. Randall and B. Kamel, in Benzodiazepines, Raven Press, New York, 1973, p. 27; (c) J. A. Ellman, Acc. Chem. Res., 1996, 29, 132.
8. (a) W. Ben-Cherif, R. Gharbi, H. Sebai, D. Dridi, N. A. Boughattas and M. Ben-Attia, C. R. Biol., 2010, 333, 214; (b) S. K. Ha, D. Shobha, E. Moon, M. A. Chari, K. Mukkanti, S.-H. Kim, K.-H. Ahn and S. Y. Kim, Bioorg. Med. Chem. Lett., 2010, 20, 3969; (c) R. Varala, R. Enugala, S. Nuvula and S. R. Adapa, Synlett, 2006, 17, 1009; (d) L.-Z. Wang, X.-Q. Li and Y.-S. An, Org. Biomol. Chem., 2015, 13, 5497; (e) Y. Huang, K. Khoury, T. Chanas and A. Dömling, Org. Lett., 2012, 14, 5916; (f) V. R. Jumde, E. Cini, A. Porcheddu and M. Taddei, Eur. J. Org. Chem., 2015, 1068.
9. (a) S. Venkatraman, S. T. Rajan, V. V. N. C. S. Bulusu, R. K. Kasturi, S. K. Kapabalu and K. Gokavalasa, US Pat. Appln 0035887, 2006; (b) C. E. Adams, M. K. Fenton, S. Quraishi and A. S. David, Br. J. Psychiatry, 2001, 179, 290; (c) J. K. Chakrabarti, T. M. Hotten and D. E. Tupper, US Pat. No. 5229382, 1993; (d) N. A. Moore, N. C. Tye, M. S. Axton and F. C. Risius, J. Pharmacol. Exp. Ther., 1992, 262, 545; (e) N. A. Moore, D. O. Calligaro, D. T. Wong, F. Bymaster and N. C. Tye, Curr. Opin. Invest. Drugs, 1993, 2, 281; (f) C. A. Tamminga, J. Neural Transm., 2002, 109, 411.
10. (a) P. J. Snyder, J. Werth, B. Giordani, A. F. Caveney, D. Feltner and P. Maruff, Hum. Psychopharmacol., 2005, 20, 263; (b) J. Levine, D. P. Cole, K. N. Roy Chengappa and S. Gerson, Depression Anxiety, 2001, 14, 94; (c) G. L. Post, R. O. Patrick, J. E. Crowder, J. Houston, J. M. Ferguson, R. J. Bielski, L. Bailey, H. G. Pearlman, V. S. Shu and M. W. Pierce, J. Clin. Psychopharmacol., 1991, 11, 249; (d) D. J. Greenblatt, J. S. Harmatz, L. Shapiro, N. Engelhardt, T. A. Gouthro and T. A. Shader, N. Engl. J. Med., 1991, 324, 1691.
11. B. Kuila, Y. Kumar, D. Mahajan, K. Kumar, P. Singh, B. Mohapatra and G. Bhargava, RSC Adv., 2016, 6, 57485–57489.
12. (a) Y. Kumar, B. Kuila, D. Mahajan, P. Singh, B. Mohapatra and G. Bhargava, Tetrahedron Lett., 2014, 55, 2793; (b) Y. Kumar, P. Singh and G. Bhargava, Synlett, 2015, 26, 363; (c) D. Bains, Y. Kumar, P. Singh and G. Bhargava, J. Heterocycl. Chem., 2016, 53, 1665.
13. (a) General procedure for the preparation of 3-allyl/propargyl-2-(2-nitrophenyl)thiazolidin-4-ones 4a–d: to a solution of compound 1a (0.5 g, 3.31 mmol, 1 equiv.) in DCE (20 ml) was added successively allylamine (0.62 mL, 8.27 mmol, 2.5 equiv.) and MgSO₄ (3.97 g, 33.11 mmol, 10 equiv.). The reaction mixture was heated at 55 °C for 2 h. Thioglycolic acid (0.36 g, 3.97 mmol, 1.2 equiv.) was added in the reaction mixture and reaction mixture was heated at 80 °C for another 16 h. The progress of the reaction was monitored by TLC taking 1a as the limiting reactant. After completion of reaction, the solvent was dried under reduced pressure. The crude product was purified via column chromatography using 20–25% mixture of ethyl acetate in hexane as eluent. The compound was recrystallized using methanol as solvent to get 4a as pure compound. 3-Allyl-2-(2-nitrophenyl)thiazolidin-4-one (4a): yellow solid; yield: 0.80 g, 92%; mp: 69–74 °C; ¹H NMR (300 MHz, CDCl₃): δ 3.16 (t, J = 7.5 Hz, 1H), 3.69 (t, J = 16.8 Hz, 1H), 3.74 (t, J = 15.6 Hz, 1H), 4.55 (t, J = 15.6 Hz, 1H), 5.07 (dt, J = 24, 0.6 Hz, 2H), 5.56–5.67 (m, 1H), 6.13 (d, J = 1.2 Hz, 1H), 7.33 (dd, J = 8.4, 1.2 Hz, 1H), 7.51 (dd, J = 8.4, 1.2 Hz, 1H), 7.76 (dd, J = 8.1, 1.5 Hz, 1H), 8.08 (dd, J = 8.1, 1.5 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 31.7, 45.7, 57.9, 119.2, 125.8, 126.2, 129.3, 130.5, 134.5, 136.2, 147.0, 172.0; LRMS: 265.1 (M + 1), HRMS calcd for C₁₂H₁₃N₂O₃S (MH⁺): 265.0647, found: 265.0645; (b) General procedure for the preparation of 6-(halomethylene)-5,6,7,11b-tetrahydrobenzo[f]thiazolo-[3,2-d][1,4]diazepin-3(2H)-one 7a–d: to a solution of compound 5b (0.1 g, 0.429 mmol, 1 equiv.) in DCM (10 ml) was added iodine (0.120 g, 0.472 mmol, 1.1 equiv.). The reaction was stirred for 20 minutes. This was followed by addition of K₂CO₃ (0.148 g, 1.07 mmol, 2.5 equiv.). The solution was stirred for 2 h. The progress of the reaction was monitored with the help of TLC taking 5b as the limiting reactant. After completion of the reaction, reaction mixture was diluted with DCM and washed with Na₂S₂O₃ and water solution followed by brine solution. The organic layer was dried over anhydrous Na₂SO₄ and solvent was evaporated. The crude product obtained after evaporation was purified via silica gel column chromatography using 25–30% mixture of ethyl acetate in hexane as eluent, to get 7a as pure compound. 6-(Iodomethylene)-5,6,7,11b-tetrahydrobenzo[f]thiazolo-[3,2-d][1,4]diazepin-3(2H)-one (7a): pale yellow solid; yield: 0.131 mg, 86%; mp: 140–144 °C; ¹H NMR (300 MHz, CDCl₃): δ 3.73–3.80 (m, 2H), 3.89 (dd, J = 15.6, 1.2 Hz, 1H), 4.03 (bs, 1H), 4.67 (dd, J = 15.6, 1.2 Hz, 1H), 5.79 (s, 1H), 6.71–6.81 (m, 2H), 7.02 (dd, J = 7.5, 1.2 Hz, 1H), 7.14 (s, 1H), 7.15–7.21 (m, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 33.1, 52.8, 56.7, 83.9, 96.8, 117.9, 119.3, 130.6, 142.1, 145.6, 171.1 ; LRMS: 358.8 (M + 1), HRMS calcd for C₁₂H₁₂IN₂OS (MH⁺): 358.9715, found: 358.9715.
14. See ESI† for data of 4a–d, 5a–d and 6a–c & 7a–d.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra23493c

---