An Environmentally Friendly Synthesis of Michler’s Ketone Analogues in Water

Abstract

An environmentally friendly method for the synthesis of a series of novel, unsymmetrical Michler’s ketone analogues, [4-(dialkylamino)phenyl](aryl)methanones, via nucleophilic aromatic substitution of (fluorophenyl)(aryl)methanones with various amines in water­ is described. The reaction products are formed in high yields and additional purification is not required. The aqueous solvent and unreacted amines can be recycled.

Michler’s ketone, 4,4′-bis(dimethylamino)benzophenone, was originally synthesized by Michler from N,N-dimethylaniline and phosgene. [¹] This particular ketone and its analogs are used in the production of cyanine and triarylmethane dyes and pigments, [²] photochromic naphthopyrans, [³] sensitizers [4] or photoinitiators for polymerization, [5] and are widely studied for their xerographic properties. [6] Some of the dyes prepared from Michler’s ketone find application in medicine as cholinesterase inhibitors [7] and antitumor agents. [8]

Michler’s ketone and its analogues are synthesized mainly by the reaction of halobenzophenones with secondary amines. Such nucleophilic substitution reactions in aromatic compounds are usually carried out in polar aprotic solvents (DMSO or tetramethylene sulfone, [9] DMF, [¹0] MeCN [¹¹] ) or in the amine itself. [¹²] The reaction gives the expected arylamines in higher yields when carried out at high pressure. [¹³] There is also a catalytic variant of the reaction. [¹4] All these methods utilize rather hazardous and toxic solvents and/or catalysts that are incompatible with regards to green chemistry. [¹5] [¹6]

In continuation of our studies [¹7] on the synthesis of new dyes including photochromic compounds, we have developed an environmentally friendly method for the formation of diarylketones bearing dialkylamino groups which can serve as starting materials for the preparation of various dyes including photochromic naphthopyrans. The method involves the reaction of fluorobenzophenones with secondary amines in water (Scheme  [¹] , Table  [¹] ).

It is known that this type of reaction occurs via an S_NAr (addition-elimination) mechanism [¹8] [¹9] (Scheme  [²] ).

In most cases of such nucleophilic substitution reactions, sodium or potassium carbonate, triethylamine or 1,4-di­aza­bicyclo[2.2.2]octane are utilized as bases. [¹9] We found that in this reaction the amine plays the role of both nucleophile and base. A four-fold excess of the amine leads to a significant increase in the reaction rate and target product yields. Another advantage of using the amine as the base in this process is the ability to recover any unreacted amine thereby reducing waste. Thus, after work-up of the reaction mixture and removal of the product by filtration, the mother liquor can be treated with aqueous sodium bicarbonate solution and the resulting suspension of amine in water can be reused.

Table 1 Nucleophilic Substitution of the Fluorine Atom in Benzophenones with Secondary Amines in Water (continued)

Entry	Substrate	Product	Yield (%)
1	1a	2a	96
2	1b	2b	88
3	1b	2c	90
4	1c	2d	93
5	1d	2e	81
6	1c	2f	98
7	1c	2g	95
8	1c	2h	99
9	1e	2i	83
10	1f	2j	96
11	1g	2k	90
12	1h	2l	80

The use of water as a solvent not only makes these reaction conditions more environmentally friendly, but in many cases, shows significant beneficial effects in terms of the reaction rates and selectivity. [²0] An important role is played by ‘on water’ processes where the reactants are not soluble in water. [²0a] There are several examples of using water as the solvent in nucleophilic substitution in aromatics, [²¹] and in these cases, the reaction rate increased compared to those in other polar solvents.

In conclusion, we have developed an environmentally friendly method for the preparation of Michler’s ketone and its analogues in excellent yields and high purities under mild reaction conditions.

Commercially available reagents (Acros or Merck) were used. Melting points were measured on a Boetius hot stage apparatus and are uncorrected. Benzophenones 1 were prepared by acylation of the appropriate arene with 2- or 4-fluorobenzoyl chloride according to literature procedures. [²²] [4-(2,3-Dihydroindol-1-yl)phenyl](4-fluorophenyl)methanone was synthesized by reaction of 4,4′-difluorobenzophenone with indoline and NaH in DMSO. [²³] ^¹H NMR spectra were recorded on a Bruker AM-300 spectrometer. Mass spectra were obtained on a Kratos mass spectrometer (70 eV) with direct sample injection into the ion source. Microanalyses were obtained using a PerkinElmer 2400 Series II CHNS/O Elemental Analyzer. Petroleum ether (PE) refers to the fraction boiling in the 40-70 ˚C range.

Michler’s Ketone Analogues; General Procedure

A mixture of 2- or 4-fluorobenzophenone 1 (5 mmol), secondary amine [20 mmol (40 mmol in the case of morpholine)] and H₂O (5 mL) was heated at reflux temperature for 30 h and then poured into cold H₂O (250 mL). The progress of the reaction was monitored by TLC (eluent: PE-EtOAc, 3:1). The resulting solid precipitate was isolated by filtration, washed with H₂O (50 mL) and PE (50 mL), and dried.

Bis[4-(piperidin-1-yl)phenyl]methanone (2a)

Yellowish powder; yield: 1.7 g (96%); mp 151.5-152.5 ˚C (PE) (Lit. [9a] 152 ˚C).

^¹H NMR (300 MHz, CDCl₃): δ = 1.60-1.76 (m, 12 H, 6 × CH₂), 3.35 (t, J = 5.1 Hz, 8 H, 4 × CH₂), 6.89 (d, J = 8.8 Hz, 4 H, ArH), 7.75 (d, J = 8.8 Hz, 4 H, ArH).

(4-Methoxyphenyl)[4-(piperidin-1-yl)phenyl]methanone (2b)

White powder; yield: 1.3 g (88%); mp 109-110 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.60-1.77 (m, 6 H, 3 × CH₂), 3.37 (t, J = 5.5 Hz, 4 H, 2 × CH₂), 3.88 (s, 3 H, CH₃), 6.89 (d, J = 8.8 Hz, 2 H, ArH), 6.96 (d, J = 8.8 Hz, 2 H, ArH), 7.72-7.82 (m, 4 H, ArH).

MS (EI, 70 eV): m/z (%) = 295 (56) [M]⁺, 280 (77) [M - Me]⁺, 264 (48) [M - OMe]⁺, 188 (100).

Anal. Calcd for C₁₉H₂₁NO₂: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.41; H, 7.13; N, 4.61.

[4-(Azepan-1-yl)phenyl](4-methoxyphenyl)methanone (2c)

Yellow powder; yield: 1.4 g (90%); mp 85-86 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.50-1.64 (m, 4 H, 2 × CH₂), 1.75-1.89 (m, 4 H, 2 × CH₂), 3.54 (t, J = 5.9 Hz, 4 H, 2 × CH₂), 3.88 (s, 3 H, CH₃), 6.69 (d, J = 8.8 Hz, 2 H, ArH), 6.96 (d, J = 8.8 Hz, 2 H, ArH), 7.72-7.82 (m, 4 H, ArH).

MS (EI, 70 eV): m/z (%) = 309 (67) [M]⁺, 294 (58) [M - Me]⁺, 278 (39) [M - OMe]⁺, 202 (100).

Anal. Calcd for C₂₀H₂₃NO₂: C, 77.64; H, 7.49; N, 4.53. Found: C, 77.33; H, 7.51; N, 4.65.

(2,4-Dimethoxyphenyl)(4-morpholinophenyl)methanone (2d)

White powder; yield: 1.5 g (93%); mp 86-87 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 3.29 (t, J = 5.1 Hz, 4 H, 2 × CH₂), 3.68 (s, 3 H, CH₃), 3.73 (t, J = 5.1 Hz, 4 H, 2 × CH₂), 3.84 (s, 3 H, CH₃), 6.62 (dd, J = 2.2, 8.1 Hz, 1 H, ArH), 6.67 (d, J = 2.2 Hz, 1 H, ArH), 6.95 (d, J = 8.8 Hz, 2 H, ArH), 7.19 (d, J = 8.1 Hz, 1 H, ArH), 7.57 (d, J = 8.8 Hz, 2 H, ArH).

MS (EI, 70 eV): m/z (%) = 327 (100) [M]⁺, 312 (78) [M - Me]⁺, 296 (44) [M - OMe]⁺.

Anal. Calcd for C₁₉H₂₁NO₄: C, 69.71; H, 6.47; N, 4.28. Found: C, 69.81; H, 6.45; N, 4.44.

(2,4-Dimethoxyphenyl)(2-morpholinophenyl)methanone (2e)

Yellow powder; yield: 1.3 g (81%); mp 82-83 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 2.87 (t, J = 4.6 Hz, 4 H, 2 × CH₂), 3.34 (t, J = 4.6 Hz, 4 H, 2 × CH₂), 3.60 (s, 3 H, CH₃), 3.86 (s, 3 H, CH₃), 6.42 (d, J = 2.0 Hz, 1 H, ArH), 6.50 (dd, J = 2.2, 8.5 Hz, 1 H, ArH), 6.96 (d, J = 7.9 Hz, 1 H, ArH), 7.07 (t, J = 7.2 Hz, 1 H, ArH), 7.35-7.47 (m, 2 H, ArH), 7.55 (d, J = 8.5 Hz, 2 H, ArH).

MS (EI, 70 eV): m/z (%) = 327 (100) [M]⁺, 312 (63) [M - Me]⁺, 296 (56) [M - OMe]⁺.

Anal. Calcd for C₁₉H₂₁NO₄: C, 69.71; H, 6.47; N, 4.28. Found: C, 69.99; H, 6.37; N, 3.96.

(2,4-Dimethoxyphenyl)[4-(piperidin-1-yl)phenyl]methanone (2f)

White powder; yield: 1.6 g (98%); mp 112-113 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.60-1.75 (m, 6 H, 3 × CH₂), 3.30-3.42 (m, 4 H, 2 × CH₂), 3.74 (s, 3 H, CH₃), 3.86 (s, 3 H, CH₃), 6.50-6.56 (m, 2 H, ArH), 6.82 (d, J = 8.5 Hz, 2 H, ArH), 7.30 (d, J = 9.2 Hz, 1 H, ArH), 7.73 (d, J = 8.5 Hz, 2 H, ArH).

MS (EI, 70 eV): m/z (%) = 325 (100) [M]⁺, 310 (54) [M - Me]⁺, 294 (47) [M - OMe]⁺.

Anal. Calcd for C₂₀H₂₃NO₃: C, 73.82; H, 7.12; N, 4.30. Found: C, 74.09; H, 7.24; N, 4.47.

(2,4-Dimethoxyphenyl)[4-(pyrrolidin-1-yl)phenyl]methanone (2g)

Yellowish powder; yield: 1.5 g (95%); mp 129-130 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.95-2.09 (m, 4 H, 2 × CH₂), 3.28-3.42 (m, 4 H, 2 × CH₂), 3.74 (s, 3 H, CH₃), 3.86 (s, 3 H, CH₃), 6.44-6.57 (m, 4 H, ArH), 7.28 (d, J = 7.9 Hz, 1 H, ArH), 7.74 (d, J = 8.5 Hz, 2 H, ArH).

MS (EI, 70 eV): m/z (%) = 311 (60) [M]⁺, 296 (100) [M - Me]⁺, 174 (57).

Anal. Calcd for C₁₉H₂₁NO₃: C, 73.29; H, 6.80; N, 4.50. Found: C, 73.41; H, 6.73; N, 4.30.

[4-(Azepan-1-yl)phenyl](2,4-dimethoxyphenyl)methanone (2h)

Yellowish powder; yield: 1.7 g (99%); mp 98-99 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.47-1.63 (m, 4 H, 2 × CH₂), 1.69-1.88 (m, 4 H, 2 × CH₂), 3.51 (t, J = 6.2 Hz, 4 H, 2 × CH₂), 3.74 (s, 3 H, CH₃), 3.85 (s, 3 H, CH₃), 6.47-6.56 (m, 2 H, ArH), 6.62 (d, J = 9.0 Hz, 2 H, ArH), 7.27 (d, J = 9.0 Hz, 1 H, ArH), 7.72 (d, J = 9.0 Hz, 2 H, ArH).

MS (EI, 70 eV): m/z (%) = 339 (66) [M]⁺, 324 (100) [M - Me]⁺, 308 (68) [M - OMe]⁺.

Anal. Calcd for C₂₁H₂₅NO₃: C, 74.31; H, 7.42; N, 4.13. Found: C, 74.24; H, 7.39; N, 4.51.

Naphthalen-1-yl[4-(piperidin-1-yl)phenyl]methanone (2i)

Yellowish powder; yield: 1.3 g (83%); mp 78-79 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.64-1.73 (m, 6 H, 3 × CH₂), 3.35-3.43 (m, 4 H, 2 × CH₂), 6.83 (d, J = 9.2 Hz, 2 H, ArH), 7.44-7.56 (m, 4 H, ArH), 7.78 (d, J = 9.2 Hz, 2 H, ArH), 7.88-8.03 (m, 3 H, ArH).

MS (EI, 70 eV): m/z (%) = 315 (100) [M]⁺.

Anal. Calcd for C₂₂H₂₁NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.86; H, 6.68; N, 4.26.

(4-Hydroxy-2-isopropoxyphenyl)[4-(piperidin-1-yl)phenyl]methanone (2j)

Yellow powder; yield: 1.6 g (96%); mp 103.5-104.5 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.38 (d, J = 6.2 Hz, 6 H, 2 × CH₃), 1.64-1.76 (m, 6 H, 3 × CH₂), 3.37 (t, J = 5.1 Hz, 4 H, 2 × CH₂), 4.63 (sept, J = 6.2 Hz, 1 H, CH), 6.38 (dd, J = 2.2, 8.8 Hz, 1 H, ArH), 6.49 (d, J = 2.2 Hz, 1 H, ArH), 6.91 (d, J = 8.8 Hz, 2 H, ArH), 7.57-7.68 (m, 3 H, ArH), 12.51 (br s, 1 H, OH).

MS (EI, 70 eV): m/z (%) = 339 (69) [M]⁺, 296 (20) [M - iPr]⁺, 161 (100).

Anal. Calcd for C₂₁H₂₅NO₃: C, 74.31; H, 7.42; N, 4.13. Found: C, 74.22; H, 7.48; N, 4.07.

(4-Morpholinophenyl)(thien-2-yl)methanone (2k)

Yellow powder; yield: 1.2 g (90%); mp 122-123 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 3.32 (t, J = 5.0 Hz, 4 H, 2 × CH₂), 3.87 (t, J = 5.0 Hz, 4 H, 2 × CH₂), 6.92 (d, J = 9.1 Hz, 2 H, ArH), 7.15 (dd, J = 3.9, 5.3 Hz, 1 H, ArH), 7.63-7.68 (m, 2 H, ArH), 7.89 (d, J = 9.1 Hz, 2 H, ArH).

MS (EI, 70 eV): m/z (%) = 273 (100) [M]⁺.

Anal. Calcd for C₁₅H₁₅NO₂S: C, 65.91; H, 5.53; N, 5.12. Found: C, 66.03; H, 5.57; N, 5.33.

[4-(Azepan-1-yl)phenyl][4-(2,3-dihydroindol-1-yl)phenyl]methanone (2l)

Yellow powder; yield: 1.6 g (80%); mp 133-134 ˚C (PE).

^¹H NMR (300 MHz, CDCl₃): δ = 1.53-1.61 (m, 4 H, 2 × CH₂), 1.77-1.89 (m, 4 H, 2 × CH₂), 3.18 (t, J = 8.3 Hz, 2 H, CH₂), 3.55 (t, J = 5.9 Hz, 4 H, 2 × CH₂), 4.04 (t, J = 8.3 Hz, 2 H, CH₂), 6.71 (d, J = 8.8 Hz, 2 H, ArH), 6.84 (t, J = 7.3 Hz, 1 H, ArH), 7.14 (d, J = 7.8 Hz, 1 H, ArH), 7.19-7.29 (m, 3 H, ArH), 7.32 (d, J = 7.8 Hz, 1 H, ArH), 7.77-7.87 (m, 4 H, ArH).

MS (EI, 70 eV): m/z (%) = 396 (100) [M]⁺.

Anal. Calcd for C₂₇H₂₈N₂O: C, 81.78; H, 7.12; N, 7.06. Found: C, 81.91; H, 7.06; N, 7.23.

Acknowledgment

This work was financially supported by the Russian Foundation for Basic Research (RFBR Grant - 11-03-00799) and the Russian Academy of Sciences (Program No. 22).

References

• 1 Michler W. Ber. Dtsch. Chem. Ges.  1876,  9:  716 
  Search in Google Scholar
• 2a Noack A. Schröder A. Hartmann H. Dyes Pigm.  2002,  57:  131 
  Search in Google Scholar
• 2b Landl M. imon P. Kvasnik F. Sens. Actuators, B  1998,  51:  114 
  Search in Google Scholar
• 3 Van Gemert B. Benzo and Naphthopyrans (Chromenes), In Organic Photochromic and Thermochromic Compounds   Vol. 1:  Crano JC. Guglielmetti R. Plenum Press; New York: 1999.  p.111-140  
  Search in Google Scholar
• 4a Reilly LW. inventors; US Patent  4507497.  ; Chem. Abstr. 1985, 103, 79453
• 4b Kuesters W, Heil G, Fischer M, Eisert M, and Kast H. inventors; US Patent  4147604.  ; Chem. Abstr. 1979, 90, 188700
• 5a Onen A. Yagci Y. Polymer  2001,  42:  6681 
  Search in Google Scholar
• 5b Zheng M. Yang M. Liu S. Zhang L. Chin. J. Polym. Sci.  1995,  13:  74 
  Search in Google Scholar
• 5c Wan T. Wang X. Yi Y. He W. Polym. Int.  2006,  55:  1413 
  Search in Google Scholar
• 6a Pillai PKC. Tripathi AK. Narula GK. Mendiratta RG. J. Mater. Sci.  1982,  17:  3017 
  Search in Google Scholar
• 6b Pillai PKC. Shroff N. Tripathi AK. J. Electrostat.  1985,  17:  269 
  Search in Google Scholar
• 6c . Pillai PKC. J. Mater. Sci.  1983,  18:  3456 
  Search in Google Scholar
• 7 Küçükkilinça T. Özer . Arch. Biochem. Biophys.  2005,  440:  118 
  Search in Google Scholar
• 8 Arbiser JL. inventors; US Patent  20100160296.  ; Chem. Abstr. 2010, 153, 126301
• 9a Spange S. El-Sayed M. Mueller H. Rheinwald G. Lang H. Poppitz W. Eur. J. Org. Chem.  2002,  4159 
• 9b Magdolen P. Mečiarová M. Toma Š. Tetrahedron  2001,  57:  4781 
  Search in Google Scholar
• 9c Sanguinet L. Twieg RJ. Wiggers G. Mao G. Singer KD. Petschek RG. Tetrahedron Lett.  2005,  46:  5121 
  Search in Google Scholar
• 9d Gorman SA. Hepworth JD. Mason D. J. Chem. Soc., Perkin Trans. 2  2000,  1889 
• 10a Mishra N. Arora P. Kumar B. Mishra LC. Bhattacharya A. Awasthi SK. Bhasin VK. Eur. J. Med. Chem.  2008,  43:  1530 
  Search in Google Scholar
• 10b Hendrickx E. Zhang Y. Ferrio KB. Herlocker JA. Anderson JV. Armstrong NR. Mash EA. Persoons AP. Peyghambarian N. Kippelen B. J. Mater. Chem.  1999,  9:  2251 
  Search in Google Scholar
• 11a Taylor EC. Skotnicki JS. Synthesis  1981,  606 
• 11b Annoura H. Nakanishi K. Toba T. Takemoto N. Imajo S. Miyajima A. Tamura-Horikawa Y. Tamura S. J. Med. Chem.  2000,  43:  3372 
  Search in Google Scholar
• 12a Gabbutt CD. Heron BM. Instone AC. Horton PN. Hursthouse MB. Tetrahedron  2005,  61:  463 
  Search in Google Scholar
• 12b Tian W. inventors; US Patent  20030171581.  ; Chem. Abstr. 2001, 135, 371752
• 13 Kotsuki H. Kobayashi S. Matsumoto K. Suenaga H. Nishizawa H. Synthesis  1990,  1147 
• 14a Van Baelen G. Maes BUW. Tetrahedron  2008,  64:  5604 
  Search in Google Scholar
• 14b Lee BK. Biscoe MR. Buchwald SL. Tetrahedron Lett.  2009,  50:  3672 
  Search in Google Scholar
• 14c Kuntz J.-F. Schneider R. Walcarius A. Fort Y. Tetrahedron Lett.  2005,  46:  8793 
  Search in Google Scholar
• 14d Witulski B. Synlett  1999,  1223 
• 15a Anastas P. Eghbali N. Chem. Soc. Rev.  2010,  39:  301 
  Search in Google Scholar
• 15b Cue BW. Zhang J. Green Chem. Lett. Rev.  2009,  2:  193 
  Search in Google Scholar
• 15c Horváth IT. Anastas PT. Chem. Rev.  2007,  107:  2167 
  Search in Google Scholar
• 15d Alfonsi K. Colberg J. Dunn PJ. Fevig T. Jennings S. Johnson TA. Kleine HP. Knight C. Nagy MA. Perry DA. Stefaniak M. Green Chem.  2008,  10:  31 
  Search in Google Scholar
• 16 Faust A. Wolff O. Waldvogel SR. Synthesis  2009,  155 
• 17a Shirinian VZ. Shimkin AA. Tipikin SN. Krayushkin MM. Synthesis  2009,  3803 
• 17b Shirinian VZ. Shimkin AA. Mailian AK. Tsyganov DV. Popov LD. Krayushkin MM. Dyes Pigm.  2009,  84:  19 
  Search in Google Scholar
• 17c Besugliy SO. Metelitsa AV. Shirinian VZ. Krayushkin MM. Nikalin DM. Minkin VI. J. Photochem. Photobiol. A: Chem.  2009,  206:  116 
  Search in Google Scholar
• 18 Schlosser M. Ruzziconi R. Synthesis  2010,  2111 
• 19 Crampton MR. In Organic Reaction Mechanisms 1998   Knipe AC. John Wiley & Sons; New York: 2002.  Chap. 7. p.275-286  
• 20a Chanda A. Fokin VV. Chem. Rev.  2009,  109:  725 
  Search in Google Scholar
• 20b Horváth IT. Green Chem.  2008,  10:  1024 
  Search in Google Scholar
• 20c Li C.-J. Chem. Rev.  2005,  105:  3095 
  Search in Google Scholar
• 20d Lindström UM. Chem. Rev.  2002,  102:  2751 
  Search in Google Scholar
• 21a Mokrushina GA. Kotovskaya SK. Baskakova ZM. Petrova GM. Kolmakova TV. Charushin VN. Rusinov VL. Chupakhin ON. Pharm. Chem. J.  1996,  30:  540 
  Search in Google Scholar
• 21b Lipford GB, and Zepp CM. inventors;  WO2008152471.  ; Chem. Abstr. 2008, 150, 56176
• 21c Rainville JP, Sinay TG, and Walinsky SW. inventors; US Patent  20030087914.  ; Chem. Abstr. 2003, 138, 205085
• 22 Dunlop RD. Gardner JH. J. Am. Chem. Soc.  1933,  55:  1665 
  Search in Google Scholar
• 23 Glamkowski EJ. Fortunato JM. Spaulding TC. Wilker JC. Ellis DB. J. Med. Chem.  1985,  28:  66 
  Search in Google Scholar

References

• 1 Michler W. Ber. Dtsch. Chem. Ges.  1876,  9:  716 
  Search in Google Scholar
• 2a Noack A. Schröder A. Hartmann H. Dyes Pigm.  2002,  57:  131 
  Search in Google Scholar
• 2b Landl M. imon P. Kvasnik F. Sens. Actuators, B  1998,  51:  114 
  Search in Google Scholar
• 3 Van Gemert B. Benzo and Naphthopyrans (Chromenes), In Organic Photochromic and Thermochromic Compounds   Vol. 1:  Crano JC. Guglielmetti R. Plenum Press; New York: 1999.  p.111-140  
  Search in Google Scholar
• 4a Reilly LW. inventors; US Patent  4507497.  ; Chem. Abstr. 1985, 103, 79453
• 4b Kuesters W, Heil G, Fischer M, Eisert M, and Kast H. inventors; US Patent  4147604.  ; Chem. Abstr. 1979, 90, 188700
• 5a Onen A. Yagci Y. Polymer  2001,  42:  6681 
  Search in Google Scholar
• 5b Zheng M. Yang M. Liu S. Zhang L. Chin. J. Polym. Sci.  1995,  13:  74 
  Search in Google Scholar
• 5c Wan T. Wang X. Yi Y. He W. Polym. Int.  2006,  55:  1413 
  Search in Google Scholar
• 6a Pillai PKC. Tripathi AK. Narula GK. Mendiratta RG. J. Mater. Sci.  1982,  17:  3017 
  Search in Google Scholar
• 6b Pillai PKC. Shroff N. Tripathi AK. J. Electrostat.  1985,  17:  269 
  Search in Google Scholar
• 6c . Pillai PKC. J. Mater. Sci.  1983,  18:  3456 
  Search in Google Scholar
• 7 Küçükkilinça T. Özer . Arch. Biochem. Biophys.  2005,  440:  118 
  Search in Google Scholar
• 8 Arbiser JL. inventors; US Patent  20100160296.  ; Chem. Abstr. 2010, 153, 126301
• 9a Spange S. El-Sayed M. Mueller H. Rheinwald G. Lang H. Poppitz W. Eur. J. Org. Chem.  2002,  4159 
• 9b Magdolen P. Mečiarová M. Toma Š. Tetrahedron  2001,  57:  4781 
  Search in Google Scholar
• 9c Sanguinet L. Twieg RJ. Wiggers G. Mao G. Singer KD. Petschek RG. Tetrahedron Lett.  2005,  46:  5121 
  Search in Google Scholar
• 9d Gorman SA. Hepworth JD. Mason D. J. Chem. Soc., Perkin Trans. 2  2000,  1889 
• 10a Mishra N. Arora P. Kumar B. Mishra LC. Bhattacharya A. Awasthi SK. Bhasin VK. Eur. J. Med. Chem.  2008,  43:  1530 
  Search in Google Scholar
• 10b Hendrickx E. Zhang Y. Ferrio KB. Herlocker JA. Anderson JV. Armstrong NR. Mash EA. Persoons AP. Peyghambarian N. Kippelen B. J. Mater. Chem.  1999,  9:  2251 
  Search in Google Scholar
• 11a Taylor EC. Skotnicki JS. Synthesis  1981,  606 
• 11b Annoura H. Nakanishi K. Toba T. Takemoto N. Imajo S. Miyajima A. Tamura-Horikawa Y. Tamura S. J. Med. Chem.  2000,  43:  3372 
  Search in Google Scholar
• 12a Gabbutt CD. Heron BM. Instone AC. Horton PN. Hursthouse MB. Tetrahedron  2005,  61:  463 
  Search in Google Scholar
• 12b Tian W. inventors; US Patent  20030171581.  ; Chem. Abstr. 2001, 135, 371752
• 13 Kotsuki H. Kobayashi S. Matsumoto K. Suenaga H. Nishizawa H. Synthesis  1990,  1147 
• 14a Van Baelen G. Maes BUW. Tetrahedron  2008,  64:  5604 
  Search in Google Scholar
• 14b Lee BK. Biscoe MR. Buchwald SL. Tetrahedron Lett.  2009,  50:  3672 
  Search in Google Scholar
• 14c Kuntz J.-F. Schneider R. Walcarius A. Fort Y. Tetrahedron Lett.  2005,  46:  8793 
  Search in Google Scholar
• 14d Witulski B. Synlett  1999,  1223 
• 15a Anastas P. Eghbali N. Chem. Soc. Rev.  2010,  39:  301 
  Search in Google Scholar
• 15b Cue BW. Zhang J. Green Chem. Lett. Rev.  2009,  2:  193 
  Search in Google Scholar
• 15c Horváth IT. Anastas PT. Chem. Rev.  2007,  107:  2167 
  Search in Google Scholar
• 15d Alfonsi K. Colberg J. Dunn PJ. Fevig T. Jennings S. Johnson TA. Kleine HP. Knight C. Nagy MA. Perry DA. Stefaniak M. Green Chem.  2008,  10:  31 
  Search in Google Scholar
• 16 Faust A. Wolff O. Waldvogel SR. Synthesis  2009,  155 
• 17a Shirinian VZ. Shimkin AA. Tipikin SN. Krayushkin MM. Synthesis  2009,  3803 
• 17b Shirinian VZ. Shimkin AA. Mailian AK. Tsyganov DV. Popov LD. Krayushkin MM. Dyes Pigm.  2009,  84:  19 
  Search in Google Scholar
• 17c Besugliy SO. Metelitsa AV. Shirinian VZ. Krayushkin MM. Nikalin DM. Minkin VI. J. Photochem. Photobiol. A: Chem.  2009,  206:  116 
  Search in Google Scholar
• 18 Schlosser M. Ruzziconi R. Synthesis  2010,  2111 
• 19 Crampton MR. In Organic Reaction Mechanisms 1998   Knipe AC. John Wiley & Sons; New York: 2002.  Chap. 7. p.275-286  
• 20a Chanda A. Fokin VV. Chem. Rev.  2009,  109:  725 
  Search in Google Scholar
• 20b Horváth IT. Green Chem.  2008,  10:  1024 
  Search in Google Scholar
• 20c Li C.-J. Chem. Rev.  2005,  105:  3095 
  Search in Google Scholar
• 20d Lindström UM. Chem. Rev.  2002,  102:  2751 
  Search in Google Scholar
• 21a Mokrushina GA. Kotovskaya SK. Baskakova ZM. Petrova GM. Kolmakova TV. Charushin VN. Rusinov VL. Chupakhin ON. Pharm. Chem. J.  1996,  30:  540 
  Search in Google Scholar
• 21b Lipford GB, and Zepp CM. inventors;  WO2008152471.  ; Chem. Abstr. 2008, 150, 56176
• 21c Rainville JP, Sinay TG, and Walinsky SW. inventors; US Patent  20030087914.  ; Chem. Abstr. 2003, 138, 205085
• 22 Dunlop RD. Gardner JH. J. Am. Chem. Soc.  1933,  55:  1665 
  Search in Google Scholar
• 23 Glamkowski EJ. Fortunato JM. Spaulding TC. Wilker JC. Ellis DB. J. Med. Chem.  1985,  28:  66 
  Search in Google Scholar