Download PDF
Synlett 2016; 27(20): 2795-2798
DOI: 10.1055/s-0036-1588595
letter
© Georg Thieme Verlag Stuttgart · New York

Zinc Chloride Catalyzed, Dipolar Aprotic Solvent-Mediated, One-Pot Synthesis of 2-[(Benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols

Vandana Cherkadu
a   Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India   Email: priyabs_chem@yahoo.com
b   R&D Centre, CJEX Biochem, 7&8, 2nd cross, Muniswamappa layout, Hosur Road, Bommanahalli, Bangalore 560 068, India
,
Praveen Kumar Kalavagunta
c   Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India
,
Narender Ravirala
c   Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India
,
Nanjunda Swamy Shivananju
d   Department of Biotechnology, Sri Jayachamarajendra College of Engineering, Mysore-570006, India
,
Babu Shubha Priya*
a   Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India   Email: priyabs_chem@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 05 July 2016

Accepted after revision: 27 August 2016

Publication Date:
08 September 2016 (online)

 
 PDF Download Permissions and Reprints All articles of this category


◊ Both the authors contributed equally.

Abstract

A three-component one-pot method has been developed for the synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols from a variety of aldehydes, 2-amino-1,3-benzothiazoles, and phenols. Phenol, substituted phenols, and polyhydroxybenzenes participated well, providing the corresponding derivatives in good yields. In the case of polyhydroxybenzenes, for which the formation of positional isomers or dimers might have been possible, the sterically less hindered positional isomer was formed exclusively via the ortho-quinone methide.


#

Key words

Betti bases - benzothiazoles - phenols - aldehydes - quinone methides

(Aminobenzyl)naphthols, known as Betti bases, were first synthesized by Mario Betti in 1900.[1] Since then, they have been extensively studied for their potential applications in synthetic chemistry, for example in asymmetric catalysis[2] or enantiomeric separations.[3] In recent years, there has been increasing research into the biological properties of Betti bases.[4] Despite the extensive research into Betti bases, most of the reported reactions for their preparation use 2-naphthol[4b] [c] , [5] as the phenol source. Even though there are reports on the use of other substrates, such as 3-hydroxyxanthone,[6] dibenzofuran-2-ol,[4a] [7] 1-naphthol,[8] naphthalenediols,[8] coumarins,[4e] [9] or quinolinols,[4d] [e] there are few reports on the use of phenols themselves in the formation of the corresponding Betti bases,[10] and screening for potential applications of these products has been limited.[10d]

Several natural and synthetic (aminomethyl)phenols display potential biological properties. 2-(Aminomethyl)phenol itself has potential biological properties.[11] The compound o-topolin (Figure [1]) and several of its derivatives are known to have multiple biological activities.[12]

Zoom Image
Figure 1 Structures of natural and synthetic (aminomethyl)phenols with biological activities

Similarly, there exist several synthetic derivatives that have antifungal,[13] anti-HIV,[14] antihypertensive,[15] antitubercular,[16] or antiamastigote[17] properties. Members of this class that have commercial applications include EDDHA,[18] olomoucine II,[19] lavendustin C,[20] adaphostin,[21] tyrphostin AG 957,[21] [22] and benserazide[23] (Figure [1]); several of these compounds have two or more phenolic protons.

We previously designed and synthesized naphthopyranopyrimidines[24] and 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]naphthols to study their biological and agrochemical properties.[4b] [c] The naphthopyranopyrimidines were found to have antibacterial and antifungal properties,[25] whereas the 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]naphthols were found to have angiotensin-converting enzyme (ACE) and calcium channel blocker (CCB) dual inhibition,[4b] antifeedant and insecticidal,[4c] antimosquito,[4f] or antimicrobial[5f] properties.

In a continuation of our efforts to develop compounds that display novel ACE and CCB dual inhibitory properties to control hypertension, or which have other potential applications, we considered 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols. There are a few reports of syntheses of (aminobenzyl)phenols[10] and a single report of a synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenol.[10f] However, the reaction required an elevated temperature (90 °C), a long reaction time (24 h), and a large excess of catalyst (71 equiv LiCl). The reaction also had a limited substrate scope: phenol and 4-methoxyphenol gave only traces of the expected products, even after 24 hours.[10f] Consequently, higher-order phenols such as catechol, resorcinol, and pyrogallol were not investigated. We therefore decided to develop a novel method for the synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols by condensing a variety of phenols with aromatic aldehydes and 2-amino-1,3-benzothiazoles.

Building on our previous experience in carrying out quinone methide (QM)-based multicomponent reactions,[4b] [c] , [6] [24] we initially attempted a solvent- and catalyst-free synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols from 4-chlorophenol, 2-amino-1,3-benzothiazole, and p-anisaldehyde at 120 °C for three hours. 4-Chlorophenol was specifically chosen to avoid any ambiguity in assigning the structure of the product, i.e. whether the product was formed via an o-QM or a p-QM. The expected product was formed, but the yield was very low (<10%). The product and 2-amino-1,3-benzothiazole were found to have almost same Rf value in TLC, as a result of which purification losses were heavy. The use of 0.9 equivalents of 2-amino-1,3-benzothiazole provided a slightly improved yield and simpler purification. Longer heating was found to cause extensive decomposition. To understand the effect of the solvent on the formation of product, we carried out the reaction in various solvents, and found that DMF and DMSO were the best solvents (Supporting Information, Tables S1 and S2), followed by xylene. The yields in refluxing protic solvents such as MeOH or EtOH were very low. However, because of the potential health risks associated with DMF[26] and DMSO,[27] the alternative solvent piperylene sulfone[28] can be used if larger-scale reactions are required.

To improve the yield, we examined the reaction in DMSO with various catalysts and we found that ZnCl2,[29] ­FeCl3, or molecular iodine were almost equally effective, with a very small difference in yields (Supporting Information, Table S3). Because of the better catalytic activity and the low byproduct formation, we chose 10 mol% of ZnCl2 in DMSO as a suitable catalyst/solvent system to carry out the reactions. A series of reactions performed over a range of temperatures, showed that 110 °C is the optimal temperature to carry out the reaction (Supporting Information, Table S4). The reaction was found to proceed well with a variety of substituents on the phenol and aldehyde, including halo, alkyl, alkoxy, or even nitro groups (Scheme [1] and Table [1]).

Zoom Image
Scheme 1

Table 1 Scope of the Reaction (Phenols and Aldehydes)a

Entry

Product

R

R′

R′′

Yield (%)

 1

4a

3-Cl

4-Br

H

67

 2

4b

2-NO2

4-Br

H

54

 3

4c

3-Cl

4-NO2

H

59

 4

4d

2-NO2

4-NO2

H

61

 5

4e

4-OMe

4-Cl

H

65

 6

4f

4-NO2

4-Cl

H

55

 7

4g

4-OMe

4-OMe

H

52

 8

4h

4-Cl

4-OMe

H

63

 9

4i

4-NO2

4-OMe

H

54

10

4j

4-OMe

4-NO2

H

57

11

4k

4-OMe

2,3-Me2

H

53

12

4l

4-OMe

4-t-Bu

H

58

13

4m b

2,4-Cl2

4-NO2

H

47

a Reaction conditions: ZnCl2 (10 mol%), DMSO (1 mL), 110 °C.

b Urea was used instead of 2-amino-1,3-benzothiazole.

We next considered reactions with phenol itself, as this can form either an o-QM or a p-QM, and so the formation of mixtures of products should be possible. We chose 2,4-dichlorobenzaldehyde as the aldehyde substrate to simplify the analysis of the product by 1H NMR spectroscopy. The product was found to be formed via the o-QM (Table [2], entry 1; see also the Supporting Information). For catechol, resorcinol, and phloroglucinol, which have more than one phenolic proton, there was a possibility for the formation of positional isomers or even dimers. However, the reactions with catechol, resorcinol, hydroquininone, and pyrogallol proceeded well under the same conditions, but with different reaction times (Table [2]).

Table 2 Reaction of Phenol or Polyhydroxybenzenes with 2,4-Dichlorobenzaldehyde and 2-Amino-1,3-benzothiazoles

Entry

Product

R

R′

R′′

Time

Yield %

1

4n

H

2,4-Cl2

H

 7 h

41

2

4o

1,2-(OH)2

2,4-Cl2

H

 7 h

54

3

4p

1,3-(OH)2

2,4-Cl2

H

15 min

28a

4

4q

1,4-(OH)2

2,4-Cl2

H

 6 h

58

5

4r

1,2,3-(OH)3

2,4-Cl2

6-NO2

 1 h

46

6

4s

1,3,5-(OH)3

2,4-Cl2

H

 3–7 h

–b

a The reaction was complete in just 15 min. Further heating resulted in the formation of impurities.

b Even with different amounts of phloroglucinol (1.0, 0.66, or 0.33 equiv), the product was not isolable.

In all the above cases, the sterically less hindered positional isomer was formed exclusively via the o-quinone methide, and no dimers were formed. The structures of the products were confirmed by spectroscopic analysis. For a description of the structural assignment, see the Supporting Information. However, the reaction with phloroglucinol did not proceed as expected; instead, decomposition occurred and no product was isolable (Table [2], entry 6). In the case of the phenols and polyhydroxybenzenes, the yields were relatively low compared with those of their 2-naphthol counterparts. This can be attributed to the facts that the products and 2-amino-1,3-benzothiazole have almost the same Rf on TLC and that both have comparable solubilities in various solvents, whereas in the case of the reactions of 2-naphthol, purification by column chromatography is not required. The products were fully characterized by means of 1H and 13C NMR, IR, ESI, and HRMS analysis (see Supporting Information). The structure of 4f was confirmed by single-crystal X-ray diffraction.[30] The ORTEP diagram of compound 4f is shown in Figure [2].

Zoom Image
Figure 2 ORTEP diagram of 2-[(benzo[d]thiazol-2-ylamino)(4-nitrophenyl)methyl]-4-chlorophenol (4f)

The protocol was successfully applied with urea as a substrate to give N-[(2,4-dichlorophenyl)(2-hydroxy-5-nitrophenyl)methyl]urea (4m) in 47% yield (Table [1], entry 13). However, reactions with an aliphatic aldehyde (isovaleraldehyde) or a conjugated aromatic aldehyde (cinnamaldehyde) were not fruitful.

In summary, we have developed a protocol using ZnCl2 in DMF or DMSO as a suitable catalyst system for the synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols by condensing a variety of phenols, aromatic aldehydes, and 2-amino-1,3-benzothiazoles.[31] The method is also applicable to a variety of polyhydroxybenzenes. Unlike an earlier report,[10f] reactions with simple or alkoxy phenols proceeded smoothly, forming the corresponding Betti bases in moderate to good yields.


#

Acknowledgment

C.V. is grateful to the management at CJEX Biochem, Bangalore, for their continuous support for this work. B.S.P. is grateful for financial assistance from SERB-India vide No: SB/FT/LS-297/2012 and UGC-India, under UGC-MRP vide No. F. No: 41/224/2012 (SR). P.K. is grateful to the CSIR, India, for the award of a senior research fellowship.

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0036-1588595.
  • Supporting Information

  • References and Notes

  • 6 Cherkadu V, Kalavagunta PK, Ningegowda M, Shivananju NS, Madegowda M, Priya BS. Synlett 2016; 27: 1116
    Thieme ConnectSearch in Google Scholar
  • 8 Olyaei A, Zarnegar M, Sadeghpour M, Rezaei M. Lett. Org. Chem. 2012; 9: 451
    CrossrefSearch in Google Scholar
    • 12a Szucova L, Zatloukal M, Spichal L, Voller J, Dolezal K, Strnad M, Massino FJ. US 2009170879, 2009
    • 12b Uksova K, Havlicek L, Krystof V, Lenobel R, Strnad M. WO 2004018473, 2004
    • 12c Shi J, Zhang J, Yue Z, Li M, Zhu C, Zhang Y, Zi J, Wang Y, Fan X, Xu R, Lin S, Li Y, Yang Y, Sheng L. EP 2511283, 2012
    • 12d Dolezal K, Popa I, Zatloukal M, Lenobel R, Hradecká D, Vojtesek B, Uldrijan S, Mlejnek P, Werbrouck S, Strnad M. WO 2004058791, 2004
    • 12e Shi J, Zhang J, Yue Z, Li M, Zhu C, Zhang Y, Zi J, Wang Y, Fan X, Xu R, Lin S, Li Y, Yang Y, Sheng L. US 2013045942, 2013
    • 13a Agliardi S, Del Sordo S, Mailland F, Legora M. WO 2011080265, 2011
    • 13b Agliardi S, Del Sordo S, Mailland F, Legora M. EP 2345642, 2011
    • 14a Zhao Z, Wolkenberg SE, Lu M, Munshi V, Moyer G, Feng M, Carella AV, Ecto LT, Gabryelski LJ, Lai M.-T, Prasad SG, Yan Y, McGaughey GB, Miller MD, Lindsley CW, Hartman GD, Vacca JP, Williams TM. Bioorg. Med. Chem. Lett. 2008; 18: 554
      CrossrefSearch in Google Scholar
    • 14b Wolkenberg SE, Zhao Z, Lindsley C. WO 2007002368, 2007
    • 15a Silverman RB, Xue F. US 2012088798, 2012
    • 15b Labby KJ, Xue F, Kraus JM, Ji H, Mataka J, Li H, Martásek P, Roman LJ, Poulos TL, Silverman RB. Bioorg. Med. Chem. 2012; 20: 2435
      CrossrefPubMedSearch in Google Scholar
    • 15c Calderone V, Fiamingo FL, Amato G, Giorgi I, Livi O, Martelli A, Martinotti E. Eur. J. Med. Chem. 2008; 43: 2618
      CrossrefPubMedSearch in Google Scholar
    • 15d Pajouhesh H, Kaul R, Grimwood M, Tan J, Zhou Y. US 2009298834, 2009
    • 15e Kuehnert S, Merla B, Bahrenberg G, Schroeder W. US 2010234429, 2010
    • 15f Harris RN. III, Repke DB, Walker KA. M. US 2012157494, 2012
  • 17 Jorda R, Sacerdoti-Sierra N, Voller J, Havlíček L, Kráčalíková K, Nowicki MW, Nasereddin A, Kryštof V, Strnad M, Walkinshaw MD, Jaffe CL. Bioorg. Med. Chem. Lett. 2011; 21: 4233
    CrossrefSearch in Google Scholar
  • 19 Nimmrich V, Barghorn S, Ebert U, Hillen H, Gross G, Draguhn A, Bruehl C, Grimm C, Krantz C. WO 2008104386, 2008
  • 20 Collins SJ, Si J. US 2008255244, 2008
  • 21 Lee W.-H, Chen P.-L, Zhou L, Zhu J. WO 2007120726, 2007
  • 22 Tiollier J, Sicard H, Bonnafous C. WO 2008059052, 2008
  • 24 Kumar KP, Satyanarayana S, Reddy PL, Narasimhulu G, Ravirala N, Reddy BV. S. Tetrahedron Lett. 2012; 53: 1738
    CrossrefSearch in Google Scholar
  • 25 Chinta RR, Harikrishna V, Tulam VK, Mainkar PS, Dubey PK. Asian J. Chem. 2016; 28: 899
    CrossrefSearch in Google Scholar
  • 26 Redlich C, Beckett WS, Sparer J, Barwick KW, Riely CA, Miller H, Sigal SL, Shalat SL, Cullen MR. Ann. Intern. Med. 1988; 108: 680
    CrossrefSearch in Google Scholar
  • 27 Kerton FK. Alternative Solvents for Green Chemistry . RSC; Cambridge: 2009. Chap. 1 14
    Search in Google Scholar
  • 28 Vinci D, Donaldson M, Hallett JP, John EA, Pollet P, Thomas CA, Grilly JD, Jessop PG, Liotta CL, Eckert CA. Chem. Commun. 2007; 1427
  • 30 CCDC 1469602 contains the supplementary crystallographic data for compound 4f. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 31 2-[(Benzo[d]thiazol-2-ylamino)(4-methoxyphenyl)methyl]-4-chlorophenol (4e); Typical Procedure ZnCl2 (14 mg, 0.1 mmol, 0.1 equiv) was added to a solution of p-anisaldehyde (136 mg, 1 mmol, 1 equiv), 4-chlorophenol (128 mg, 1 mmol, 1 equiv), and 2-aminobenzothiazole (135 mg, 0.9 mmol, 0.9 equiv) in DMSO (1 mL), and the mixture was heated at 110 °C for 3 h. The mixture was then cooled and extracted with EtOAc (3 × 10 mL). The combined extracts were washed sequentially with H2O (5 mL) and brine (5 mL) then dried (MgSO4) and filtered. The organic layer was concentrated under reduced pressure, and the crude product was purified by column chromatography (silica gel, hexane–EtOAc) and washed with pentane to give a brownish-yellow solid; yield: 233 mg (65%); mp 194 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 9.97–9.84 (br s, 1 H), 8.43 (d, J = 7.6 Hz, 1 H), 7.48 (d, J = 7.6 Hz, 1 H), 7.31 (d, J = 7.9 Hz, 1 H), 7.25–7.08 (m, 4 H), 7.00–6.89 (m, 2 H), 6.82–6.72 (m, 3 H), 6.35 (d, J = 6.6 Hz, 1 H), 3.68 (s, 3 H). HRMS: m/z calcd for C21H18ClN2O2S = 397.0772; found: 397.0746.

  • References and Notes

  • 6 Cherkadu V, Kalavagunta PK, Ningegowda M, Shivananju NS, Madegowda M, Priya BS. Synlett 2016; 27: 1116
    Thieme ConnectSearch in Google Scholar
  • 8 Olyaei A, Zarnegar M, Sadeghpour M, Rezaei M. Lett. Org. Chem. 2012; 9: 451
    CrossrefSearch in Google Scholar
    • 12a Szucova L, Zatloukal M, Spichal L, Voller J, Dolezal K, Strnad M, Massino FJ. US 2009170879, 2009
    • 12b Uksova K, Havlicek L, Krystof V, Lenobel R, Strnad M. WO 2004018473, 2004
    • 12c Shi J, Zhang J, Yue Z, Li M, Zhu C, Zhang Y, Zi J, Wang Y, Fan X, Xu R, Lin S, Li Y, Yang Y, Sheng L. EP 2511283, 2012
    • 12d Dolezal K, Popa I, Zatloukal M, Lenobel R, Hradecká D, Vojtesek B, Uldrijan S, Mlejnek P, Werbrouck S, Strnad M. WO 2004058791, 2004
    • 12e Shi J, Zhang J, Yue Z, Li M, Zhu C, Zhang Y, Zi J, Wang Y, Fan X, Xu R, Lin S, Li Y, Yang Y, Sheng L. US 2013045942, 2013
    • 13a Agliardi S, Del Sordo S, Mailland F, Legora M. WO 2011080265, 2011
    • 13b Agliardi S, Del Sordo S, Mailland F, Legora M. EP 2345642, 2011
    • 14a Zhao Z, Wolkenberg SE, Lu M, Munshi V, Moyer G, Feng M, Carella AV, Ecto LT, Gabryelski LJ, Lai M.-T, Prasad SG, Yan Y, McGaughey GB, Miller MD, Lindsley CW, Hartman GD, Vacca JP, Williams TM. Bioorg. Med. Chem. Lett. 2008; 18: 554
      CrossrefSearch in Google Scholar
    • 14b Wolkenberg SE, Zhao Z, Lindsley C. WO 2007002368, 2007
    • 15a Silverman RB, Xue F. US 2012088798, 2012
    • 15b Labby KJ, Xue F, Kraus JM, Ji H, Mataka J, Li H, Martásek P, Roman LJ, Poulos TL, Silverman RB. Bioorg. Med. Chem. 2012; 20: 2435
      CrossrefPubMedSearch in Google Scholar
    • 15c Calderone V, Fiamingo FL, Amato G, Giorgi I, Livi O, Martelli A, Martinotti E. Eur. J. Med. Chem. 2008; 43: 2618
      CrossrefPubMedSearch in Google Scholar
    • 15d Pajouhesh H, Kaul R, Grimwood M, Tan J, Zhou Y. US 2009298834, 2009
    • 15e Kuehnert S, Merla B, Bahrenberg G, Schroeder W. US 2010234429, 2010
    • 15f Harris RN. III, Repke DB, Walker KA. M. US 2012157494, 2012
  • 17 Jorda R, Sacerdoti-Sierra N, Voller J, Havlíček L, Kráčalíková K, Nowicki MW, Nasereddin A, Kryštof V, Strnad M, Walkinshaw MD, Jaffe CL. Bioorg. Med. Chem. Lett. 2011; 21: 4233
    CrossrefSearch in Google Scholar
  • 19 Nimmrich V, Barghorn S, Ebert U, Hillen H, Gross G, Draguhn A, Bruehl C, Grimm C, Krantz C. WO 2008104386, 2008
  • 20 Collins SJ, Si J. US 2008255244, 2008
  • 21 Lee W.-H, Chen P.-L, Zhou L, Zhu J. WO 2007120726, 2007
  • 22 Tiollier J, Sicard H, Bonnafous C. WO 2008059052, 2008
  • 24 Kumar KP, Satyanarayana S, Reddy PL, Narasimhulu G, Ravirala N, Reddy BV. S. Tetrahedron Lett. 2012; 53: 1738
    CrossrefSearch in Google Scholar
  • 25 Chinta RR, Harikrishna V, Tulam VK, Mainkar PS, Dubey PK. Asian J. Chem. 2016; 28: 899
    CrossrefSearch in Google Scholar
  • 26 Redlich C, Beckett WS, Sparer J, Barwick KW, Riely CA, Miller H, Sigal SL, Shalat SL, Cullen MR. Ann. Intern. Med. 1988; 108: 680
    CrossrefSearch in Google Scholar
  • 27 Kerton FK. Alternative Solvents for Green Chemistry . RSC; Cambridge: 2009. Chap. 1 14
    Search in Google Scholar
  • 28 Vinci D, Donaldson M, Hallett JP, John EA, Pollet P, Thomas CA, Grilly JD, Jessop PG, Liotta CL, Eckert CA. Chem. Commun. 2007; 1427
  • 30 CCDC 1469602 contains the supplementary crystallographic data for compound 4f. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 31 2-[(Benzo[d]thiazol-2-ylamino)(4-methoxyphenyl)methyl]-4-chlorophenol (4e); Typical Procedure ZnCl2 (14 mg, 0.1 mmol, 0.1 equiv) was added to a solution of p-anisaldehyde (136 mg, 1 mmol, 1 equiv), 4-chlorophenol (128 mg, 1 mmol, 1 equiv), and 2-aminobenzothiazole (135 mg, 0.9 mmol, 0.9 equiv) in DMSO (1 mL), and the mixture was heated at 110 °C for 3 h. The mixture was then cooled and extracted with EtOAc (3 × 10 mL). The combined extracts were washed sequentially with H2O (5 mL) and brine (5 mL) then dried (MgSO4) and filtered. The organic layer was concentrated under reduced pressure, and the crude product was purified by column chromatography (silica gel, hexane–EtOAc) and washed with pentane to give a brownish-yellow solid; yield: 233 mg (65%); mp 194 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 9.97–9.84 (br s, 1 H), 8.43 (d, J = 7.6 Hz, 1 H), 7.48 (d, J = 7.6 Hz, 1 H), 7.31 (d, J = 7.9 Hz, 1 H), 7.25–7.08 (m, 4 H), 7.00–6.89 (m, 2 H), 6.82–6.72 (m, 3 H), 6.35 (d, J = 6.6 Hz, 1 H), 3.68 (s, 3 H). HRMS: m/z calcd for C21H18ClN2O2S = 397.0772; found: 397.0746.

   Permissions and Reprints All articles of this category
Zoom Image
Figure 1 Structures of natural and synthetic (aminomethyl)phenols with biological activities
Zoom Image
Scheme 1
Zoom Image
Figure 2 ORTEP diagram of 2-[(benzo[d]thiazol-2-ylamino)(4-nitrophenyl)methyl]-4-chlorophenol (4f)