Facile one-pot synthesis of 10-aryl derivatives of 9-aminoanthracenes and 9,10-dihydroanthracen-9-imines

A series of 9-amino-10-arylanthracenes was easily prepared from bromobenzene and arylacetonitriles via benzyne and α -lithiated 2-arylmethylbenzonitrile intermediates. In addition, several mono-, di-, tri-, and tetra-peri -substituted derivatives of 10-aryl-9-aminoanthracenes and 9,10-dihydroanthracen-9-imines were obtained from the reaction of the respective bromoarenes as precursors of in situ generated benzyne, 3-methoxy-, 6-methoxy-3- methyl-, and 3-,6-dimethoxybenzyne with preformed α -lithiated 2-arylmethyl-benzonitriles.

The products were identified on the basis of IR, 1 H NMR, 13 C NMR and UV spectra.The UV spectra of the bright yellow 9-aminoanthracene derivatives exhibit characteristic absoprtion bands at λ max 420, 380, 340 nm.The 1 H NMR spectra of 9i-9s display characteristic downfield shifts (δ ~ 8.1) and coupling patterns (doublet of doublet) characteristic of peri protons (resulting from 3 J and 4 J).These coupling patterns are absent in the 1 H NMR spectra of 1,8-dimethoxy-substituted 9-aminoanthracenes 9m and 9n.
Interestingly, ).This is consistent with the weak inductive effect of the methyl group in 3-methylbenzyne. 10No attempt was made to separate the mixture, it rather was made to react with 2-bromotoluene 1f and LDA to give a single product, 10-(2-methoxyphenyl)-1,5-dimethyl-9,10dihydroanthracen-9-imine 8e (62% yield); none of the 1,8-or 1,5dimethyl regioisomers was detected.The structure of 8e was confirmed by single crystal X-Ray spectrometry, the ORTEP 7 drawing is shown in Figure 1.

Scheme 5
Most likely, the exclusive formation of 8e involves the regioselective addition of αlithiated 5-methylbenzonitrile 7j to the 2-position of the aryne 3f and the opposite addition of 7k to the 3-position of 3f (Scheme 5).The regioselectve formation of 8e from both isomeric α-lithiated nitrile intermediates 7j and 7k is caused by steric effects.Obviously, the carbanion 7j adds exclusively to the 2-position of 3-methylbenzyne 3f, whereas the carbanion 7k adds to the 3-position of 3f.The opposite regioselective additions by the two isomeric nucleophiles 7j and can not be explained on the basis of the inductive effect of the methyl (which is weak) but rather on the steric effect of the methyl.Inspection of molecular models reveals that steric interactions between the methyl groups and the 9-imino and 10-aryl group in 8e are less severe than those in which the two methyl groups flank either the 9-imino or the 10-aryl group.Consequently, the tricyclic ring in 8e is not strongly puckered, and hence, it is more stabilized by resonance as compared to the situation of the other two possible isomers.Similarly, the reaction of bromotoluene 1f with 6f and LDA gave a single product, 1methoxy-10-(4-methoxyphenyl)-4,8-dimethyl-9,10-dihydroanthracen-9-imine 8f (57% yield) (eq 2).Again, nucleophilic addition occurred in such a way to place the two methyl groups on opposite sides of the tricyclic ring.
In conclusion, the otherwise not easily accessible 10-aryl-substituted derivatives of 9- Chromatography of this material on silica gel (hexane/ethyl acetate, 4:1) gave the pure product 9a-h.The yields, mp and elemental analyses for 9a-h are shown in Table 1 and spectral data of 12ag are given below.

General procedure for the preparation of N-acetyl derivatives 11a-f,h
A 100 mg sample of the appropriate 9-aminoanthracene 9 was added to 5 mL of acetic General procedure for the preparation of peri-substituted 10-aryl-9-aminoanthracenes (9i-s) and 10-aryl-9,10-dihydroanthracen-9-imines (8a-f) The reactions were carried out in similar manner as those described for 9-aminoanthracenes 9a-h with the exception that the appropriate 2-arylmethylbenzonitrile 6 (10 mmol) and the bromoarene 1 (20 mmol) were added sequentially to a solution containing LDA (50 mmol) in THF (10 mL).The spectral data of the products 9i-s, 8a-f are given below.

aminoanthacenes 9
and 9,10-dihydroanthracen-9-imines 8 are readily prepared by the one-pot synthesis described herein.Utilizing readily available and inexpensive starting materials provides an efficient access to these products in multi-gram quantities.Experimental SectionGeneral Procedures.Melting points were taken on a Mel-Temp II capillary apparatus, and are uncorrected with respect to stem correction.IR spectra were recorded on a Nicolet Magna-IR TM 550 FTIR spectrometer and the 1 H and13  C NMR spectra were recorded on a 400 MHz Bruker AVANCE DRX-400 Multi-nuclear NMR spectrometer; chemical shifts were referenced to TMS as internal standard.The UV/VIS spectra were recorded on a Beckman DU 660 Spectrometer.Elemental analyses were obtained from SMU Analytical Services Laboratories.Bromobenzene, arylacetonitriles, diisopropylamine, 2,2,6,6-tetramethylpiperidine, and n-BuLi were purchased from Aldrich Chemical Company.Diisopropylamine and 2,2,6,6tetramethylpiperidine were refluxed over and distilled from calcium hydride.Tetrahydrofuran (THF) was distilled from Na/benzophenone immediately prior to use.The glassware was heated at 125 o C in an oven overnight prior to use.Benzyne reactions were carried out under an atmosphere of dry O 2 -free N 2 utilizing a balloon.General procedure for the preparation of 10-aryl-9-aminoanthracenes 9a-hThe reactions and the work-up were carried out in subdued light.Fresh LDA (40 mmol) was prepared in a flame-dried flask flushed with nitrogen by adding n-BuLi (40 mmol, 2.5 M in hexane) to a solution of diisopropylamine (4.0 g, 40 mmol) in THF (50 mL) at -70 ºC.After stirring for 10 min, the appropriate arylacetonitrile 2 (10 mmol) was added, and stirring was contiuned for 20 min to ensure complete anion formation.Bromobenzene 1b (0.312 g, 20 mmol) was added, the resulting solution was allowed to warm to room temperature and was stirred for 6 h.The reaction was then quenched with saturated NH 4 Cl solution (30 mL) and extracted with methylene chloride.The combined extracts were washed with dilute HCl then dried (Na 2 SO 4 ) and concentrated (rotary evaporator) to give a crude material.
1H NMR spectra of these two aminoanthracenes 9m and 9n are particularly revealing: the signals of the 9-amino protons occur at δ 8.10 and 8.26, respectively.These signals are considerably shifted downfield (approximately 1.5-1.75ppm) as compared to those of the other 9-aminoanthracenes reported in this study.This shift probably reflects extended intramolecular H-bonding between the two amino hydrogen atoms and the adjacent 1,8-dimethoxy substituents.On the other hand, the 1 H NMR spectra of the imines 8a-d exhibit a characteristic NH signal at δ ~ 11.0, and a 10-H singlet at δ 5.5, whereas the13C NMR spectra show characteristic C=N signals at δ ~ 186.