Aromatic Nitro-group Displacement Reactions.Part 6.1 Structure of the Compound Formed by theAction of Morpholine on 2,2',4,4'-Tetranitrobenzophenone$John H. Gorvin*a and Richard N. Sheppardba(The former) Wellcome Research Laboratories, Langley Court, Beckenham, Kent, UK andDepartment of Pharmaceutical and Biological Chemistry, The School of Pharmacy,29¡Ó39 Brunswick Square, London, UK, WC1N 1AXbDepartment of Chemistry, Imperial College of Science, Technology and Medicine,South Kensington, London, UK, SW7 2AYMorpholine has been shown to displace the two ortho-nitro groups in 2,2',4,4'-tetranitrobenzophenone.The reaction of 2,2',4,4'-tetranitrobenzophenone 1 with aprimary aromatic amine leads initially to the displacementof a 2-nitro group.1,2 Formation of a 10-arylacridine-9-onemay then follow by a cyclodehydronitration involving the2'-nitro group. With a secondary aliphatic amine such asmorpholine, 1 reacted with the independent displacement oftwo nitro-groups.On the grounds of earlier arguments2 we assumed theproduct to have the structure 2 but this assumption hadto be proved. Lack of solubility in cold dimethyl sulfoxideruled out 1H NMR studies on 2 but the remaining twonitro-groups in 2 were readily replaced by methoxy to yielda compound probably, not denitely, with structure 3.Earlier 1H NMR studies on 3 failed to give an unequivocalconclusion owing to similarity of chemical shifts and lack ofshift parameters for morpholine.The problem can now beresolved by NOE dierence studies at higher eld.The three aromatic protons of structure 3 (or its possibleisomer) form a three-spin system whose couplings allowassignment to the partial structure shown in Fig. 1.The three aromatic multiplets and the methoxy signal at3.82 ppm were irradiated in standard NOE dierenceexperiments, giving the enhancements shown in Table 1.Irradiation of the two CH2 signals of the morpholinegroup produced the expected large NOE responses to eachother and also the following results shown in Table 2.Considered together, the observed enhancements are onlyconsistent with a structure which has the methoxy groupsat R1 in the partial structure, as originally proposed.Thenegative NOE observed on irradiation of the methoxy is arelayed eect (via the proton at 6.68 ppm) often seen insuch systems.ExperimentalNOE dierence spectra were recorded in [2H6]dimethyl sulfoxidesolutions at 400 MHz (Bruker DXR-400).Reaction of 2,2',4,4'-Tetranitrobenzophenone 1 with Morpholine.The nitro-compound (1.81 g, 0.5 mmol) was reuxed with mor-pholine (8.7 g, 0.1 mol) for 7 h.Filtration gave 1.48 g (67%) of2,2'-dimorpholino-4,4'-dinitrobenzophenone 2, which formed yellowcrystals from DMF¡ÓEtOH, mp 285¡Ó286 8C (Found: C, 56.7; H, 4.8;N, 12.6. C21H22N4O7 requires C, 57.0; H, 5.0; N, 12.7%); max/cm£¾1(KBr) 1640 (CO), 1520 and 1351 (NO2). No other compound wasisolated.4,4'-Dimethoxy-2,2'-dimorpholinobenzophenone 3.To the nitro-compound (3.8 g) in hot dimethyl sulfoxide (100 ml) was added1 M MeONa¡ÓMeOH (25 ml); the solution was left overnight.Addition of water led to the precipitation of the methoxy compound3 (3.5 g) which crystallised from DMF¡ÓEtOH, mp 205¡Ó206 8CJ.Chem. Research (S),1998, 812¡Ó813$Table 1Observed NOE enhancements atSignalirradiated7.47ppm6.68ppm6.50ppm3.82ppm2.60ppm7.47 ppm 14% nil nil nil6.68 ppm 14% nil 2.5% nil6.50 ppm nil nil 2.3% 2.3%3.82 ppm £¾1.4% 10% 4.7% nilTable 2Observed NOE enhancements atSignal irradiated 7.47 ppm 6.68 ppm 6.50 ppm2.98 ppm 3.4% 2.5% nil2.60 ppm 3.7% nil 10.4%Fig. 1$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem. Research (M).*To receive any correspondence.812 J. CHEM. RESEARCH (S), 1998(Found: C, 66.8; H, 6.9; N, 6.7. C23H28N2O5 requires C, 67.0; H, 6.8; N, 6.8%); max/cm¡1 (KBr) 1635 (CO); m/z 413 (MáHá). One of us (J.H.G.) thanks Professor W. A. Gibbons for laboratory facilities. We thank Mr A. G. Seaborn for typing the manuscript and Emeritus Professor C. W. Rees, CBE, FRS for his continuing interest. Received, 17th August 1998; Accepted, 4th September 1998 Paper E/8/06468G References 1 Part 5, J. H. Gorvin, J. Chem. Res., 1993, (S) 406; (M) 2779. 2 J. H. Gorvin and D. P. Whalley, J. Chem. Soc., Perkin Trans. 1, 1979, 1346. J. CHEM. RESEARCH (S), 1998 813