摘要:
884 J.C.S. Perkin I:Reactions of Nitrobenzothiazoles with Grignard Reagents. Orientationof Alkylation with Respect to the Nitro-group PositionBy Giuseppe Bartoli,’ Rino Leardini, Maria Lelli, and Goffredo Rosini, lstituto di Chimica Organica, VialeNitrobenzothiazoles react with Grignard reagents giving alkyl-nitroso-compounds, except the 4-nitro-isomer whichaffords alkyl-nitro-derivatives. The observed highly regiospecific alkylation can be interpreted in terms of theRisorgirnento 4,401 36 Bologna, Italy.stability of a cyclohexadiene-type intermediate.NrTRoARENEs are reported 1-4 to react with Grignardreagents giving N-alkylamines or N-alkylhydroxyl-amines by reductive alkylation. The only reportedexception 696 is a polyaddition to the aromatic nucleus inpolynitrobenzenes.We have reported that alkyl-magnesium halides react with 6-nitrobenzothiazole (1)to give an intermediate which is decomposed to a 7-alkyl-6-nitroso-derivative by aqueous hydrochloric acid (seeScheme). This represents the first example of reductivealkylation of a nitroarene leading to the correspondingnitroso-derivative which has undergone alkylation in thearomatic ring. In the present work we wished toascertain whether this unusual reactivity was ascribableto the particular influence of the nitro-group in position6 of benzothiazole, and to rationalize the high positionalselectivity of alkylation, which cannot be accounted forby the different electronic effects of the S and C=Nmoieties on the reactivity of C-5 and C-7. We report thereactions of 4-, 5-, and 7-nitrobenzothiazoles [ (12), (4),and (7)] with some Grignard reagents.RESULTS AND DISCUSSIONThe previously reported procedure was modified.Reaction times were reduced to a few minutes. More-over boron trifluoride-diethyl ether complex, instead ofaqueous hydrochloric acid, was used to decompose thet The product was tentatively identified as the correspondingazoxy-derivative on the basis of mass spectral data.1 K.Nutsel in Houben-Weyl, ‘ Methoden der OrganischenChemie,’ ed. E. Muller, 4th edn., Vol. XIIT/2a, Thieme Verlag,Stuttgart, 1973, p. 47.2 P. Buck, Angsw. Chem., 1969, 81, 136; AngPw. C’hem.Internat. Edn., 1969, 8. 120.Detailed mass spectra- of the products are.reported.intermediate (see Scheme). Comparative experimentsshowed these changes to increase yields from 50-60 to70- SO%, at least in the reaction of 6-nitrobenzothiazole(1) with phenethylmagnesium halides.The results in Table 1 show that 5- and 7-nitrobenzo-thiazoles behave similarly to the 6-nitro-isomer.How-ever, whereas the 5-nitro-isomer (4) affords only 4-alkyl-5-nitroso-derivatives (6a and b), the 7-nitro-isomer (7)gives two nitroso-derivatives, i.e. 6-alkyl-7-nitroso- (9aand b) and 4-alkyl-7-nitroso-benzothiazole (1 l a and b),in comparable yields.All the nitroso-compounds were obtained in the mono-meric form; they were stable, both in the solid state andin solution in the usual aprotic solvents (benzene, n-hexane, chloroform, etc.) in the dark. The only excep-tion was (9a), which decomposed rapidly in solution; tthus, the low yields in this case can be attributed todecomposition during work-up.The reactivity of 4-nitrobenzothiazole (12) is anomal-ous: under the same experimental conditions it affords4-nitro-7-alkyl derivatives (14a and b) in moderate yields.Traces of 4-butyl-7-nitrobenzothiazole (15a) were alsoisolated when compound (7) reacted with n-butylmag-nesium bromide (see Table 1 ) .At present the experi-mental data are not sufficient to explain these anomalies,but oxidation either of the intermediate (13) or of theM. S . Kharasch and 0. Reinmuth, ‘ Grignard Reactions ofNon-metallic Substances,’ Prentice-Hall, New York. 1954.M. Gilman and R . McCracken, J. Amsr. Chem.SOC., 1963,75,6041.T. Severin and M. Adam, Chem. Rev., 1964, 97. 186.T. Severin and M. Adam, Chem. Ber., 1963, 96, 448. <; Rartoli and G . Rosini, S y t h ~ s i s , 1976. 4, 2701977 885corresponding ni troso-derivative during the addition ofboron trifluoride and water could account for our findings.Orientation of the Entering Alkyl Group.---In every casea high positional selectivity of alkylation is observed(see Scheme). In view of the well known mode ofn-that the orientation is affected by the relative stabilitiesof the intermediate adducts is strengthened by the factthat substitution at the ortho- and fiara-positions iscompetitive in 7-nitrobenzothiazole. The 4-nitro-isomersuffers only para-substitution.Y H R Ri 12)6- H 'R(51reaction of Grignard reagents and the nature of theproducts, we suggest that the first step of the reaction isan addition of RMgX to give the adducts (2), ( 5 ) , (8), (lo),and (13).In the case of 5- and 6-nitrobenzothiazolestwo ortho-positions (4 and 6, and 5 and 7, respectively)are available for nucleophilic attack by the alkyl group,but only attack at the 4- and 7-positions, respectively,leads to an adduct in which the aromatic character of thethiazole ring is preserved [(2) or (5)J. The possibilityCharacterizationRRR(14 a, b)of Products.-The products wereidentified as nitro-- or nitroso-derivatives 8 by theusual methods of analysis (see Table 2); their exactstructures were deduced from lH n.m.r. and massspectra.Structures (3b and c) and (6a and b) were assigned onthe basis of lH n.m.r.coupling constants (7.5-8.5 Hz),Part 1, ed. H. Feuer, Interscience, New York, 1969.J. H. Boyer, ' The Chemistry of Nitroso and Nitro Groups,886 J.C.S. Perkin ITABLE 1Reactions of nitrobenzothiazoles with RMgXSubstrate H Products M.p. (“C) t Yield (yo) Column eluant 180-82 70-80 CH-EA (4 : 1 V/V)90-92 65-75 CH-EA (4 : 1 V/V)(7) Bun (9a) ca. 45 5 10-15 CH-EA (4 : 1 V/V)PhCH2*CH2 (3b)Bun (64(1)(4)PhCH2.CH2 (6b) ca. 80s 70-80 Benzene(114 ca. 50 9 30-35( 154 68-69 TI acePhCH,*CH, (9b) 87-88 35-40 CH-EA (9 1 V/V)(12) Bull ( 14a) 40-4 1 40-50 CH-EA (9 : 1 V/V)PhCH2CH2 (1 4b) 144-1 46 65-70 CH-EA (7 : 3 V/V)(1lb) 84-86 35-40t From n-hexane. 1 CH = cyclohexane, EA = ethyl acetate.5 Decomp.TABLE 2Analytical and spectroscopic data of nitroso- and nitro-alkylbenzothiazolesAnalysis (yo) *C; H; N60.0; 5.5; 12.759.55; 5.45; 12.867.15; 4.5; 10.4568.85; 4.3; 10.7560.0; 5.5; 12.759.75; 5.15; 12.9567.15; 4.5; 10.4567.3; 4.65; 10.560.0; 5.5; 12.759.8; 5.35; 12.8567.15; 4.5; 10.4566.9; 4.65; 10.6555.9; 5.1; 11.8556.2; 4.9; 12.063.35; 4.25; 9.8563.55; 4.1; 10.163.35; 4.25; 9.8566.6; 4.3; 10.11 45014601 42014601 4001510134015101 340725750 (39)700 (45)715 (43)T (CDCl,)d, H-7), 5.4-5.8 and 7.7-9.3 (2 H and 7 H, m, Bu)(s H, m, CPh), 3.8 (1 H, d, H-7): 5.2-5.5 and 6.6-6.9 (2 H and 2 H, m, CH2CH2)(1 H,d,H-5), 5.9-6.3and7.9-9.3 (2Hand 7 H, m,Bu)(1 H, d, H-5), 2.85 (5 H, m, Ph), 5.4-5.8 and 6.4-6.8 (2 H and 2 H, m, CH,CH2)H-5), 6.6-7.0 and 7.9-9.2 (2 H and 7 H, m, Bu)(1 H, d, H-5), 2.8 (5 H, m, Ph), 6.2-6.5 and 6.7-7.0(2 H and 2 H, m, CH2CH,)(1 H, d, H-6), 6.8-7.2 and 7.9-9.2 (2 H and 7 H,m, Bu)(5 H, m, Ph), 2.7 (1 H, d, H-6), 6.4-7.1 (4 H, m,CH,*CH,)0.9 (1 H, S, H-2), 2.45 (1 H, d, J6.7 Hz, H-6), 3.7 (1 H,1.1 (1 H, S, H-2), 2.60 (1 H, d, J6 7 8.5 Hz, H-6), 3.01.31 (1 H, S, H-2), 2.0 (1 H, d, J4.5 8.5 Hz, H-4), 2.650.95 (1 H, S, H-2), 1.65 (1 H, J4.5 8.5 Hz, H-4), 2.400.8 (1 H, d, J5.6 Hz, H-6), 1.20 (1 H, S, H-2), 2.4 (1 H, d,0.65 (1 H, d, J5,6 8.0 Hz, H-6), 0.9 (1 H, S, H-2), 2.360.85 (1 H, S, H-2), 1.9 (1 H, d, 55.6 8.0 Hz, H-5), 2.750.7 (1 H, S, H-2), 1.8 (1 H, d , 8.5 Hz, H-5), 2.5-3.01170I 330* Upper line required; lower line found.TABLE 3Mass spectra of ortho-nitroso-alkyl and para-nitroso- or -nitro-alkylbenzothiazoles ; relative intensities of major peaksCompound :Mol.wt. :IonMM - - HM - 0M - OHM - NOM - C,H,M - NO2M - C4HsM - C&5M - C,H,C6H5C,H,C5H531 3033100 1009566I8107.5 7I;? 16ti 7(6b)2684.55.51002974921(942204781100437226.5(9b) (16b) (16c)268 282 2688 14 6765100 100 100238 6 1046 29 87 5 1514 10 6(1 la)22015591 31810073.5(lib)268551.55100114.5(1442361003.5137594(14b) (15a)284 23629 221003353 8100 263.5 6212 23which were characteristic of aromatic ortko-protons.o-alkylnitrobenzenes,9 o-alkyl-diary1 sulphines,1° andThese assignments were confirmed by the mass spectra ; o-alkylaryl arylsulphonyl sulphines.llthe base peak is consistent with loss of OH from the Mass spectrometry was veq7 useful in determining themolecular ion, showing the same ‘ ortlzo-effect ’ as in structures of the alkyl-nitroso-compounds arising from* S. Meyerson, I. Puskas, and E. K. Fields, J. Amev. Chem. the reaction of the 7-nitro-compound (7); indeed10 A. Tangerman, L. Thijs, A. P. Anker, and B. Zwanenburg,SOC., 1966, 88, 4974.J.C.S. Perkin 11, 1973, 458.l1 A. Tangerman and B. Zwanenburg, J.C.S. Perkin IZ, 1973,4611977 887n.m.r. spectra of the products (9) and (11) showed thecoupling constants of the two aromatic protons for thestructures to be distinguished.However the massspectrum of (9) shows the same ' ortho-effect ' as allo-alkyl-nitroso-compounds; in contrast, loss of NO isobserved with the isomer ( l l ) , as expected for a meta- orpara-derivative (see Table 3). On the basis of similarspectroscopic behaviour, structures (14a and b) were alsoassigned. Mass spectroscopy coupled with lH n.m.r.analysis thus appears to represent a useful tool fordistinguishing an o-a1 kyl-ni troso-derivative from itspositional isomers.EXPERIMENTALl.r., u.v., 'H n.m.r. and mass spectra were recorded with aPerkin-Elmer 402, a Perkin-Elmer 257, a JEOL 60 MHz(tetramethylsilane as internal standard), and a JEOLMS-D 100 instrument, respectively.Nitrobenzothiazoles were prepared by nitration ofbenzothiazole.1'Tetrahydrofuran (thf) was purified by distillation overlithium aluminum hydride and then stored over sodiumwire under nitrogen.n-Butyl bromide, phenylethyl brom-ide, and boron trifluoride-diethyl ether complex are com-mercial products (Schuchardt).Synthesis of A lkyl-nitroso- or A lkyl-nitro-benzothiazoles .General Procedure.-A solution of alkylmagnesium halide(0.02 mol) in thf (50 ml) was added dropwise a t room tem-perature under nitrogen to the nitrobenzothiazole derivative(0.01 mol) dissolved in thf (20-50 ml). A red colourimmediately appeared. The mixture was stirred for a fewmin and then boron trifluoride in thf was added until theresulting solution appeared yellow (in some cases a paleyellow precipitate was obtained).After addition of water,the mixture was extracted with methylene chloride; theorganic layer was washed several times with water, dried(MgSO,), and evaporated at reduced pressure. The crudeproduct was chromatographed on a silica gel column.In the reaction of the 7-nitro-compound (7) with n-butyl-magnesium bromide all the operations were performed inthe dark so as to avoid decomposition of the product (9a).Keactions, products, and physical data are reported inTable 1. Elemental analyses and Lr., u.v., and 1H n.m.r.data of new alkyl-nitroso- and alkyl-nitro-benzothiazolesare collected in Table 2; the lH n.m.r. spectrum of 4-butyl-7-nitrobenzothiazole ( 15a) could not be recorded owing to lackof material. The E value for compound (9a) is not reportedbecause of its fast decomposition in solution. Mass spectraof compounds (6a and b) , (9a and b) , (1 l a and b) , ( 14a and b) ,and (15a) are collected in Table 3 with those of 7-benzyl-6-nitroso benzothiazole (3c), 2-methyl-6-nitroso-7-phenethyl-and 7-benzyl-2-methyl-6-nitroso-benzothiazole ( 16b and c) ,prepared as reported previ~usly.~[6/1518 Received, 3rd August, 19761l2 E. R. Ward and W. H. Poesche, J , Chem. SOC., 1961,2825
ISSN:1472-7781
DOI:10.1039/P19770000884
出版商:RSC
年代:1977
数据来源: RSC