1977 1989Nitration of 7-Substituted I ,3,5-Triaza-adamantanesBy Afarin Edwards and Grabam A. Webb,' Department of Chemical Physics, University of Surrey, GuildfordGU2 5XH, SurreyNitrations of some 7-substituted 1,3,5-triaza-adamantanes with various nitrating mixtures are described. Theproducts are in general NN'-dinitro-l,3-diazacyclohexane derivatives. The mechanism of the reactions is similarto that suggested for the nitration of hexamine with nitric acid.As part of a programme of work related to the nitrolysisof hexamine, the synthesis of 7-nitro-1,3,5-triaza- produced the dinitrate salt of the amine (2).adamantane (1) and its reactions with nitric acid andwith nitric acid-ammonium nitrate have been described.lA further study of the nitration of this compound and ofthe imine (5) was hydrolysed under these conditions andXa with number various of other nitrating 7-substituted mixtures 1,3,5-triaza-adamantanes is now reported.+ 02N*N$N-CHiOHThe following systems were used as nitrating agents:concentrated nitric and glacial acetic acids (NA), con-centrated nitric and sulphuric acids (NS), a mixture offuming nitric acid, acetic acid, and acetic anhydride(NAA), concentrated nitric acid and ammonium nitrate(NAN), and fuming nitric acid.X( 1 ) X=NO;!( 2 ) X=NH2X1XIN02\NO2( 3 ) X=Br ( 8 ) X=Br The reaction of 7-nitro-l,3,5-triaza-adamantane (1)( 4 ) X=NHAc with NAN to give a monocyclic product (10) of type (A)( 5 ) X =N:CH-C6HiOMe-p was considered t o proceed as shown in Scheme 1 .l Sucha pathway is directly analogous to that proposed by The preparation of the triaza-adamantanes (1)-( 5)and their nitrate salts (6)-(9) has been reported.3 A.F. Farminer and G. A. Webb, J.C.S. Perkin I, 1976, 940.T. Urbanski, ' Chemistry and Technology of Explosives,' Treatment of the triaza-adamantanes (1)-(3) withNA gave only the corresponding nitrate Salts (6)-(8);(9) X=NHAcvol. 1, Pergamon, Oxford, 1967.3 A. Edwards and G. A. Webb, in preparation1990 J.C.S. Perkin Iseveral authors4-' to account for the formation of pro-ducts of type (B) by nitration of hexamethylenetetramine(Scheme 2).In the current study in general the 7-substitutedtriaza-adamantanes (1)-(5) reacted with nitratingagents to yield products of type (A).Thus, treatmentof 7-amino- (2) and 7-bromo-triaza-adamantane (3) witheither NAN or NS gave the salt (11) or (12), respectively.The corresponding product (10) was obtained from thereaction of 7-nitrotriaza-adamantane (1) with NAN, buttreatment of the triaza-adamantane (1) with NS gave thebicyclic product (13), which presumably arises directlyfrom an intermediate of type (a,) (X - NO,) as shownin Scheme 1. This reaction has a parallel in the reactionof hexamine with nitric acid, in which the bicyclic nitro-compound (14) was obtained in low yield; 4 ~ 6 9 8 this wasgiven as evidence for the existence of an intermediate oftype (b,) (Scheme 2).With NAA a t room temperature 7-nitro- (1) and 7-bromo-triaza-adamantane (3) reacted similarly to givethe acetates (15) and (16), respectively.However theacetate (16) is accompanied by a small amount of thenitrate salt (12), detected by lH n.m.r. spectroscopy.When these reactions are carried out at 0 "C a mixtureof the acetate (15) and the nitrate (10) is obtained(ratio 2 : 1) from 7-nitrotriaza-adamantane (1) whereasthe 7-bromotriaza-adamantane (3) under these condi-tions yields the nitrate salt (12) as the only detectedproduct. Presumably the slower acetylation reaction at0 "C fails to trap any of the hydroxymethylamine inter-mediates.In contrast 7-aminotriaza-adamantane (2) reactsslightly differently with NAA, giving a high yield of theacetate (17) at 0 "C and at room temperature.The isolation of the products (15)-(17) from thereactions with NAA provides clear evidence for theexistence of intermediates of type (a,).The acetamide (4) gave no isolable product on treat-ment with NA or NS, and the unstable, sticky solidobtained from its reaction with NAA was not identified.T. Urbanski, ' Chemistry and Technology of Explosives,' vol.3, Pergamon, Oxford, 1967, p.87.G. F. Wright, ' The Chemistry of the Nitro and NitrosoGroups,' Part 1, ed. H. Feuer, Wiley, New York, 1969, ch. 9.However when 7-acetamidotriaza-adamantane (4) wasnitrated with NAN a low yield of the spiro-compound(18) was obtained. A similar product (19) was obtainedin good yield from the nitration of 7-aminotriaza-adamantane (2) with fuming nitric acid a t ca. 2 "C. Thisreaction was also carried out on a small scale in an n.m.r.tube and followed by recording lH spectra at intervals.A spectrum recorded after ca.5 min showed no trace ofthe amine (2), and the subsequent spectra were verycomplex so that the structure of any intermediate couldnot be determined. However as the reaction proceededthe spectrum of the product (19), emerged and thereaction was almost complete in about 45 min. Theseresults agree with an earlier kinetic study of the nitrationof hexamine with nitric acid, which indicated theimmediate formation of an intermediate which in turngave a product of type (B) (Scheme 2) by a relativelyslow, rate-determining step.'The reaction of 7-aminotriaza-adamantane (2) withfuming nitric acid when carried out at -10 "C gives aNO2 IINO2(10) X=NO2(11) X=NHNO;!(12) X = B r02N*N(16) X=Br ,Y=N02(17) X=N(N02)Ac,Y =CHiO-N02(18) X=Ac(19) X=NO2(20) X = Hmixture of compound (19) (identified by comparison oflH n.m.r.spectra) and some other products which havenot been separated and identified.The imine (5) when treated with the above nitratingmixtures gave only 4-me t hoxy-3-ni trobenzaldehyde. Infuming nitric acid a high yield of a white crystallineproduct was also obtained; this was shown to be amixture of several compounds by the lH n.m.r. spectrum.The major product, separated by repeated recrystalliz-ation from acetone-ether, was the spiro-amine (20).6 W. L. Mospy, ' Heterocyclic Systems with BridgeheadNitrogen Atoms, Part 2, Interscience, New York, 1961, pp.J.A. Bell and I. Dunstan, J . Chem. SOC. (C), 1969, 1559.W. J . Chute, D. C. Downing, A. F. McKay. G. S. Myers,1393-1398.and G. F. Wright, Canad. J . Research, 1949, 27B, 2181977 1991EXPERIMENTAL a clear solution; addition of ethanol did not precipitatelH N.m.r. spectra were recorded for solutions in deuteri- any product.ated solvents containing Me,Si with a Varian HA-100 The nitrate salts were recrystallized from water orinstrument operating a t 100 MHz. 1% N.m.r. spectra were methanol and identified by comparison (m.p.s and lHrecorded for solutions in deuteriated solvents containing n.m.r. spectra) with the authentic compo~nds.~Me,Si with a Bruker WH-SOFT instrument operating a t Reactions wzth Concentrated Nitric Acid-Anznzonium22.64 MHz with broad-band proton decoupling. 1.r Nihate (NAN) (1 : 1) .-(i) 7-Nitro-l,3,5-triaza-adamantaneTABLE 1100 MHz lH N.m.r.data [solvent (CD,),SO; S values; J in Hz]Compound CH,(a) (2 H, dd) CH,(b) 4 H) X Y(10) 5.10, 7.15 (J 15) 4.18, 5.50 (dd, J 16)(11) 4.98, 6.83 (J 14) 3.71, 5.04 (dd, J 15)4.07, 5.17 (dd, J 16)4.2, 5.4 (dd, J 15)3.65 (2 H, s), 8.6vbr (3 H, NH,+)3.43 (2 H, s), 8.3vbr (3 H , NH,+)3.54 (2 H , s), 8.5vbr (3 H , NH,+)2.08 (3 H, S , CH,), 4.7 (2 H, s, C*CH,.N), 5.7NH not obs.5.05, 7.05 (J 15)5.07, 6.9 (J 14)(2 H, s, N*CH,.O)(16) 4.9, 7.0 (J 15) 4.02, 4.96 (dd, J 16) 2.12 (3 H, s, CH,), 4.25 (2 H, s, C*CH,.N), 6.3(2 H, s. NCH,*OI(17) 5.03, 6.87 (J 14) 4.01, 5.45 (dd, J 16) 1.9 (3 H, s, CH,) 2.08 (3.H; 8, CH,j, 4.58 (2 H, s, C*CH,.N), 5.64(4 H, S , NCH,*O)(18) 5.30, 6.48 (J 14)(19) 5.77, 6.24 (J 14)(20) 5.07, 6.8s (J 15) 3.72, 4.80 (dd, J 15)4.52 (s) [dd in (CD,),CO]4.7 (s) [dd in (CD,),CO]3.02 (3 H, s, CH,), 4.02 (2 H, s, C.CH,-N), 5.37 (2 H, s, N.CH,-N)4.28 (2 H, s, C*CH,*N), 5.68 (2 H, s, NCH,.N)3.65 (2 H, s, C-CH,*N), 4.62 (2 H, d, N.CH,.N), 3.6-3.9 (NH)TABLE 222.64 MHz 13C N.m.r.data [S values w.r.t. Me,Si; solvent (CI>,),SO]NO,Compound C(a) C(b) C(c) X Y(11) 61.1 48.6 79 57.5(12) 59.3 54.9 60.8 44.7(10) 58.6 48.7 8.16 40.6(15) 59.7 49.4 85.4 20.3 (CH,), 53 (C*CH,-N), 74 (N*CH,*O), 169.4 (CO)(17) 60.8 49.7 65.8 19.5 (CH,), 168.9 (CO) 20.3 (CH,), 51.9 (C*CH,*N), 70 (CH,-O.NO,), 74.5 (CH,*O), 169.4(CO)(18) 60.4 50 60.9(19) 60.1 49.3 63.4(20) 59.7 50.8 62L a23.5 (CH,), 56 (C*CH,*N), 64.7 (N*CH,-$, 168.7 (CO)56.8 (C.CH,*N), 66.1 (NCH,*N)53.1 (C.CH,*N), 65.7 (NCH,*N)spectra (Nujol mulls) were recorded with a Unicam SP200 instrument.M.p.s were determined with an electro-thermal apparatus.Reactions with Concentrated Nitric A cid-Glacial AceticAcid (NA) (1 : 2) .-7-Nitro-1,3,5-triaza-adamantane (1)(0.5 g) was added in portions to NA (8 ml) a t 0 "C. Themixture was stirred for 2-3 h, then filtered to give 7-nitrotriaza-adamantane nitrate salt (6) (0.4 g). (Thisreaction a t room temperature overnight gave the sameproduct .)Similar treatment of the amine (2) and the bromide (3)gave high yields (80-90%) of the nitrate salts (7) and (8),respectively. The imine (5) when treated with NA gave ahigh yield (800/,) of 7-aminotriaza-adamantane dinitratesalt (7).The acetamide (4) under the same conditions gave(1) (0.5 g) was dissolved in NAN (10 ml) and left a t roomtemperature for about 2 days. The solution was thenpoured into ice-water to give 5-ammoniomethylene- 1,3,5-trinitro- 1,3-diazacyclohexane nitrate (10). The product(0.4 g) was filtered off and recrystallized from methanol;m.p. 145" (lit.,l 145"); vmax. 1 540 and 1 570 (NO,), 3 000,1 620 (NH,+), and 1 300 cm-l (NO,-). (This reaction wasalso carried out for a shorter time (3 h) and the sameproduct was obtained in lower yield.)(ii) The bromide (3) (0.5 g) treated similarly gave 5-anznzoniomethylene-5-brorno- 1, 3-dinitro;? ,3-diazacyclohexanenitrate (12) (0.4 g) m.p.165" (from water); vmBx. 1530 and1 560 (NO,), 3 000, 1 630 (NH,+), and 1 300 cm-l (NO,-)(Found: C, 17.25; H, 3.15; N, 24.4. C,HllBrN,O,requires C, 17.3; H, 3.2; N, 24.2%)1992 J.C.S. Perkin I(iii) The reaction mixture from the amine (2) (0.5 g) withNAN when poured into ice-water gave a clear solutionwhich was left in a fume-cupboard for a few days t o eva-porate. In this way 5-ammoniomethylene- 1,3-dinitr0-5-nitroamino- 1,3-diazacyclohexane nitrate ( 1 1 ) (0.25 g) wasobtained; m.p. 185" (from water); v,,,. 1530 and 1550(NO,), 3 000 and 1 590 (NH,+), and 1 300 cm-l (NO,-)(Found: C, 18.3; H, 3.75; N, 33.8. C,Hl,N,O, requiresC, 18.3; H, 3.65; N, 34.1%).(iv) The acetamide ( 4 ) (0.5 g), treated as described in(iii) gave l-acetyl-3,7,9-trinitro- 1,3,7,9-tetra-nzaspiro[4.5]-decane (18) (70 mg), m.p.220-230"; v , , , ~ ~ . 1500-1 570(NO,) and 1 660 cm-l (GO) (Found: C, 30.1; H, 4.1; N,30.2. C,Hl,N707 requires C, 30.1; H, 4.1; N, 30.7%).(v) The imine ( 5 ) when treated with KAN gave 4-methoxy-3-nitrobenzaldehyde, m.p. 81-83" (from chloro-form-petroleum) (lit.,, 86"); v,,,, 1 700 ( G O ) , 1 610(C=C), and 1530 cm-l (NO,); 8 (CDC1,) 4.08 ( 3 H, s, CH,),7.2-8.3 ( 3 H, m, aromatic), and 9.9 ( 1 H , s, CHO).Reactions with Concentrated Nitric Acid-ConcentratedSulphuric Acid ( N S ) ( 1 : 1). (i) 7-Nitro- 1,3,5-triaza-ada-mantane (1) (0.5 g) was added in portions to NS (6 ml) a t-5 "C. The mixture was stirred for 1 h then poured intoice-water and left for cn.1 h to give 3,5,7-trinitro-1,3,7-triazabicyclo[3.3. llnonane (13) (0.3 g ) , m.p. 222" (fromacetone) ; v,,,. 1 520 and 1 550 cm-l (NO,) ; 8~ [(CD,),SO]3.62 ( 2 H, s, CH,), 4.22 and 5.10 ( 4 H, dd, 2 CH,), and 4.65and 5.53 ( 4 H, dd, 2 CH,); 8~ [(CD,),SO] 77.38, 67.37, and51.91; 8~ [(CD,),CO] 78.4, 68.4, 53.7, and 53.2 (Found: C,27.35; H, 3.75; N , 32.05. C6HloN,0, requires C , 27.5; H,3.85; N, 32.050,/,).(ii) The amine (2) and the bromide ( 3 ) under similarconditions gave the salts (11) and (12) in 50-60% yields.(iii) White fumes were evolved when the acetamide ( 4 ) wasadded to NS and no product was isolated.(iv) The only product obtained from the reaction ofthe imine ( 5 ) was 4-methoxy-3-nitrobenzaldehyde.Reactions with Fuming Nitric A cid-Glacial Acetic A cid-Acetic Anhydride (NAA) ( 1 : 2 : 2).-(i) 7-Nitro-1,3,5-triaza-adamantane ( 1 ) (0.5 g) was added in portions toNAA (7.5 ml) a t 0 "C.(a) The mixture was then stirred a t room temperaturefor 1.5 h and poured into ice-water, giving 5-[(acetoxy-methy1ene:nitro) aminometlaylene]- l13,5-trini&o- 1,3-diaza-cyclohexane (15) (0.4 g), m.p.114-116" (from ethanol);vmax. 1 730 ( G O ) and 1 550 and 1 580 cm-l (NO,) (Found:C, 26.15; H, 3.5; N, 26.85. C,Hl,N,Ol, requires C , 26.15;H, 3.55; N, 26.7%).(b) The mixture was stirred at 0 "C for 1 h then pouredinto ice-water. The acetate (15) (0.25 g) was filtered offand the filtrate was left for 1-2 days a t room temperature.More solid obtained was identified (by the 1H n.m.r.spec-trum) as the nitrate (10) (120 mg).(ii) The amine (2) when treated similarly gave an 80%yield of 5-[acetoxymethylene(nitro-oxymethylene)amino-methylenel- 1, 3-dinitro-5-(N-nitroacetamido]- 1,3-diazacyclo-hexane (17) a t 0 "C or a t room temperature; m.p. 155" (fromacetone-ether); vrnaX. 1 730 ( G O ) and 1 530 and 1590 cm-l(NO,) (Found: C, 29.4; H, 4.05; N, 24.65. C1,H1,N80,,requires C, 29.1; H, 4.0; N , 24.65%).(iii) The bromide ( 3 ) (0.4 g) was treated with NAA at- 2 "C, giving the nitrate (12) (0.4 g). The reaction a troom temperature [as described in (i) (a)] afford a whitesolid (0.25 g) mixture of the acetate (16) with a small amountof the nitrate (12), as judged by the lH n.m.r. spectrum.The acetate (16) was not purified; it was identified bycomparison (i.r.and lH n.m.r. spectra) with the analogousacetates (15) and (17).(iv) The acetamide (4) when treated with NAA at 0 "Cgave a low yield of a sticky, unstable solid mixture of two orthree compounds by the lH n.m.r. spectrum [the presenceof a trace of the spiro-compound (18) was suspected].Reactions with. Fumic Nitric Acid.-(i) 7-Amino-l,3,5-triaza-adamantane (0.3 g) was added in portions to fumingnitric acid ( 5 ml) a t ca. 2 "C. The mixture was stirred for40 min then poured into ice-water. The product (0.3 g)was recrystallized from dimethyl sulphoxide-methanol-ether to give 1,3,7,9-tetranitro- 1,3,7,9-tetra-azaspiro[4.5]de-cane (19), m.p. 200"; v,,,. 1 530-1 570 cm-l (NO,) (Found:C, 22.6; H, 3.1; N, 35.25.C,H,,N,O, requires C, 22.35;H, 3.1; N, 34.7%). When carried out at -10 "C thisreaction gave a white solid (0.3 g) mixture of compound (19)and some other, unidentified products (lH n.m.r. spectrum).(ii) The imine ( 5 ) , (400 mg), treated with fuming nitricacid at -10 "C, gave a mixture of several compoundslH n.m.r. spectrum). 4-Methoxy-3-nitrobenzaldehyde wasremoved by extraction with chloroform. The remainingsolid was recrystallized several times from acetone-etheruntil 3,7,9-trinitro-1,3,7,9-tetra-az~s~iro[4,5]decane (20) wasobtained pure (120 mg); m.p. 235-240"; Y,,,. 3 300(NH) and 1500-1 560 cm-l (NO,) (Found: C, 25.95;H, 4.0; N , 35.55. C6HllN70, requires C, 26.0; H, 4.0; N,35.35%). The imine ( 5 ) a t 0 "C gave a similar mixture,but the proportion of compound (20) appeared to be lower(n.m.r.).N.m.r. Study of the Nitration of 7-Amino-1,3,5-triaza-adamantane.-The instrument (Varian HA- 100) was lockedon the proton of the nitric acid (8 ca. 8 ) . The temperaturewas maintained a t 2-4 "C. The amine (ca. 40 mg) wasadded to fuming nitric acid (0.5 ml) a t 0 "C. The solutionwas immediately transferred to an n.m.r. tube and thespectrum recorded in the region 6 0-8 within 5 min of theaddition of the amine and then a t 10-15 min intervals.Support from the European Research Office, U.S.Government, is gratefully acknowledged.[7/377 Received, 3rd March, 197739 ' Dictionary of Organic Compounds,' Eyre and Spottiswoode,London, 1965