B.d,T (U,K, ~ Expor;) L:d,, Research h 3evelapmtsi Cen~f9, SOUTHAMPTON, OA~laTn1120 REACTIONS OF CARBONY1 COMPOUNDS UITH IINES REPORT NO, T,176 1i,2,1987 AUTHOR: D,A. Hatti n CO·WORKER: B,G, B~nn ISSUER: R,R, Baker DISTRIBUTION: Dr, R, Binns Copy Nd, 1 ~r, A,L, Heard 2 Mr, E,E, Kohnhorst " Y 3, 4 Or, P.J. Dunn I Y S Dr~ S,R, Massey " " 6 Mr, R,G, Nic~olls " " 1, 8 Heff E. Rittershaus 9 " " ',O Or, C.J,P, de Si~ueira " " i: Mr, H,V, rhomsun " 12 Mr, R,F, Giloerdale " " 13, Li~rarr " 1B, 1S COPY H1, I Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 B~A,T (U.K. 1 IX30r:! 1Td., Research a ocvc;b~mrat centre, SOUTHAHPTON , DRHIBmll20 i7th February, !987 REACIIONS OF CdRBONVI COMPOUNOS W;TH AH(NES RE!ORT NO, t,I76 SU~MARY The current study nls undertaken as part o: Project SHIP, to investigate Mnc:~lr caf~onyT sRoke conponen:s would react with amjne cono3nents at conditions oceurinF In the burning rone of the cfgarllte, It had beer hy3o:heslsed:hat such reactions could occur in US b]endec ci;arel:es andthat conseouently carSonyl irritants for~cd predoninanlly fro;n Iluc·curod:ooacca could react with anine irritants de~fvc? fron Burley tobacco to fO~ neutral COmpbnenlS. A literature survey has been unde~:aien on such reactions, bu~ only It~~~ ol the nac~orn In IolJ:ion Ire indudcd, No infornatlan on gas phase reactions at elevated tc~pcraturcs, which would be relevent to the cigarette burning cone, could be found, conreouen;!v, ~t~rs of Icer3nl sr Ir~~cyhyoe Inc a~o~a have 3een npi:5~ in a Wrolysis fcr?aCe at ten0erl~~res u; to 900"C and tne cases exiting frsn:ae f~mac: aedi~sec by n~s; spec:roPe:~, 3or~ ae~~a In~:ne e~r30n~ con3oun~ de~amoos~ 3e ::tir 3Hn Or in ox~F~n a:;a~?z·J:ures dDOvi fS~O~. 'hr c?":cl!!s and a~c~~ ~o $3: reE:I t3~~r~2' I· f·. r. '. ClibPDF - v~~fastio.soni below 550'C. ~lr.he~ore, there is no evidence that there is any additional reacion between the carSonyls and arrPnonia at ~elnpera:vres above 55O'C, ~Hever, it must Se bor:e in mind that the system was not Set up:o specifically detect possible reaction ~rocucts, Consequently, the lacit of experimental evidence for such reactions cannot be considered definitive above jjClC, KEY blORDS Combustion Acetane Pyroiysis Acetaldehyde ki nes Argon Carbonyls Mass Soecromelry Reaction ?roduc:s Nitric Oxide Chemical Mo:cl Svsteen Ketene Ammonia ~t?r :: :'~: 9 ~ ' ; h Inc Elp~nlL~mllr: TLI:r~r, a·Jlr aol s~;nu: ur mo*n IJ cr.lc:~Jnlc~ x~nl ' W Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 IbTaOOuC:~3a Pr3lect SXI~ was a combine? project of R10 Soutaamoton, BB~ and 3~; Hamburg aimed at achieving specified smoke sensory qsali:irs in US alended cigar·tter (Ij, One area of the wort: was to determine the influence of flue·cured and aurley tobacco grdportioa upon the production of suspected irritants in saole. It had been hypothesised that in US blended cigarettes, irritant carbdoyl smoke constituents derived predominantly :rom:1Ue·i3r2d tobacco would react with irritant amiaes and ammonia derived from ni:rooen·rich Bllrley tobaccos (?)I The resultant proouc:s were hy~othesisei to be rela:lveiy ntllrai, or even able to react further to form flavour comoonents, 'his type of occurence tould explain the success of 115 5iended cicaret:es at least partly, Tne objectives of the present study were: To conduct a literature survey to examine the caenicai validity of the hypothesis, 2, To de:e~'ne experioentatly the ex~en: of reaction of carsbnyl and anine coniponents under conditions similar to those In the cigarette burning lone, PI;~ O: 5T:!L)Y :ii:2rt;~re study has been carried out tl oa~~er inij~atios on:L li~~!y reactions of canonyl co~pou~ds with aaines, and :nij is in:iudel: as an dFiiendix in tnis leaor~, T:is nviu daris esjen;ially with haopeneour reactions in Ij~i;:i;n at dl;~2nl :pnlarjtlor since no inionatioo could be isun~ OA j!i 31!ia rea;:io:s at tbe elen:1? :c~seri;lrer s;~llar :J :aa: ~x:arianccC in a 5urn'nF ci3E'?i:' coal, Ir :'j::n~ ~~r3;vj:S aric i:isti',la:';on, ~: ·I: a ~ , i h ~~~ IIR'61:lmllc: TIII:(~m null ~Olh:~3cE or Inown in rDEl~onl~E X~Klnl Chi ... ~-CC Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 To investigate high temperature effects a simple experimental chemical model was studied as it is not feasible to investigate specific chemical reactions in a system as chemically complex as tobacco smoke, It was anticipated that such a model would provide information on the likely reactions of amines and carbonyls in 1 burning cigarette, M xtures of anmoni a with acetone or acetaldehyde were heated up to 900'0 in argon or In argonloxygen mixtures and the depletion of the reactants measured Iv~ a mass spectrometer, Acetone and acetaldehyde were selected because they are the most abundant carbonyl compounds in cigarette smoke, MPERIMENTS .Apoarat'Js and heating Regime Concentrations of 10r vlv of reactants in the carrier gas were fed into a silica reaction tube (200 mllmin) Where they were mixed (see Figures r and 2), The tube Has heated in a furnace to enable the temperature to be ramped up from ambient to 900'0 at a rate of approximately 1'C per second, The concentrations of ammonia and the carbonyl compound exiting from the furnace were monitored on the mass spectrometer (YG IOf OF ) ( 3 i, Before mixtures were examined the effect of heating on single components was studied, RESULTS dDO OISCUSSION Single Comoonent Studies Knen a i?: vlv mixture of arrmonia in argon was passed through the furnace, the intensities of the mass spectrum peaks of mle 29 and 17 exiting from the furnace at different furnace Laperallrer Ire Shoun in Figure 3. These mass peaks correspond e t3 n2 (~i? 29! dnd ~H] (m/e 17) and the intssi;? vaiues are N ~r3por:i~nal ts the concentntion o~ i~e csponentj, L*l ~ iunl a ~; . U n mJ El~nlLmlaJ Thll aun aull at k i'ngcd or IhOul Ip u0lut,lonl~ p30nl. 03 C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 i~e !li:;nE ammonia concentration ii constant until SjS't, 1;3re roicn it decreases Slightly and nitrogen is :omeC, pr::C:l~ by the reverse of the Lber process: Cl~j * 12~3H2 liner; aolonia is heated up to jjS't in the presence of 10: ox!een in atgon, no neion occurs until jjO'C (Figure:j, ~~CVp this teaperature there is a sharp decrease in its mnc~n~·ilion. This coincider ~ita the production of Hater n;l! 13, nitrogen ~mie 29) and ni:rlc oxiie [Ile 30), Ii le3it al!elr that at teperatureS ~red:er rhar 333' an~lonia is ;e'ne oxidised: 211i:3 t 302 ' 2N? t 6H2C cfi'i:, i 51)? · 480'6H20 ~t~rsne (nle :56) is I:aole in arqon up to aplraxiiMleiY iS': ajcve rhiih the concentration rapidly diminisher ('iFsre i:, Tnp Paler products aJpear to Le high molecular Weigh: :Sg33nCE lions, mle 92, 202i, 3ui addl!i~nlily there is ::oe3:::an of an ion with IIC 12 whiCh could :3rrefi)0nd 13 :ne fona:ian of ketene, C~3.~'[93 lolgners g2.1·3 tpo:yeeri i :31 ··..P.CU, ~etene I L m~ f\pm~::.II~::Il~ :~~r; ~ul: Xcl x::31~e or IsoY" !3 YnllYlnL ~~WDI ._.. -· Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 It is posjiale that at high ;emperaturer ac!tlne Foly~e:ires dir!cly ;: high molecular recg~t compounds, or perhaps ~eane is involved as a ..ransien: internediare, 7ir is Igpond a? the fact that laxi~wl Le~ene fonation c~r:el7anes :o:i~~ i~eden ?rao in aceione canern:n:igns (ca. 6J6·;3i') ~i~iisl higher molecular weight caPjauodi are famed as ketene tancPnt:a:ilnr drop (100·BOC'), Kerene is normally prepared hy the tnernl decaporitloo a: acetone and is tnown to poiynerist readily, ~er;ldes?de (nls 8$) heated in arlon appears to he s:lbie ul to 553C' above which there is a steady drop in conceara~ian ane ver:, little II left by aO~i' jfigure 5), Some higher aoleiviar wei2nt comoaunds are 3:Ocuced but the major produ:: ao3clrs to crrjoc nonoxide (81! 29! ;vC COROdn?ni Studier kher ;S: ammonia id 10: ~IROoe vere heated in arson the anr;0rlia Concentration was vir.,;lail,v unchanged even a: tsr;)en:j:es above 700' (iig~ra I]~ a drop in t$a diatilne CleCer:rl:im (nie 581 is ojr,rved, as before 01 dCe;0n2 alone, at temperatures above 500'C and there iS again the pradu::ior, ai niln tolocl:a: ailh! natelill, jno; illur:r~t~dj. I: wociC a)oear that acetlne and asonia do rot react at ttmPera:~rss up to 950'0, When a~oria and acPtaloe"?oe are I~ea~rd toge'ler in arlen there is aloarenlll no change in:he armonia concenlrdll0n at t!me:ltlrei up to B2C'. te!lidehpea:"n~ver as ior ~le single t~l:aaen: lysta (F'F~rP SI and ~eal)3ses at t2npera:1:lS e·??:~r:lan jjg' to carloo aonoxide ~nd ni?her aalraiir *eici:;alourdl. It wOlij dCleEI :hat ace~~ldenidl an: j~0'.j :3 no; rel:: aI :~5:Vr!tsr?l 113 tC 303'tl i .ui; 3 ~ . L L ~~ iloun Il.lsr :'1~'~2m suit IP1 * :n)llC J Im.n IO ullld~lve 1C1011. C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 C961USiGAS Although the rescions of earSonyl compounds with aminer in solution are well doamented (see Appendix) this study has shown that simple aldehydes and ke~ones do not react with anrmmia at temperatures below SjO'C, At temperatures above 550'C both the carbonyl and ammonia decompose on their own and then is no nidence that there is any additional reaction when they are together, However, the experimeoiai systern was not set up to look at all possible reaction products, Conszluen:lyl the lack of exseriment~l evidence for such reac'ons cannot Se considered definitive above 5jS'r:, Z: ;v~: a ~' I i, m~ tlJlnl L~3111~ ;ha rrNa auA ul * rcrllJ Jr Inusn IS ~UIIY:hlOLK.;mOn~ ____ ~~___~ ,,_ ._~-c-----···-· -- -··· Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 APPEIGIX IITIIATU)i S9Pltl OF RIC.IONS Oi UIGOIIYL COROUNOS Ulii k"!YiS Tne matlridl presented here is ~rimar;iy tj~e" from solu:ia" reactions. Primarv r2mines at fsnaeaiz:ion of priiMry amioer ni:h clr:onyl :nnpouldr rES first relor:9d by Scniif (41, and the cmdenra:ion praduc:s are o:t2n r"ilrred to as Schiff bases, T~iJ reaction [S:n!al ii has be!" reviexerl several tiles ij,5), 1 R1 C ·sa"-~20 i·~·"'' -i RZ 12 Scheme 1 For comoie:fon oi reaction it is neclrsarg :o relnove the water pro:1:!? using an aleotrPpe·:o~ino Solvent (;,9! in the ase ~i diarvl or arylalkyl ker3nts, Lu: aidrhvdeS and dialhv~ i':3nes can usually be codenred ritn amines Hiilcur water re139~~ Ssomali c al denydes rlac: smoothly under Rii: ,i:n or witnout a solve~:~ clndi:ioes :nd at room temperature :;: ones, hiph temper?t~r~s, With i~et35eSI especially with arol lonel·:nes, an: a larolys; are usally rsluired, in adct:lon tl:le rt·:r~~ oi.he ~arer as ii is fon?i, Se~ofi:Er: ;~incr me ··l··:cr! ai j"3"da'Y d~inPS ~i:n clr30oyl ;o:oauoi~ c?nn3: 131C :a E Scni ffi base riYC~: r??':40?"!"en:. ~Oue~?r, wnen 3 st': gf:he anine is treatre ,i:n an aijenrce or a 'ir:?e?. i' :~mg''u~ ldl: 15 I;;~iPP" ;~;?!le: · P :ui: a ~. ; h ~Y Elaln I I:pnc~ Thll r~Nn aull xl X:~:IIE JI sKI*n ;o.r~i~uC ~oa;l U C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 Sense 2 R R2 /R2 aH,Hx ~ N" X' ~H20 R1/ / ' R1 R %j When HX is water (i,e, fne:rse) a limilar produc: (X' i 0~) is fonnell and:his is known as a Mannich base (9), 30th Schiffs BtS22 anC Ra~::~ Bases are versatile reagents anC are useful in organi: rjl:nesis j10) especially in the pre~aralion or oitroce~ L?rSIY]jCS (11). Terriarv and Oua:ern~j~ :ertidrv amioer rare: reversibly ui:h earbonyl compounds (SQe~e ?) ane ?o no: f:r 3:niifs 3r Mannich Baser line pri~narl and se:an~ar~ dri?!s :lli (ScherPe 3). Scheme 3 3' O' pi :Hi) 12/ t\liZI/ .I · These luit:?r'Cn 5:!1'21 :!F! a e2nd2ncg :s dirsn:fa:~ Sa:u ts:h! I:rr:in~ :!~::!~ E;nisp and cirbonyl ca;n3ouod, L;::le Inisn;i~:lon ir !:i'ii:le on t$e re~::iJn oi q~~irrltr! i·i~es ni:h 51'3(1:r] ::.:!JI:j~ O!~e ts:n2 'dcl; 3f a: 1:snirir electron pair je :nO nl:::e al:s:ne readiviiy i3war1S j: ;ur; 3 4 · I h IrZ l~h21 It::: :::l'~~~r: cyll 103r ~~i(P 0l~wun in u~~uil~cu: 31-33( Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 Scheme a \ NO RUCTIOII Rla~,X~ c /C f3 82 Hovever, qua:ernary Iminer ~re readily degraded by hedt to ter:ilry dmines and hydroo:jasr; this is known as the P,oi~ann elimination (12) (Scnene Sil Scheme 5 131i. C'2 :Y] Tlen reaction of :ne Ic ;r3cuce tcrriar? a~ine wi:h rarjon?l comoouads tay Se possiSic bonia Ammonia adds to aldehyC2s and ~etones; but the adducts, Ifke gemdipl~, are usually ;30 Pelcive to be isolated and Hater lorr iolioled ay lol?"er'aion occurs (13/ (Scsene 6)~ Scheme 6 1 R R· \ · n~ c H10 C · O ~'~,I · F · I" c~~ /C :HH; t R2/ R2 R2 70LYIlEP.iSkT:01 Tr·a:~mt a! SJlltigni 3: 4:e:0rl i" bdlO[llbOn IO;YII:i roii; ~hic~ ac;aren::~ has a rt:l;:cr"~ C~; 4 ·0H O 512 C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 l;bP~ raaei the material undergoes deom)osition and ~c:!a~ri~at'on, Forn;ll~anyde reacts with anunonij to give an interesting poiyt?clic canpound, henimethy~enetct:Cai ne j131. Each oi t~~ four nitrogen atoms in the ~olec~ic ii a'. a Sfidgehead joining two rinrjs (Scheme 7), S:neae I 5:llil?~6CH20- R~Lc:ions of Carboxvlic Acids with Pminsr .bcd:~er class of carbonyl compound which has not yet been C's:~sse~ Is the car~oxylic acids, C~r3oxvlic acids read with ammonia and aikyl subslitut!d a~ar,ia ~eri~atives ii,e, aminer) to prpbct anonium salts o; tho acid (14) (Seheme S)~ S:n2me 9 ~~s~ salts are reasonably Stable wi:~ th~ excelrions of l~snlr an: Irinary amine salts ~Jhic? nag ?ecwnpose on heatiny ::;ne C~r9nt anine and carbox:,lic acid b? a reversal of:~e E:lre reaction (15). Izz~·i:~ rnC Irinari a~ine lanoxylii a~i; salts obhydra:a to r.ii~r On L~et;ing (16) iScseme 9!, ··: j , ' 1 L ~I: I~ou~; L.mtlrs ;h.!~ln 3Ell :E: X .·DI~E ~I I:OYn 13 YDILao~llC Fl~fil IU _~__ Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·!0· Sc~eae 9 II O BE R: C·n.,Htl--l: ·(·Upl, iiP Unlubrrietad amices (i,e, dsived :rain aeonia) can be furth~" cehye:alzd ta a nitrile rap6una (lli (IchePe 10), Scheme 10 E · t · 'IH? - R · t r N i LI2C ·bdd:nlbrider (derived fron crrSoxyiil acidsi relc: readily wiln anronia and prina:y and leconCary dmines :o produce amides (Sche~e 11) Scntme 11 \ _ , ~ c · ii (R2al1 i HC', 51 . G ·C! C ,INH Intll( :Lii ii :np 81f ilu~url: rEut~ :ul thd pra)lil:ioa oi pldcS, !rpsr.laiiY nitrogen Ju~nituted amideJ, Si~i:dli? i?lbOY?!il dljd Innyd:idll relc: will ~a~nid End anioes tG ?:bOUCI g~id!S I~C1PRe i:!· primary ane se~oodar~ Sc~e~e 1? S O ;11 3 ?.2 / ?! .~aa B :·.C-3·: P.· i :u·: il~' i 6 in: E~.'I Iml.e 31,:~pr, aal mrl r:nalld sr Imm in unCMald r3bl 1l C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·11· This is not as In efficient method a reaction with the acid chloride as only half the molecule is aminat2t ano a ~ar~oxllic acid molecule is produced, ileac:ions of CarSoh?drates with konia and Fmlnes The ease with which certain carbohydrate~, especially sugars react with amines is well known and it is thought that the resulting products play an important role in the changes of soiubility and of colour that take place during the drying of foods (meianoidin reaction), The most corwnon type of nitrogenous derivative is that which is formed by the reaction of the aidehyde (or heniacet.al .group of the sugar) with eoasounds containing amino groups, These compounds can then rearrange to form Pinadori compounds whi:n are thought to be important intermediates in flavour formation (Schese 13) Scheme 1! H H \tP NR r'r HG1IHBI HCOH HC3H HCOH +a11~2 O HOCH HOCH HOCH h~l Amadori compound HCIH HC3H HC ·-- H~ Oii 1'?OU e~PU i. ~': 3 ~ · I ~ laJ Z1*~n~ L.~~:r: T·:l 'rN' *ull 91r :nOn~ ·1: ]M*l:P ~elcllYmIIC XrYm~ l..-.r.--- -I---- I' Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·1?- in Snoice CarSan?l Coinlaundr round Inerert in the pas: has largely focllsse~ on al?PBgdes ant ke:onei in ~iglr!;:e I;aoKe. Stedsan 13 his rcviev j!8) listed iO alaqCer anC ?O uetples (;able 1), ~odDr raC H~ifnlnn in another rei~iew (!0! It approximately the Sane:i~e, listed 12 aidehvdes and i retoner and lurp;ied inisw:1Po on tneil deliveries (Tabie ?jl bldeivdes Acetalaenyde is 5? !ar the nos: inpor:?nt ildei~rde in terms of delivery and 3E? account fOr 72: of:~e t0:?; aidehvdic conten:, Otner a;aehyder such as ac~o;eie, BoliP"6l"ehyPe .and :onaidehyll are present in much spiicr ~o: still significant amoun:j, ~ddi;ionally, hicaer;aalecullr vei;"t aldehyces sucn as cro;onaice"yde are present i: even szlalier amounts tsoiz:lently, wi:h re?ard t~ rrl::~cer of alderlydeS with olner rmonP conrtit~enrs, it is pr3jtabiy IL:ficient to w::i:: is:errr::3 dcelaldehvae, alr,ilin, ;:spionaldenyde asC fonbidehy3Pl Ke-3nps Ace'one is :he 14:ces: Component of tne tetanic colpounds i~:1~ ?), acl~ur:inj for Ip to ii: oi :ae:::r' I?;'veriel oi le:~n·r, Ibuever, unli~e the aldeo?de si:J~'lon there Ir? ?:ar.~ia5ie amounts Or Or'ler tet:nzr, sue: as 2,3 · bl;ir·~i3~e 1!1:~ and ?·~ut3non~ (13:j , ~ .~!: a . L h lr; Ila·nl L~.I,~ :·Il:l~un Jvlr aol x :rplle i! l:l'n !o LIYIIXIYd *M1I ..7 ~D Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 ~3!E i ALOEHYOES ANO K~OslZ I;e S~CE !S;E5~4# (!8)) 6L31iYDfS dcesalde~yde Methacroleln k:oiein 2·N~~~yibutyralde~yde 3ertaidehyle j-metiyiglyoxal aup:alde~yde 2·neth?l·4·pentenal CElraldehyde 2·4e~hyivalerdidehyde Crc~anaidehyde ~iv~ldenyde ;onaldehyde 3r3pj pn~ldenyde i~riura~ raieraldehyde G;soxal j-;iydroxymet~yl furiu ral Iroour~~aldenyde Issvaleraldehyd! ~"~I~Ej ~Ct:One 2·9et~vl-3·pen~anone 2,j-auladi one 3·yei.n;l ·2·lellanone 9u:en·2·one a·~eth~l·2·pe~t~none Su:cl-!·one ?,j·)entadione ~ciopenEanone 2·lentanone ~·3i~ethyi-3·Pentanone 3-oentanone r-~e~;anone r·)aten·t·one 2-·exEnOne l-3cnten·j-cne j·cex~none Z·ler~~i-2-autanbne 3-'"ethrl -3-Bl;en-2-one ?e~~~l'napthyl ketone ~·~;9~ Irl I ii ~nil flpnl L,rllci: :·:~ ~:Sr, cull ,101k:opv0 JI moun i~ IlelL~Mn~~C X~PIII Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 .14. TABLE 2 ALSEHYOES ANO KFTOHES IH SMOKE · (WNDW AID HOFFIH j19)) JilNFI1TERm CIGARETIES) Rldehyder Delivery per ~ ei, Puff Relative Rmavot (pg) (r) Fdnnaidehyde 4.1 4 Acetaldehyde 81.0 /2 Propionaidehyde 6,9 6 Acrolein 8,2 7 isobutyraldehyde 3,6 3 Methacroiein 0,9 1 Pivaldehyde trace ND Butylralde~yde 0,8 Irovaleraldehyde 3.3 3 Yaleraidehyde 0,1 1 Crotonaldekyde 1,6 1 Zdethylval eraldehyde 1,3 Ketones Acetone 12.0 56 B~tan·2·one 10,0 13 Butan·l-one 3,1 5 t,3·autanedione 15,0 20 3-krhyl·2-butanone 1,0 1 2·Pentanone 2,3 3 3-Pentandne 0,5 NO: - Nor det.ernined ~ Irrl I I: C 6 ~1 Elrnll;mla Tbll ~~lsa nol k ~lnd Jr shown so uouhon~d ylwnl. IO C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 .lj· ~nints Found in Cioar!r:l Smn~e (Ex:1?Bing :licaloiOs] in ~tadnan'r nvier j18; 27 rimple anine compounds are listed (;aolt 3), Most Of there are alilnltic but also include some Su3s;i$ted anilines iaramcric amines), CMDPOUndr range from the s'rucural;y sin7ie a~nnoEia to large molecular weight amines su:B as Isoarylaaine, Scbe!lz ane Hoffman 120) list alilnatil amines wita regard to Elrlon numjer (TJle 4)~ According to kbmel:I and Hb:ban, of the aliphati: amines stu:ied tne simpler;, selhylaline is present in the largert amounts (S.j vglcig) and accounts for approxinately 451 of tile tot!'. Alterate amounts pi dincrlyla~:ne (131,1 etnylamine (!0:I, trinethylamine (Ell irobutriaine (Il;j and n· a?virmine (13:) are founG, Mber alisna:ic aleines are present in only insignifican: anounts. It fs fnr~res;ing to no;e:$rr alipna:ic anines are present in smoke in much smaller Cldoli:ieS:~an aliphatic aidenydes (;aale 2 and a). ca?r 3 RMrars Is Sa3KE · SrlO~n (181 Riiviam'nr Si~henylamine ~anonia DiproPylamine See·byl E.mine Ethyl anine 2.9hylaniline Aniline m·;nisisllle :·E~hrlanil ine Bu:llania~ Hcnyl~mfne !soan~vl Imi ne S~c·~ul~~amice Iso3u;yianiae Oiar.hylamine tso:r~~~lanine ~;~etny;aeine ?,!-?ils:nylanilina ~e!hlla!aine ?.~e~~y]jutllacin2 !~:.~i3erqldniline l,t.Sile:nyi ani i i ne ?lel~!le:hylaniae ?.?henyl~~~yl3c:ne ?~;3ine~syl~niline S,i.~i~~glyldbij(~P 5 Yi: 3 ~::6 m3 rlLlr' I.r~;r: fl:l ~c`~ pyl: !D1~:ea: ~r Iho·n:S ~n~ulronlK yaosl N ·--e Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 IAB!E a kine O~ivery ~gld~ I Relltive kdunt I I cl----~c"- ~! !CI ~:~~a~ne plylettla~ne ;f 13 0.96 10 Etnylanine Vinyllmine Allylanine Methyl cthylamlnen.3rdpylamine O,C? O.lt (1 Ilopropyiamlne 0.71 icns!h~adne /3/ But~nylanineIso~utyl~mlnr / n.gut~lamine I Stc-Bu:~~ine O,iO i Ole!hylamfne O,!I 0.3C P: I IsoamylaPine !3 rk~l~P 1,? NO: - Not dctenined. ~ ~:1~: C L ·u ~pa Lie ~n nre e~ ~:;a:~'~"'""~~" "~R VW ClibPDF - v~~fastio.soni ~l~aiolds and Yoir:li~ e152E in Smoke Alkaloids formally contain a basic nitrogen atom, thus tay be reclardell as aainer :n3u9h they may not react analogously, The alkaloid levels in cigarettes are well recorded, i,e,, the levels of major al~~iaids, as recorded by Wynder and Hoif;nan (!~), are ~iv~n in Table 5, Nicotine is by far the major component accounting for up to 9t: of the alkaloid det iverJ, ~ornico~ine, Elyosisine, Gnabasine, Anatabine an: 2,3-8f?yridyl are present in much smaller amounts, Consa:ueatly, with regard to possible reactions of carbonyl compounds with aikaloids in smoke only nicotine should be viewed as a likely reactan:, althouEr. i: lust be reme~bered that nicotine is a tertiary am;ne wnlie nornic3tine, mysosimine, anabaslne and anatabine are se:oncary anines, As outlined at the beginning of this review, secondary SnineS are much more reacive:~an tertiary amines towards :ar3onji compounds, so even tnougn their relative concentrations are low, preferential reaction may occur, Even if tnis Is the case only low levels of these products are anticipated. Table 5 also lists the vc;atile bases in smoke as reported by yvnder and Ho::se, It would appear that pyridine is the major com:onent Inc the concentrations of other bases an comparatively low, hi E 1 ~ ~h: EIS' ~ -I:I: ;:l)'!p' 3Ull tOl 3~ ;npl~P SI lea*n to ;elcl~w~mn: Jc~onl .-I-- ,,~--C·· Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·;8- nllE 5 blC!Oi3S :~C b:I~ assre HIipos;Nou5 co~ou~es ~ID 3 11~ ·1118 PC ~~R nM1 ;n~~aIc smKE.(~NO~ ANe MOFi~ I1P!1 )~~1~ ~M~ / compound ~td~CI Nleptlnr i t9~·:1500 Nornicotfnc 1·50 I~orfalnl Inlbalf no 3.3·J1 ~atlbine 2,3·~py~dyl 1-21 Y~lt!l~ 91111 Pyridint 27·52 p·Plc~lne 61·~ 2,6-iutldlnl t5·1J 5 and y ~C~lne 1 2,0.5,! 2 d·lutf dl ne LS·;J 2,~,6-C~11dlns 3·tthyl~ridln~ LS·3~ 3.Ylnylpy~dlnr 13-25 5 ··: II' ·I ~ *I s*a ~II 81 a*l III1I ~:·11 · I·~ Ilr~l* rll ClibPDF - v~~fastio.soni ihf j sarrq has shown that the individual concentrations of certain crrjonpl compounds dre1Uca greater then the concentrations of individual amines, For Ixaqle, acesaldehyde deliveries far exceed deliveries of aliphatic atines, Possibly, any reaction of carjPnyl ca~oun~s with anines occurs near the pyrolysis tone of the Sutnin~ cigarette, Or along its length, thus depleting the anine levels and leaving an excess of car~onyls, Reaction 3roducts in Smoke I: is o~?ert~ne now to turn our attention '!:he likely prs0ves oi roacrion of carba?vls and aaiar coe;ao~nds in smoi;e, Consider:irst the reaction of alde~ydes Hitn araonia or .si,:;e amrnes (Scheme 14), In the firs::152 the reaction of for:!lde?~je and ar~nonia (at high:ts3era:3:es ijO~'C) is consijerec, Sche~e !r Heat H P - HCab t :i(H H' /1 '~r :HHju/ [0] Initial reaction would produce an "imine" or S:rifis basl in:17leCi3ta, and oxidatioo of tnir in:enedia:e would then IcJ:;3 ~ydragen cyanide which has Seen rer:i!l:et~se~ in ci;!r?f:! rsske in appreciable amaun',s j!3C·:03:oicig! liable Ei :??], Reaction of acetaideiyde with asnoni~ by this reaction 3alaur would lead to dcetocit:ile ~Eica is Known :;:D ~.irr?: in cigarat:e smoke jkne~e ii' (Tll;e 6i. Cr·~,o ': C': C~3 \ r ·.: I ·': a ~' I ~ ~w Ilhrll.all~e TI.II:r~ur, erll Lol k:::lr: J! a,un in Il~lr:~onlce fa~l ~ i N ItJ Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 .2'3· B,v tais scSe~e aote highly subs:iauC rilenyder, sucb Is pr~lionaijlny?e, wo~id give Iropioli::iie. II. is suggested b.v the author tnal the Paler pro~uc: of reacion of aldehydes with mmonia It high ~eoperatures in to be borne out by the rnearlred sinole are cyanides, This seems I~ueir in rilaratP moiP ITabl,li, although i: ar: ~D apprer.ialed thal there are other routca of nitriles e~3~ anino acids and protein, TABLE 6 NITRI1ES fN SI~OY,E HOF:inA# (201 StHHR;Z RAO (liglcig) / Nitrile I Oe!ivery i -· r 100·?00 1 ~dragn Cyanide gb·!40 k2tonitrlle Iropionitr'le 5.6·30 [ '--c~e ihe rea::ion oi other camonyt comoounds with ar~nonia ma.v dlrb be imoor:ant· Fo' exarple, wi*~ aatone a sisilar rcre:ion cll;d ocar jphe~e 161, Scnne ~ J\ t·3-:llii] C~:·' C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·?!· Yorever, it is unliiely that ;ne "inine' so forne~ could easily be converted into a ni:rile. it is nore likely that Ci:nor the reaction would reverse (i,e, hydration), or the "i;nine" would polymerise to higher molecular weight compounds, for Ixanple n'troqen he~eragclils, Such cc~poundr;;n~y we;l onrribure to the flavour of cigarette smoke, ;he reaction of primary amines with nldehydes and ketaer uo~ld also load to similar "i~incr" ikhiffs baser), for cxaoie Hjth acelone and accrildejyde (Schse 171, Senerne Ii CHj CH· J~C·N-R ~'O'ill~= ;·d CH; C~; c;o,leHZ = Hj CIN·II ~ain, such cempounCs woui~ ?robahly polvme'ise, at hien :tr~etra;lrer near the burning coal, to nitrogen heteracy:lic caDounds jScheme 13), R CHJ ""-~ CH 8: 41 I j li~ b N-R " et.e h: n- R Ca; w f ·~: 3 ~: L ~ In~ Elalnl L.~lr: ;~a ·:-~n 3al D k nol~l 01 tnuun 12 3lllcnllC yrwn~ Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·??· P,l!ctior, oi sellnOES~ znim ni~L ~esones or eaeliai:Y Elden?der 9":: lead :3 :he lynisetirally versatile ~lnaicn bases (Sde~e 19). Schene 10 :3t CH] /R a 'CIN ~ OY u /~ ii 'a Not onl? cza:nese c3Ppollnds pc'yaer'se a: hiEn:eperrt"rer but theY are :e;:iw :swardr nu:leophilic at:ac'c· ior example, ·"!::lo" ri:3 ni;rite in thp:lbaco is Ln~un:3 produce ?i::ss;ninel (Scnene 20!~ Sche!:e ?'; 0-~ r3 IR o O- OH' CHI /Ci 6~ 1~`3 '[-u: H' \R t~r i:0 ihil aa.V Id::illiY ell?idin :~ie ~nlul:isn ~i di,e!synl:rora~is~ ianllii ~:: nilno"''l''"e (!INNi dllring the mroiyrfr 3: io~ac:o, e·f· Wi:" "O'"ico:i"e (Scheme Z!j~ Schele 21 C·N:O f!tl/ I rl;/+ ;51:H5 C H/ x;ll C~~t~? X:IIOIIP 31!eJul~ :s ~rlu:~nrd monl W ~ lul; S~' i )I ~IJIIRF· ilmlllC T'II::an ~~a la Clit; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·23· In this case the ?Idehyd~ is acting as a catalyst as it is regenerated at the end of the reaction seguence, Tertiary aminel, such as nicotine, are unlikely to react readily with carlonyl compounds In smoke, Is outlined earlier i n t~i s revi ew, It has been suf~cs;ad that ~Jocs would be a major product from the reaction of carbonyi compounds with anines In smoke. From the known chemistry of carSonyls and amines this can he viewed as highly unlikely. CONCL~SiOXS Carbonvil .0: the carSoay:r present in smoke, acetalcenyoe represents inc laroest tcn30nent, Ketones such as ace;one are also present tu: they are In smaller concentrations and Ire less reac;:ve:ouarcs amines than aldenydes, Ami nes ~onia is tne major component and the sim~cr: aaine present in smoke, ano may combine with reactive carbonyl compounds, espe~idily formaldeh.vde and acl:?ld2hyde, Hitriles are a likely final product from tnis reaction, ihe silnplist nirr~le, bydropen:yaoice, is a ~noHn smoker constituent, Primary amines may react wl:h aiaenydel anc ketones to praduce "imines" (Schiffr basesi, and these compounds can ~~r bbCe ~j to st p~s cnlql uc ·Lq r under high teinser3ture, poiy~~~S~~ Nitrogen helerocyclic csnoounCj miC~;3~]d be ~Or~eC in this way may enhance the flavour s::he E~oke, S~c3nC~r~ anines and c~r~on~l c3mD3undr ~av !~361CS Lnni~~ ;~s21, dn?:ags~ ve"sa:!l~ cs~so~nCs C3~j~ 6150 lead to ~·l~~~r3c~C1IC e3n30unds, ~ ~oiyme~ra:i~~, or re!C: ~':" 'r~i;? nu;lc~phils!, ~~~ as 61;*::?:C 3':~~;! ~::~~SE~;*!!~ S :LtJ~. I i; r: Elm Lrl:;~l:*t ~u~ n k pla * I*~I lo ·Il~a* *Jli ClibPDF - v~~fastio.soni It Is oji En;iiiPE:ed:~at anides wOa~C Se ;:;5:2C al the combination of catbonyls and anines, !ike!~ ~t!Cion Products O~ Clf)cnvjg end biner a:;enlrratarel a~o~e 600' in hoi~e Cdrbonyl k~ PFedlcted PrOdudS bi:eriydei Aonia Hydrogen ganide or nitriiell polynerisation products KeIonrr ~O"id Paiynerisation Irodu2i, N-hetrocyclics blten?da PriMrl aniner Polper:lr:ion pro3ucts, N·het:oelc!ics Ke:on.r Primary Jnes Palvmerisa:ion p'oducts, N-hetrscycl ics ~1Cel?dai Seco"dlry arniner Nit:oraminer, g.he;~ocy~iici Ke:sner Secondary aninel Hi'rosanin'l, N·he:roWclils g r!:l i · It ~i i~wl' Lara')ll.lZlr,iP I ~:~L JILII·n·lO;nlYMnd *1S. C: I i I; PDF -!::!!::!!::!.f3 StlC.i: 0111 ·?I- nlP:r fiE:3EHC:S 1~ 9~: ?elort, No. 91, ?5?'·3 Res;ric:td, 18,10.85 2. 3a~ Report ~o, RO. 5015,34 3. a~T Report, ~o, RO, 14?0 Fier:rfcteC, 15,6,83, 4, ii. Scni~f, Ann. Ches,, 131, 5, 6.M. Sprung, Chem. Rev,, 26, 297 j!940), 6, R,U, !~ver, Chem, Rev,, 63, 489 (1953), 7, ~~9~ Moff2tt, Orp. Svl:~., Call. loT. 4, 605 j1963); n, Freifelder, J, CFE~ Cheln,, 31, 3875 (19Si!, e. rl. Greive, R. Hancnn, 5. Jr:~Lran, E~ Li:e ane K. ;liec~e, Ann, Chem,, 5a!, ~Z i!953!. "~~Enced Organic Chais:~", ~ iicser and Fieser, )uj, Reinnold (1962), iO, "Practical Organic c~elis;q', by ~II, Vogei, nub, Lon~aans (1961), i!. 3.L.S. Sni:h'Opec·chaie ni:ngeo compounds' vol, i, aace 298, pub, U,~, 3enfanin, Inc,, New Yorii, 1965, 12. :.b.S. Smith and 5.:tanr,;. h~ Chem. Sec., 14, 50" (19521, tram and G,S. Faraonl, )aPD 2P6 "Oroanic [hePisrg", Hd:aw-H111, London, 2ne 9., 1964, See Reference 91 Page S!~~ 15, "3eac:ilns of Organic Clqouadr" by R,C, Fuson, Pub. Jonn Ual~y i Sonr Inc., (13623, Page 320, 16, ISid, page 333, i;. '"ne "I~iliard leact:an lo Rdr and Ilvtri:ion", ACS S~,arivm Series ?!5, e~ ~.1. tollr~ock, 3ub. kmrrican Chemical Society (IF~3), iR, fi.L. 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