Synthesis, Physical and Antimicrobial Studies of Ferrocenyl-N

184 Pages·2017·6.25 MB·English

RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 51
S. Afr. J. Chem., 2016,69, 51–66,
<http://journals.sabinet.co.za/sajchem/>.
Synthesis, Physical and Antimicrobial Studies of
Ferrocenyl-N-(pyridinylmethylene)anilines and
Ferrocenyl-N-(pyridinylmethyl)anilines
Eric M.Njogu,Bernard Omondi and Vincent O.Nyamori
School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
E-mail: [email protected] / [email protected] / [email protected]
Received 20 January 2016, revised 12 February 2016, accepted 12 February 2016.
ABSTRACT
Ferrocenyl-N-(pyridinylmethylene)anilinesSchiffbasesweresynthesizedbyreactionof3-or4-ferrocenylanilinewitheither
2-,3-,or4-pyridinecarboxaldehydeundersolvent-freeconditionsviamechanochemistrytechnique.Productswereobtainedin
excellentyieldswithin10minofgrinding.Thereactionsaffordedameltorgummysemi-solidthatsolidifiedtothedesiredSchiff
baseswithinashorttime.TheseSchiffbaseswerereducedtotheircorrespondingamines,ferrocenyl-N-(pyridinylmethyl)ani-
lines,withNaBH overneutralAlO solidsupportviagrinding.Amineswereobtainedinexcellentyieldsafterintermittent
4 2 3
grindingforapproximately1h.Herein,fivenovelferrocenyl-N-(pyridinylmethylene)anilines(compounds3, 4,6–8)andsix
ferrocenyl-N-(pyridinylmethyl)anilines (compounds 9–14) are reported. Compounds were characterized through FT-IR,
1H-NMR,13C-NMR,HRMSandSC-XRDtechniques.Thesecompoundsshowvisiblesolvatochromism,whenUV-Visabsorption
wasmeasuredinpolarandnonpolarsolvents.Inchangingsolventfrompolartonon-polar,theSchiffbasesexhibitedablueshift
whiletheaminesportrayedaredshift.Electrochemicalstudiesonthesecompoundsrevealthatredoxbehaviouroftheironcentre
isinfluencedbythepositionimineoraminegroups.AntimicrobialpropertiesofthesecompoundswerestudiedforEscherichia
coli,Staphylococcusaureus,SalmonellatyphimiriumandCandidaalbicans.HighestactivitywasrecordedagainstGram-positive
bacteria and fungi.
KEYWORDS
Ferrocenyl-N-(pyridinylmethylene)anilines, ferrocenyl-N-(pyridinylmethyl)anilines, mechanochemistry technique, solvent-
free synthesis, antimicrobial activity.
1.Introduction ingtheirredoxpropertiesinapplicationssuchasamperometric
Ferrocene(dicyclopentadienyliron)isatreasuredcompound sensors for metal ions31,32 since they facilitate long-range
discoveredserendipitously1,2anditsstructurewasdetermined3–5 metal–metal interactions in binuclear complexes. The ferro-
intheearly1950s.Thisdiscoveryhasimpactedgreatlyonthe cenylpyridinemetalloligandshavebeenemployedincoordina-
rapidgrowthofinorganicandbio-organometallicchemistry.6,7 tionofothermetalsyieldingbimetallicsystemswithexcellent
Theunrelentingstudyonferroceneanditsutilizationinmany anti-cancerpotenciescomparabletothedrugcisplatin,courtesy
diverse applications are attributed to; (i) the stability of the ofthesynergisticeffectbetweenthetwoactivemetals.21,33,34Also,
ferrocenescaffoldtomoisture,airandtemperature;(ii)theease ferrocenylpyridineSchiffbaseshavebeenfoundtoshowbroad-
offunctionalizingthecyclopentadienylringsinferroceneskeleton spectrum biological activity against pathogenic microbes.35,36
via electrophilic substitution to give monosubstituted, 1,1’-di- Complexesofferrocene-derivedSchiffbaseligandshaveshown
substitutedor1,2-disubstitutedmoietiesrenderingitapertinent exceptionalhighactivitiestowardsringopeningofcyclicesters.37
buildingblock;(iii)sufficientrigidityofthesandwichstructure Inaddition,liquidcrystallineferrocenylSchiffbasesalsoknown
providing an appropriate chiral environment; (iv) its readily asferrocenomesogens,showinterestingmagnetictraitssuchas
accessiblereversibleredoxcouple;(v)stabilityoftheferrocenyl paramagnetism and control of the molecular orientation in
groupinaqueousaerobicmediaand(vi)itshighelectrondensity magneticfields.38,39Moreover,thereishighinterestintransition
andaromaticity.7,8Theferrocenylunitisalsoknowntomodify metal complexes with electronically communicating metal
theshapesofmoleculesaswellasthephysicalpropertiessuchas centres spanned by conjugated systems that make ferrocenyl
colour, polarizability and magnetism.9 Generally, studies on metalloligands appealing.31,40,41
ferrocene revolve around generation of compounds that are Nonetheless, the chemistry and applications of ferrocenyl
usedinmaterialsscience,10electrochemistry11,12catalysis,13–15me- ligands with pyridine nitrogen-donors have not been fully
dicinalapplications16–24andnonlinearoptics25,26amongstothers. developed. Studies on ferrocenylpyridines only began in the
Ferrocene derivatives containing organic fragments bearing recent past and their properties have not been exhaustively
oneormoreheteroatomssuchassulphur,27nitrogen,28oxygen,29 described and their optimal potential usage has not hitherto
and phosphorous30 have gained prominence. Amongst the been explored.42 Furthermore, there are limited precedents,
N-heterocyclic ferrocenyl metalloligands, ferrocenylpyridine especiallywhencomparedtotheferrocenylphosphineligands
metalloligandshavebeenstudiedforthepossibilityofexploit- where extensive work has been carried out as independently
ISSN 0379-4350 Online / ©2016 South African Chemical Institute / http://saci.co.za/journal
DOI: http://dx.doi.org/10.17159/0379-4350/2016/v69a7
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 52
S. Afr. J. Chem., 2016,69, 51–66,
<http://journals.sabinet.co.za/sajchem/>.
reviewedbyP.Barbaroetal.43andA.Fihrietal.44Potentialusesof PerkinElmerspectrum100FT-IRspectrometerandthedataare
ferrocenylpyridinesSchiffbasesincludessynthesisofmaterials reportedaspercentagetransmittancesatgivenwavenumbers.
forusageinelectrochemicalsensors,45homogenouscatalysis,46 High-resolutionelectro-sprayionization(ESI)massspectrometry
cytotoxicagents,16antimicrobialcompounds,47–49antiparasitic,50 spectrawererecordedusingaWatersMicromassLCTPremier
liquidcrystals,51non-linearopticalmaterials,52luminescentsys- TOF-MS.Onlythemolecularions(M+)andthemajorfragmen-
tems,53 as well as coordination of a variety of metal centres to tationpeaksarereported.Theintensitiesarequotedaspercent-
yield novel bimetallic complexes with fascinating architec- ages of the base peak. UV-Vis spectra were recorded on a
tures,54,55organometallicpolymers56andconductingpolymers.57 PerkinElmerLambda35UV/VISspectrophotometerinmethanol,
In view of the aforementioned potential applications of dichloromethane,toluene,N,N-dimethylformamideorchloro-
ferrocenylpyridinesandferrocenederivedSchiffbases,wehave form. The emissions on the other hand were recorded on
preparedaseriesofnovelmono-substitutedferrocenyl-N-(pyri- PerkinElmer LS55 Fluorescence spectrometer in methanol,
dinylmethylene)anilines Schiff bases and their corresponding dichloromethane, N,N-dimethylformamide or chloroform. All
ferrocenyl-N-(pyridinylmethyl)anilines secondary amines. meltingpointsweredeterminedusingStuartScientificmelting
Thesecompoundsreportedhereinhavegreatpotentialinthe point apparatus (SMP10) and co-related with those from the
fields of antimicrobial, nonlinear optics, electrochemistry and DSC instrument and are uncorrected. DSC thermal analyses
coordination chemistry wereconductedonaSDTQ600V20.9Build20,UniversalV4.7A
ThoughmajorityofferrocenylSchiffbasederivativesaresyn- TAInstrument.Thesampleswereheatedfromroomtempera-
thesizedinsolutionviareflux,58–60inthisstudy,thecompounds tureto600°Catarateof5°Cmin–1undernitrogenatmosphere
were synthesized via mechanochemistry (Section 2.2), a rela- withagasflowrateof50mLmin–1.Priortoanalysis,theDSC
tively faster and greener technique. Reduction of ferrocenyl wascalibratedwithsapphirecalibrantwhiletemperaturewas
Schiff bases has previously been reported by use NaBH in calibrated using indium and zinc standards. Cyclic voltam-
4
methanol over a period of long periods;61,62 however, in this mogramswereperformedusingaMetrohm797VAComputrace
study reduction of the imines was achieved timeously with electrochemical analyzer with a one compartment three elec-
NaBH overasolidneutralAlO supportviamechanochemistry trodesystemconsistingofAg/AgCl (0.01M)referenceelectrode,
4 2 3 2
technique as reported in Section 2.3. Electrochemical, thermal platinum wire auxiliary electrode and platinum disc working
andspectroscopicstudiesofthecompoundsarereported.The electrode. Samples (ca. 0.1 mM) were prepared in acetonitrile
compounds were also investigated for antimicrobial activity anddataaquiredatasweeprateof100mVs–1undernitrogen
against Gram-negative bacteria Escherichia coli and Salmonella atmosphere at ambient temperature. Sodium perchlorate
typhimirium;Gram-positivebacteriumStaphylococcusaureusand (0.1M)wasusedasthebackgroundelectrolyte.Solutionswere
the fungal speciesCandidaalbicans. saturatedwithnitrogenbybubblingnitrogengasfor5minprior
to each run. A standard protocol, the platinum disc working
2.Experimental electrodewasthoroughlypolishedbetweenruns.Thereference
and auxiliary electrodes were also rinsed between runs.
2.1. Materials and Instrumentation
Allchemicalswereofreagentgradequalitypurchasedfrom 2.2. General Synthesis of Ferrocenyl-N-(pyridinyl-
commercial sources and used as received. These included: methylene)anilines
ferrocene 98 % (Aldrich, USA), sodium borohydride 99 % 4-Nitrophenylferrocene and 3-nitrophenylferrocene were
(Merck, Germany), 4-nitroaniline 98 % (Merck, Germany), synthesized according to reported procedure via arylation of
3-nitroaniline 98 % (Fluka, Switzerland), methanol 99.5 % ferrocenebydiazoniumsaltunderphasetransferconditions.63
(Aldrich, USA), sodium nitrite 98.5 % (Associated Chemicals Thereafter,thesenitro-derivativeswerereducedwithmolecular
Enterprises, South Africa), hexadecytrimethylammonium H gas and 5 % Pd/C in a Parr reactor to obtain 4-ferro-
2
bromide 99 % (Aldrich, USA), hydrochloric acid 32 % (Merck, cenylaniline(1)and3-ferrocenylaniline(2),respectively.Their
Germany), n-hexane 98 % (Glassworld, South Africa), diethyl characterizationdataaresimilartothosereportedinliterature.21,64
ether99.8%(Aldrich,USA),CDCl-d 99.8%atomD(Aldrich, The ferrocenyl-N-(pyridinylmethylene)anilines 3–8 were
3 1
USA), 2-pyridinecarboxaldehyde 99 % (Aldrich, USA), synthesizedbygrindingferrocenylaniline,compound1or2in
3-pyridinecarboxaldehyde 98 % (Aldrich, USA), 4-pyridine- combinationwithappositepyridinecarboxaldehydeinapyrex
carboxaldehyde97%(Aldrich,USA),methanol99.5%(Associ- tube fitted with ground joint and a side arm.65 Grinding for
atedChemicalEnterprise,SouthAfrica),dichloromethane99% 2–10minresultedinapasteorinsomecasesagummymeltthat
(Aldrich,USA),N,N-dimethylformamide99.8%(Aldrich,USA), wasdriedunderreducedpressuretogetproductasadrysolid.
toluene99.9%(PromarkChemicals,SouthAfrica)andchloro- All the physical and spectral data for the known compound,
form99%(Merck,Germany).Nitrogen5.0,gastechnicalgrade 4-pyridylimine-4’-phenylferrocene(5),i.e.colour,m.p,1H-and
(Airflex Industrial Gases, South Africa), hydrogen gas 5.0 (Air 13C-NMR were in line with the ones previously reported.21
Products,SouthAfrica)Silicagel60,0.063–0.2mm/70–230mesh Experimental data for the novel compounds 3, 4, and 6–8 are
(Merck, Germany), aluminium-coated TLC plates, Müeller- reported in the subsequent subsections 2.2.1 to 2.2.5.
Hinton agar (Scharlab) and nutrient broth (Scharlab).
1H-and13C-NMRspectrawererecordedonBRUKER400MHz 2.2.1.Synthesis of (E)-4-ferrocenyl-N-(pyridinyl-2-
spectrometer (AVANCEIII 400) in CDCl. Chemical shift values methylene)aniline(3)
3
are reported in ppm and coupling constants in Hz. 1H-NMR 4-Ferrocenylaniline (1) (0.3004 g, 1.08 mmol) and pyri-
spectrawerereferencedinternallyusingresidualprotonsinthe dine-2-carboxyaldehyde (0.1140 g, 1.06 mmol). The reaction
deuteratedsolvent(CDCl:d=7.24ppm)andvaluesreported yielded an orange yellow solid that was recrystallized in
3
relativetotetramethylsilane(d=0.00ppm).13C-NMRspectra methanollayeredwithhexaneandthisprovidedorangecrystals
were similarly referenced internally to the solvent resonance suitable for X-ray crystallography. Yield 0.3461 g, 89 %, m.p.
(CDCl:d=77.0)withvaluesreportedrelativetotetramethyl- 138–140°C,DSCpeakm.p.141.41°C.DH =4.55×106Jmol–1.
3 f
silane(d=0.0ppm).Theinfraredspectrawererecordedusinga DS =1.1×104Jmol–1K–1.Calc.forC H NFe:M+=366.0819.
f 22 18 2
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 53
S. Afr. J. Chem., 2016,69, 51–66,
<http://journals.sabinet.co.za/sajchem/>.
Found[M+]366.0825.FT-IR(cm–1):3084,1630,1567,1521,1468, (CHN),122.32(CH),119.02(CH),117.72(CH),84.56(CH),
5 4 6 4 6 4 6 4 5 4
1281,816,503488.1H-NMR(400MHz,CDCl,dppm):d=8.69 69.68 (CH), 69.18 (CH), 66.60 (CH) ppm.
3 5 4 5 4 5 5
(2H,m,CHN),8.22(1H,d,J=7.8Hz,-CH=N),7.81(1H,t,J=
5 4
7.5Hz,C5H4N),7.51(2H,d,J=8.0C6H4),7.34(1H,d,J=5.4Hz, 2.2.5.Synthesis of (E)-3-ferrocenyl-N-(pyridinyl-4-
C5H4N),7.27(2H,m,C6H4),4.65(2H,t,J=1.8Hz,C5H4),4.32(2H, methylene)aniline(8)
t,J=1.8Hz,C5H4),4.04(5H,s,C5H5)ppm.13C-NMR(400MHz, 3-Ferrocenylaniline(2)(0.3017g,1.09mmol)andpyridine-4-
CDCl3, d ppm): d = 152.67 (-CH=N-), 149.70 (C5H4N), 143.44 carboxyaldehyde (0.1141 mg, 1.06 mmol). Yield 0.3721, 95 %:
(C6H4), 136.69 (C5H4N), 136.11 (C5H4N), 129.92 (C6H4), 126.80 m.p = 125–126 °C, DSC peak m.p 127.68 °C, DHf = 2.7 ×
(C5H4N), 124.99 (C6H4), 121.82 (C5H4N), 121.44 (C6H4), 84.76 106Jmol–1,DSf=6.77×103Jmol–1K–1.Calc.forC22H18N2Fe:[M+]=
(C5H4),69.65(C5H4),69.39(C5H4),69.11(C5H4),66.48(C5H5)ppm. 366.0819.Found[M+]=366.0813.FT-IR(cm–1):3089,2876,1900,
1623,1411,1324.1H-NMR(400MHz,CDCl,dppm):d=8.76(2H,
3
2.2.2.Synthesis of (E)-4-ferrocenyl-N-(pyridinyl-3- s,CHN),8.47(1H,s,-CH=N),7.77(2H,s,CHN),7.32(3H,m,
5 4 5 4
methylene)aniline(4) CH)7.04(1H,s,CH),4.67(2H,t,J=1.8Hz,CH),4.32(2H,t,
6 4 6 4 5 4
4-Ferrocenylaniline(1)(0.3000g,1.08mmol)andpyridine-3- J=1.8Hz,CH)4.04(CH)ppm.13C-NMR(400MHz,CDCl,
5 4 5 5 3
carboxaldehyde(0.1132g,1.06mmol).Theproductwasvacuum d ppm): d = 157.98 (-CH=N), 151.11 (CH), 150.63 (CHN),
6 4 5 4
dried and gave an orange-yellow solid. Recrystallization in di- 142.81(CHN),140.81(CH),129.27(CH),124.80(CH),122.32
5 4 6 4 6 4 6 4
chloromethane/methanol solution gave orange crystalline (CH),119.02(CH),117.72(CHN),69.69(CH),69.17(CH),
6 4 6 4 6 4 5 4 5 4
plates suitable for X-ray crystallography. Yield 0.3579 g, 92 %, 66.60 (CH) ppm.
5 5
m.p. = 146–148 °C, DSC peak m.p. 146.71 °C, DH = 6.81 ×
f
106 J mol–1, DS = 1.61 × 104 J mol–1 K–1. Calc. for C H NFe: 2.3. General Synthesis of the Ferrocenyl-N-(pyridinyl-
f 22 18 2
[M+]=366.0819.Found[M+]=366.0818.FT-IR(cm–1):3089,2876, methyl)anilines
1901, 1623, 1411, 1324, 1281, 821. 1H-NMR (400 MHz, CDCl, The Schiff bases 3–8 were reduced to their corresponding
3
dppm):d=9.05(1H,s,CHN),8.72(1H,s,CHN),8.56(1H,s, secondaryaminesusingNaBH oversolidneutralAlO support
5 4 5 4 4 2 3
-CH=N),8.30(1H,d,J=7.8Hz,CHN),7.50(2H,d,J=8.4Hz, via grinding under solvent-free conditions.66 The NaBH and
5 4 4
CH),7.42(1H,s,CHN),7.19(2H,d,J=8.4Hz,CH),4.65(2H, neutralAlO solid-phasemixturewaspreparedinaporcelain
6 4 5 4 6 4 2 3
t, J =1.8 Hz, CH), 4.32 (2H, t, J = 1.8 Hz, CH), 4.40 (5H, s, mortar by grinding neutral alumina (2.0 g, 20 mmol) with
5 4 5 4
CH) ppm. 13C-NMR (400 MHz, CDCl, d ppm): d = 156.43 sodium borohydride (0.34 g, 9.0 mmol) for 5 min. Thereafter,
5 5 3
(-CH=N),149.78(CHN),148.92(CHN),144.27(CH),138.21 appropriateimine(1.0mmol)wasaddedfollowedbyadditionof
5 4 5 4 6 4
(CHN), 134.77 (CH), 126.79 (CHN), 122.50 (CH), 121.14 fivedropsof99%methanol.Thegrindingwascontinuedinter-
5 4 6 4 5 4 6 4
(CH),84.71(CH),69.66(CH),69.43(CH),69.12(CH),66.45 mittentlyandtheprogressofeachreactionwasmonitoredby
6 4 5 4 5 4 5 4 5 4
(CH) ppm. theTLCusingdichloromethane.Onceallthesubstratereacted,
5 5
(45–60 min), the reaction mixture was poured into 20.0 mL of
2.2.3.Synthesis of (E)-3-ferrocenyl-N-(pyridinyl-2- dichloromethaneandfilteredthroughasinteredglassfunnel.
methylene)aniline(6) Theresiduewaswashedfurtherwithtwo15.0mLportionsof
3-Ferrocenylaniline(2)(0.3020g,1.09mmol)andpyridine-2- the same solvent. The solvent from the filtrate containing the
carboxyaldehyde(0.1144mg,1.07mmol).Yield0.3658g,94%, productwasevaporatedandproductpurifiedviacolumnchro-
m.p=93–94°C,DSCpeakm.p.93.91°C,DH =6.89×106Jmol–1, matography to obtain the secondary amine. All these amine
f
DS =1.88×104Jmol–1K–1.Calc.forC H NFe:[M+]=366.0898. derivatives are new and their experimental characterization
f 22 18 2
Found[M+]=366.0840.FT-IR(cm–1):3089,2876,1900,1623,1411, data are given in the subsequent subsections 2.3.1 to 2.3.6.
1324.1H-NMR(400MHz,CDCl,dppm):d=8.72(1H,d,J=4.3
3
Hz,CHN),8.66(1H,s,CHN),8.22(1H,d,J=7.9Hz,CHN), 2.3.1.Synthesis of 4-Ferrocenyl-N-(pyridinyl-2-methyl)aniline(9)
5 4 5 4 5 4
7.82(1H,td,J=7.6Hz,J=1.4Hz,CHN),7.39(3H,m,CH),7.32 Compound3,(0.3662g,1mmol).Recrystallizationinmethanol
5 4 6 4
(1H,t,J=7.7Hz,CH),7.11(1H,s,-CH=N),4.67(2H,t,J=1.6 gave orange plates suitable for X-ray crystallography. Yield
6 4
Hz,CH),4.32(2H,t,J=1.6HzCH),4.04(5H,s,CH).13C-NMR 0.3360g,92%,m.p.=184–186°C,DSCpeakm.p184.76°C,DH =
5 4 5 4 5 5 f
(400MHz,CDCl,dppm):d=160.58(-CH=N-),154.60(CHN), 3.34×106Jmol–1,DS =7.23×103Jmol–1K–1.Calc.forC H NFe:
3 5 4 f 22 20 2
151.08 (CH), 149.76 (CHN), 140.65 (CHN), 136.76 d = [M+]=368.0976.Found[M+]368.0975.FT-IR(cm–1):3343,3082,
6 4 5 4 5 4
(CHN), 129.20 (CH), 127.87 (CH), 125.20 (CH), 124.522 2882, 1611, 1594, 1532, 1323, 1293. 1H-NMR (400 MHz, CDCl,
5 4 6 4 6 4 6 4 3
(CHN),122.00(CH),118.98(CH),69.46(CH),69.10(CH), dppm):d=8.58(1H,d,J=3.6Hz,CHN),7.64(1H,t,J=7.5Hz,
5 4 6 4 6 4 5 4 5 4 5 4
66.57 (CH) ppm. CHN),7.34(1H,d,J=7.7Hz,CHN),7.29(2H,d,J=8.1Hz,
5 5 5 4 5 4
CH),7.18(1H,t,J=5.4Hz,CHN),6.60(2H,d,J=8.1Hz,CH),
6 4 5 4 6 4
2.2.4.Synthesis of (E)-3-ferrocenyl-N-(pyridinyl-3- 4.48 (4H, m, C5H4), 4.20 (2H, s, -CH2-) 4.00 (5H, s, C5H5) ppm.
methylene)aniline(7) 13C-NMR(400MHz,CDCl3,dppm):d=149.89(C5H4N),142.5
3-Ferrocenylaniline (2) (0.3000 g, 1.08 mmol) and (C6H4) 136.73 (C6H4N), 127.20 (C5H4N), 122.16 (C6H4N), 121.68
pyridine-3-carboxyaldehyde (0.1136 g, 1.06 mmol). Yield (C6H5), 113.10 (C6H4), 69.36 (C5H4), 68.11 (C5H4), 65.77 (C5H5),
0.3650g,94%;m.p.=95–96°C,DSCpeakm.p96.16°C,DHf= 49.43 (-CH2-) ppm.
4.3×106Jmol–1,DS =1.15×104Jmol–1K–1.Calc.forC H NFe:
f 22 18 2
[M+]=366.0819.Found[M+]=366.0807.FT-IR(cm–1):3089,2876, 2.3.2.Synthesis of 4-Ferrocenyl-N-(pyridinyl-3-methyl)aniline(10)
1900,1623,1411,1324.1H-NMR(400MHz,CDCl,dppm):d= Compound4(0.366g,1mmol).Recrystallizationinmethanol
3
9.03(1H,s,CHN),8.70(1H,s,CHN),8.53(1H,s,CHN),7.37 gavegoldenyellowplates.Yield0.3421g,93%,m.p.172–174°C;
5 4 5 4 5 4
(4H,m,CH),7.03(1H,s,-CH=N),4.67(2H,t,J=1.8,CH),4.32 DSCpeakm.p.174.70°C,DH =4.572×106Jmol–1,DS =1.02×
6 4 5 4 f f
(2H,t,J=1.8Hz,CH),4.05(5H,CH)ppm.13C-NMR(400MHz, 104Jmol–1K–1Calc.forC H NFe:M+=368.0976.Found[M+]=
5 4 5 4 22 20 2
CDCl, d ppm): d = 157.98 (-CH=N), 151.11 (CHN), 150.63 368.0985. FT-IR (cm–1): 3393, 3260, 3079, 2860, 1611, 1533, 1315,
3 5 4
(CHN), 142.81 (CH), 140.82 (CHN), 129.27 (CH), 124.80 1293,1251,1186.1H-NMR(400MHz,CDCl,dppm):d=8.67(1H,
5 4 6 4 5 4 6 4 3
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 54
S. Afr. J. Chem., 2016,69, 51–66,
<http://journals.sabinet.co.za/sajchem/>.
s,CHN),8.55(1H,s,CHN),7.70(1H,d,J=7.7CHN),7.27 1417,1246,1068,1024.1H-NMR(400MHz,CDCl dppm):d=
5 4 5 4 5 4 3
(3H,m,1H-CHN,2H-CH),6.56(2H,d,J=8.5Hz,CH),4.51 8.75(1H,s,CHN),8.60(1H,s,CHN),7.77(1H,d,J=6.0Hz,
5 4 6 4 6 4 5 4 5 4
(2H,t,J=1.8Hz,CH),4.36(2H,s,-CH-),4.21(2H,t,J=1.8, CHN),7.32(1H,s,CH),7.08(1H,t,J=7.5Hz,CHN),6.9(1H,
5 4 2 5 4 6 5 5 4
CH), 4.00 (5H, s, CH) ppm. 13C-NMR (400 MHz, CDCl, d,J=7.6Hz,CH),6.71(1H,s,CH),6.47(1H,d,J=7.6Hz,
5 4 5 5 3 6 5 6 5
dppm):d=149.2(CH),148.75(CHN),145.98(CHN),135.18 CH),4.53(2H,t,J=1.8Hz,CH),4.41(2H,s,-CH-),4.24(2H,t,
6 4 5 4 6 4 6 5 5 4 2
(CHN), 128.55 (CHN), 127.24 (CH), 113.05 (CH), 86.58 J=1.8Hz,CH),3.97(5H,s,CH)ppm.13C-NMR(400MHz,
5 4 5 4 6 4 6 4 5 4 5 4
(CH),69.38(CH),68.21(CH),65.79(CH),46.03(-CH-)ppm. CDCl,dppm):d=149.12(CHN),148.68(CH),147.51(CHN),
5 4 5 4 5 4 5 5 2 3 5 4 6 4 5 4
140.30(CHN),135.16(CH),129.19(CH),116.55(CH),111.00
5 4 6 4 6 4 6 4
2.3.3.Synthesis of 4-Ferrocenyl-N-(pyridinyl-4-methyl)aniline(11) (C6H5),110.8(C6H4),85.88(C5H4),69.60(C5H4),68.73(C5H4),66.61
(CH), 45.95 (-CH-) ppm.
Compound 5, (0.366 g, 1 mmol) used. Recrystallization in 5 5 2
methanolgaveshinnyorangeplatessuitableforX-raycrystal-
lography.Yield0.3533g,96%,m.p=189–191°C,DSCpeakm.p 2.4. Crystal Structure Determination and Refinement
191.31°C,DH =3.84×106Jmol–1,DS =8.28×103Jmol–1K–1. Asinglecrystalofeithercompound4,9,10and11wasselected
f f
Calc. for C H NFe: [M+], 368.0976. Found [M+] 368.0961. andattachedontothetipofglassfibresusingepoxyglue.The
22 20 2
FT-IR(cm–1):3324,3086,2917,1603,1535,1417,1283.1H-NMR(400 crystalsweremountedonaMitegenMicromountandcentredin
MHz,CDCl dppm):d=8.58(2H,d,J=4.0Hz,CHN),7.32(2H, theX-raybeambyusingavideocamera.Thecrystalevaluation
3, 5 4
d,J=4.0Hz,CHN),7.28(2H,dd,J=6.7Hz,J=1.8Hz,CH), and data collection were done on a Bruker Smart APEX2
6.51(2H,d,J=58.64 Hz,CH),4.50(2H,t,J=1.8Hz,CH),64.347 diffractometerwithMoKaradiation(l=0.71073Å)equipped
6 4 5 4
(2H, s, -CH-), 4.21 (2H, t, J = 1.8 Hz, CH) 4.0 (5H, s, CH). withanOxfordCryostreamlowtemperatureapparatusoperat-
2 5 4 5 5
13C-NMR(400MHz,CDCl,dppm):d=149.97(CHN),147.6 ingat100K.Theinitialcellmatrixwasdeterminedfromthree
3 5 4
(CH), 144.63 (CHN), 139.24 (CH), 127.25 (CH), 122.21 seriesofscansconsistingoftwelveframescollectedatintervals
6 4 5 4 6 4 6 4
(CHN), 112.97(CH), 69.37 (CH),, 68.21(CH), 65.81(CH), of0.5°ina6°rangewiththeexposuretimeoftensecondsper
5 4 6 4 5 4 5 4 5 5
47.31 (-CH-) ppm. frame.Eachofthethreeseriesofscanswascollectedatdifferent
2
startinganglesandtheAPEX2programsuitewasusedtoindex
thereflections.67Thedatacollectioninvolvedusingomegascans
2.3.4.Synthesis of 3-Ferrocenyl-N-(pyridinyl-2-methyl)aniline(12)
of0.5°widthwithanexposuretimeof20secondsperframe.The
Compound 6 (0.366 g, 1 mmol) used. Recrystallization in
totalnumberofimageswasbasedonresultsfromtheprogram
methanol gave orange blocks. Yield; 0.3390 g, 92 %, m.p =
COSMO,wherebytheexpectedredundancywastobe4.0and
110–112°C,DSCpeakm.p111.79°C,DH =9.27×106Jmol–1,
f completeness of 100 % out to 0.75 Å. Cell parameters were
DS =8.29×104Jmol–1K–1..Calc.forC H NFe:[M+]368.0976.
f 22 20 2 retrievedusingAPEX2andrefinedusingSAINTonallobserved
Found[M+].368.0984.FT-IR(cm–1):3362,3014,1730,1603,1585,
reflections. Data reduction was performed using the SAINT.67
1521, 1434, 1418, 1246, 1144, 1045. 1H-NMR (400 MHz, CDCl
3 software and the scaling and absorption corrections were
dppm):8.59(1H,s,CHN),7.63(1H,d,J=7.3Hz,CHN),7.36
5 4 5 4 applied using SADABS68 multi-scan technique. The structures
(1H,d,J=7.6Hz,CHN),7.17(1H,d,J=5.1Hz,CH),7.08(1H,
5 4 6 4 weresolvedbythedirectmethodusingtheSHELXSprogram
t,J=7.7Hz,CHN),6.83(1H,d,J=7.3Hz,CH),6.76(1H,s,
5 4 6 4 andrefined.68Thevisualcrystalstructureinformationwasper-
CH),6.51(1H,d,J=7.5Hz,CH),4.55(2H,t,J=1.8Hz,CH),
6 4 6 4 5 4 formedusingORTEP-3systemsoftware.69Non-hydrogenatoms
4.45 (2H, s, -CH-), 4.23 (2H, t, J = 1.8 Hz, CH), 3.97 (5H, s,
2 5 4 werefirstrefinedisotropicallyandthenbyanisotropicrefine-
CH) ppm. 13C-NMR (400 MHz, CDCl, d ppm): d = 158.74
5 5 3 mentwithfull-matrixleastsquaresmethodbasedonF2using
(CHN), 149.02 (CH), 147.79 (CHN), 140.12 (CHN), 136.78
5 4 6 4 5 4 5 4 SHELXL.68Allhydrogenatomswerepositionedgeometrically,
(CHN), 129.12 (CH), 122.19 (CHN), 121.66 (CH), 116.14
5 4 6 4 5 4 6 4 allowedtorideontheirparentatomsandrefinedisotropically.
(CH), 111.16 (CH), 111.01 (CH), 86.04 (CH), 69.56 (CH),
6 4 6 4 6 4 5 4 5 4 The crystal data and structural refinement information are
68.64 (CH), 66.61 (CH), 49.42 (-CH-) ppm.
5 4 5 5 2 summarized in Table 1. All data were subjected to the online
checkCIF evaluation criteria.
2.3.5.Synthesis of 3-ferrocenyl-N-(pyridinyl-3-methyl)aniline(13)
Compound 7 (0.366 g, 1 mmol) used. Recrystallization in 2.5. Biological Studies
methanolgavedeeporangeblocks.Yield;0.3240g,88%,m.p=
88–90 °C. Calc. for C22H20N2Fe: [M+] 368.0976. Found [M+]. 2.5.1.Inoculation Procedure
368.0981. FT-IR(cm–1): 3267, 3096, 2920, 1723, 1602, 1536, 1460, Inoculationofthemicroorganismusedwasdoneinnutrient
1423,1309,1236,1103,1024.1H-NMR(400MHz,CDCl3dppm): brothaftersterilization.Nutrientbroth(1.3g)wasdissolvedin
d=8.67(1H,s,C5H4N),8.53(1H,s,C5H4N),7.72(1H,d,J=6.8Hz, distilledwater(100mL).Approximately10mLportionsofthe
C5H4N),7.28(1H,s,C5H4N),7.07(1H,t,J=7.6Hz,C6H4),6.85(1H, nutrient broth solution were poured into test tubes. The test
d,J=7.2Hz,C6H4),6.69(1H,s,C6H4),6.46(1H,d,J=7.4Hz, tubeswereclosedwithcottonwoolplugswhichwerewrapped
C6H4),4.52(2H,t,J=1.8Hz,C5H4).4.39(2H,s,-CH2-),4.24(2H,t, withaluminiumfoilandthensterilizedbyautoclavingat121°C
J=1.8Hz,C5H4),3.97(5H,s,C5H5)ppm.13C-NMR(400MHz, for15min.Thebrothwasallowedtocoolto37°Cafterwhichthe
CDCl3,dppm):d=149.12(C6H4),148.68(C5H4N),147.50(C5H4N), microorganisms were inoculated. Inoculation was done via
140.30(C5H4N),135.16(C5H4N),129.19(C6H4),123.10(C5H4N), sterilizedcottonswab.Theinoculumswereincubatedat37°C
120.00 (C6H4 ), 116.55 (C6H4), 111.00 (C6H4), 85.81 (C5H4), 69.60 for 24 h.
(CH), 68.73 (CH), 66.61 (CH), 45.95 (-CH-) ppm.
5 4 5 4 5 5 2
2.5.2.Preparation of Müller-Hinton Agar Test Plates
2.3.6.Synthesis of 3-ferrocenyl-N-(pyridinyl-4-methyl)aniline(14) Müller-Hintonagar(38g)wasdissolvedindistilledwater(1L).
Compound 8, (0.366 g, 1 mmol) used. Recrystallization in The resulting agar medium was sterilized by autoclaving at
methanol gave orange blocks suitable. Yield 0.3136 g, 85 %; 121°Cfor15minandthereafterallowedtocoolinawaterbath
m.p = 141–143 °C. Calc. for C H NFe: [M+] 368.0976. Found set at 45 °C. After cooling, approximately 25 mL of the agar
22 20 2
[M+]. 368.0981. FT-IR(cm–1): 3375, 2919, 2850, 1726, 1586, 1456, medium were poured into previously washed and sterilized
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 55
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<http://journals.sabinet.co.za/sajchem/>.
Table1 Crystallographic and structural refinement data for compounds4,9,10and11.
4 9 10 11
Empirical formula C H Fe N C H Fe N C H Fe N C H Fe N
22 18 2 22 20 2 22 20 2 22 20 2
Formula weight 366.23 368.25 366.23 368.25
Temperature/K 173 173 173 298
l/Å 0.71073 0.71073 0.71073 0.71073
Crystal system Monoclinic Monoclinic Orthorhombic Monoclinic
Space group P2/c P2/c Pca2 P2/c
1 1 1 1
Unit cell dimensions/Å,° a = 20.5507(8),a= 90 a = 20.549(7),a= 90 a = 12.262,a= 90 a = 18.584(5),a= 90
b = 7.5111(3),b= 93.278(2) b = 10.023(4),b= 94.008(13) b = 7.683,b= 90 b = 7.734(2),b=
107.099(7)
c = 10.5766(4),g= 90 c = 8.220(3),g= 90 c = 34.538,g= 90 c = 12.289(3),g= 90
V/Å3 1629.92(11) 1688.8(11) 3253.8 1688.1(8)
Z 4 4 8 4
s /Mg m–3 1.492 1.448 1.495 1.449
calc
Abs. coefficient/mm–1 0.931 0.899 0.933 0.899
F(000) 760 768 1520 768
Crystal size/mm 0.220 × 0.180 × 0.120 0.430 × 0.300 × 0.150 42.000 × 0.280 × 0.140 0.48 × 0.37 × 0.13
qrange 1.985 to 28.715 ° 1.987 to 25.500 ° 2.359 to 32.683 ° 2.29 to 26.00 °
Index ranges –27£h£26 –24£h£24 –15£h£17 –22£h£22
–9£k£10 –12£k£12 –10£k£10 –9£k£9
–13£l£14 –9£l£9 –51£l£52 –15£l£13
Reflections collected 33419 22531 35237 19059
Independent reflections 4114 [R(int) = 0.0220] 3134 [R(int) = 0.0476] 9830 [R(int) = 0.0849] 3321 [R(int) = 0.0578]
Completeness toq25.242 ° 99.7 % 99.9 % 97.2 % 99.9 %
Data / restraints / parameters 4114 / 0 / 226 3134 / 0 / 226 9830 / 1 / 452 3321 / 0 / 230
Goodness-of-fit onF2 1.137 1.050 1.130 1.052
Final R indices [I>2sigma(I)] R1 = 0.0508, R1 = 0.0350, R1 = 0.1008, R1 = 0.0318,
wR2 = 0.1340 wR2 = 0.097 wR2 = 0.2354 wR2 = 0.0826
R indices (all data) R1 = 0.0533 R1 = 0.0437 R1 = 0.1245 R1 = 0.0386
wR2 = 0.1352 wR2 = 0.1037 wR2 = 0.2486 wR2 = 0.0886
Absolute structure parameter – – 0.40(6) –
Largest diff. peak and hole/e.Å–3 1.108 and –0.808 0.683 and –0.529 1.116 and –3.077 0.341 and –0.323
Full-matrix least-squares onF2refinement method was applied for all the compounds.
flat-bottomed glass petri dishes to give a uniform depth of vacuumtoobtainthefinalproductinexcellentyields.Alltheim-
approximately4mm.Theagarmediumwasallowedtocoolto inesexceptcompound5,arenewandhavenotbeenreported
roomtemperature(ca.25°C)andset.Thetestorganismswere before.
thenstruckonthesurfaceoftheagarmediumusingwireloops Theaminederivativescompounds9–14synthesizedhereare
sterilizedbyheatingredhotinaflamethatwasthencooled.The all new and have not been reported. These compounds were
paperdiscscontainingthe20µgofcompoundunderinvestiga- obtainedinexcellentyieldsbysolvent-lessreductionofcorre-
tionwerethenloadedontothealready-inoculatedagarplates sponding imines via the mechanochemistry technique.66 The
usingsterilizedforcepsandthenincubatedat37°Cfor24h.The iminederivativesweregroundonNaBH supportedonneutral
4
diameterofthezoneofinhibitionwasmeasuredaroundthedisc. AlO solid-phaseandthereactionproceededviatheproposed
2 3
Arepresentativesampleofeachbatchofplateswithoutany plausiblemechanismshowninFig.1.Theproductwasextracted
microorganismwasalsoincubatedatthesametemperaturefor by dichloromethane and thereafter purified through column
24htoexamineforsterility.Viabilityoftheorganismswastested chromatography.Progressofreactionsfortheformationofthe
byincubatingtestplateswithoutthecompoundsbeinginvesti- secondaryaminederivativeswasmonitoredbyFT-IR,aswellas
gated.Chloramphenicolwasusedasthestandardantibacterial TLC on aluminium-coated plates. Synthesis techniques em-
agent whereas fluconazole was used in the technique as the ployedhereareecologicallybenignandalsoofferconsiderable
standard antifungal agent. synthetic advantages in terms of yield, selectivity, time and
simplicity of the reaction procedure.
3.0.Results and Discussion
3.2. Characterization
3.1. Syntheses The synthesized anilines show N-H stretching absorption
The ferrocenyl-N-(pyridinylmethylene)anilines, compounds bands at 3396 and 3217 cm–1 characteristic of the aromatic
3–8,wereobtainedviacondensationof3-or4-ferrocenylanilines amines. These N-H stretching bands are absent in the corre-
withappropriatepyridinecarboxaldehydes(Schemes1and2). spondingSchiffbasesformed.Hence,thecompletedisappear-
Thereactionswerecarriedoutbygrindingofthereactantsun- anceoftheN-Hstretchingbandaswellasthatofthealdehyde
dersolvent-freeconditionsinaquartztube.Progressesofreac- C=Ostretchingbandat1708to1699cm–1andthecorresponding
tionsfortheformationofSchiffbasesweremonitoredbyFT-IR. appearanceofC=Nsp2stretchingbandsrangingfrom1623to
Theobtainedmeltsandinsomecasespastesweredriedunder 1630cm–1confirmstheformationoftheSchiffbases3–8.These
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 56
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<http://journals.sabinet.co.za/sajchem/>.
Scheme 1
Solvent-free synthesis route for compounds3–5and9–11.
Scheme 2
Solvent-free synthesis route for compounds6–8and12–14.
characteristic stretching frequencies of the ferrocenyl-N-(pyri- mentswerefurthersupportedbythe1H-NMRspectraforcom-
dinylmethylene)anilinesSchiffbasesareconsistentwiththose pounds3–8wheretheimineN=CH-protonpeakappearsinthe
reportedforsimilarcompoundsandtheoreticalexpectations.21,70,71 aromaticregion.Thesepeakscorrespondstoup-fieldshiftofthe
Important infrared absorption bands along with their band aldehydepeakofthepyridinecarboxaldehydesfrom10.5ppm,
assignmentsarelistedinTable2.Alltheaminederivativesshow to 7.2–8.5 ppm in the imines.
a medium frequency stretching band between 3260 and 3362 Forinstance,inthe1H-NMRforcompound4,theimineproton
cm–1assignedtothesecondaryamineN-Hstretch.Moreover, resonatesat8.56ppm.Theprotonsofthepyridineringappearat
theaminederivativesshowstretchingfrequenciesrangingfrom 9.05,8.72,8.56,8.30and7.42ppm.Thetwosetsofprotoninthe
1023to1188cm–1thatwereassignedtothestretchingbandof phenylringappearat7.50and7.19ppmwiththeircouplingcon-
secondaryamineC-Nsp3bond.Thesesecondaryaminestretch- stant being 8.4 Hz. The two sets of protons in the substituted
ing frequencies are lower than their corresponding C=N sp2 cyclopentadienylringappearat4.65and4.32ppmwhilethefive
stretchingfrequencies.Thisisexpectedsincetheaminebonds protons in the unsubstituted ring appear at 4.40 ppm. The
aremuchweakerwhencomparedtotheiminebondsandthus 13C-NMRspectraofthesecompoundsshowtheiminecarbonis
theformerrequirelesserenergytostretch.Theaminesalsoshow themostdeshieldedanditisregisteredbetween150to160ppm.
astretchingbandrangingbetween3000and2840cm–1,charac- For instance, the 13C-NMR spectrum of compound 4 shows a
teristictoC-Hstretchofthesp3methylenegroup.Thesecom- peakassociatedwiththemostdeshieldedcarbonat156.43ppm
poundsshowcharacteristicabsorptionpeaksforFe-Cpstretch- andthispeakisaccordinglyassignedtotheiminecarbon.The
ing vibrations ranging from 479 to 490 cm–1. These infrared aromaticcarbonsappearintheregionfrom121–149.78ppmand
stretching bands are not unusual and have been observed in thoseofthecyclopentadienylat66.65–84.71ppm.Thesedistri-
otherferrocenylSchiffbases.9Thecondensationreactionlead- butions of protons and carbon peaks is in tandem with the
ing to formation of the Schiff bases and the structural assign- proposed structure and confirms the formation of the target
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 57
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Figure1 Proposed plausible mechanism for reduction of the imines3–8with NaBH activated on AlO solid-phase.
4 2 3
compound.Theotheriminesreportedhereshowsimilartrends shiftoftheiminecarbonpeaksto46.03ppmincompound10
inboththeprotonandcarbonspectraasindicatedintheexperi- from156.43ppmincompound4.Thisisinagreementwiththe
mentalsectionforeachofthem(seeSupplementarymaterial). conversionofthecarbonfromthesp2tosp3afterreduction.Simi-
TheseNMRdataareconsistentwiththereporteddataofsimilar larly, the amine carbon peaks in the other ferro-
compounds.21,71 cenyl-N-(pyridinylmethyl)anilines 9, 11–15 appear between
Uponreductionofimines3–8totheircorrespondingamines 45–50 ppm. As expected, these carbon atoms exhibit negative
9–14,majorupfieldshiftsinpeaksforalmostalltheprotonsare peaksintheDEPT13C-NMRinthesameposition(ppm).TheESI
observed.Uponconversionoftheiminetoamine,theproton massspectrumofeachofthesecompoundsshowedamolecular
peaksforthesp2methinegroup,=CH–,areshiftedupfieldtoca ionpeak(100%)thatcorrespondstothemassparentmolecule.
4.4ppm,characteristictosp3methylenegroup–CH–.Incom- Nomajorfragmentationswererecorded.Thesedatacorrelate
2
pound 10 for instance, these proton are now observed at wellwiththatreportedinliteratureforferrocenylcompounds
4.36ppmandtheirpeakintegratestotwoprotons.Theprotons havingsecondaryaminefunctionalgroups.29Theabsolutestruc-
on the alpha carbon atoms of phenyl ring (with respect the tures of some of these compounds were confirmed by X-ray
aminogroup)nowresonateat6.56ppmdownfrom7.50ppm. crystallography technique as discussed in Section 3.3.
Thealphaprotonsofthepyridinering(withrespecttothesub-
stitution and N atom) resonate at 8.67 ppm in compound 10, 3.3. X-ray Crystallography of Compounds4and9–11
downfrom9.05ppmincompound4.Alltheotheraminesshow SinglecrystalsforX-rayanalysisforcompound4weregrown
similartrendsinshiftofprotonpeaks.Thereisalsoanupfield indichloromethane/methanolwhilethoseofcompounds9,10
Table2 IR spectral data (selected stretching frequencies).
Compound n(C-H) methylene n(C-H) methine n(C-N) Ph-N n(C=N) imine n(C-N) amine n(N-H)
3 – 3084 1281 1630 – –
4 – 3090 1280 1629 – –
6 – 3089 1283 1623 – –
7 – 3089 1251 1623 – –
8 – 3089 1286 1623 – –
9 3082 – 1248 – 1186 3343
10 2860 – 1251 – 1186 3260
11 3027 – 1270 – 1188 3325
12 3014 – 1246 – 1023 3362
13 3096 – 1236 – 1024 3267
14 2919 – 1246 – 1023 3326
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 58
S. Afr. J. Chem., 2016,69, 51–66,
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and11wereobtainedfrommethanol,allasorangeplates.The Theconformationincompound4seemstobedifferentfrom
asymmetric unit for compound 10 contains two independent thoseofcompounds9–11.In4thesubstitutedcyclopentadienyl
moleculesrelatedbyaninversioncentre,similartothatreported ringandthephenyliminemoietyarenotcoplanarandhavea
inthecrystalstructureofcompound5.21Ontheotherhand,the dihedralangleof15.69(0.175)°.Thephenyliminemoietyisalso
asymmetricunitsincompounds4,9and11eachcontainasingle twistedfromtheplaneofthemethylpyridinylmoietythrougha
molecule.Thetwomoleculesinthestructureofcompound10 dihedral angle of 49.18(07) ° very similar to those reported in
havedifferentconformations.Eachofthesecompoundsbearsa literatureforsimilarcompounds.72,73Theconformationsofthe
ferrocenyl imine moiety (from the starting ferrocenyl aniline) moleculesinthestructuresofcompounds9and11seemtohave
and a methyl pyridinyl moiety from the starting pyridine twomajorplanessimilartothoseofthetwomoleculesincom-
carboxaldehyde forming the (E)-4-ferrocenyl-N-(pyridinyl- pound10.However,inthemolecularstructuresofthetwocom-
3-methylene)aniline Schiff base 4, and ferrocenyl-N-(pyri- pounds the dihedral angle between the ferrocenyl phenyl
dinylmethyl)anilines, compounds 9–11 on reduction of the aminemoietyandamethylpyridinylmoietyis72.097(0.048)and
respectiveSchiffbases.Figure2showsORTEPdiagramsforfour 83.059(0.055)°in9and11,respectively.Theobserveddisparities
compounds. inorientationofthevariousmoietiesintheSchiffbase4com-
ThetwomoietiesreferredinFig.2seemtobethetwomainsets pared to the ferrocenyl-N-(pyridinylmethyl)anilines, com-
of planes that describe the conformations in some of the four pounds9–11canbeattributedtothepresenceofiminegroupin
compoundsdiscussedhere.Thedihedralanglesbetweenthese 4thatisadequateinprovidingpiorbitalstomaintainconjuga-
twoplanesseemtodifferfromcompoundtocompoundandin tionwithintheentiremolecule.71Thisconjugationis,however,
compound10,betweenthetwomoleculesinthecrystalstructure. brokenuponreductionoftheiminetosecondaryaminesincom-
Inthestructureofcompound10thedihedralanglebetweenthe pounds 9–11. This behaviour of secondary amines bearing a
twomolecules89.011(0.082)°inoneand84.129(0.089)°inthe ferrocenyl moiety is not exceptional and has been previously
second.Thedifferenceintheconformationsofthetwomole- documented.38
cules is further depicted in the molecule overlay diagram in Fundamentalbondlengths,angles,planesandinteractionsare
Fig. 3. The root mean square deviation of one from the other presentedonTable3.TheC-N andN -C bonddistances
imine imine Ph
molecule is 0.0748 Å. In the overlay it is also evident that the in4aresignificantlydifferentfromthosein9–11asexpected.In
methylpyridinylmoietyistwistedbyabout180°inthesecond compound4,theC—N bonddistanceis1.276(5)Åwhilethe
imine
molecule. N -C is 1.422(4). The corresponding bond distances, i.e.
imine Ph
Figure2 ORTEPdrawingsforcompounds4(a),9(b),10(c),and11(d),showingtheatomnumberingschemeandthermalmotionellipsoids(50%
probabilitylevel).Onlyoneofthetwomoleculesincompound10isshownhereandforallcompoundshydrogenatomshavebeenomittedforclarity.
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 59
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Table3 Selected bond lengths (Å), bond angles (°) and planes for compounds4,9,10and11.
Compound: 4 9 10 11
Bond length
Ph-N 1.422(4) 1.381(2) 1.388(2) 1.387(2)
imine/amine
1.374(2)
C -N 1.272(5) 1.445(2) 1.445(2) 1.443(3)
methine/methylene imine/amine
1.465(2)
Bond angles
C -N -C 118.57(3) 121.90(1) 119.70(1) 120.49(2)
Ph imine methylene
119.52(1)
N -C -C 122.08(3) 111.04(1) 111.29(1) 110.61(2)
imine methylene py
111.25(1)
Planes
[Cp ]-[PhN] 15.69(0.175) 7.114(0.117) 2.356(0.237) 2.96(1)
(subs)
1.481(0.235)
[PhN]-[CPy] 49.18(0.072) 72.097(0.048) 89.011(0.082) 83.059(0.055)
84.129(0.089)
[Cp PhN]-[(CPy)] – – 84.66(3) –
(subs)
88.95(2)
Cp –Cp torsion angles 1 2
(subs.) (unsubs.)
C1-C6 7.76 12.97 23.77 20.97 21.48
C2-C7 7.98 13.37 24.22 22.22 21.66
C3-C8 7.47 13.27 23.78 21.28 21.03
C4-C9 7.39 12.67 23.20 20.78 21.47
C5-C10 7.21 13.00 23.29 21.09 21.97
Average 7.56 13.06 23.75 21.27 21.52
Table4 Hydrogenbondingparametersandintermolecularinteractions
for compounds4,9,10and11.
Compound: 4 9 10 11
Lengths 2.66(3) 2.54(2) 2.14(1) 2.37(2)
Angles/H-D…A) 160 161 167 166
p–pinteractions
Lengths/Å
Py-Ph 3.929 – – 3.532 3.797
Figure3 Anoverlayofthetwomoleculesintheasymmetricunitof C-H35-p – – – 2.868 –
cp-subs
compound10. Hydrogen atoms omitted for clarity. C-H39-p – – – 2.993 –
cp-subs
Angles/°
C-N and N -C in 9–11 are much longer than those in
amine amine Ph C-H35-p – – – 156 –
compound4.TheC-Naminedistancesare1.445(2)and1.465(2)Å C-H39-pccpp--ssuubbss – – – 172 –
forthetwomoleculesin10,1.445(2)and1.443(3)Åin9and11,
respectively.TheNa -C distancesare1.388(2)and1.374(2)Å
mine Ph
in10,1.381(2)and1.387(2)forcompounds9and11.Compounds genbondingwithbonddistancesof2.54(3)and2.37(2)Å,respec-
6hasaniminebondwhichhasgreaterelectrondensityinthe tively. The donor atoms are pyridinyl nitrogen atoms in both
inter-nucleiregionthatcontributetoastrongerbondwhichis cases.Thisresultsinastep-likesupramolecularstructureincom-
shorter whereas compounds 9–11 have single amino bond pound9anddimerincompound11.Thehydrogenbondingand
which relatively weaker and thus longer. stabilityofthedimerincompound11arefurtherbuttressedby
Table 4 lists important intermolecular interactions in com- intermolecular p–p interactions involving the pyridinyl rings.
pounds4,9,10and11.Thecompoundsalsoshownonclassical Compound10,showsintermolecularp–pinteractionsbetween
interactions yielding supramolecular structures. Compound 4 thepyridinylandphenylringsandC-H…pinteractionsinvolv-
for instance shows significant intermolecular p–p interactions ing the substituted Cp ring in one of the molecules.
involvingthepyridinylandphenylrings.Consequently,thisori-
entsthemoleculeinamannerleadingtoformationofC—H…N 3.4. Thermal Studies
andp…pintermolecularinteractionsformingchainsinwhich Despite having both the phenyl and pyridinyl moieties, in
molecules are stacked in an alternating head-to-tail manner additiontotheferrocenylgroup,thecompoundsreportedhave
downbcrystallographicaxis.Compound9hasN—H…Ninter- sharp melting points similar to ferrocenyl derivatives having
actionsdowntheccrystallographicaxis:Thisinteractionleadsto onlyasinglephenylunit74Ferrocenylcompoundshavingone
the formation of a step-like supramolecular structure. longeraxiswheretwophenylunitsarelinkedtooneCpringin
Compounds9and11showreasonableintermolecularhydro- series forming a chain generally show crystal-crystal phase
RESEARCHARTICLE E.M. Njogu, B. Omondi and V.O. Nyamori, 60
S. Afr. J. Chem., 2016,69, 51–66,
<http://journals.sabinet.co.za/sajchem/>.
transitionswhilethosewiththreeormorephenylusuallyshow -(pyridinylmethyl)anilinesareattributedtothemixingofappre-
liquidcrystallinepropertiesandcrystalphasetransitions.10,29,38,74 ciable metal-to-ligand charge transfer (MLCT) character into
Compoundsreportedherelackthesecredentials(i.e.longlinear theirlow-energyelectronicexcitedstates.76ThisMLCTcontribu-
shapeandlargelength-depthratio)togenerateintermolecular tion originate from vectorial displacement of electron density
interactionsleadingtomesomorphism.Therefore,theDSCdata fromthemetaltotheligand.Conjugationbetweentheporbitals
forcompoundsreportedshowasinglekeyevent,i.e.melting of the cyclopentadienyl, phenyl and pyridyl rings allows the
andsubsequentdecomposition.Thedataobtainedforthecom- transferredchargetobedelocalizedoverseveralatoms,conse-
poundsarelistedinTable5.Themoleculesfortheiminederiva- quentlystabilizingtheMLCTexcitedstaterelativetotheground
stateandloweringthetransitionenergy.Also,thepolarsolvents
Table5 Physical and analytical data. lower the transition energy owing to the greater Coulombic
stabilization of the dipolar (charge-separated) excited state.
Compound Yield HRMS (ESI-TOF) m/z: [M]+ Melting Increaseintheintensityoftheabsorptionbandsisasaresultof
/% point/°C
mixingchargetransfercharacterintothetransitionthusreduc-
Calc. Found ing the Laporte forbidden character.76 The observed shifts of
bandmaximatohigherenergiesinpolarsolventspointtopresence
3 89 366.0819 366.0825 138–140
ofapolargroundstateandnonpolarexcitedstateinimines,i.e.
4 92 366.0819 366.0818 146–148
compounds3,4and6–8.
5 94 366.0898 366.0840 93–94
On the other hand, the amine compounds 9–14 showed
6 94 366.0819 366.0807 95–96
8 94 366.0819 366.0831 125–126 hypsochromicshift77wheninpolarsolvent(methanol)compared
9 91 368.0976 368.0975 184–186 to the non-polar (toluene), an indication of possible hydro-
10 93 368.0976 368.0985 172–174 gen-bondingbetweenthecompoundsandpolarsolventmole-
11 96. 368.0976 368.0961 189–191 cules.ThesecompoundshaveadipoleinvolvingtheaminoN
12 92 368.0976 368.0984 110–112 atomanditsHatom.Thepolarsolventincreasesthecontribu-
13 88 368.0976 368.0981 88–90 tionofthepolarunitofthemoleculeinthegroundstate.Upon
14 85 368.0976 368.0981 141–143
transition, the dipole associated with the molecule is either
reversed or rotated, subsequently this alteration leads to a
tivesfrom3-ferrocenylanilinehavelowermeltingpointscom- hypsochromic shift (negative solvatochromism).77,78 The
paredtothosederivedfromthe4-ferrocenylaniline.Among,the hypsochromicshiftisconsistentwithdiminishedconjugationin
imine derivatives from 3-ferrocenylaniline the melting points theamine.Theaminesabsorbatlongerwavelengthswhencom-
increaseintheordercompound6<7<8.Fromthesestudies,it paredtotheircorrespondingiminesandthisisduetochangein
isalsoevidentthattheaminederivativeshavehighermelting thehybridizationofNatomuponreduction.Thesolvatochromic
pointsthantheircorrespondingiminesfromwhichtheywere behaviourofthesecompoundsiswellinlinewiththenonlinear
obtained.Therefore,theaminesexhibitstrongerintermolecular opticalproperties(Table6)andwarrantsfurtherinvestigation
forcesthatmightalsobereinforcedbyhydrogenbondinglikein and application. The absorption spectra of the compounds in
compound9.Thepositionofthepyridinenitrogenandalsothe methanol and toluene are shown in Fig. 4. The absorption
positionofsubstitutiononthephenylring(i.e.3-or4-ferrocenyl-
Table6 Maximumabsorptions(l )/nmofthecompoundsinvarious
aniline) influence the thermal properties of the compounds. max
solvents.
3.5. Photophysical Studies Compd Solvent
TheUV/Visabsorptionandemissionofthecompoundswere Methanol DMF Chloroform Acetonitrile Toluene
carried out in solution at room temperature.
3 289 288 286 286 284
3.5.1.Solvatochromism Studies
252 343 242, 346 242, 340 347
Themetalloligandsreportedaresolubleinavarietyoforganic
4 286 287 285 284 285
solvents and this allowed detailed investigation of their
245, 330 344 245, 346 242, 340 347
solvatochromicbehaviour.Thesolvatochromismcharacteristics
6 289 284 283 283 284
werestudiedbymeasuringtheUV-Visspectraofcompounds3,
– – 242 242
4 and 6–14 in polar (methanol, N,N-dimethylformamide),
7 289 283 280 286 284
mid-polar(acetonitrileandchloroform),andnonpolar(toluene)
252 – 243 340
solvents. As anticipated, in all solvents, all the compounds
8 291 281 277 279 285
showed a bathochromic (red) shift in comparison to pristine
– – 241 235
ferrocene. The imines and amines displayed both n–p* and
9 294 299 296 295 298
p–p*transitions60,75inmethanol.Thestrongerandhigherenergy
257 226, 446 258 258 –
peak were attributed to the p–p* transition of the Schiff base
10 292 299 295 295 297
chromophoresandthebenzeneringwhiletheweakerandless
256 – 257 257 –
energeticpeakswereassignedtothen–p*60transitioninvolving
11 294 298 294 294 296
thepromotionofthelonepairelectronofiminenitrogenatomto
256 – 256 256 –
theantibondingporbitalassociatedwiththeSchiffbasegroup.
12 231 268 243 231 284
Weaker bands appearing at longer wavelengths can be attrib-
316 321 314 317 317
utedtothed–dtransitions.Onchangingsolventfromnonpolar
13 231 268 243 231 286
to polar, all the imines showed a bathochromic shift of p–p*
316 317 315 317 317
transitions75anindicationoftheirnon-linearopticscharacter,a
14 231 267 243 231 286
behaviourthathasalsobeenobservedinotherferrocenylimine
316 319 314 317 317
derivatives.52,75,Thesespectralcharacteristicsoftheferrocenyl-N