<<

Article OSU-6: A Highly Efficient, Metal-Free, Heterogeneous Catalyst for the Click Synthesis of 5-Benzyl and 5-Aryl-1H-tetrazoles

Baskar Nammalwar, Nagendra Prasad Muddala, Rajasekar Pitchimani and Richard A. Bunce *

Received: 18 November 2015; Accepted: 11 December 2015; Published: 19 December 2015 Academic Editor: Derek J. McPhee

Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA; [email protected] (B.N.); [email protected] (N.P.M.); [email protected] (R.P.) * Correspondence: [email protected]; Tel.: +1-405-744-5952; Fax: +1-405-744-6007

Abstract: OSU-6, an MCM-41 type hexagonal mesoporous silica with mild Brönsted acid properties, has been used as an efficient, metal-free, heterogeneous catalyst for the click synthesis of 5-benzyl and 5-aryl-1H-tetrazoles from in DMF at 90 ˝C. This catalyst offers advantages including ease of operation, milder conditions, high yields, and reusability. Studies are presented that demonstrate the robust nature of the catalyst under the optimized reaction conditions. OSU-6 promotes the 1,3-dipolar addition of azides to nitriles without significant degradation or clogging of the nanoporous structure. The catalyst can be reused up to five times without a significant reduction in yield, and it does not require treatment with acid between reactions.

Keywords: 5-benzyl and 5-aryl-1H-tetrazoles; carboxylic acid bioisosteres; click 1,3-dipolar addition; heterogeneous catalysis; recyclable catalyst

1. Introduction Tetrazoles are versatile heterocyclic systems, which have attracted considerable interest in diverse applications ranging from pharmaceuticals [1–3] and agrochemicals [4] to photographic compounds [5], [6], new materials [7–9], and in coordination compounds [10,11]. In biological studies, tetrazoles play a critical role as pharmacophores and also as metabolic surrogates for carboxylic acids in various therapeutic agents to treat cancer, AIDS, bacterial infections, hypertension, convulsions, and allergies [12,13]. Currently, the commercial antihypertensives Losartan and Valsartan [14] as well as an experimental 2-arylcarbapenem antibiotic [15] all incorporate a tetrazole ring within their structures. Tetrazoles have been synthesized primarily by the reaction of azides with nitriles in polar aprotic media. This process has been promoted by various metal-based agents, including aluminum chloride, aluminum bisulfate, cadmium chloride, -, zinc- and iron-based salts, copper delafossite nanoparticles, palladium complexes, silver benzoate, metal-based triflates, tungstates, zinc-copper alloys, and zinc sulfate nanospheres [16,17]. Additionally, other heterogeneous catalysts, including CoY zeolites [18,19], SiO2–H2SO4 [20], Amberlyst-15 [21], and cuttlebone [22], as well as soluble additives NH4OAc and NH4Cl [23,24] have also been used to facilitate this reaction. We therefore wish to report a new catalyst which performs this conversion under metal-free conditions, at moderate temperatures, and with superior conversion rates, stability toward traces of water, and recyclability.

2. Results and Discussion OSU-6, an MCM-41 type hexagonal mesoporous silica [25], has recently proven useful as a mildly acidic, reusable catalyst for several transformations in our laboratory, affording products in excellent yields with minimal purification requirements [26–28]. Encouraged by these results, we sought to

Molecules 2015, 20, 22757–22766; doi:10.3390/molecules201219881 www.mdpi.com/journal/molecules Molecules 2015, 20, page–page

Molecules 2015, 20, 22757–22766 2. Results and Discussion OSU-6, an MCM-41 type hexagonal mesoporous silica [25], has recently proven useful as a exploremildly OSU-6 acidic, as areusable catalyst catalyst for the for click several synthesis transformations of tetrazoles in our from laboratory, azide and affording nitriles [products29,30]. In in order to gaugeexcellent the yields feasibility with ofminimal this process, purification the requir reactionements of benzyl[26–28]. cyanideEncouraged (1a ,by 1 equiv.)these results, with we sodium azidesought (1.2 equiv.) to explore to OSU-6 generate as a catalyst 5-benzyl-1 for theH-tetrazole click synthesis (2a) of was tetrazoles chosen from as azide a model and nitriles reaction. [29,30]. Various solventsIn order were to gauge evaluated the feasibility using 15of this wt pr %ocess, of the the catalyst reaction (relativeof benzyl to 1a) under(1a, 1 equiv.) varying with temperature (1.2 equiv.) to generate 5-benzyl-1H-tetrazole (2a) was chosen as a model reaction. Various conditions (Table1). Our optimization study determined that the reaction performed in DMF solvent solvents were evaluated using 15 wt % of the catalyst (relative to 1a) under varying temperature at 90 ˝C using 15 wt % of OSU-6, afforded the highest yield (94%) of the tetrazole product. More conditions (Table 1). Our optimization study determined that the reaction performed in DMF solvent or lessat 90 catalyst °C using did 15 wt not % improve of OSU-6, theafforded yields, the andhighes lowert yield temperatures (94%) of the tetrazole led to product. inefficient More conversions. or less In general,catalyst polardid not aprotic improve media the yields, gave and superior lower temperat resultsures since led they to inefficient solubilized conversions. both reacting In general, partners ˝ at temperaturespolar aprotic mediaě90 C.gavePolar superior protic results and since nonpolar they solubilized media, on both the reacting other hand,partners led at totemperatures unsatisfactory outcomes.≥90 °C. SolventlessPolar protic and conditions nonpolar affordedmedia, on reasonablethe other hand, conversions led to unsatisfactory for the model outcomes. reaction, Solventless but were not practicalconditions for afforded solid nitriles, reasonable and conversions the requisite for higherthe model temperatures reaction, but led were to greaternot practical impurity for solid profiles. Earliernitriles, syntheses and the [23 requisite,31] generally higher temperatures utilized reaction led to greater temperatures impurity of profiles. 120–150 Earlier˝C forsyntheses this reaction, [23,31] and thus,generally the conditions utilized employed reaction temperatures in this work of are 120–150 somewhat °C for milder. this reaction, and thus, the conditions employed in this work are somewhat milder. Table 1. Reaction optimization. Table 1. Reaction optimization.

Entry Solvent OSU-6 (wtOSU-6 %) Temperature (oC) Time (h) Isolated Yield (%) Entry Solvent Temperature (oC) Time (h) Isolated Yield (%) EtOH 15(wt %) 90 12 trace EtOH 15 90 12 trace 2 CH3CN 15 90 24 18 23 dioxaneCH3CN 1515 95 90 18 24 trace 18 34 THFdioxane 15 15 70 95 18 18 trace 10 45 solventlessTHF 15 15 120 70 6 18 76 10 56 DMSOsolventless 15 15 140 120 6 6 84 76 67 DMFDMSO 50 15 120 140 6 6 88 84 78 DMFDMF 25 50 120 120 6 6 87 88 9 DMF 15 120 6 90 8 DMF 25 120 6 87 10 a DMF 15 90 4 94 9 DMF 15 120 6 90 11 DMF 15 75 6 10 a 1012 DMFDMF 10 15 90 90 6 4 73 94 1113 DMFDMF 0 15 120 75 12 6 trace 10 12 DMF 10 90 6 73 a Optimized conditions. 13 DMF 0 120 12 trace a Optimized conditions. Based on our preliminary findings, we now report our investigation of this catalyst for the synthesisBased of 5-benzyl- on our preliminary and 5-aryl-1 findings,H-tetrazoles we now report using our a investigation click approach. of this catalyst The optimized for the synthesis conditions (15 wtof %5-benzyl- OSU-6, and DMF, 5-aryl-1 90 ˝C,H 4–12-tetrazoles h) proved using generala click approach. for promoting The optimized the conversion conditions of benzyl (15 wt and % aryl nitrilesOSU-6, to tetrazoles. DMF, 90 °C, In addition4–12 h) proved to the general parent for systems, promoting substrate the conversion derivatives of benzyl bearing and methyl, aryl nitriles methoxy, fluoro,to tetrazoles. chloro, nitro, In addition and 3-butenyl to the parent moieties systems, were substrate evaluated, derivatives and the bearing results methyl, are summarized methoxy, fluoro, in Table 2. All ofchloro, these nitro, groups and survived 3-butenyl the moieties reaction were conditions evaluated, andand the gave results high are yields summarized of products, in Table regardless 2. All of theirof electronic these groups character survived or positionthe reaction on conditions the ring, thus and demonstratinggave high yields theof products, general applicabilityregardless of their of OSU-6 electronic character or position on the ring, thus demonstrating the general applicability of OSU-6 in in this transformation. Furthermore, in the conversion of 4-(3-butenyl)benzonitrile (1p) to tetrazole this transformation. Furthermore, in the conversion of 4-(3-butenyl)benzonitrile (1p) to tetrazole 2p, 2p, thethe reactionreaction showedshowed excellent excellent chemoselectivity chemoselectivity for forthe the nitrile over over the theterminal terminal alkene. alkene. Finally, Finally, attemptsattempts to react to react aliphatic aliphatic nitriles nitriles lacking lacking aromaticaromatic substitution substitution gave gave incomplete incomplete conversion conversion to the to the targettarget tetrazoles tetrazoles and and unacceptable unacceptable impurity impurity levelslevels under our our conditions. conditions.

2

22758 Molecules 2015, 20, page–page

Molecules 2015, 20, 22757–22766 Table 2. Synthesis of tetrazoles. Molecules 2015, 20, page–page

Table 2. Synthesis of tetrazoles. Table 2. Synthesis of tetrazoles.

Substrate R Product Time (h) Isolated Yield (%) 1a C6H5CH2 2a 4 94 Substrate1b Substrate 4-CH3C R6 RH4CH2 Product Product2b Time Time (h)5 (h) Isolated Isolated Yield 87 (%)Yield (%) 1c 4-CH3OC6H4CH2 2c 4 92 6 5 2 1a 1a CCH6HCH5CH 2 2a 2a 44 94 94 1q 4-ClC6H4CH2 2d 5 90 1b 1b 4-CH4-CH3C36CH6H4CH4CH2 2 2b2b 55 87 87 1e 4-FC6H4CH2 2e 5 86 1c 1c 4-CH4-CH3OC3OC6H64HCH4CH2 2 2c 2c 44 92 92 1f 1q 4-ClCC6H6H5 4CH2 2d 2f 58 90 89 1q 4-ClC6H4CH2 2d 5 90 1e 4-FC H CH 2e 5 86 1g 4-CH63C64H4 2 2g 8 90 1e 4-FC6H4CH2 2e 5 86 1f C6H5 2f 8 89 1h 2-CH3C6H4 2h 6 94 1f 1g 4-CHC6H35C 6H4 2g 2f 88 90 89 1i 4-CH3OC6H4 2i 6 92 1g 1h 4-CH2-CH3C3C6H6H4 4 2h2g 68 94 90 1j 1i 4-NO4-CH2COC6H4H 2i 2j 612 92 84 1h 2-CH33C6H64 4 2h 6 94 1k 1j 3-NO4-NO2C2C6H6H4 4 2j 2k 1212 84 80 1i 4-CH3OC6H4 2i 6 92 1k 3-NO2C6H4 2k 12 80 1l 4-ClC6H4 2l 8 91 2 6 4 1j 1l 4-NO4-ClCC 6HH4 2l 2j 812 91 84 1m 4-FC6H4 2m 8 87 1k 1m 3-NO4-FC2C66H44 2m2k 812 87 80 1n (C6H5)2CH 2n 12 94 1l 1n 4-ClC(C6H56H)2CH4 2n 2l 128 94 91 1o 1o 4-CH4-CH3(CH3(CH2)62C)6HC64H 4 2o 2o 44 87 87 1m 4-FC6H4 2m 8 87 1p 4-CH =CH(CH ) C H 2p 4 95 1p 4-CH2=CH(CH2 2)2C62H24 6 4 2p 4 95 1n (C6H5)2CH 2n 12 94 1o 4-CH3(CH2)6C6H4 2o 4 87 The 1,3-dipolar addition of azide to nitriles hashas the potential to proceed via a concerted or 1p 4-CH2=CH(CH2)2C6H4 2p 4 95 stepwise mechanism. In either event, OSU-6 would se serverve as a mild proton source to convert azide to hydrazoicThe 1,3-dipolar acid or to activateaddition theth ofe nitrileazide functionto nitriles by ha protonationprotonations the potential (Scheme(Scheme to proceed1 1).). HydrazoicHydrazoic via a acidconcertedacid hashas twotwo or stepwisemajor resonanceresonance mechanism. contributors, In either Aevent, and BOSU-6. OfOf these,these, would contributorcontributor serve as a B mild illustrates proton the source concerted to convert reaction azide best, to hydrazoicundergoing acid a smooth or to activate six-electron six-electron the nitrile cyclization cyclization function with with by nitrile protonation nitrile 2a2a to toform (Scheme form tetrazole tetrazole 1). 3aHydrazoic. 3aIt .is It also is alsoacid possible possiblehas twothat majorthatOSU-6 OSU-6 resonance protonates protonates contributors, the nitrile the nitrile to A some and to degree,B some. Of these, degree, which contributor would which activate would B illustrates activatethis group the this concerted toward group attack toward reaction by attack azide best, undergoingbyin a azide stepwise in a process. smooth stepwise Manysix-electron process. earlier Manycyclization papers, earlier both with with papers, nitrile [14,32,33] both2a to withform and withouttetrazole [14,32,33 [12,19,23]]3a and. It is without also metal possible [catalysts,12,19 that,23]

OSU-6metalhave presented catalysts,protonates havestepwise the nitrile presented mechan to some stepwiseisms degree, for mechanisms whichthis transformation. would for activate this transformation.In this our group experiments, toward In our attack experiments,however, by azide no inhowever,intermediates a stepwise no process. intermediates were observed Many earlier were byobserved papers,thin layer both by chro thinwithmatographylayer [14,32,33] chromatography and during without the [12,19,23] duringcourse theof metal coursethe catalysts,reaction. of the havereaction.Additionally, presented Additionally, the stepwise minimal the minimalmechan substitutionisms substitution for in thisthe in transformation.reactants the reactants provided provided In ourno nostereochemicalexperiments, stereochemical however, evidence evidence noto intermediatestoilluminate illuminate the the concertedwere concerted observed or stepwise or stepwiseby thin nature naturelayer of the chro of process. thematography process. during the course of the reaction. Additionally, the minimal substitution in the reactants provided no stereochemical evidence to illuminate the concerted or stepwise nature of the process.

Scheme 1. Plausible mechanisms for the reaction of azide with nitrile 2a in the presencepresence ofof OSU-6OSU-6 toto form tetrazoletetrazole 3a.. Scheme 1. Plausible mechanisms for the reaction of azide with nitrile 2a in the presence of OSU-6 to form tetrazole 3a.

3 22759 3 Molecules 2015, 20, 22757–22766 Molecules 2015, 20, page–page

OneOne of of the the most most attractive attractive features features of of OSU-6 OSU-6 in in our our previous previous studies studies [26–28] [26–28 ]was was its its recyclability, recyclability, andand thus, thus, the the catalyst catalyst was was evaluated evaluated for for this this possibility. possibility. The The acidity acidity of of this this silicic silicic material material apparently apparently derivesderivesMolecules from from 2015aging aging, 20, page–pagein in 2 2 M M HClHCl for for two two weeks weeks during during its its preparation preparation [34]. [34]. In In the the current current application, application, OSU-6OSU-6 was was reused reused up up to to five five times times without without signific significantant loss loss of of activity activity (Figure (Figure 11)) andand requiredrequired onlyonly minimalminimal reconditioning reconditioningOne of the most after afterattractive each each features cycle. cycle. This Thisof OSU-6 reconditioning reconditioning in our previous involved involved studies filtering filtering[26–28] was the the its catalyst, catalyst, recyclability, washing washing and thus, the catalyst was evaluated for this possibility. The˝ acidity of this silicic material apparently with 1:1 EtOH:H 22O,O, and and drying drying under under high high vacuum vacuum at at 80 80 °CC for for 2 2 h. h. Employing Employing this this protocol, protocol, OSU-6 OSU-6 retainedretainedderives its its proton proton from aging donor in properties2 M HCl for without two weeks th the eduring need itsfor preparation acid treatment [34]. In between the current reactions. application, OSU-6 was reused up to five times without significant loss of activity (Figure 1) and required only minimal reconditioning after each cycle. This reconditioning involved filtering the catalyst, washing with 1:1 EtOH:H2O, and drying under high vacuum at 80 °C for 2 h. Employing this protocol, OSU-6 retained its proton donor properties without the need for acid treatment between reactions.

Figure 1. Recyclability of OSU-6. Figure 1. Recyclability of OSU-6.

In order to understand the high catalyticFigure 1. activityRecyclability of OSU-6, of OSU-6. we monitored changes to the catalyst surfaceIn orderover five to understand cycles of the the re highaction catalytic using activityscanning of electron OSU-6, wemicroscopy monitored (SEM). changes A series to the of catalyst SEM imagessurface at over In~26,000× order five cyclesto magnificationunderstand of the the reaction high(Figure catalytic using 2) show scanning activity 100 of µm electronOSU-6,2 areas we microscopy onmonitored the catalyst changes (SEM). surface to A the series catalystbefore of SEM and surface over five cycles of the reaction using scanning µelectron2 microscopy (SEM). A series of SEM afterimages use. at Comparison ~26,000ˆ magnification of the surface (Figure topography2) show of 100fresh OSU-6m areas (A) on with the material catalyst recovered surface before after andthe images at ~26,000× magnification (Figure 2) show 100 µm2 areas on the catalyst surface before and thirdafter ( use.B) and Comparison fifth (C) reactions of the surface revealed topography that while of some fresh roughening OSU-6 (A) occurred with material due to recovered the loss of after water, the third (afterB) and use. fifth Comparison (C) reactions of the revealedsurface topography that while of some fresh rougheningOSU-6 (A) with occurred material due recovered to the lossafter of the water, the exposedthird (B features) and fifth of(C )the reactions catalyst revealed remained that while larg elysome unchanged. roughening Overall,occurred duethe tocatalyst the loss morphology of water, the exposed features of the catalyst remained largely unchanged. Overall, the catalyst morphology showedthe only exposed minor features observable of the catalystdegradation remained after larg fiveely iterations. unchanged. Overall, the catalyst morphology showed only minor observable degradation after five iterations. showed only minor observable degradation after five iterations.

(A) (A) (B(B) ) (C)( C) Figure 2. SEM images of OSU-6: (A) Fresh; (B) After three cycles; and (C) After five cycles. FigureFigure 2. 2. SEMSEM images images of of OSU-6: OSU-6: ( (AA)) Fresh; Fresh; ( (BB)) After After three three cycles; cycles; and and ( (CC)) After After five five cycles. cycles. The change in catalyst structure during multiple reactions was further investigated for one The change in catalyst structure during multiple reactions was further investigated for one Thecharge change of catalyst in catalyst using structure a Brunauer-Emmett-Teller during multiple reactions(BET) surface was furtherarea determination. investigated The for oneresults charge charge of catalyst using a Brunauer-Emmett-Teller (BET) surface area determination. The results of catalystrevealed using that a fresh Brunauer-Emmett-Teller OSU-6 had a total surface (BET) area surface of 880 m area2/g. Measurements determination. after The each results reaction revealed cycle that revealed that fresh OSU-6 had a total surface area of 880 m2/g. Measurements after each reaction cycle freshshowed OSU-6 hada gradual a total decrease surface in areasurface of 880area, m with2/g. a Measurementstotal loss of only 21.6% after eachto 690 reaction m2/g after cycle five cycles showed a showed a gradual decrease in surface area, with a total loss of only 21.6% to 690 m2/g after five cycles gradual(Figure decrease 3). Thus, in surface the catalyst area, suffered with a totalonly lossminimal of only damage 21.6% and to was 690 able m2/g to afterretain five its pore cycles size (Figure and 3). (Figurevolume 3). Thus, throughout the catalyst the five-reaction suffered only sequence. minimal These damage observations and was verified able the to structuralretain its stabilitypore size of and Thus, the catalyst suffered only minimal damage and was able to retain its pore size and volume volumeOSU-6 throughout toward conditions the five-reaction requiring sequence. extended exTheseposure observations to a polar aprotic verified solvent the atstructural 90 °C. stability of throughout the five-reaction sequence. These observations verified the structural stability of OSU-6 OSU-6 toward conditions requiring extended exposure to a polar aprotic solvent at 90 °C. toward conditions requiring extended exposure to a polar aprotic solvent at 90 ˝C.

4 22760 4 Molecules 2015, 20, 22757–22766 MoleculesMolecules 20152015,, 2020,, page–pagepage–page

FigureFigure 3. 3. BETBET measurementsmeasurements of of the the surface surface area area of of OSU-6. OSU-6.

In a further study of the behavior of OSU-6 over an extended reaction series, thermogravimetric In a further study of the behavior of OSU-6 over an extendedextended reactionreaction series, thermogravimetric analysis (TGA) was used to assess the extent of clogging in the catalyst pores by reagents and products. analysis (TGA) was was used used to to assess assess the the extent extent of of cloggi cloggingng in in the the catalyst catalyst pores pores by by reagents reagents and and products. products. The results revealed a weight loss of 2%–4% below 150 °C, corresponding to the loss of adsorbed The resultsresults revealedrevealed a a weight weight loss loss of of 2%–4% 2%–4% below below 150 150˝C, °C, corresponding corresponding to the to loss the ofloss adsorbed of adsorbed water. water. Upon further heating, relatively little additional weight loss (≤6%) was noted from the reused water.Upon furtherUpon further heating, heating, relatively relatively little additional little additional weight weight loss (ď 6%)loss was(≤6%) noted was fromnoted the from reused the reused OSU-6 OSU-6 samples between 150–500 °C, indicating that the catalyst pores experienced no significant OSU-6samples samples between between 150–500 150–500˝C, indicating °C, indicating that the that catalyst the porescatalyst experienced pores experienced no significant no significant clogging clogging during the reaction (Figure 4). Lastly, though not shown in the Figure, OSU-6 did not breakdown cloggingduring the during reaction the reaction (Figure4 (Figure). Lastly, 4). though Lastly, notthou showngh not inshown the Figure, in the Figure, OSU-6 OSU-6 did not did breakdown not breakdown until until the temperature reached ca. 800 °C, confirming the robust character of the material. untilthe temperature the temperature reached reachedca. 800 ca.˝ C,800 confirming °C, confirming the robust the robust character character of the of material. the material.

100100

9595

9090 CycleCycle 11 Cycle 2 8585 Cycle 2 Cycle 3 Weight (%) Cycle 3 Weight (%) CycleCycle 44 8080 CycleCycle 55

5050 100 100 150 150 200 200 250 250 300 300 350 350 400 400 450 450 500 500 οο TemperatureTemperature (( C)C)

Figure 4. Thermogravimetric analysis (TGA) of recovered OSU-6. FigureFigure 4. 4. ThermogravimetricThermogravimetric analysis analysis (TGA) (TGA) of recovered OSU-6.

Finally,Finally, toto moremore fullyfully elucidateelucidate thethe rolerole ofof OSU-OSU-66 inin thethe reaction,reaction, twotwo separateseparate experimentsexperiments werewere Finally, to more fully elucidate the role of OSU-6 in the reaction, two separate experiments were performedperformed onon thethe modelmodel conversionconversion ofof benzylbenzyl cyanidecyanide ((1a1a,, 1.01.0 mmol)mmol) andand sodiumsodium azideazide (1.2(1.2 mmol)mmol) performed on the model conversion of benzyl cyanide (1a, 1.0 mmol) and sodium azide (1.2 mmol) to toto 2a2a underunder thethe optimizedoptimized conditionsconditions (15(15 wtwt %% ofof OSU-6,OSU-6, DMF,DMF, 9090 °C,°C, 44 h).h). InIn thethe firstfirst run,run, thethe reactionreaction 2a under the optimized conditions (15 wt % of OSU-6, DMF, 90 ˝C, 4 h). In the first run, the reaction waswas heatedheated inin thethe presencepresence ofof OSU-6OSU-6 forfor aa periodperiod ofof 22 h,h, afterafter whichwhich thethe catalystcatalyst waswas removedremoved byby was heated in the presence of OSU-6 for a period of 2 h, after which the catalyst was removed by filtrationfiltration andand thethe filtratefiltrate waswas heatedheated forfor aa secondsecond 2-h2-h period.period. ThisThis procedprocedureure gavegave roughlyroughly 68%68% ofof 2a2a filtration and the filtrate was heated for a second 2-h period. This procedure gave roughly 68% of duringduring thethe firstfirst 22 h,h, butbut onlyonly anan additionaladditional 5%5% ofof productproduct duringduring thethe susubsequentbsequent 2-h2-h period.period. TheThe 2a during the first 2 h, but only an additional 5% of product during the subsequent 2-h period. The sequencesequence waswas thenthen reversed,reversed, heatingheating thethe reactionreaction inin thethe absenceabsence ofof OSU-6OSU-6 forfor thethe initialinitial 2-h2-h period,period, sequence was then reversed, heating the reaction in the absence of OSU-6 for the initial 2-h period, followedfollowed byby introductionintroduction ofof catalystcatalyst andand heatingheating forfor anotheranother 22 h.h. ThisThis procedureprocedure yieldedyielded onlyonly ~10%~10% followed by introduction of catalyst and heating for another 2 h. This procedure yielded only ~10% ofof 2a2a afterafter thethe firstfirst 22 h,h, butbut anan additionaladditional 76%76% duriduringng thethe secondsecond 2-h2-h period.period. TheseThese resultsresults clearlyclearly of 2a after the first 2 h, but an additional 76% during the second 2-h period. These results clearly establishedestablished thatthat OSU-6OSU-6 waswas essentialessential inin promotingpromoting thethe clickclick additionaddition processprocess toto formform tetrazoles.tetrazoles. established that OSU-6 was essential in promoting the click addition process to form tetrazoles.

22761 55 Molecules 2015, 20, 22757–22766

3. Experimental Section

3.1. General Information The OSU-6 catalyst can be purchased from XploSafe, LLC (Product No. 9001, Stillwater, OK, USA; www.xplosafe.com). All reactions were run under dry N2. Reactions were monitored by thin layer chromatography (TLC) on silica gel GF plates (Analtech No. 21521, Newark, DE, USA). Column chromatography, when necessary, was performed using silica gel (Davisilr grade 62, 60–200 mesh) mixed with UV-active phosphor (Sorbent Technologies, No. UV-05, Norcross, GA, USA); band elution was monitored using a hand held UV lamp. The following instrumentation was used: Mp determinations: Laboratory Devices Mel-temp apparatus (Cambridge, MA, USA); FT-IR spectra: Varian Scimitar FTS 800 spectrophotometer (Randolph, MA, USA); 1H- (400 MHz) and 13C-NMR (100 MHz) spectra: Bruker Avance 400 system (Billerica, MA, USA); HRMS: Thermo LTQ-Orbitrap XL system (Waltham, MA, USA); BET surface areas: Quantachrome Autosorb 1 instrument (Boynton Beach, FL, USA); SEM images: Hitachi S4800 system (Shaumburg, IL, USA); TGA measurements: Mettler-Toledo TGA/DSC 1 instrument (Columbus, OH, USA).

3.2. Representative Procedure for the Preparation of 5-Benzyl and 5-Aryl-1H-tetrazoles

5-Benzyl-1H-tetrazole (2a). To a DMF solution of benzyl cyanide (1a, 100 mg, 0.85 mmol) and NaN3 (67 mg, 1.02 mmol, 1.2 eq) was added OSU-6 (15 mg, 15 wt% relative to 1a). The reaction mixture was heated at 90 ˝C (oil bath temperature 95–100 ˝C) for 4 h at which time TLC indicated the reaction was complete. The crude reaction mixture was filtered to remove the catalyst, and the filtrate was added to water and extracted with EtOAc (3 ˆ 15 mL). The combined extracts were washed with H2O (3 ˆ 15 mL) and saturated aq. NaCl (1 ˆ 15 mL), dried (MgSO4), filtered, and concentrated under vacuum to give 2a (129 mg, 94%) as a white solid, mp 121–122 ˝C (lit. [31] mp 123–124 ˝C). IR: 1603, ´1 1 1549, 1532, 1494, 1457, 1073, 733, 695 cm ; H-NMR (DMSO-d6): δ 16.1 (br s, 1H), 7.34 (t, J = 7.4 Hz, 13 2H), 7.27 (d, J = 7.4 Hz, 3H), 4.29 (s, 2H); C-NMR (DMSO-d6) δ 155.7, 136.4, 129.1, 128.8, 127.5, 29.4; HRMS (ESI): m/z Calcd for C8H8N4: 161.0827 [M + H]; Found: 161.0831. Other tetrazoles (below) were prepared in the same fashion by heating for the times indicated in Table2.

5-(4-Methylbenzyl)-1H-tetrazole (2b): Yield: 115 mg (87%) as a white solid, mp 151–152 ˝C (lit. [31] mp ˝ ´1 1 153–154 C); IR: 1635, 1540, 1496, 1448, 1382, 869 cm ; H-NMR (DMSO-d6): δ 16.1 (br s, 1H), 7.15 13 (apparent s, 4H), 4.23 (s, 2H), 2.27 (s, 3H); C-NMR (DMSO-d6) δ 154.6, 135.5, 132.2, 128.6, 127.9, 27.9, 20.0; HRMS (ESI): m/z Calcd for C9H10N4: 175.0984 [M + H]; Found: 175.0982.

5-(4-Methoxybenzyl)-1H-tetrazole (2c): Yield: 119 mg (92%) as an off-white solid, mp 160–162 ˝C (lit. [35] ˝ ´1 1 mp 162–164 C); IR: 2834, 1613, 1514, 1246, 836 cm ; H-NMR (DMSO-d6): δ 16.1 (br s, 1H), 7.19 13 (d, J = 8.2 Hz, 2H), 6.90 (d, J = 8.2 Hz, 2H), 4.21 (s, 2H), 3.72 (s, 3H); C-NMR (DMSO-d6) δ 157.7, 155.0, 129.2, 127.1, 113.7, 54.5, 27.4; HRMS (ESI): m/z Calcd for C9H10N4O: 191.0933 [M + H]; Found: 191.0938.

5-(4-Chlorobenzyl)-1H-tetrazole (2d): Yield: 115 mg (90%) as a white solid, mp 155–156 ˝C; IR: 1641, 1586, ´1 1 1536, 1493, 1409, 827, 764 cm ; H-NMR (DMSO-d6): δ 16.1 (br s, 1H), 7.41 (d, J = 8.1 Hz, 2H), 7.31 13 (d, J = 8.1 Hz, 2H), 4.30 (s, 2H); C-NMR (DMSO-d6) δ 154.5, 134.3, 131.1, 130.0, 128.0, 27.6; HRMS (ESI): m/z Calcd for C8H7N4Cl: 195.0438, 197.0408 (ca. 3:1) [M + H]; Found: 195.0442, 197.0411 (ca. 3:1). Anal. Calcd for C8H7N4Cl: C, 49.37; H, 3.63; N, 28.79. Found: C, 49.46; H, 3.55; N, 28.89.

5-(4-Fluorobenzyl)-1H-tetrazole (2e): Yield: 113 mg (86%) as a light yellow solid, mp 154–155 ˝C; IR: ´1 1 1601, 1582, 1508, 1413, 1223, 828, 767 cm ; H-NMR (DMSO-d6): δ 16.1 (br s, 1H). 7.33 (m, 2H), 7.18 13 (t, J = 8.7 Hz, 2H), 4.30 (s, 2H); C-NMR (DMSO-d6) δ 160.7 (d, J = 241 Hz), 154.7, 131.5 (d, J = 4 Hz), 130.1 (d, J = 8.1 Hz), 114.9 (d, J = 22.2 Hz), 27.5; HRMS (ESI): m/z Calcd for C8H7N4F: 179.0733 [M + H];

22762 Molecules 2015, 20, 22757–22766

Found: 179.0737. Anal. Calcd for C8H7N4F: C, 53.93; H, 3.96; N, 31.45. Found: C, 54.02; H, 3.92; N, 31.37.

5-Phenyl-1H-tetrazole (2f): Yield: 126 mg (89%) as an off-white solid, mp 215–216 ˝C [lit. [36] mp 216 ˝C ´1 1 (dec)]; IR: 1608, 1563, 1485, 1465, 1409, 1162, 746, 703 cm ; H-NMR (DMSO-d6): δ 8.09–8.03 (m, 2H), 13 7.66–7.57 (m, 3H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 130.7, 128.8, 126.4, 123.5; HRMS (ESI): m/z Calcd for C7H6N4: 147.0671 [M + H]; Found: 147.0668.

5-(4-Methylphenyl)-1H-tetrazole (2g): Yield: 122 mg (90%) as a tan solid, mp 249–250 ˝C (lit. [31] mp ˝ ´1 1 247.5–247.7 C); IR: 1612, 1569, 1505, 1369, 822, 742 cm ; H-NMR (DMSO-d6): δ 7.94 (d, J = 7.8 Hz, 13 2H), 7.42 (d, J = 7.8 Hz, 2H), 2.40 (s, 3H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 154.5, 140.6, 129.7, 126.3, 120.9, 20.5; HRMS (ESI): m/z Calcd for C8H8N4: 161.0827 [M + H]; Found: 161.0829.

5-(2-Methylphenyl)-1H-tetrazole (2h): Yield: 128 mg (94%) as an off-white solid, mp 152–153 ˝C (lit. [31] ˝ ´1 1 mp 153.2–153.8 C); IR: 1608, 1564, 1465, 1387, 782, 744 cm ; H-NMR (DMSO-d6): δ 7.70 (d, J = 7.6 Hz, 13 1H), 7.54–7.36 (m, 3H), 2.51 (d, J = 2.0 Hz, 3H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 154.7, 136.5, 130.7, 130.1, 128.8, 125.7, 123.3, 19.9; HRMS (ESI): m/z Calcd for C8H8N4: 161.0827 [M + H]; Found: 161.0831.

5-(4-Methoxyphenyl)-1H-tetrazole (2i): Yield: 122 mg (92%) as a white solid, mp 230–232 ˝C (lit. [35] mp ˝ ´1 1 232–233 C); IR: 2859, 1608, 1249, 828, 749 cm ; H-NMR (DMSO-d6): δ 8.01 (d, J = 8.4 Hz, 2H), 7.18 13 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 160.9, 154.1, 128.0, 115.7, 114.3, 54.9; HRMS (ESI): m/z Calcd for C8H8N4O: 177.0776 [M + H]; Found: 177.0773.

5-(4-Nitrophenyl)-1H-tetrazole (2j): Yield: 109 mg (84%) as a yellow solid, mp 219–221 ˝C (lit. [35] ˝ ´1 1 mp 218–220 C); IR: 1603, 1551, 1512, 1337, 1318, 1293, 861, 728 cm ; H-NMR (DMSO-d6): δ 8.46 13 (d, J= 8.4 Hz, 2H), 8.32 (d, J = 8.4 Hz, 2H), tetrazole H off-scale; C-NMR (DMSO-d6) δ 154.9, 148.2, 130.0, 127.6, 124.0; HRMS (ESI): m/z Calcd for C7H5N5O2: 192.0522 [M + H]; Found: 192.0525.

5-(3-Nitrophenyl)-1H-tetrazole (2k): Yield: 103 mg (80%) as a tan solid, mp 153–155 ˝C (lit. [31] mp ˝ ´1 1 144.7–145.6 C); IR: 1625, 1525, 1348, 1250, 872, 823, 712 cm ; H-NMR (DMSO-d6): δ 8.84 (s, 1H), 8.49 (d, J = 7.7 Hz, 1H), 8.44 (d, J = 8.3 Hz, 1H), 7.92 (t, J = 8.0 Hz, 1H), tetrazole NH off-scale; 13C-NMR (DMSO-d6) δ 155.5, 148.7, 133.5, 131.7, 126.6, 126.1, 122.0; HRMS (ESI): m/z Calcd for C7H5N5O2: 192.0522 [M + H]; Found: 192.0528.

5-(4-Chlorophenyl)-1H-tetrazole (2l): Yield: 119 mg (91%) as a yellow solid, mp 259–260 ˝C (lit. [33] mp ˝ ´1 1 262 C); IR: 1635, 1535, 1492, 1419, 886, 755 cm ; H-NMR (DMSO-d6): δ 8.07 (d, J = 8.2 Hz, 2H), 13 7.71 (d, J = 8.2 Hz, 2H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 155.4, 136.4, 130.0, 129.2, 123.7; HRMS (ESI): m/z Calcd for C7H5N4Cl: 181.0281, 183.0252 (ca. 3:1) [M + H]; Found: 181.0283, 183.0255 (ca. 3:1).

5-(4-Fluorophenyl)-1H-tetrazole (2m): Yield: 117 mg (87%) as an off-white solid, mp 203–205 ˝C; IR: 1606, ´1 1 1499, 1444, 1241, 839, 749 cm ; H-NMR (DMSO-d6): δ 8.14–8.04 (m, 2H), 7.48 (t, J = 8.6 Hz, 2H), 13 tetrazole NH off-scale; C-NMR (DMSO-d6) δ 163.1 (d, J = 247. Hz), 154.2 (br), 128.9 (d, J = 9.1 Hz), 120.3, 116.0 (d, J = 21.5 Hz); HRMS (ESI): m/z Calcd for C7H5N4F: 165.0577 [M + H]; Found: 165.0581. Anal. Calcd for C7H5N4F: C, 51.22; H, 3.07; N, 34.13. Found: C, 51.36; H, 3.11; N, 34.29.

5-(Diphenylmethyl)-1H-tetrazole (2n): Yield, 109 mg, (94%) as a white solid, mp 161–163 ˝C (lit. [31] mp ˝ ´1 1 164.2–165.2 C); IR: 1564, 1494, 1452, 767, 718 cm ; H-NMR (DMSO-d6): δ 7.40–7.25 (m, 10H), 5.97 (s, 13 1H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 139.5, 128.1, 127.8, 126.6, 45.1; HRMS (ESI): m/z Calcd for C20H16N4: 313.1453 [M + H]; Found: 313.1461.

22763 Molecules 2015, 20, 22757–22766

5-(4-Heptylphenyl)-1H-tetrazole (2o): Yield: 105 mg (87%) as a white solid, mp 184–186 ˝C; IR: 1615, ´1 1 1504, 1438, 1352, 844, 751, 722 cm ; H-NMR (DMSO-d6): δ 7.94 (d, J = 7.8 Hz, 2H), 7.43 (d, J = 7.9 Hz, 2H), 2.66 (t, J = 7.7 Hz, 2H), 1.60 (quintet, J = 7.0 Hz, 2H), 1.30 (m, 4H), 1.25 (m, 3H), 0.85 (t, J = 6.6 Hz, 13 3H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 145.4, 145.3, 128.7, 126.3, 120.9, 34.4, 30.6, 30.1, 28.0, 27.9, 21.5, 13.3; HRMS (ESI): m/z Calcd for C14H20N4: 245.1766 [M + H]; Found: 245.1771. Anal. Calcd for C14H20N4: C, 68.82; H, 8.25; N, 22.93. Found: C, 68.87; H, 8.19; N, 22.85.

5-[4-(3-Butenyl)phenyl]-1H-tetrazole (2p): Yield: 121 mg (95%) as a yellow solid, mp 189–191 ˝C; IR: ´1 1 1641, 1618, 1509, 1478, 998, 918, 844, 743 cm ; H-NMR (DMSO-d6): δ 7.95 (d, J = 7.8 Hz, 2H), 7.45 (d, J = 7.9 Hz, 2H), 5.84 (ddt, J = 17.1, 10.2, 6.5 Hz, 1H), 5.05 (d, J = 17.1 Hz, 2H), 4.98 (d, J = 10.2 Hz, 13 1H), 2.77 (t, J = 7.6 Hz, 2H), 2.38 (q, J = 7.0 Hz, 2H), tetrazole NH off-scale; C-NMR (DMSO-d6) δ 145.1, 137.7, 130.0, 129.4, 126.9, 121.7, 115.5, 34.5, 34.3; HRMS (ESI): m/z Calcd for C11H12N4: 201.1140 [M + H]; Found: 201.1137. Anal. Calcd for C11H12N4: C, 65.98; H, 6.04; N, 27.98. Found: C, 65.90; H, 6.11; N, 28.09.

4. Conclusions In summary, we have successfully used OSU-6 as an efficient, metal-free, heterogeneous catalyst for the high-yield click synthesis of 5-benzyl- and 5-aryl-1H-tetrazoles from nitriles in DMF at 90 ˝C. This MCM-41 type hexagonal mesoporous silica permits the synthesis of these targets using a simple procedure, under mild conditions, and can be readily recycled. Studies are presented which demonstrate the robust properties of the catalyst under the optimized reaction conditions. The catalyst promotes the 1,3-dipolar addition without significant surface erosion or clogging of the nanoporous structure. The catalyst can be reused up to five times without a significant reduction in yield, and it does not require treatment with acid between reactions.

Supplementary Materials: Electronic Supplementary Information (ESI) available: Copies of the 1H and 13C-NMR spectra for each tetrazole prepared, see http://www.mdpi.com/1420-3049/20/12/19881/s1. Acknowledgments: The authors wish to thank XploSafe, LLC (Stillwater, OK, USA) for a generous gift of OSU-6. The authors are also grateful to the Oklahoma State University College of Arts and Sciences for funds to purchase a new 400 MHz NMR for the Oklahoma State-wide NMR facility. This facility was established with support from NSF (BIR-9512269), the Oklahoma State Regents for Higher Education, the W. M. Keck Foundation, and Conoco, Inc. (Houston, TX, USA). Author Contributions: B.N. and N.P.M. performed the compound synthesis work, R.P. assisted with the acquisition and interpretation of the SEM, BET and TGA data, and R.A.B. wrote the paper. All authors read and approved the final version of the manuscript before submission. Conflicts of Interest: The authors declare no conflict of interest.

References and Notes

1. Mohite, P.B.; Bhaskar, V.H. Potential pharmacological activities of tetrazoles in the new millennium. Int. J. PharmTech Res. 2011, 3, 1557–1566. 2. Ostrovskii, V.A.; Trifonov, R.E.; Popova, E.A. Medicinal chemistry of tetrazoles. Russ. Chem. Bull. 2012, 61, 768–780. [CrossRef] 3. Mohammad, A. Biological potentials of substituted tetrazole compounds. Pharm. Methods 2014, 5, 39–46. 4. Camilleri, P.; Kerr, M.W.; Newton, T.W.; Bowyer, J.R. Structure activity studies of tetrazole urea herbicides. J. Agric. Food Chem. 1989, 37, 196–200. [CrossRef] 5. Tuites, R.C.; Whiteley, T.E.; Minsk, L.M. Polymers Containing Tetrazole Groups, Useful in Photographic Emulsions. Patent GB1245614A, 8 September 1971. 6. Matyas, R.; Pachman, J. Primary Explosives; Springer: Berlin, Germany; Heidelberg, Germany, 2013; p. 338. 7. An, P.; Yu, Z.; Lin, Q. Design of oligothiophene-based tetrazoles for laser-triggered photoclick chemistry in living cells. Chem. Commun. 2013, 49, 9920–9922. [CrossRef][PubMed] 8. Tariq, M.; Hameed, S.; Bechtold, I.H.; Bortoluzzi, A.J.; Merlo, A.A. Synthesis and characterization of some novel tetrazole liquid crystals. J. Mater. Chem. C 2013, 1, 5583–5593. [CrossRef]

22764 Molecules 2015, 20, 22757–22766

9. Henkensmeier, D.; Duong, N.M.H.; Brela, M.; Dyduch, K.; Michalak, A.; Jankova, K.; Cho, H.; Jang, J.H.; Kim, H.J.; Cleemann, L.N.; et al. Tetrazole substituted polymers for high temperature polymer electrolyte fuel cells. J. Mater. Chem. A 2015, 3, 14389–14400. [CrossRef] 10. Aromi, G.; Barrios, L.A.; Roubeau, O.; Gamez, P. Triazoles and tetrazoles: Prime ligands to generate remarkable coordination materials. Coord. Chem. Rev. 2011, 255, 485–546. [CrossRef] 11. Popova, E.A.; Trifonov, R.E.; Ostrovskii, V.A. Advances in the synthesis of tetrazoles coordinated to metal . Arkivoc 2012, 1, 45–65. 12. Herr, R.J. 5-substituted-1H-tetrazoles as carboxylic acid isosteres: Medicinal chemistry and synthetic methods. Bioorg. Med. Chem. 2002, 10, 3379–3393. [CrossRef] 13. Myznikov, L.V.; Hrabalek, A.; Koldobskii, G.I. Medicinal preparations in the series of tetrazoles. Chem. Heterocycl. Compd. 2007, 43, 1–9. [CrossRef] 14. Aureggi, V.; Sedelmeier, G. 1,3-dipolar cycloaddition: for the synthesis of 5-substituted tetrazoles from organoaluminum azides and nitriles. Angew. Chem. Int. Ed. 2007, 46, 8440–8444. [CrossRef] [PubMed] 15. Adams, A.D.; Heck, J.V. Preparation of (Triazolyl- and Tetrazolylphenyl) Carbapenems as Antibiotics. U.S. Patent 5350746A, 27 September 1994. 16. Wittenberger, S.J. Recent developments in tetrazole chemistry–A review. Org. Prep. Proced. Int. 1994, 26, 499–531. [CrossRef] 17. Butler, R.N. Tetrazoles. In Comprehensive Heterocyclic Chemistry; Schorr, R.C, Ed.; Pergamon: Oxford, UK, 1996; Volume 4. 18. Rama, V.; Kanagaraj, K.; Pitchumani, K. Syntheses of 5-substituted 1H-tetrazoles catalyzed by reusable CoY zeolite. J. Org. Chem. 2011, 76, 9090–9095. [CrossRef][PubMed] 19. Roh, J.; Vavrova, K.; Hrabalek, A. Synthesis and functionalization of 5-substituted tetrazoles. Eur. J. Org. Chem. 2012, 6101–6118. [CrossRef] 20. Du, Z.; Si, C.; Li, Y.; Yin, W.; Lu, J. Improved synthesis of 5-substituted 1H-tetrazoles via the [3 + 2] cycloaddition of nitriles and sodium azide catalyzed by silica sulfuric acid. Int. J. Mol. Sci. 2012, 13, 4696–4703. [CrossRef][PubMed] 21. Shelkar, R.; Singh, A.; Nagarkar, J. Amberlyst-15 catalyzed synthesis of 5-substituted 1H-tetrazole via [3 + 2] cycloaddition of nitriles and sodium azide. Tetrahedron Lett. 2013, 54, 106–109. [CrossRef] 22. Ghodsinia, S.S.E.; Akhlaghinia, B. A rapid metal free synthesis of 5-substituted-1H-tetrazoles using cuttlebone as a natural high effective and low cost heterogeneous catalyst. RSC Adv. 2015, 5, 49849–49860. [CrossRef] 23. Finnegan, W.G.; Henry, R.A.; Lofquist, R. An improved synthesis of 5-substituted tetrazoles. J. Am. Chem. Soc. 1958, 80, 3908–3911. [CrossRef] 24. Yao, Y.W.; Zhou, Y.; Lin, B.P.; Yao, C. Click chemistry for the synthesis of 5-substituted 1H-tetrazoles from boron-azides and nitriles. Tetrahedron Lett. 2013, 54, 6779–6781. [CrossRef] 25. Al Othman, Z.A.; Apblett, A.W. Synthesis and characterization of a hexagonal mesoporous silica with enhanced thermal and hydrothermal stabilities. Appl. Surf. Sci. 2010, 256, 3573–3580. [CrossRef] 26. Nammalwar, B.; Muddala, N.P.; Murie, M.; Bunce, R.A. Efficient syntheses of substituted (˘)-3-oxoisoindoline-1-carbonitriles and carboxamides using OSU-6. Green Chem. 2015, 17, 2495–2503. [CrossRef] 27. Muddala, N.P.; Nammalwar, B.; Bunce, R.A. Expeditious synthesis of (˘)-diethyl 2-alkyl- and 2-aryl-(3-oxoisoindolin-1-yl)phosphonates catalysed by OSU-6. RSC Adv. 2015, 5, 28389–28393. [CrossRef] 28. Nammalwar, B.; Muddala, N.P.; Watts, F.M.; Bunce, R.A. Efficient conversion of acids and esters to amides and transamidation of primary amides using OSU-6. Tetrahedron 2015, 71, 9101–9111. [CrossRef] 29. Demko, Z.P.; Sharpless, K.B. A click chemistry approach to tetrazoles by Huisgen 1,3-dipolar cycloaddition: Synthesis of 5-sulfonyl tetrazoles from azides and sulfonyl . Angew. Chem. Int. Ed. 2002, 41, 2110–2113. [CrossRef] 30. Demko, Z.P.; Sharpless, K.B. A click chemistry approach to tetrazoles by Huisgen 1,3-dipolar cycloaddition: Synthesis of 5-acyltetrazoles from azides and acyl cyanides. Angew. Chem. Int. Ed. 2002, 41, 2113–2116. [CrossRef] 31. Jursic, B.S.; LeBlanc, B.W. Preparation of tetrazoles from organic nitriles and sodium azide in micellar media. J. Heterocycl. Chem. 1998, 35, 405–408. [CrossRef]

22765 Molecules 2015, 20, 22757–22766

32. Jin, T.; Kitahara, F.; Kamijo, S.; Yamamoto, Y. Copper-catalyzed synthesis of 5-substituted 1H-tetrazoles via the [3 + 2] cycloaddition of nitriles and trimethylsilyl azide. Tetrahedron Lett. 2008, 49, 2824–2827. [CrossRef] 33. Esmaeilpour, M.; Javidi, J.; Dodeji, F.N.; Abarghoui, M.M. Facile synthesis of 1- and 5-substituted 1H-tetrazoles catalyzed by recyclable complex of copper(II) supported on superparamagnetic

Fe3O4@SiO2 nanoparticles. J. Mol. Catal. A Chem. 2014, 393, 18–29. [CrossRef] 34. Materer, N.F.; (Stillwater, OK, USA). Personal communication, 2015. After ref. [25] appeared, reseachers at Xplosafe, LLC found that aging OSU-6 with 2 M HCl for two weeks during its preparation gave a more active catalyst, and this is thought to account for its acidic properties. 35. Patil, D.R.; Wagh, Y.B.; Ingole, P.G.; Singh, K.; Dalal, D.S. β-Cyclodextrin-mediated highly efficient [2 + 3] cycloaddition reactions for the synthesis of 5-substituted 1H-tetrazoles. New J. Chem. 2013, 37, 3261–3266. [CrossRef] 36. Aldrich 2012–2014 Handbook of Fine Chemicals; Sigma-Aldrich, Inc.: Milwaukee, WI, USA, 2011; p. 2053. Sample Availability: Samples of the compounds are not available from authors (or from MDPI).

© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).

22766