Cite this: RSC Advances, 2013, 3,5889

Ruthenium-catalyzed one-pot synthesis of primaryamides from aldehydes in water3

Received 5th December 2012,Accepted 5th February 2013

DOI: 10.1039/c3ra23195j

www.rsc.org/advances

Rocıo Garcıa-Alvarez, Alba E. Dıaz-Alvarez, Pascale Crochet* and Victorio Cadierno*

The readily available arene–ruthenium(II) complex [RuCl2(g6-C6Me6){P(NMe2)3}] (5 mol%) proved to be an

efficient catalyst for the direct synthesis of primary amides from aldehydes and hydroxylamine

hydrochloride (NH2OH?HCl) in water at 100 uC. The process, which requires the presence of NaHCO3 to

catch the HCl released during the formation of the key aldoxime intermediates, was operative with both

aromatic, heteroaromatic, a,b-unsaturated and aliphatic aldehydes, and tolerated several functional

groups. A greener approach using commercially available NH2OH solution (50 wt.% in water) is also

presented.

Introduction

The amide bond is unarguably one of the most abundantfunctional groups in natural products, polymers and pharma-ceuticals.1 Amides are routinely prepared through the union ofcarboxylic acids and derivatives (halides, anhydrides or esters)with amines.1,2 However, these classical methods presentseveral drawbacks, such as the use of toxic, corrosive and/orexpensive materials, highly exothermic reactions, low toler-ance to sensitive functional groups, complex reaction condi-tions and wasteful procedures. The availability of new efficientand sustainable synthetic routes for this important class ofcompounds is therefore needed.3 In the search for improvedmethods, metal-catalyzed transformations have emerged inthe last two decades as the most promising alternatives for theatom-economical and cost effective synthesis of amides,opening also previously unavailable routes from substratesother than carboxylic acids and their derivatives.4

Aldehydes are highly desirable starting materials for amidesynthesis due to their availability and non-toxic nature. In thiscontext, the one-pot coupling of aldehydes with hydroxylaminecatalyzed by metal complexes has been revealed in recent yearsas an appealing tool for the generation of primary amides(Scheme 1).4,5 The reaction involves the Beckmann-typerearrangement of an aldoxime intermediate, generated in situby the condensation of an aldehyde with NH2OH, via initialdehydration to the corresponding nitrile followed by hydration

of the CMN bond.4 Several catalytic systems, based onruthenium,6 iron,7 rhodium,8 iridium,9 palladium,10 copper,11

zinc,12 indium12 and scandium13 compounds, able to promotethis catalytic transformation have already been described inthe literature.14

On the other hand, the development of organic transforma-tions in water has become one of the major cornerstones inmodern chemistry.15 In addition to the enhanced reactivitiesand selectivities observed in some cases,16 the use of water asan alternative, available, safe, and cost-effective solvent fulfilsthe principles of ‘‘Green Chemistry’’,17 thus creating ananswer to the growing concerns associated with the environ-mental impact of chemical processes.18 Despite this growinginterest, metal catalysts that are able to promote the couplingof aldehydes with hydroxylamine in water remain scarce.Pioneering work in the field was published by Mizuno and co-workers in 2007 using the heterogeneous system Rh(OH)x/Al2O3 (4 mol% of Rh).8 The reactions, performed with thehydroxylammonium salt (NH2OH)2?H2SO4, delivered thedesired amides in high yields after 7 h of heating at 120–160uC. FeCl3 (5 mol%), in combination with Cs2CO3, proved alsoeffective for the coupling of several aldehydes with hydro-xylammonium hydrochloride in water under homogeneousand milder conditions (100 uC). However, longer reaction

Laboratorio de Compuestos Organometalicos y Catalisis (Unidad Asociada al CSIC),

Departamento de Quımica Organica e Inorganica. Instituto Universitario de Quımica

Organometalica ‘‘Enrique Moles’’, Universidad de Oviedo. Julian Claverıa 8, 33006

Oviedo, Spain. E-mail: crochetpascale@uniovi.es (PC); vcm@uniovi.es (VC);

Fax: (+34)985103446; Tel: (+34)985103453

3 Electronic supplementary information (ESI) available: Copies of the 1H and13C{1H} NMR spectra of all the amides synthesized in this work (the 19F NMRspectrum in the case of amide 2k). See DOI: 10.1039/c3ra23195j

Scheme 1 Catalytic formation of primary amides by the coupling of aldehydeswith hydroxylamine.

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times (17–32 h) were needed in this case.7 Faster transforma-tions (15–35 min) were subsequently described by Singh andAllam, employing scandium(III) triflate (10 mol%),NH2OH?HCl and Na2CO3, but a relatively high temperaturewas still required to attain good conversions (135 uC undercontrolled MW irradiation).13 Quite recently, a protocolinvolving Cu(OAc)2 (2 mol%) and aqueous hydroxylaminesolution has been reported by Ramon and co-workers.11b Thedirect use of NH2OH(aq), instead of a hydroxylammonium salt,eliminated the need for a base, thus minimizing thegeneration of wastes. However, the extremely long reactiontimes required (2 days at 110 uC) is a serious drawback forfurther applications of this catalytic system.

Following on with our current interest in catalytic amidebond forming reactions,4c,19 herein we report an alternativeand more efficient catalyst, namely [RuCl2(g6-C6Me6){P(NMe2)3}] (Fig. 1), for the direct conversion ofaldehydes to primary amides in water. This versatile arene–ruthenium(II) complex, which contains the inexpensiveP-donor ligand tris(dimethylamino)phosphine, has alreadyproved to be effective for the catalytic hydration of organoni-triles19e,f and the catalytic rearrangement of aldoximes19g inaqueous media. As the reader will see, by means of [RuCl2(g6-C6Me6){P(NMe2)3}], the coupling process depicted in Scheme 1can be conveniently performed using solid hydroxylammo-nium hydrochloride in the presence of NaHCO3, or by directlyemploying commercially available hydroxylamine solution (50wt% in H2O) under base-free conditions.

Results and discussion

The ability of [RuCl2(g6-C6Me6){P(NMe2)3}] to promote thecatalytic conversion of aldehydes into primary amides wasevaluated by employing commercially available hydroxylaminehydrochloride (NH2OH?HCl) as the ‘‘NH2 source’’, andbenzaldehyde (1a) as a model substrate (results are collectedin Table 1). For the initial reaction conditions, we took thosepreviously employed in our nitrile hydration and aldoximerearrangement studies, i.e., the use of a 0.33 M solution of thesubstrate in water, a ruthenium loading of 5 mol% and aworking temperature of 100 uC.19e–g Under these conditions,when benzaldehyde (1a) was reacted with 1 equiv. ofNH2OH?HCl, the desired benzamide (2a) was formed in only21% GC-yield after 7 h of heating (Table 1, entry 1). In additionto unreacted 1a (ca. 24%) and benzonitrile (ca. 15%), the majorproduct of the reaction turned out to be benzoic acid (ca.

40%), resulting from the hydrolysis of 2a promoted by the HClreleased during the generation of the key benzaldoximeintermediate (see Scheme 1). This latter intermediate wasnot observed by GC in the crude reaction mixture, inaccordance with the great ability shown by [RuCl2(g6-C6Me6){P(NMe2)3}] to promote its dehydration into benzonitri-le.19g To avoid the competitive hydrolysis of the amide, 1 equiv.of NaHCO3 was introduced into the medium, and the yield of2a could be increased to 60% without detecting benzoic acid inthe crude product (Table 1, entry 2). Further improvements tothe yield of 2a were achieved by increasing the quantities ofNH2OH?HCl and NaHCO3 employed (Table 1, entries 3–5),reaching a maximum 88% GC-yield with 1.3 equiv. of thesereagents (Table 1, entry 5; ca. 4% of unreacted 1a and 8% ofbenzonitrile were detected by GC in the crude reactionmixture). As shown in Table 1, entries 6–10, different alkalimetal hydroxides and carbonates were screened as potentialbases for this reaction. Marked differences in reactivitycompared with NaHCO3 were not observed. Similarly, theuse of (NH2OH)2?H2SO4 instead of NH2OH?HCl led tocomparable results (Table 1, entry 11). In contrast, remarkablypoorer yields of 2a were attained when the catalytic coupling of1a with NH2OH?HCl was carried out in organic media (e.g.,toluene, 1,2-dichloroethane or 2-propanol), even after 24 h ofheating (Table 1, entries 12–14). These last observations are incomplete accordance with the need for an excess of water forthe effective rearrangement of the intermediate benzaldoxime

Fig. 1 Structure of the arene-ruthenium(II) catalyst employed in this work.

Table 1 Ruthenium-catalyzed one-pot synthesis of benzamide (2a) frombenzaldehyde (1a) in water using hydroxylammonium hydrochloridea

Entry NH2OH?HCl Base Yield of 2ab

1 1 equiv. — 21%c

2 1 equiv. NaHCO3 (1 equiv.) 60%3 1.1 equiv. NaHCO3 (1.1 equiv.) 69%4 1.2 equiv. NaHCO3 (1.2 equiv.) 80%5 1.3 equiv. NaHCO3 (1.3 equiv.) 88%6 1.3 equiv. NaOH (1.3 equiv.) 83%7 1.3 equiv. KOH (1.3 equiv.) 81%8 1.3 equiv. Na2CO3 (1.3 equiv.) 84%9 1.3 equiv. K2CO3 (1.3 equiv.) 87%10 1.3 equiv. Cs2CO3 (1.3 equiv.) 88%11d 0.65 equiv. NaHCO3 (1.3 equiv.) 85%12e 1.3 equiv. NaHCO3 (1.3 equiv.) 22%13f 1.3 equiv. NaHCO3 (1.3 equiv.) 57%14g 1.3 equiv. NaHCO3 (1.3 equiv.) 63%15h 1.3 equiv. NaHCO3 (1.3 equiv.) 55%16i 1.3 equiv. NaHCO3 (1.3 equiv.) 46%

a Reactions performed under a N2 atmosphere at 100 uC startingfrom 1 mmol of benzaldehyde (0.33 M in water). b Yields determinedby GC (uncorrected GC areas). c Benzoic acid in ca. 40% yield isformed. d Reaction performed using (NH2OH)2?H2SO4 instead ofNH2OH?HCl. e Reaction performed in toluene for 24 h. f Reactionperformed in 1,2-dichloroethane for 24 h. g Reaction performed in2-propanol for 24 h. h Reaction performed at 80 uC. i Reactionperformed using a ruthenium loading of 2 mol%.

5890 | RSC Adv., 2013, 3, 5889–5894 This journal is � The Royal Society of Chemistry 2013

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since, as previously discussed in ref. 19g, the hydration of theinitially formed benzonitrile is the rate limiting step of therearrangement process. As expected, the use of lowertemperatures or ruthenium loadings also reduced the yieldof 2a considerably (Table 1, entries 15–16).

Using the optimal reaction conditions (0.33 M solution ofthe aldehyde in water; aldehyde/Ru/NH2OH?HCl/NaHCO3 ratio= 100/5/130/130; 100 uC), the generality of the process was thenexplored. The results obtained are summarized in Table 2.Thus, as observed for 1a (Table 2, entry 1), [RuCl2(g6-C6Me6){P(NMe2)3}] was able to convert other aromatic alde-hydes (1b–r; Table 2, entries 1–18) into the correspondingprimary amides 2b–r in moderate to good yields (63–99% GC-yield), regardless of the substitution pattern of the aromaticring. However, an important influence of the electronicproperties of the substituents on the efficiency of the processwas observed. Thus, aldehydes with electron-donating groupsshowed lower reactivities (Table 2, entries 14–18) compared tosubstrates with electron-withdrawing functionalities (Table 2,entries 2–13), the former requiring longer reaction times (24vs. 7 h) to generate the final products in high yields.

As expected, this coupling reaction is not restricted toaromatic aldehydes, heteroaromatic (1s–t; Table 2, entries 19–20), aliphatic (1u–w; Table 2, entries 21–23) and a,b-unsatu-rated ones (1x–z; Table 2, entries 24–26) also gave the desiredamides 2s–z in 76–95% GC-yield after 7 h of heating.Remarkably, as shown in entry 27 (Table 2), the use of[RuCl2(g6-C6Me6){P(NMe2)3}] allowed, for the first time, thedirect preparation of the fragrance (S)-(2)-citronellamide (2aa)from the naturally occurring aldehyde (S)-(2)-citronellal(1aa).19g,20 In all cases, the starting aldehydes, and the nitrilesderived from these, were the only by-products detected at theend of the reactions by GC. Solvent removal, extraction of thecrude product with dichloromethane, and recrystallizationfrom hot water, provided analytically pure samples of theamides 2a–aa in 50–92% isolated yield (in some casesadditional purification by column chromatography wasneeded).

It is also worthy of note that the present coupling processproved useful for the synthesis of diamides. Thus, using anexcess of hydroxylammonium hydrochloride and NaHCO3 (2.6equiv. of each), [RuCl2(g6-C6Me6){P(NMe2)3}] (5 mol%) wasable to convert 1,2-, 1,3- and 1,4-benzenedicarboxaldehyde(1ab–ad) into phthalamide (2ab), isophthalamide (2ac) andterephthalamide (2ad), respectively, after 24 h of heating(Scheme 2).21

The outstanding performance of [RuCl2(g6-C6Me6){P(NMe2)3}] was further exploited in the catalyticsynthesis of ferrocenecarboxamide (2ae), a valuable startingmaterial in the chemistry of ferrocene,22 by the coupling offerrocenecarboxaldehyde (1ae) with NH2OH?HCl (Scheme 3).Thus, performing the reaction in a water/MeOH (10 : 1 v/v)mixture for 24 h, 2ae could be isolated in 79% yield followingthe standard work-up procedure described above. The use of asmall amount of methanol was key to ensure the totalsolubilisation of 1ae during the process, with the same

Table 2 Ruthenium-catalyzed one-pot synthesis of primary amides (2) fromaldehydes (1) in water using hydroxylammonium hydrochloridea

Entry Aldehyde 1 Yield of 2b

1 R = Ph (1a) 2a; 88% (79%)2 R = 2-F-C6H4 (1b) 2b; 92% (82%)3 R = 3-F-C6H4 (1c) 2c; 94% (83%)4 R = 4-F-C6H4 (1d) 2d; 85% (71%)5 R = 2-Cl-C6H4 (1e) 2e; 97% (87%)6 R = 3-Cl-C6H4 (1f) 2f; 86% (74%)7 R = 4-Cl-C6H4 (1g) 2g; 97% (89%)8 R = 2-Br-C6H4 (1h) 2h; 87% (76%)9 R = 3-Br-C6H4 (1i) 2i; 90% (80%)10 R = 4-Br-C6H4 (1j) 2j; 82% (70%)11 R = C6F5 (1k) 2k; 99% (90%)12 R = 3-NO2-C6H4 (1l) 2l; 99% (92%)13 R = 4-NO2-C6H4 (1m) 2m; 88% (79%)14c R = 2-Me-C6H4 (1n) 2n; 80% (71%)15c R = 4-Me-C6H4 (1o) 2o; 74% (63%)16c R = 2-OMe-C6H4 (1p) 2p; 72% (61%)17c R = 4-OMe-C6H4 (1q) 2q; 63% (50%)18c R = 4-SMe-C6H4 (1r) 2r; 80% (70%)19 R = 3-Furyl (1s) 2s; 84% (72%)20 R = 2-Thienyl (1t) 2t; 92% (85%)21 R = n-C6H13 (1u) 2u; 95% (88%)22 R = Cy (1v) 2v; 91% (80%)23 R = CH2CH2Ph (1w) 2w; 89% (79%)24 R = (E)-CHLCHPh (1x) 2x; 90% (80%)25 R = (E)-CHLCH-2-C6H4OMe (1y) 2y; 76% (63%)26 R = (E)-CHLCH-4-C6H4OMe (1z) 2z; 83% (75%)27 R = (S)-CH2CH(Me)(CH2)2CHLCMe2 (1aa) 2aa; 92% (83%)

a Reactions performed under N2 atmosphere at 100 uC starting from1 mmol of the corresponding aldehyde (0.33 M in water). Substrate/Ru/NH2OH?HCl/NaHCO3 ratio: 100/5/130/130. b Yields determined byGC (uncorrected GC areas). Isolated yields after appropriate work-upare given in brackets. c Reaction time: 24 h.

Scheme 2 Catalytic transformation of benzenedicarboxaldehydes 1ab–ad intobenzenediamides 2ab–ad using complex [RuCl2(g6-C6Me6){P(NMe2)3}].

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reaction performed in pure water delivering 2ae in aremarkably lower yield (ca. 60%).

To the best of our knowledge, this is the first protocoldescribed in the literature for the direct formation of 2aestarting from 1ae. The method commonly used for thepreparation of ferrocenecarboxamide (2ae) involves a two-stepsequence consisting of the conversion of ferrocenecarboxylicacid into the corresponding acid chloride, by action of harmfulthionyl chloride, followed by treatment with aqueous ammo-nia.22 In comparison with this classical method, the syntheticroute depicted in Scheme 3 presents the following advantages:(i) it involves a single synthetic operation, (ii) it makes use of acheaper starting material,23 (iii) it proceeds in environmentallyfriendly aqueous medium, and (iv) it does not require tediouspurification procedures.24

Finally, taking advantage of the operability of [RuCl2(g6-C6Me6){P(NMe2)3}] in aqueous medium, a simpler and greenerprocedure that employs commercially available hydroxylaminesolution (50 wt% in H2O) instead of solid NH2OH?HCl wasdeveloped. The direct use of NH2OH(aq) avoided the introduc-

tion of a base in the medium to catch the acid released duringthe generation of the corresponding aldoxime intermediate,thus simplifying the isolation of the amide and minimizingthe generation of waste (extraction with CH2Cl2 to eliminatesalts was not longer required). As shown in Table 3, in thestudied examples, no marked differences in terms of activityrelative to those observed using NH2OH?HCl were found.

Conclusions

In summary, simple and general protocols for the one-potconversion of aromatic, heteroaromatic, a,b-unsaturated andaliphatic aldehydes into primary amides in water have beendeveloped with the aid of the readily available arene–ruthenium(II) catalyst [RuCl2(g6-C6Me6){P(NMe2)3}]. In theprotocols, solid hydroxylammonium hydrochloride or hydro-xylamine solution (50 wt% in H2O) were employed as the ‘‘NH2

source’’. The possibility of using the latter is particularlyattractive because it prevents the introduction of a base intothe medium, thus reducing the cost and generation of waste.In general, compared to other catalytic systems previouslydescribed in the literature for this one-pot transformation,[RuCl2(g6-C6Me6){P(NMe2)3}] shows a superior activity underlower temperature regimes, attributes which provide it with agreat potential for practical applications.

Experimental

General methods

The manipulations were performed under an inert N2 atmo-sphere using vacuum-line and standard sealed-tube techni-ques. All reagents were obtained from commercial suppliersand used as received, with the exception of [RuCl2(g6-C6Me6){P(NMe2)3}], which was prepared following the methodpreviously reported by us.19e,f GC measurements were per-formed on Hewlett-Packard HP6890 equipment using aSupelco Beta-DexTM 120 column (30 m length; 250 mmdiameter).

General procedure for the ruthenium-catalyzed conversion ofaldehydes into primary amides using NH2OH?HCl

Under a nitrogen atmosphere, the corresponding aldehyde (1mmol), hydroxylamine hydrochloride (0.090 g, 1.3 mmol; 0.180g, 2.6 mmol in the case of aldehydes 1ab–ad), NaHCO3 (0.109g, 1.3 mmol; 0.218 g, 2.6 mmol in the case of aldehydes 1ab–ad), 3 mL of water (a water/methanol mixture (10 : 1 v/v) in thecase of aldehyde 1ae), and the ruthenium(II) catalyst [RuCl2(g6-C6Me6){P(NMe2)3}] (0.025 g, 0.05 mmol; 5 mol%) wereintroduced into a teflon-capped sealed-tube and the reactionmixture was stirred at 100 uC for 7–24 h. After this time, themixture was evaporated to dryness, the solid residue extractedwith CH2Cl2 (10–20 mL) and filtered over kieselguhr.Evaporation of the extract led to a solid, which was redissolvedin hot water (5–10 mL) and stored in a freezer at 220 uC for 10h. This led to the crystallization of the corresponding amide,

Scheme 3 Catalytic transformation of ferrocenecarboxaldehyde (1ae) intoferrocenecarboxamide (2ae) using [RuCl2(g6-C6Me6){P(NMe2)3}].

Table 3 Ruthenium-catalyzed one-pot synthesis of primary amides (2) fromaldehydes (1) in water using hydroxylamine solutiona

Entry Aldehyde 1 Yield of 2b

1 R = Ph (1a) 2a; 83% (73%)2 R = 2-F-C6H4 (1b) 2b; 93% (84%)3 R = 3-F-C6H4 (1c) 2c; 91% (80%)4 R = 4-Cl-C6H4 (1g) 2g; 94% (86%)5 R = C6F5 (1k) 2k; 97% (89%)6 R = 3-NO2-C6H4 (1l) 2l; 99% (91%)7c R = 4-Me-C6H4 (1o) 2o; 78% (70%)8c R = 4-OMe-C6H4 (1q) 2q; 70% (61%)9 R = 2-Thienyl (1t) 2t; 93% (86%)10 R = n-C6H13 (1u) 2u; 95% (87%)11 R = Cy (1v) 2v; 82% (73%)12 R = CH2CH2Ph (1w) 2w; 85% (74%)13 R = (E)-CHLCHPh (1x) 2x; 93% (81%)14d R = Ferrocenyl (1ae) 2ae; 87%

a Reactions performed under a N2 atmosphere at 100 uC, startingfrom 1 mmol of the corresponding aldehyde (0.33 M in water).Substrate/Ru/NH2OH ratio: 100/5/130. b Yields determined by GC(uncorrected GC areas). Isolated yields after appropriate work-up aregiven in brackets. c Reaction time: 24 h. d Reaction performed in awater/methanol mixture (10 : 1 v/v) for 24 h (the isolated yield isgiven).

5892 | RSC Adv., 2013, 3, 5889–5894 This journal is � The Royal Society of Chemistry 2013

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which was separated, washed with hexane (2 6 5 mL) andvacuum-dried (in some cases additional purification bycolumn chromatography over silica gel, using a methanol/CH2Cl2 mixture as the eluent, was needed). The identities ofthe resulting primary amides 2a–ae were assessed by compar-ison of their 1H and 13C{1H} NMR spectroscopic data withthose reported in the literature, and by their fragmentation inGC/MSD.

General procedure for the ruthenium-catalyzed conversion ofaldehydes into primary amides using NH2OH(aq) solution

Under a nitrogen atmosphere, the corresponding aldehyde (1mmol), hydroxylamine (50 wt% solution in water; 80 mL, 1.3mmol), 3 mL of water (a water/methanol mixture (10 : 1 v/v) inthe case of aldehyde 1ae), and the ruthenium(II) catalyst[RuCl2(g6-C6Me6){P(NMe2)3}] (0.025 g, 0.05 mmol; 5 mol%)were introduced into a teflon-capped sealed-tube and thereaction mixture stirred at 100 uC for 7–24 h. After this time,the hot mixture was passed through a filter paper, allowed toreach room temperature, and subsequently stored in freezer at220 uC for 10 h. This led to the crystallization of thecorresponding primary amide, which was separated, washedwith hexane (2 6 5 mL) and vacuum-dried (in some casesadditional purification by column chromatography over silicagel, using a methanol/CH2Cl2 mixture as the eluent, wasneeded).

Acknowledgements

Financial support from the Ministerio de Economıa yCompetitividad of Spain (Projects CTQ2010-14796/BQU andCSD2007-00006) is gratefully acknowledged.

References

1 See for example: (a) The Chemistry of Amides, ed. J. Zabicky,Wiley-Interscience, New York, 1970; (b) The Amide Linkage:Structural Significance in Chemistry, Biochemistry andMaterials Science, ed. A. Greenberg, C. M. Breneman andJ. F. Liebman, John Wiley & Sons, New York, 2000; (c)Polyesters and Polyamides, ed. B. L. Deopura, B. Gupta, M.Joshi and R. Alagirusami, CRC Press, Boca Raton, 2008; (d)I. Johansson, in Kirk-Othmer Encyclopedia of ChemicalTechnology, John Wiley & Sons, New York, 2004, vol. 2,pp. 442–463.

2 (a) See for example: Methoden Org. Chem. (Houben Weyl),ed. D. Dopp and H. Dopp, Thieme Verlag, Stuttgart, 1985,vol. E5(2), pp. 1024–1031; (b) P. D. Bailey, T. J. Mills,R. Pettecrew and R. A. Price, in Comprehensive OrganicFunctional Group Transformations II, ed. A. R. Katritzky andR. J. K. Taylor, Elsevier, Oxford, 2005, vol. 5, pp. 201–294; (c)E. Valeur and M. Bradley, Chem. Soc. Rev., 2009, 38, 606.

3 Industrial-led surveys highlighting the need for efficientamide formation methods can be found in: (a) J. S. Carey,D. Laffan, C. Thomson and M. T. Williams, Org. Biomol.Chem., 2006, 4, 2337; (b) D. J. C. Constable, P. J. Dunn, J.D. Hayler, G. R. Humphrey, J. L. Leazer Jr., R. J. Linderman,

K. Lorenz, J. Manley, B. A. Pearlman, A. Wells, A. Zaks andT. Y. Zhang, Green Chem., 2007, 9, 411.

4 For recent reviews covering innovative approaches foramide bond formation see: (a) C. L. Allen and J. M.J. Williams, Chem. Soc. Rev., 2011, 40, 3405; (b) V.R. Pattabiraman and J. W. Bode, Nature, 2011, 480, 471;(c) R. Garcıa-Alvarez, P. Crochet and V. Cadierno, GreenChem., 2013, 15, 46.

5 This method is complementary to the catalytic amidationof aldehydes with amines which proved particularly usefulfor the preparation of secondary and tertiary amides. For aspecific review on this reaction, see: K. Ekoue-Kovi andC. Wolf, Chem.–Eur. J., 2008, 14, 6302.

6 (a) D. Gnanamgari and R. H. Crabtree, Organometallics,2009, 28, 922; (b) J. F. Hull, S. T. Hilton and R. H. Crabtree,Inorg. Chim. Acta, 2010, 363, 1243; (c) N. Raja, M. U. Rajaand R. Ramesh, Inorg. Chem. Commun., 2012, 19, 51; (d) R.N. Prabhu and R. Ramesh, RSC Adv., 2012, 2, 4515.

7 R. R. Gowda and D. Chakraborty, Eur. J. Org. Chem., 2011,2226.

8 (a) H. Fujiwara, Y. Ogasawara, K. Yamaguchi andN. Mizuno, Angew. Chem., Int. Ed., 2007, 46, 5202; (b)H. Fujiwara, Y. Ogasawara, M. Kotani, K. Yamaguchi andN. Mizuno, Chem.–Asian J., 2008, 3, 1715.

9 N. A. Owston, A. J. Parker and J. M. J. Williams, Org. Lett.,2007, 9, 73.

10 M. A. Ali and T. Punniyamurthy, Adv. Synth. Catal., 2010,352, 288.

11 (a) N. C. Ganguly, S. Roy and P. Mondal, Tetrahedron Lett.,2012, 53, 1413; (b) A. Martınez-Asensio, M. Yus and D.J. Ramon, Tetrahedron, 2012, 68, 3948.

12 C. L. Allen, C. Burel and J. M. J. Williams, Tetrahedron Lett.,2010, 51, 2724.

13 B. K. Allam and K. N. Singh, Tetrahedron Lett., 2011, 52,5851.

14 The use of a glycerol-based carbon catalyst and silicachloride both in organic media, has also been recentlydescribed: (a) K. Ramesh, S. N. Murthy, K. Karnakar, K. H.V. Reddy, Y. V. D. Nageswar, M. Vijay, B. L. A. P. Devi and R.B. N. Prasad, Tetrahedron Lett., 2012, 53, 2636; (b) B. Dattaand M. A. Pasha, Bull. Korean Chem. Soc., 2012, 33, 2129.

15 For leading books covering this field see: (a) C. J. Li and T.H. Chan, Comprehensive Organic Reactions in AqueousMedia, John Wiley & Sons, New Jersey, 2007; (b) OrganicReactions in Water Principles, Strategies and Applications, ed.U. M. Lindstrom, Blackwell Publishing Ltd., Oxford, 2007;(c) Handbook of Green Chemistry, ed. C.-J. Li and P. T.Anastas, Wiley-VCH, Weinheim, 2010, vol. 5; (d) Water inOrganic Synthesis, ed. S. Kobayashi, Thieme-Verlag:,Stuttgart, 2012; (e) Aqueous-Phase Organometallic CatalysisConcepts and Applications, ed. B. Cornils and W. A.Herrmann, Wiley-VCH, Weinheim, 1998; (f) AqueousOrganometallic Catalysis, ed. I. T. Horvath and F. Joo,Kluver, Dordrecht, 2001; (g) Metal-Catalyzed Reactions inWater, ed. P. H. Dixneuf and V. Cadierno, Wiley-VCH,Weinheim, 2013; (h) V. Polshettiwar and R. S. Varma,Chem. Soc. Rev., 2008, 37, 1546; (i) V. Polshettiwar and R.S. Varma, Chem.–Eur. J., 2009, 15, 1582; (j) A. Fihri, D. Cha,M. Bouhrara, N. Almana and V. Polshettiwar,ChemSusChem, 2012, 5, 85.

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16 The pioneering discoveries made by Breslow and Grieco inthe early 1980s on the positive effect of water on the rateendo/exo selectivity of Diels–Alder reactions are the mostillustrative examples: (a) D. C. Rideout and R. Breslow, J.Am. Chem. Soc., 1980, 102, 7816; (b) P. A. Grieco, K. Yoshidaand P. Garner, J. Org. Chem., 1983, 48, 3137.

17 (a) P. T. Anastas and J. C. Warner, Green Chemistry: Theoryand Practice, Oxford University Press, Oxford, 1998; (b) P.T. Anastas and T. C. Williamson, Green Chemistry: Frontiersin Benign Chemical Synthesis and Processes, OxfordUniversity Press, Oxford, 1998; (c) A. S. Matlack,Introduction to Green Chemistry, Marcel Dekker, New York,2001; (d) M. Lancaster, in Handbook of Green Chemistry andTechnology, ed. J. H. Clark and D. J. Macquarrie, BlackwellPublishing, Abingdon, 2002; (e) M. Lancaster, GreenChemistry: An Introductory Text, RSC Publishing,Cambridge, 2002.

18 (a) W. M. Nelson, Green Solvents for Chemistry: Perspectivesand Practice, Oxford University Press, New York, 2003; (b) J.H. Clark and S. J. Taverner, Org. Process Res. Dev., 2007, 11,149; (c) F. M. Kerton, Alternative Solvents for GreenChemistry, RSC Publishing, Cambridge, 2009.

19 (a) V. Cadierno, J. Francos and J. Gimeno, Chem.–Eur. J.,2008, 14, 6601; (b) R. Garcıa-Alvarez, J. Dıez, P. Crochet andV. Cadierno, Organometallics, 2010, 29, 3955; (c)V. Cadierno, J. Dıez, J. Francos and J. Gimeno, Chem.–Eur. J., 2010, 16, 9808; (d) S. E. Garcıa-Garrido, J. Francos,V. Cadierno, J.-M. Basset and V. Polshettiwar,ChemSusChem, 2011, 4, 104; (e) R. Garcıa-Alvarez,J. Francos, P. Crochet and V. Cadierno, Tetrahedron Lett.,2011, 52, 4218; (f) R. Garcıa-Alvarez, J. Dıez, P. Crochet andV. Cadierno, Organometallics, 2011, 30, 5442; (g) R. Garcıa-Alvarez, A. E. Dıaz-Alvarez, J. Borge, P. Crochet andV. Cadierno, Organometallics, 2012, 31, 6482; (h)R. Garcıa-Alvarez, S. E. Garcıa-Garrido, J. Dıez, P. Crochetand V. Cadierno, Eur. J. Inorg. Chem., 2012, 4218; (i) A.E. Dıaz-Alvarez, R. Garcıa-Alvarez, P. Crochet andV. Cadierno, in Glycerol: Production, Structure andApplications, ed. M. D. S. Silva and P. C. Ferreira, NovaScience Publishers, New York, 2012, pp. 249–262; (j) M.L. Buil, V. Cadierno, M. A. Esteruelas, J. Gimeno, J. Herrero,S. Izquierdo and E. Onate, Organometallics, 2012, 31, 6861.

20 (a) A. G. Caldwell and E. R. H. Jones, J. Chem. Soc., 1946,599; (b) L. Field, P. B. Hughmark, S. H. Shumaker and W.S. Marshall, J. Am. Chem. Soc., 1961, 83, 1983; (c) M. Oku,Y. Fujikura and J. Etsuno, Jpn. Pat., JP07138213, 1995; (d) A.P. S. Narula and A. J. Janczuk, US Pat. Appl.,US20070055082, 2007.

21 Due to the competitive formation of phthalimide as theresult of an intramolecular cyclization process, the yield ofphthalamide (2ab) was remarkably lower (59%) in compar-ison with those of 2ab and 2ac (87–90%). Several successiverecrystallizations were, in this case, required to obtain 2abin pure form. We must note that the catalytic synthesis ofphthalimides from 1,2-benzenedinitriles, via double hydra-tion followed by cyclization of the corresponding 1,2-benzenediamide intermediates, has been recentlydescribed: P. K. Verma, U. Sharma, M. Bala, N. Kumarand B. Singh, RSC Adv., 2013, 3, 895.

22 Compound 2ae possesses interesting coordinating electro-chemical and photochemical properties, it is an advancedintermediate for the preparation of other ferrocenederivatives, including optically active ligands for asym-metric catalysis, and has been employed in recent years forthe design of nanocomposite electrodes, new conductingpolymeric materials and photoelectronic devices. Forleading references, see: (a) L. H Ali, A. Cox and T.J. Kemp, J. Chem. Soc., Dalton Trans., 1973, 1468; (b) P.J. Costanzo, E. Liang, T. E. Patten, S. D. Collins and R.L. Smith, Lab Chip, 2005, 5, 606; (c) S. Y. Oh, H. S. Choi, H.J. Kim and J. K. Park, Polymer, 2005, 29, 331; (d) D. Salazar-Mendoza, S. A. Baudron, M. W. Hosseini, N. Kyritsakas andA. D. Cian, Dalton Trans., 2007, 565; (e) E. Baciocchi,M. Bietti, M. D. Fusco and O. Lanzalunga, J. Org. Chem.,2007, 72, 8748; (f) R. Zhang, Z. Wang, Y. Wu, H. Fu andJ. Yao, Org. Lett., 2008, 10, 3065; (g) S. Y. Oh, C. M. Chung,D. H. Kim and S. G. Lee, Colloids Surf., A, 2008, 313–314,600; (h) C. Wang, G. Wang and B. Fang, Microchim. Acta,2009, 164, 113; (i) D. F. Fischer, A. Barakat, Z.-Q. Xin, M.E. Weiss and R. Peters, Chem.–Eur. J., 2009, 15, 8722; (j)Y. Jiang, J. Yu, L. Li and Z. Ma, Faming Zhuanli Shenquing,CN102208559, 2011; (k) E. Baciocchi, M. Bietti,C. D’Alfonso, O. Lanzalunga, A. Lapi and M. Salamone,Org. Biomol. Chem., 2011, 9, 4085.

23 According to the current quotations of the chemicalsupplier companies Sigma-Aldrich, Alfa Aesar and AcrosOrganics, ferrocenecarboxaldehyde (1ae) is ca. 3–5 timescheaper per gram than ferrocenecarboxylic acid.

24 Transformation of ferrocenecarboxylic acid into the corre-sponding acid chloride is a capricious reaction that oftenresults in low yields. This is due to the high nucleophilicityof the ferrocene nucleus, which leads to the competitiveformation of dimeric and oligomeric by-products arisingfrom Friedel–Crafts-type acylations, thus complicating itspurification and isolation: T. H. Galow, J. Rodrigo,K. Cleary, G. Cooke and V. M. Rotello, J. Org. Chem.,1999, 64, 3745.

5894 | RSC Adv., 2013, 3, 5889–5894 This journal is � The Royal Society of Chemistry 2013

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