Indian Journal of Chemistry Vol. 43B, February 2004, pp. 432-436

Note

Reduction of polyfunctional aromatic nitro compounds using lithium aluminium hydride

M M Joseph & Dominic E Jacob*

Research Centre, Department of Chemistry. Nirmala College. Muvattupuzha. Ernaku lum, Kerala. 68666 1, India

E-mail :ejdomi n ie@ red iffmai l.eom

Received J J April 2002; accepted (revised) 18 June 2003

Aromatic nitro compou nds containing yet anothcr functional group are reduced using lithium aluminium hydride in ether. The reduction of nitrobenzanilides resu lts in preferenti al reduction of amide functionality while the isomeric N- (nitrophenyl ) ben­zamides results in preferenti al cleavage of the ami de bond . Be­sides, the reduction of 2,2'-dinitrodiphenyl amine Sa, reduction of (bis-2- nitroanilino) methane Sb, 2, 2'-dinitrodipheny lether Se, 2-nitrophenyl-2'-nit rophenoxy methane Sd, I, 3-dinit robenzene 6a, 2-nit robenzaldoxime 6b, 2-N (2'- nitrophenylmethyl) amino ben­zoic acid 6e, 2-nit rophenoxy methyl phenyl ketone 6d are carried out. Nitro group is found reluctant towards red uction in some cases whereas in some others it is reduced into different extents. Thi s points to the limitation of the suggested azo tcst for aromatic nitro compounds.

IPC: Int.CI.7 C 07 B 31100

The selective reduction of aromatic polyfunctional nitro compounds can be effected by a variety of re­ducing agents l

-3

• Lithium aluminium hydride (LAH) is a very versatile reducing agent and is of much im­portance in its synthetic utilit/·9

. It has been re­ported 10· 14 that aromatic nitro compounds afford cor­responding azo compounds on treatment with excess of LAH and the red azo colour has been suggested 15 as a sensitive test for such compounds. In continuation of our stud ies l6

.17 on the reduction of various poly-

functional compounds, herein we report the results of the reduction of some aromatic nitro-amido, dinitro­am ido, nitro-oximino, and nitrophenoxy compounds.

Results and Discussion All reductions were done by the dropwise additi on

of a solution of the reagent in ether to an etherea l so­lution of the compounds with constant stirring at room temperature followed by treatment at refl ux temperature for 2-3 hr. The excess reagent was de­stroyed using ei ther water or by dil. NaOH so luti on and the products were seorthoted by column chroma­tography.

It is seen that the cleavage of the amide linkage is preferred to the reduction to secondary amines in compounds la and lc where the ni tro group is at the ortho and para positions of the N-phenyl group. These compounds when refluxed with LAH resulted in the cleavage of the N-C bond. But Id and If where the nitro group is at orlho and para positions of the C-phenyl group, afforded the reduced products under similar condi tions. Reverse tendencies are noticed in the cases of lb and Ie. In the case of Ib, the reduced product and for Ie the cleaved products are formed in higher yield (Scheme I, Table I ).

It is interesting to note that the treatment of LAH with compounds Ia-f did not produce the red azo col­our as suggested 15. Infact a pale brown solution was resulted in the case of la. These reactions indicate an obvious subst ituent effect on the reduction reaction o f LAH . A genera li sed mechani stic path may be visual­ized in these reactions of ami des with LAH (Scheme II) .

Table I - Results of reduction of la - f

Compd R R' Yi eld of Reduction product (2)

(%)

la H o-N02 12

Ib H III-N02 73

Ie H p-N02 14

Id o-N02 H 84

Ie m-N02 H 24

If p-N02 H 78

m.p. Yield of cleaved products (%) (0C)

Alcohol (3) Amine (4)

73 68 66

107 14

147 8 1 83

44 10 8

84 58 66

72 14 8

Average yield of cleaved products

67

14

82

9

62

II

m. p. of 4 (0C)

73

11 2

149

NOTES 433

o II

©JC-N~ __ ©!CH,-NH'@ +

R R' R Reduced product R'

©rCH: OH QNH, R Cleaved products R'

1a-f 2a-f

Scheme I

3d-e 4a-f

R LAH ?A1H3 /H R

R-C-NHR'----' ... R-C--N ---'l.~R-y + R'NH2

~ I 'R' ~ t RCH;PH

R-CH=N R' ... ... R CH2-NHR

Scheme II

In the cases of compounds la and Ie the electron withdraw ing ni tro group weakens the C-N bond and therefore reducti vely cleaved product resulted. In the meta substituted amide Ib the nitro group will not weaken thi s, because of its di fferent orientation power. But when the nitro group is present on C­phenyl group as in the case of Id and If the reverse effect is noti ced . The e lectron withdraw ing nitro group on artha and para pos itions of the C-phenyl group strengthens the carbon - nitrogen bond resulting the reduction product. When nitro group is present on the meta position of the C-phenyl group, the reso­nance effect on the am ide lin kage is not effec ti ve and reducti ve ly cleaved products result.

]n the cases of reductions o f Sa-d and 6a-d a very interesting observation is that the nitro group is reluc­tant to LAH reduction compared with the other fun c­tional groups (see Scheme III, Table II). The selec­ti ve reduction of an aromatic nitro group into an amino group is noticed in Sa and 6d. Compound Sb shows reducti ve cleavage. It is seen that both the nitro

groups in Sc are reduced forming 2-nitroso-i­hyd roxy laminod iphenyl ether. Reducti ve cleavage of the CH2-O bond is fo und along with reducti ve cou­pling in the case of Sd. Onl y one of the two nitro groups in the ring is found reduced in 6a to yield the 3,3' -di nitroazoxy benzene. Similar reducti ons using Bi were reported 1.3. Compound 6b produced benzopyrazo le 7 by the action o f reduction intermed iates of nitro group viz. nitroso group with NH2 group formed by the reducti on of the oximino group IS. 19. The formation of IIH,1 2H-dihydro­dibenzo[c,g][l ,S]-di azoc in-S-N-ox ide 8 from 6c also shows the poss ible interaction of the intermediates

interaction of the intermediates fo rmed during the reduction. The fo rmation of 2-nitrobenzaldehyde by deox imination of 6b is due to ac idic hydro lys is2o dur­ing the work-up.

It is to be noticed that among the di fferent com­pounds Sa-d and 6a-d only Sd could yield the ex­pected azo product as the majo r one. Even though the mechani sm is not clear the nature of the reduced products in diffe rent reacti ons agrees with the general mechani sm fo r reduction of aromatic nitro group to y ie ld azo compound .

These resul ts along with the selecti ve reductions I6.17

o f the nitro-phenolic esters, nitro-halogeno com­pounds show that the LAH test for aromatic nitro compounds is not conclusive at least for bifunctional compounds.

Experimental Section General. Melting points are uncorrected. TLC was

done on pre-coated aluminium plates. TLC spots were visuali zed using UV fluorescent lamp. Column chromatography was conducted using silica (1 00-200 mesh) or neutral alumina. LA H was purchased from E Merck and Ll sed as such. Spectra were recorded at RSIC Madras. IH MR spectra were recorded in CDCl3

solution containing TMS as the internal standard on 500 MH z Vari an EM instrument and mass spectra on a Vari an MAT -CH7 mass spectrometer. The reported yields are based on the amount of substrates converted in the reactions. The yields of products were determined by weighing of the dried samples.

Preparation of compounds. The compounds la-c were prepared21a by the reaction of corresponding acid

434 INDIAN J. CHEM. , SEC S, FEBRUARY 2004

©('N R

©lNo, 0i'J N0 2

5a-d 6a-d

Compd X Compd R

5a NH 5b NH-CH2-NH 5c -0 -5d -CH2-O

NH

ij' ; ~CH

7

6a m-N0 2 6b o-CH=NOH

6c O-CH,NH-Q COOH

6d o-OCH2-COC6HS

reyNH-CH:'1J

~CH=N~

8

I o

Scheme III

Table II-Rcsu lts of the rcduct ions of bifuncti onal compounds using LAH

Compd Major product Yield m.p. Minor product Yield m.p. (% ) °C (% ) °C

Sa 2-nitro-2'-amino diphenylamine 73 103 2-nitroanilinc 2 1 72

Sb N-mcthy l-2-nit ro anilinc 73 36 2-nitroanilinc 64 72

Sc 2-nitroso-2'-hydroxy l aminod ipheny l cther 72 nitrobenzcnc 88

2-nit rophcnol II 45

Sd (2'-mcthy l)-2-hydroxy- azobcnzenc 53 85 2-nitrophcnol 3 1 45

6a 3,3'-d initroazoxy- bcnzcnc 86 146 3,3'-d init roazobenzene 8 153

6b benzopyrazolc 67 146 2-nitrobcnzaldchyde \6 43

6c I I II. 12/-I ,dihydro- dibenzo[c,glll,51- diazoc in-5-N-oxidc 68 2-aminobcnzy l alco- 17 82

6d I -pheny lethanol

chloride with aniline. The melting points are respec­ti vely lSSoC, I S4°C and 2 11 °C. Id -f were prepared2 1b

by the benzoylation of corresponding nitroaniline in acetone in presence of SO% aq ueous sod ium hydrox­ide, melting points are 9]DC, I Ss oC, 196°C respec­ti vely. Compound Sa was prepared2 1c by the acti on of 2-nitroaniline and 2-chloronitrobenzene in presence of copper bronze, m.p. l64°C. 5b was prepared2 1d from 2-nitroaniline by treatment with 40% forma ldehyde solution in water, m.p.194°C. 5c was prepared2 1c from a mi xture of potass ium-2-nitrophenolate and 2-

. ' I f chloronltro benzene, m.p. 114°C. 5d was prepared-fro m the reacti on of 2-bromomethyl nitrobenzene and

hoi

6 1 2-aminophenol 78 174

potass ium-2-nitrophenolate, m.p. l54°C. 2-Nitroben­za ldoxime 6b was prepared2 1g by the action of hydro­xy lamine hydrochloride on 2-ni trobezaldehyde in rec­tified spirit, cream coloured solid , m.p.96°C. 6c was prepared21h by the action of 2-bromomethyl­nitrobenzene and 2-aminobenzoic acid, pale yellow crystals, m.p. 204°C. Compound 6d was prepared2 1i

by the action of potass ium -2-ni trophenolate and phenacyl bromide, m.p. Il 8°C.

Reduction of N- (nitrophenyl) benzamides la-c. A solution of LAH (304 mg, 8 mmole) in ether (60 mL) was dropped into a solution of la (484 mg, 2 mmole) in ether ( I OOmL) at room temperatu reo It was stirred for

OTES 435

5 min . A pale brown solution was obtained. It was then refluxed for 31lr. The excess reagent was destroyed us­ing 10% NaOH (10mL). The concentrated dried ether extract was chromatographed on a column of sili ca ge!. Elution of the column with a mixture of petroleum ether and benzene (1: I v/v) afforded a red crystalline compound identi fied as 2,2'- (bis-N-benzyl) di aminoa­zobenzene (46 mg, 16%):UV (EtOH):A.max 249, 269, 3 15,500 nm; IR (KCI ): 3350 (N-H), 3 100 (ArH), 3050 and 2850 (C-H aliphatic), 1556 (N-H), 1504 (C-C Ar), 1450 (N=N), 1327 (ArC-N), 11 55 (C-N) cm· l

; IH MR (COCI:1 ): (COCI 3,500MHz):8 7.8-7.2 (1OH, m, 2C6Hs), 6.9-6.6 (8H, m, 2C6H4) , 5.15 (2H, s, 2N H), 4.5 (4H, d); MS: m/z (%) 392 [M+ (15)], I 96[M+-N2CI3 Hn ( 100)1, 105 f1 96-C7H7 (74)], 9 1[ (benzy l group), 196-N2C7Hs (86)]. This was fo llowed by N-benzyl-2-nitroaniline 2a (40 mg, 2%), m.p.73°C, Ia (13 1 mg, 27%), 2-nitroaniline 4a (132 mg, 66%) nd benzyl alcohol 3d (107 mg, 68%). Compounds Ib and Ic were reduced by the same procedure. Ib produced N-benzy l-3-nitroaniline (73%), 3-nitroaniline (14%) with small amounts of intractable substance. Ic produced N­benzyl-4-nitroaniline ( 14%), benzyl alcohol (8 1%) and 4-nitroaniline (83%).

Reduction of nitrobenzanilides Id-f. A solution of LAH (155 mg, 4 mmole) in ether (I OOmL) was added drop wise into a solution of the compound Id in ether ( IOOmL). A pale ye llow solution was resulted. The mixture was refluxed for 2hr. The excess of the reagent was destroyed by the addition of di!. NaOH solution in drops. 1t was then extracted with ether. The concen­trated and dried extract was chromatographed on a col­umn of silica gel. Elu tion of the column using a mix­ture of petroleum ether and benzene (l: I v/v) afforded N- (2-nitrobenzyl) aniline 2d (169 mg, 84%); m.p.44°e. Further el ution gave Id (29 mg, 12%), ani­line 7 mg, 8%) and 2-nitrobenzyl alcohol 3d (14 mg, II %). Compounds Ie and If were reduced accept­ing the same procedure. Ie gave N- (3-nitrobenzy l) -aniline (24%), 2-nitrobenzyl alcohol (58%) and aniline (66%). 1f produced N- (4-nitrobenzy l) aniline (78%), an iline (8%) and 2-nitrobenzyl alcohol (14%).

Reduction of 2,2'-dinitrodiphenylamine 5a. A solution of LAH (450 mg. 12 mmole) in ether ( IOOmL) was dropped from a soxh let aporthotu s into a slurry of 5a (775 mg, 3 mmole) in ether (120mL). The solution was turned blue. It was refluxed for 2hr. The excess reagent was destroyed by the additi on of cold water followed by 10% aqueous NaOH solution (30 mL). It was extracted with ether, concentrated

dried and chromatographed on a column of si lica ge!. Elution of the column using benzene afforded ni tro­benzene (30 mg, 12%), 5a (248 mg, 32%), nitroani­line (59 mg, 2 1 %) and 2-n itro-2'-aminodiphenylami ne (339 mg, 73%); m.p. 103°e.

Reduction of (bis-2-nitroanilino) methane 5b. A solution of LAH (460 mg, 12 mmole) in ether was added drop wise to a solution of Sb (576 mg, 2 mmole) in ether (l20mL). It was stirred for 10 min­utes . The reaction mixture was then refluxed for 2hr. The excess reagent was destroyed by the addition of cold water. NaOH solution (2N, 20mL) was added to it and st irred for 30 min. The ether layer was seorl/ /O­

ted, dried and concentrated. [t was chromatographed on a co lumn of silica ge!. El ution of the column using a mixture of petroleum ether and benzene (1 : I v/v) afforded N-methyl-2-n itro ani line (182 mg, 73%); m.p. 36°C, unreacted Sb (104 mg, 18%) and 2-nitroaniline (145 mg, 64%).

Reduction of 2, 2'-dinitrodiphenylether Sc. A so­lution of LAH (380 mg, 10 mmole) was dropped into a so lution of Sc (780 mg, 3 mmole) in ether (80mL) in a three necked flask under an atmosphere of nitrogen during a period of 3h at room temperature. It was then refl uxed for 2hr. The excess reagent was destroyed by the addition of cold water and acidifi ed using di!. HC!. The ether layer was seor/hoted , concentrated. dried and chromatographed on a column of alumi na. Elution of the column with a mixture of petroleum ether and benzene ( 1:2 v/v) afforded nitrobenzene ( 18 mg, 8%), 2-ni trophenol (28 mg, I L %) and unreacted 5c (296 mg, 38%). Further elution with benzene gave an orange liquid identified as 2- nitroso-2'-hydroxyl amino diphenylether (308 mg,72%). IR (KBr): 3500 (O-H), 3355 (N-H), 3 102 (ArH), 2890 (O- H in­tramolecularly bonded), 1900 (ArH ), 150 I (CN=O), 1266 (C-N), 1145 (C-O), cnf'; IH NMR (COCI 3): 86-7.2 (8H, m, ArH), 5.6 (lH , s, NH). MS: mlz (%) 230 [M+ (20)], 213 [M+ -OH (l6)J , 212 [M+ -H20 (65 )1 . 196 r212-0 (100)] , I 68f196-N2 (80)].

Reduction of 2-nitrophenyl-2-nitrophenoxy­methane Sd. A solution of LAH (460 mg, 12 mmole) in ether (100mL) was added from a soxhlet extractor into a slurry of Sd (820 mg, 3 mmole) in ether (l40mL). It was refluxed for 3hr. The excess reagent was destroyed by co ld water and acidified using di!. HC!. The concentrated extrac t on column chromatog­raphy over si lica afforded the following ; (2'- methyl) -2-hydroxyazobenzene (107 mg, 53%), 2-nitrophenol (82 mg, 31 %) and Sd (295 mg, 36%).

-+36 I DIAN J_ C II EM_. SEC B, FEBRUARY 2004

Reduction of 1, 3-dinitrobenzcne 6a _ A sol ution of LAH (460 mg, 12 Illmole) in ether (60 mL) was added drop w ise into a solution of 6a (504 mg, 3 mmole) in ether (60mL)_ The mixture was reflux ed for 2hr. The excess reagen t was destroyed. The con­centrated ether ex tract on column chromatography over sil ica gel afforded 3,3'-di n i troazobenzene ( I I mg, 8%) crys talli zed from petroleum ether, m.p. 153°C, 6a (328 mg, 65%), 3,J'-d initroazoxyben zene (129 mg, 86%), m.p. 146°C.

Rcduction of 2-nitrobcnzaldoxime 6b. A solu tion of LAH (230 mg, 6 mmole) in ether was dropped into an ether sol ution of 6b (330 mg, 2 mmole) . It was refl uxed for 4hr. The excess regent was destroyed and the so lution was ex tracted w ith ether. The concen­trated dried ex trac t was chromatographed over a co l­umn of sili ca gel. Elution of the co lumn using a mi x­ture or benzene and dichloromethane ( I :2v/v) af­rorded 2-n itrobenza ldehyde (26 mg, 16%), ben­zopyrazole (85 mg, 67%) and 6b ( 152 mg, 46%). Bellzopyrazole (m.p. 146°C) was identified by com­pari ng w ith authentic sample.

Reduction of 2-N- (2'-nitrophcnylmcthyl) ami­nobcnzoic acid 6c. A solution of LAH (570 mg, 15 mmole) in ether was added drop wise into a reflux ­ing solution of 6c (820 mg, 3 mmole). The so lution was kept stirred for 2hr. The excess reagent was de­.. troyed using cold water, acidified using dil. HCI and ex tracted with ether. The concentrated ex tract was chromatographed over sil ica. Elution of the column using a mixture of dich lorometh ane and ethy l acetate (2: I v/v ) afforded the following substances in se­quence, 2-aminobenzy l alcohol (45 mg, 17%), I I f-I , 12f-1-di hyd rodibenzorc, glll.51-diazocin -4-N­ox ide (330 mg, 68%); IR (KCI): 3370 (N-H), 3059 (ArH), 2925 , 2845 (C-H aliphatic), 1595 (C= ), 1521, 1340 (N-O): IH MR (COCl,): 88_35 ( 11-1, S,

CH ), 7.8-7.2 (8 H, m, ArH) , 6.9 (I H. s, broad, NH), 4_5 (2 H, s, CH2); MS: mlz (%) 224 IM+ (45)], 207 1 M+-OH (88)1, 195[M+-CH1NH (86) ], 1791195-0 (100)1, 1041207-C7HsN (60)1 and unreacted 6c (230 mg. 28%).

Reduction of 2-nitrophcnoxymethylphenyl ke­tone 6d. A so lution of LAH ( 150 mg, 4 mmole) was dropped into a refluxing so lution of 6d (510 mg, :2 mmole) ill ether ( lOOmL) at room temperature. It was kept sti rred at refl uxing condition for 2 hr. The

excess reagent was destroyed by co ld water and treated with ammonium chloride .ol ution (20mL). The seorlhoted ether layer was concen trated, dried and chrom:ltographed ovec si li ca gel. Elution or the column using a mix ture of benzene and dichloro­methane ( 1:2 v/v) gave 2-aminophenol ( 170 mg, 78%). Further elution wi th dichloromethane gave I-pheny l ethanol ( 149 mg, 61%) identi fied by com­paring with an authentic sample.

Acknowledgcment

One of the authors (MMJ) is ex tremely thankful to Prof.M.P Varghese, Secretary, Mar Athanas ius Col­lege Associa tion for the support received .

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