Megatherium (Stranger)
12-15-02 23:15
No 389752
      4-nitropyridine synthesis requested  Bookmark   

Pyridine is a rather tough substrate for electrophilic substitution.  Nitrating it with NaNO3 - fumant H2SO4 at 300 °C yields only 4,5 % 3-nitropyridine.

To obtain 4-nitropyridine, one has to nitrate pyridine-N-oxide.  I am searching for a lab procedure or references for this synthesis.  Help would be appreciated.
12-16-02 09:31
No 389934
      synth for pyridine n-oxide  Bookmark   

synth for pyridine n-oxide?
are you thinking about reducing the pyridine ring also?
12-16-02 10:05
No 389942
      No, afterwards SWIM is going to reduce the nitro ...  Bookmark   

No, afterwards SWIM is going to reduce the nitro ...  The only problem is a procedure for the nitration of pyridine-N-oxide.  After the nitration, one has to convert the 4-nitropyridine-N-oxide to the 4-nitropyridine.  I 'm wondering if this can be done simultaniously with the reduction of the nitro.
(Master Whacker)
12-16-02 23:53
No 390078
      Hello, I have studied this issue extensively.
(Rated as: excellent)

I have studied this issue extensively. This is easiest, highest yielding synth of pyridine 1-oxide I have found:

J. Org. Chem.; 1953; 18(5); 534-551
Pyridine 1-oxide. To a solution of 40 g. of pyridine in 300 cc. of glacial acetic acid, 50 cc.
of 35% aqueous hydrogen peroxide was added and the mixture was heated in a water-bath
a t 70-80". After three hours a further 35 cc. of hydrogen peroxide solution (altogether ca.
1.7 moles of peroxide) was added and the mixture was maintained an additional nine hours
at the same temperature. The mixture was concentrated t o about 100 cc. in a vacuum, di-
luted with 100 cc. of water, and then again concentrated in a vacuum as far as possible.
The residue was made strongly alkaline with anhydrous sodium carbonate, shaken with 250
cc. of chloroform, and allowed to stand. The resulting deposit of sodium carbonate and
sodium acetate crystals was collected. The filtrate was dried with sodium sulfate, the sol-
vent removed by distillation, and the residue distilled in a vacuum. The yield of pyridine
1-oxide, b.p. 138-140"/15 mm., was 46 g. (96%).

Get a copy of that paper, it will expand your overall knowledge of pyridine oxide chemistry immensly.

The nitro group and N-oxide will not reduce simultaneously without high PSI hydrogenation.  The best format is to reduce the N-oxide first with PCl3 or one of these procedures:

A novel and efficient deoxygenation of heterocyclic N-oxides using ZrCl4/NaBH4.    
Chary, K. Purushothama; Mohan, G. Hari; Iyengar, D. S.   
Chemistry Letters  (1999),   (12),  1339-1340. 
A practical and novel reagent system ZrCl4/NaBH4 was used for the deoxygenation of N-Oxides to amines.  E.g., pyridine N-Oxide gave 985 pyridine, isoquinoline N-Oxide gave 94% isoquinoline, 3-methylpyridine N-Oxide gave 95% 3-methylpyridine, 4-chloropyridine N-Oxide gave 95% 4-chloropyridine, etc.

Mono-deoxygenation of Nitroalkanes, Nitrones, and Heterocyclic N-Oxides by Hexamethyldisilane through 1,2-Elimination: Concept of "Counterattack Reagent".
Hwu, Jih Ru; Tseng, Wen Nan; Patel, Himatkumar V.; Wong, Fong Fuh; Horng, Den-Nan; Liaw, Ben Ruey; Lin, Lung Ching.       
J. Org. Chem.  (1999),  64(7),  2211-2218.  Abstract
Transformation of secondary nitroalkanes to ketoximes was achieved in 40-73% yields by treatment of the corresponding nitronate anions with hexamethyldisilane.  In this new mono-deoxygenation process, hexamethyldisilane acted as a counterattack reagent.  The conversion of nitrones to imines was also achieved in 82-88% yields by use of trimethylsilyllithium.  Similarly, heterocyclic N-oxides were converted to the corresponding N-heterocycles in 73-86% yields.  These deoxygenation processes presumably involve a 1,2-elimination.

An efficient general method for the deoxygenation of N-arylnitrones, azoxybenzenes, and N-heteroarene N-oxides.
Konwar, Dilip; Boruah, Romesh C.; Sandhu, Jagir S.    Synthesis  (1990),   (4),  337-9.
A method for the deoxygenation of the title compds. is described.  Thus, PhCH:N(O)Ph was treated with AlI3 in MeCN at reflux to give 91% PhCH:NPh.  Similar treatment of 3-chloropyridine (I) N-oxide gave 80% 3-chloropyridine (II). 

Selective deoxygenation of amine N-oxides using borohydride exchange resin-copper sulfate in methanol.     Sim, Tae Bo; Ahn, Jin Hee; Yoon, Nung Min.
Synthesis  (1996),   (3),  324-6. 
Borohydride exchange resin-CuSO4 in MeOH readily deoxygenates quant. both tertiary amine N-oxides and heteroarom. N-oxide at room temp. or under reflux.  It tolerates many functional groups such as C:C, chloride, epoxide, ester, amide, nitrile, sulfoxide, sulfone, and aliph. disulfide moieties.

New aspect of methanesulfonyl chloride: unusual deoxygenations of pyridine N-oxides with methanesulfonyl chloride and triethylamine.    
Morimoto, Yoshiki; Kurihara, Hajime; Yokoe, Chiho; Kinoshita, Takamasa.
Chem. Lett.  (1998),   (8),  829-830.
Treatment of several pyridine N-oxides with an excess of methanesulfonyl chloride and NEt3 brought about a deoxygenation reaction to give efficiently the corresponding redn. products without chlorination of the pyridine nucleus.

Selective reduction of the nitrogen-oxygen bond in heteroaromatic N-oxides by titanium tetrachloride-tin dichloride.  
Balicki, Roman; Kaczmarek, Lukasz; Malinowski, Marek. 
Synth. Commun.  (1989),  19(5-6),  897-900.  Abstract
Pyridine N-oxides I (R1 = halo, CONH2, cyano, CO2Et, NH2; R2 = H, OMe, Ph, Me) were treated with TiCl4-SnCl2 to give the resp. pyridines II.  Similarly prepd. was 2-chloroquinoline. 

Some deoxygenation and reduction reactions with samarium diiodide.
Zhang, Yongmin; Lin, Ronghui.    
Synth. Commun.  (1987),  17(3),  329-32.
Pyridine N-oxides were deoxidized by SmI2 and anilines were obtained by the redn. of nitrobenzenes with SmI2 in MeOH.  Triphenylarsine oxide and (C8H17)3NO also underwent deoxidn. with SmI2. 

Chemistry of heterocyclic N-oxides and related compounds.  VII.  Deoxidation of pyridine and quinoline N-oxides by organic reducing agents on a palladium catalyst.
Kurbatova, A. S.; Kurbatov, Yu. V.; Otroshchenko, O. S.; Sadykov, A. S.   
Khim. Geterotsikl. Soedin.  (1976),   (7),  920-1. 
Treatment of the N-oxides of pyridine and quinoline with cyclohexene, 1,4-dihydronaphthalene, Tetralin, or HCO2H on a Pd catalyst gave pyridine and quinoline, resp.

Mechanism of reduction by dimethyl sulfoxide:  deoxygenation of pyridine N-oxide.
Biffin, Malcolm E. C.; Miller, Joseph; Paul, David B.   
Tetrahedron Lett.  (1969),   (13),  1015-18. 
Redns. by Me2SO may be rationalized as proceeding via an initial coordination complex (I), formed by attack of a nucleophilic O atom in the oxidant on the S atom of Me2SO or its conjugate acid to give a sulfone and the reduced form of the oxidant in the subsequent redox step (scheme A).  An alternative redox step involves attack of a nucleophile Y on I, resulting in rupture of the S-R and O-X bonds and formation of a sulfinate: Y + I ® RSO2-(H) + YR+ + X- (scheme B).  C5H5NO (0.05 mole) heated 20 hrs. at 195° with 0.8 mole Me2SO contg. 6% H2SO4 and the mixt. dild. with H2O and washed with Et2O gave a soln. of pyridinium salt from which C5H5N was isolated as the picrate.  Only 2% Me2SO2 was present and redn. by scheme A is relatively insignificant.  The reaction mixt. in the absence of acid contained C5H5N.MeSO3H salt, m. 185°.  The results were rationalized by the mechanism in scheme B with subsequent formation of MeSO3H from MeSO2H, also affected by Me2SO.  Redn. of C5H5NO with Ph2SO gave equal amts. of Ph2SO2 and C5H5N as in scheme A.  Successful deoxygenation of several N-oxides confirmed the generality of the reaction.  Lower yields were given by o-substituted N-oxides.  Only 9% azobenzene was obtained from azoxybenzene and nitro compds. were inert under the reaction conditions. 

Reducing organic nitrogen oxides to amines using iron and active carbon.    
Gerber, Samuel M.   U.S.  (1968),     3 pp.
US  3386991  19680604
Org. N-mono- and -dioxides are reduced in water or aq. alc. with Fe and activated C.  Thus, a mixt. of 2-(4-acetamidophenylazo)pyridine N-oxide (I) 25.6, 60-mesh chem. Fe 27.4, and activated C 1 g. in 345 ml. 30% EtOH was refluxed 22 hrs. for complete redn. to give a product (II), which when quaternized with MeI dyes polyacrylonitrile a bright yellow-orange.  In the absence of activated C, the reaction is 91% complete in 30 hrs., while in the absence of Fe, the redn. is only 2% complete in 23.5 hrs.  Using PrOH as solvent, the redn. was complete in 4 hrs.  A mixt. of 60-mesh Fe 80, activated C 6, and 3-nitro-N,N-bis(2-carbamoylethyl)benzenesulfonamide 172.2 g. in 16 ml. HOAc and 1920 ml. water was stirred 1 hr. at 90-5° to give 81.2% 4-amino-N,N-bis(2-carbamoylethyl)benzenesulfonamide, m. 186-7°.  In the absence of activated C, a yield of only 48.4% was obtained.

Reduction of pyridine N-oxides.    
Hoefling, Wilhelm; Eilhauer, Dieter; Reckling, Gerhard.    (1965),     3 pp. 
DD  36422  19650625  Patent  language unavailable. 
Pyridine N-oxide (I) and its alkyl derivs. were reduced with SOCl2 at 50° with yields of 60-85%.  Thus, to 240 g. SOCl2 at 50° was added dropwise 100 g. I.  During the addn. the temp. increased to 70°.  The mixt. was left for 30 min. and then the excess SOCl2 distd.  The residue was added to ice-water, the soln. basified and steam-distd.  The distillate was treated with NaOH to free the pyridine.  Final distn. yielded 54.7 g. pyridine.

Reduction of pyridine N-oxides.    
Daniher, Francis A.; Hackley, Brennie E., Jr.
US  3467659  19690916    
Pyridine N-oxides, whose N-attached O has an electron density greater than that of N-attached O of pyridine N-oxides having an electron-withdrawing, meta-directing group in the 4-position, are reduced to the corresponding pyridines with a 2-3 molar excess of SO2 in H2O or dioxane at 70-110° for 2-6 hrs.  Thus, a slow stream of SO2 was bubbled into a refluxing soln. of 0.10 mole pyridine N-oxide, in 100 ml. 1,4-dioxane for 3 hrs. to give 66% pyridine, b. 114°; picric acid salt, m. 166-7°.  I also prepd. were [R, % yield, b.p., (or b.p./mm. and picrate m.p. given]:  2-Me, 34, 126-7°, 166-7°; 4-Me, 31, 141-2°, 165-6°; 3-Cl, 21, 54°/20, 138-9°; 2,4-Me(MeO), 62, 89°/15, 146-7°; 2,5-Me(EtO2C), 68, 67°/0-5, 167-8°; 2,6-Me(AcNH), 65, - (m. 88-9°), -; 2,4-Me(Cl), 41, 61°/19, 176-7°; 2,6-Me2, 67, 142-3°, 167-8°; 2,5-Me, 65, 55°/17, 167-9°; 2,5-Me(Et), 63, 72°/19, 166-8°; 2,6,3-Me2(O2N), 31, -, (m. 36-8°), -.  Two compds. which have electron-withdrawing, meta-directing groups in the 4-position, 2-methyl-4-nitropyridine N-oxide and 4-carbomethoxypyri-dine N-oxide, did not react. 

Efficient catalytic conversion of pyridine N-oxides to pyridine with an oxorhenium(V) catalyst.
Wang, Ying; Espenson, James H.
Organic Letters  (2000),  2(22),  3525-3526.
The Me oxorhenium dithiolate I is a catalyst for the rapid and efficient transfer of an oxygen atom from a wide range of ring-substituted pyridine N-oxides II (R = 4-Me, 2-HO, 3-CO2H, etc.; R1 = O) to triphenylphosphine, yielding the corresponding pyridines II (R = 4-Me, 2-HO, 3-CO2H, etc.; R1 = lone pair) in high yield.

Deoxygenation of Pyridine N-oxides with sulphur monoxide generated from -2,3-diphenylthiiran-1-oxide
Bianca F. Bonini, Gaetano Maccagnani, Germana Mazzanti and Paola Pedrini
Tetrahedron Lett 1979, 20, 1799
(I can get pdf)
Pyridine N-oxides are deoxygenated by sulphur monoxide. Electron withdrawing substituents lower drastically the yields of reduction.

Synthetic methods and reactions; 87.  Deoxygenation of pyridine N-oxides with trimethyl(ethyl)amine-sulfur dioxide complexes.
Olah, George A.; Arvanaghi, Massoud; Vankar, Yashwant D.    
Synthesis  (1980),   (8),  660-1. 
Pyridine N-oxides I (R = H, Me; R1 = H, 3-Me, 4-Me, 6-Me, 5-Et, 4-MeO, 3-Cl,) were deoxygenated by R23N.SO2 (R2 = Me, Et) to give the corresponding pyridines in 60-81% yield.  I (R1 = 4-NO2) underwent little reaction. 

A new method for deoxygenation of heteroaromatic N-oxides with chlorotrimethylsilane/sodium iodide/zinc.
Morita, Tsuyoshi; Kuroda, Koji; Okamoto, Yoshiki; Sakurai, Hiroshi.  
Chem. Lett.  (1981),   (7),  921-4.
Deoxygenation of pyridine N-oxides I (R = H, Me, Cl, MeO, CN; R1,R3 = H, Me; R2 = H, Me, CN; RR1 = benzo) with Me3SiCl/NaI/Zn in MeCN gave 45-92% pyridines II. 

The deoxygenation of heterocyclic N-oxides. I. A novel oxygen- and peroxide-catalyzed reduction of pyridine 1-oxide with triethyl phosphite.   
Emerson, T. R.; Rees, C. W. 
J. Chem. Soc.  (1962),     1917-23. 
Pyridine 1-oxide (I) is reduced to C5H5N at room temp. by (EtO)3P (II) in (EtOCH2CH2)2O (III) if both O and a peroxide, formed adventitiously from the solvent, are present.  The 4-MeO deriv. (IV) of I reacts similarly.  These redns. do not go to completion even with II in a 100-fold excess.  The results are discussed and a free-radical chain mechanism is proposed.  4-NO2 deriv. (V) of I with NaOMe in MeOH yielded IV. H2O, m. 80-2° (EtOAc); picrate m. 142-4°.  IV reduced by the method of den Hertog and Combe (CA 46. 8654i) yielded 4-methoxypyridine, b18 75-7°, n2D5.2 1.5148.  The deoxygenations with II were followed spectrophotometrically.  Sep. solutions of the N-oxide (10-3M) and II, b13 46-7°, (10-1M) in III, m. 189-90°, were mixed, and aliquots withdrawn at appropriate times, dild. suitably with abs. EtOH, and analyzed.  I was stable at room temp. in III but was deoxygenated by II; at 85°, however, I decompd. erratically in III (10-3M) with or without II.  C5H5N does not react with II. IV was deoxygenated by II.  V was deoxygenated to only 8% in 24 hrs. and when I was added after 48 hrs. to the mixt., the I was deoxygenated normally.  Under N no deoxygenations occurred with II; if the soln. was exposed to air or aerated, deoxygenation began.  A series of deoxygenation rams was performed with 10-3M I and 10-1M II in III at 30° using differently pretreated III (treatment of solvent, reaction time in hrs., and % reaction given): fractionally distd. old stock, 24, 60(48, 67); fractionally distd. new stock, 24, 40; treated with Na and distd., 23, 5; Na-dried, distd. III with a little H2O, 24, 10; Na-dried, distd. and aerated 3 days at room temp., 24, 15; Na-dried, distd. and aerated 18 hrs. at room temp. under ultraviolet irradiation, 24, 16; aerated 72 hrs. under irradiation and contg. 3.5 ´ 10-2 g.-atom active O, 24, 43 (48, 60); same but contg. 7.0 ´ 10-2 g.-atom, 48, 42 (66, 56); same but contg. 7.5 ´ 10-2 g.-atom, 24, 33 (48, 34); distd. old stock under N, 31, 0;
same and then opened to air for 64 hrs., 95, 65; aerated and irradiated 72 hrs. contg. 3.5 7times 10-2 g.-atom active O but under N, 24, 4; same but then opened to air for 18 hrs., 42, 40; same under N, 24, 50. At 85 and 100° the deoxygenations were more erratic.  The deoxygenations of I with Et2S, tetrahydrothiophene, or Me2SO in III at 30-80° were much slower than with II 

The para- nitro group can than be reduced via standard catalytic hydrogenation, Fe/HCl, etc.

There are better ways of making anilinopiperidines from pyridines than the way you have chosen, though this route is clean and high yielding.  There is a post under my name containing an excellent ref for alkylating aminopyridine with halobenzene.

Another way of making piperidines/piperidones from  pyridines is to react the p-nitro pyridine-N-oxide with sodium benzyloxide(made by adding sodium metal to simple benzylalcohol) to produce p-Benzyloxy pyridine-N-Oxide.  This reaction is described in the same paper the above peracid oxidation was taken from.  The N-oxide group would be reduced with one of the many ways mentioned above then the amine group would be quaternized with i.e. phenethylbromide.  Reduction via catalytic hydrogenation w/ Pd/C will yield N-Phenethyl-4-piperidinol.  The -OH can be easily oxidized to the piperidone with any common oxidation reagent.

You're on the right track, keep studying!
12-18-02 16:21
No 390517
      Great post Ritter
(Rated as: excellent)

What a great post, Ritter.  Thank you very much.  But mabey it isn't even necessary to reduce the intermediate 4-nitropyridine-N-oxide before reducing the nitro group.  In the following article, they do the two reactions in one step.


Vladimir N. Bulavka*, Igor I. Boiko

“Technologist Co. Ltd.”, 2 Mendeleev sq., Pereslavl-Zalessky, Yaroslavl reg., 152020, Russian Federation
*at present time: “Slavich Company”, 2 Mendeleev sq., Pereslavl-Zalessky, Yaroslavl reg.,152020, Russian Federation. E-mail:

Received: 9 August 2000 / Uploaded: 16 August

The usual way of commercial 4-aminopyridine preparation is a two-stage synthesis starting from pyridine and including 1-(4-pyridyl)pyridinium chloride hydrochloride as an intermediate. The total yield is 36-40% [1, 2, 3].

A semipreparative scale three-stage synthesis including pyridine-N-oxide and 4-nitropyridine-N-oxide as an intermediates is preferable. At the third stage 4-nitro-pyridine-N-oxide was reduced with iron and acetic acid at reflux temperature to produce 4-aminopyridine in quantitative yield. The reaction demands continuous extraction with diethyl ether of the title compound. The total yield is 65% [4].

In order to avoid the use of special equipment for continuous extraction with diethyl ether (or a large amount of diethyl ether for ordinary extraction) we tried to minimize the acid excess. All our attempts to minimize the amount of acetic acid or replace its excess with water failed. The precipitation of basic ferric acetates and/or extensive 4-aminopyridine hydrolysis to 4-pyridone were observed.

We studied the reduction of 4-nitropyridine-N-oxide with iron and aqueous mineral acids. The reduction with iron and hydrochloric acid gives mainly 4-aminopyridine (80-85%), and as by-products 4-aminopyridine-N-oxide, 4-pyridone, and 4,4’-azopyridine. The reduction with iron and 25-30% sulphuric acid proceeds slowly, but the yield of the desired 4-aminopyridine is better. The isolation of the reaction product after reduction, subsequent neutralization with sodium carbonate, and filtration was carried out by two methods. The first method was extraction with ethyl acetate. After removal of the solvent 4-aminopyridine was obtained in 85-90% yield. The second method was the concentration of the filtrate on the rotatory evaporator, extraction with ethanol, and after evaporation of ethanol reextraction with hot benzene to give a title compound after cooling (85%).

After evaporation of the solvent, crude 4-aminopyridine, if desired, was acetylated with acetic anhydride to produce 4-acetylaminopyridine in 80-85% yield [5].

When the neutral or basic aqueous solutions containing of 4-aminopyridine were heated for concentration, partial hydrolysis to 4-pyridone was observed. It caused some decreased yields of desired compound.


1. Koenigs, E., Greiner, H. 4-Pyridylpyridinium dichloride and the synthesis of g-derivatives of pyridine. Ber. 1931, 64B, 1049.

2. Koenigs, E., Greiner, H. Verfahren zur Darstellung von Pyridinderivaten. DRP 536891 (12p 1/01), 28.10.1931, appl. K115847 (IVa/12p), 24.07.1929.

3. Wibaut, J. P., Herzberg, S., Schlatmann, J. Note on the preparation of 4-amino-pyridine. Rec. trav. chim., 1954, 73, 140-142.

4. den Hertog, H. J., Overhoff, J. Pyridine and quinoline derivatives. LXXXII. Pyridine-N-oxide as an intermediate for the preparation of 2- and 4-substituted pyridines. Rec. trav. chim., 1950, 69, 468-473.

5. 4-Acetylaminopyridine monohydrate, m. p. 145-147oC (from 96% ethanol);
MS (“Selmi” TOF-spectrometer, +25kV), (m/z): M+ 136,8.
PMR (Bruker AC-300), (CCl4 and (D3C)2SO) (p. p. m.): 3,02 (3H, s, CH3);
7,52 (2H, d, 3- and 4-H); 8,33 (2H, d, 2- and 5-H); 10.05 (1H, bs, NH).

Further details about the reduction can be found here:


Vladimir N. Bulavka1, Igor’ I. Boiko2

1) "Slavich Company", Mendeleev sq. 2, Pereslavl-Zalesskiy, Yaroslavl reg., 152025, Russian Federation. E-mail:
2) "Technologist Co., Ltd.", Mendeleev sq. 2, Pereslavl-Zalesskiy, Yaroslavl reg., 152025, Russian Federation. E-mail:

Received: 20 August 2001 / Uploaded 21 August 2001
4-Pyridone (4-hydroxypyridine) is a convenient synthon for obtaining plurality of biologically active pyridine derivatives. For our opinion, elaboration of one more method for its synthesis proved to be useful.

Earlier we have described formation of 4-pyridone as by-product in the synthesis of 4-aminopyridine at reduction of 4-nitropyridine-N-oxide with iron and mineral acids. We also have assumed that the process can to be modified for 4-pyridone synthesis [1]. Here we present the procedure elaborated for one-pot synthesis of 4-pyridone from 4-nitropyridine-N-oxide.

Experimental part

In the 100 ml round-bottom flask were placed 1,4 g (0,01 mol) of 4-nitropyridine-N-oxide, 2,23 g (0, 04 mol) of iron powder, and 18 ml of water. During 1 hr 6,8 ml (0,08 mol) of 36% hydrochloric acid was added to the reaction mixture with stirring. The reaction mixture became warm. After the addition complete, the reaction mixture was gentle refluxed for 3 hr. After cooling, the solution 3,6 g (0,09 mol) of sodium hydroxide in 8 ml of water was added and reaction mixture was refluxed again for 2 hr (until the formation of ammonia ceased). Then the reaction mixture was neutralised with ca.0,85 ml (0,01 mol) of 36% hydrochloric acid to pH 7. The solvent was evaporated in vacuo (rotatory evaporator) almost to dryness. Ethanol (20 ml) was added to the residue, mixture was warmed, filtered with suction and precipitate washed twice with additional 5 ml portions of hot ethanol. The filtrate was evaporated to dryness and the residue exstracted with 6 ml of hot ethanol in 1,5-2 ml portions. The extract was evaporated, 2 ml benzene added, the crystals filtered, washed 1 ml of bezene and dried. Crude 4-pyridone 0,86 g (0,009 mol, 90%) was obtained. M. p. 148-150oC. 1H NMR (CD3OD): 6,5 (d., 2H), 7,8 (d., 2H). MS (m/z): (M+1)+ 96 (20%); 40 (60%), 38 (100%), 23 (40%).


1. V. N. Bulavka, I. I. Boiko. Formation of 4-pyridone at obtaining of 4-aminopyridine. IX All-Russian conference "Carbonyl compounds in the synthesis of heterocycles". (Russian Federation, Saratov, September 25-28, 2000). (In the scientific book: "The new achivements in the chemistry of carbonyl and heterocyclic compounds" Edited by Prof. A. P. Kriven’ko. Saratov university edition, 2000. P. 28-30). (Russian).

A procedure for the nitration of  of 3-methylpyridine-N-oxide can be found at:

I 've also found a little review about the chemistry of pyridine-N-oxide:
(Master Whacker)
12-20-02 01:28
No 390948
      Damn! Excellent Find!!!  Bookmark   

Damn!  Excellent Find!!!  Plain old Fe and acid is a lot simpler than all those exotic methods I quoted to say the least, not to mention the N-oxide is also reduced simultaneously as the ring substituent without using thousands of pounds of hydrogen pressure--simply fantastic!
Please keep up the good work!  You way find that our interests are somewhat complimentary in due timewink
(Master Whacker)
12-22-02 21:33
No 391795
      Due Credit where its deserved  Bookmark   

One important thing I forgot to mention in my original post is that all of those pyridone-N-oxide reduction references in blue were researched for me by Foxy2.

Foxy2, where are you???frown
(Hive Addict)
01-16-03 19:28
No 398747
      Pyridine oxidation with Oxone  Bookmark   

JOC (1985) 50, 16, 2849:

Oxidation of Pyridine to its Oxide by Oxone Slurry:

Oxone (18.3g, 0.0298mol) in H2O (100ml) is added dropwise to a solution of Pyridine (1.0g, 0.0126 mol) in acetone (5ml, 0.068mol) and a phosphate buffer (50ml).  KOH solution is added dropwise, as needed, to maintain a pH of 7.5-8.0.   Stir the solution for a period of 2 hours and extract with DCM.  Evaporate the DCM to leave the crude product. Recrystallize from a mixture of DCM/Hexane to give Pyridine oxide (1.1g, 93% yield) as crystals with; MP: 64-65*C.
(Hive Bee)
01-16-03 21:12
No 398781
      That 's a rather swift reaction and a nice...  Bookmark   

That 's a rather swift reaction  and a nice yield smile.  Thanks Aurelius smile.
(Hive Addict)
01-17-03 03:08
No 398900
      No problem  Bookmark   

Thought you might like that.  saw that synth in some library research aurelius was doing and desided to post it.
(Hive Bee)
01-18-03 01:25
No 399210
      Synthesis of 4-chloropyridine
(Rated as: excellent)

for a route to 4-halopyridines via 4-nitropyridine-N-oxide -> 4-aminopyridine and then doing the Sandmeyer reaction to a 4-halopyridine?
There a easier synths on the market..if the chems are the following one:


200 g N-pyridyl-(4)-pyridiniumchloride hydrochloride are finely pulverized and intimately mixed with 180 g phosphorus pentachloride. The mixture is transferred into a 500 ml flask which is equipped with a thermometer and an air cooler (a simple glass tube with about 12 mm diameter should make good substitute) and heated in an oil bath to 160 °C. The temperature of the reaction will climb to 160-170 °C and a dark melt will form. The reaction is continued for 6 hours at 180 °C (temperature of oil bath). Ice-water is then added cautiously through the air cooler while very efficient cooling of the flask has to be maintained (they say nothing about it, but I'd cool the reaction mix to room temperature before adding any water) until a clear solution is obtained. The solution is transferred into a larger flask and alkalinized with sodium hydroxide solution, again efficient cooling of the solution is neccesary. This mixture is steam distilled, pyridine and 4-chloropyridine pass over with the water. The distillate is saturated with potassium carbonate and the pyridines are separated from the water in a sep funnel. Aqueous phase is extracted with diethyl ether, the extracts and the previously obtained bases are pooled and dried over potassium hydroxide. After filtration the ether is removed under normal pressure in a super dried fractional distillation unit (60 cm vigreux column, receiving flask has to be cooled at least with ice/salt, they recommend methanol/dry ice). Distillation unit is dried by rinsing all parts with a solution of potassium hydroxide in ethanol.
After all the ether is removed, vacuum is applied. Pyridine distills first at 57-59 °C (100 Torr), then the 4-chloropyridine at 63-64 °C (50 Torr). Yield of 4-chloropyridine is 72 g, equals 73% of the theory.

[Translated from:
"Neuere Methoden der Präparativen Organischen Chemie" Vol. 3, Wilhelm Foerst, Verlag Chemie, 1960, pp. 47-71]

Italics mine

Now the good news...according to Chem. Berichte 89, 2921 (1956) the phosphorous pentachloride can be substituted with anhydrous aluminium chloride - yield almost the same, about 70 % 4-chloropyridine cool

Quidquid agis, prudenter agas et respice finem!
(Hive Bee)
01-18-03 21:11
No 399444
      The use of AlCl3 instead of PCl5 is certainly...  Bookmark   

The use of AlCl3 instead of PCl5 is certainly very interesting smile.  I 'll take a look at that Chem. Ber. article as soon as I can.  Now, I 'll put my Sandmeyer idea in a little black coffin ... wink
(Hive Bee)
01-19-03 01:03
No 399516
      No need to put the Sandmeyer...  Bookmark   

..into that little black coffin, the Sandmeyer will still work if anything else should fail. For 4-chloropyridine from 4-aminopyridine via diazotation and reaction with hydrochloric acid you just may have a look - if you are in the library anyway - at "Ber. dtsch. chem. Ges. 57, 1179 (1924)". For the 4-bromopyridine synthesized directly from 4-aminopyridine + sodium nitrite + concentrated hydrobromic acid you should dig up "Recueil Trav. chim. Pays-Bas 58, 885 (1939)".
After going through the ref mentioned in my previous post, I came to the conclusion that I should write an amendment to that post wink
First, some properties of the 4-halopyridines. These are water-white liquids that can be distilled without decomposition at normal pressure and under vacuum. But upon distillation and under storage special precautions have to be taken to avoid the formation of condensation products. This condensation reaction takes place when traces of a strong acid or of a quarternary pyridinium salt are present. These have to be excluded by the addition of alkali, hence the coating of the distillation set with a thin layer of alcoholic potassium hydroxide solution, which forms a thin film of KOH on your glassware. The same measure is recommended for the glassware you intend to store your 4-halopyridines in.
Second, I think you will really need (no offense intended) wink a procedure for the synth of the precursor N-pyridyl-(4)-pyridiniumchloride-hydrochloride...


In a 1000 ml three-necked flask equipped with thermometer, dropping funnel, overhead stirrer and reflux condensor with drying tube (filled with calcium chloride) attached, to 300 ml of pyridine under vigorous stirring 900 ml of thionyl chloride are added. The reaction has to be cooled to maintain a reaction temperature of 20 °C. After all of the thionyl chloride has been added, the mixture is allowed to stand three days at room temperature. Then the mixture is subjected to vacuum distillation to remove the excess of thionyl chloride while heating on a water bath (no vacuum mentioned here, I think since thionyl chloride boils at about 79 °C under normal pressure, aspirator vacuum will be sufficient). After no more thionyl chloride distills over, the temperature of the batch is held for 2 hours at about 100 °C.
Then to the solid mass in the flask 200 ml of methanol are addded and the mixture brought to a boil, a homogenous slush should be the result. This slush is cooled to 0 °C and filtered by suction on a Büchner funnel. The crystals of product are washed with little ice-cold methanol  and are then dried at 110 °C. The raw product after drying shows a melting range of 145-149 °C, the yield is 260 g (60 % of the theory). The raw product is pure enough for the synth of the 4-chloropyridine, raw product was in fact employed for the above mentioned synth.
If desired, it can be purified by dissolving it in hot 2M hydrochloric acid, filtering while hot and treating the filtrate with activated carbon several times (until the filtrate is only lightly coloured, you won't be able to remove all the impurities by charcoal treatment alone without a hefty loss of product+time, so don't ever bother trying it more than 2 or 3 times).
The again filtrated solution is concentrated under vacuum, alcohol (methanol) is added and the solution cooled to 0°C. The product crystallizes from the solution and the now almost white, needle-like crystals are filtered by suction. A final recrystallisation from methanol gives colourless needles, melting point 151 °C (no yields given after purification, but I bet your yield will now be down from 60 % to 50 % or even less, so why not go with the raw product?).

[Translated from: "Neuere Methoden der Organischen Präparativen Chemie" Vol. 3, Wilhelm Foerst, Verlag Chemie, 1960]

Italics mine

Quidquid agis, prudenter agas et respice finem!
(Hive Bee)
01-19-03 02:41
No 399549
      Thanks for those reference.  Bookmark   

Thanks for those reference.  I 'll look into it.  You are some fine researcher Hermanroempp.  I appreciate your input very much smile.
(Hive Bee)
04-09-03 13:01
No 425051
      4-pyridylpiperidinium dichloride  Bookmark   

Patent DE536891
(Hive Addict)
04-10-03 09:09
No 425340
      just curious fellas  Bookmark   

What can you do with these substituted pyridines?
I know what you can do but why the interest?
(Hive Bee)
04-10-03 17:48
No 425400
      Bird poison  Bookmark   

4-Aminopyridine is an extremely effective bird poison. It is one of the most prominent avicides. It is registered with the U.S. Environmental Protection Agency for use against red-winged blackbirds, blackbirds in agricultural fields, grackles, pigeons, and sparrows around public buildings, and various birds around livestock feeding pens.

It can also be used for the synthesis of DMAP (i.e. 4-dimethylaminopyridine) a rather good acylation catalyst.
(Hive Addict)
04-10-03 18:37
No 425404
      Oh I see well why don't you buy it from an agricul  Bookmark   

agricultural supply company?
I'm aware of DMAP it increases the rate of acylation 10,000 times over that of pyrindine if you look it up on sigma-aldrich's website they have very good information about that substance.