Author Topic: Mononitration of 1,4-dimethoxybenzene  (Read 3328 times)

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Lego

  • Guest
Mononitration of 1,4-dimethoxybenzene
« on: November 28, 2003, 10:41:00 AM »
Now you ask: What does anybee want with 1,4-dimethoxy-2-nitrobenzene? The nitro group itself is pretty useless but reduction to the 2,5-dimethoxyaniline can bee done with lots of reagent systems (Fe/HCl to mention the most easy one) and this opens lots of synthetic possibilites via diazonium intermediates. E.g.
2C-T-X precursors via

Post 473295 (missing)

(azole: "ArNH2 --> ArSMe via aryldiazonium + CuSMe", Novel Discourse)

2,5-dimethoxy-P2P via

Post 448826 (missing)

(Lego: "P2Ps via Meerwein arylation Actually Lego was...", Methods Discourse)

2,5-dimethoxybenzaldehyde via

Post 355321

(foxy2: "formylation by the "nitroso" method", Novel Discourse)

2-Cl/Br/I/CN-1,4-dimethoxybenzene via Sandmeyer reaction

Of course 2,5-dimethoxy-4-nitrotoluene can bee used as a DOM precursor.....


For our ADHS-bees see the practical, short version below  ;)




J. Chem. Res. (S), 2000, 106-107

The dichotomy between nitration of substituted 1,4-dimethoxybenzenes and formation of corresponding 1,4-benzoquinones by using nitric and sulfuric acid


C. Waterlot, B. Haskiak and D. Couturier
Université des Sciences et Technologies de Lille, Laboratoire d’Ingéniérie Moléculaire,
Bâtiment C4, ler étage 59655 Villeneuve d’Ascq Cedex, France


Abstract: Various alkyl-substituted p-dimethoxybenzenes (ArH) react readily with nitric acid and sulfuric to form nitroproducts (ArNO2). When the nitric acid is used in excess, the nitro-product react via either nitration to dinitrocompound (Ar(NO2)2) or via oxidative demethylation to nitro- p-quinone (Q). As such, the competition between the nitration, polynitration and oxidative dealkylation is effectively modulated by the added nitric acid and the alkyl-substituted p-dimethoxybenzenes.

Aromatic nitration is conventionally carried out with nitric acid, either alone or in combination with either Lewis or Brönsted acid1. It has long been known that most of the aromatic compounds are nitrated with a mixture of nitric acid and sulfuric acid according to ionic mechanism.2 For compounds as (polymethoxy)benzenes, more reactive than toluene, it has been shown that nitric acid was a sufficient nitration reagent to nitrate them.1 Only in this case, it has been suggested that the nitration of the (polymethoxy)benzenes with nitric acid occurs via a radical pathway (Scheme 1.)3,4 In the meantime, other nitration reagents have been studied for nitration of activated-arenes.5 It has been proved that the mechanism given for the nitration reactions with NO2 and HNO3 (Scheme 1) is generally valid for the nitration of donoractivated benzenes with nitric acid.6 Nevertheless, the mechanism  is not clear in all details and it is still under discussion.1,4-8
In connection to our interest in deoxygenation of dissolved oxygen in water, we investigated the nitration of dimethoxybenzene derivatives with a mixture of nitric and sulfuric acid. For the first time, nitration and oxidative demethylation of (polymethyl)-1,4-dimethoxybenzenes were observed in the studied conditions. On the other hand, because the tetramethyl-p-dimethoxybenzene is oxidatively demethylated by nitrogen dioxide to form duroquinone,9,10 we thought that it could be interesting to examine the dichotomy between aromatic nitration and quinone formation by using (polymethyl)-1,4-dimethoxybenzenes 1 (Scheme 2) with an excess of nitric acid (molar ratios : HNO3/H2SO4 = 1.5/1.1).

Results and discussion

Our starting point was to consider that the nitration of 1,4-dimethoxybenzene derivatives with nitric acid followed the radical reaction scheme to form quinone-type compounds by oxidative demethylation if reactions occurred in weakly acidic medium. We then investigated the nitration of (mono or polymethyl)-1,4-dimethoxybenzenes with a mixture of nitric and sulfuric acid in acetic acid (Scheme 2). Several experiments were performed at various temperatures and times, in order to find the best conditions to synthesize nitro-compounds 2 without any side products. The results are summarized in Table 1.

Results show that the nitration of aromatic compounds 1 is more important than the oxidative demethylation (Table 1, entries 2, 4, 6, 10 and 12). On the other hand, the dichotomy is less pronounced in the studied conditions (polar solvent) than Kocki’s system10 (entry 8). By using H2SO4, the first corresponding step is the formation of NO2+ to give a cation intermediate (s-complex) and then, the electrophilic substitution of the donor-arenes to form the compounds 2 (Scheme 3, path A).9 However, we cannot exclude by the presence of traces of nitrous acid in nitric acid, the formation of NO2 and so the reaction between NO2· and so the reaction between NO2· with the radical cation 1+ to give the s-complex (Scheme 3, path B).4,8

In a second step, the chemical behaviour of nitro-(mono or polymethyl)-1,4-dimethoxybenzenes 2 towards nitric acid in excess is different. Thus, the reaction of 2-nitro-1,4-dimethoxybenzene (Table 1, entry 2) with HNO3/H2SO4 produce the 2,5-dinitro-1,4-dimethoxybenzene. On the other hand, tetramethyl-1,4-dimethoxybenzene (Table 1, entries 13 and 14) react with HNO3/H2SO4 to produce p-benzoquinones via oxidative demethylation.10 Other products are obtained by nitration and oxidative demethylation of certain p-dimethoxybenzene derivatives (Table 1, entries 2, 8 and 12). According to previous work,4,6,8 the reaction of compounds 2 with an excess
of HNO3 to form nitro-benzoquinones derivatives proceeds probably via a radical pathway but we cannot confirm if the radical 2· is generated by electron transfer between the arenes 2 and NO2+4 or by electron transfer from the arenes 2 to NO+8.


Scheme 1



Scheme 2



Scheme 3


Nicodem

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Something more about the nitro group
« Reply #1 on: November 29, 2003, 06:22:00 AM »
The nitro group is useful for other interesting reactions besides the mentioned ones:

1.)   The nitro group on some benzylchlorides allow the nitroethane to be C-alkylated. Instead of the benzaldehides trough O-alkylation/oxidation you can, for example, make the 1-(p-nitro-phenyl)-2-nitro-propane that can be reduced to p-amino-amphetamine with simple reductions (Zn/HCOOH should do). I don’t know how general is this knowledge, but the anilinic amino group of the p-amino-amphetamine can be effectively submitted to the Sandmeyer reactions without deleterious effects for the aliphatic amino group. Check:  
Hoover F.W., Hass H.B., Synthesis of paredrine and related compounds. J. Org. Chem., 12, 501 (1947).

2.)   The nitro group activates the ortho- and para-halogens on the aromatic ring toward aromatic nucleophilic substitution (NAS) with the ease of substitution following the rule F >> Cl ~ Br > I. This means that, for example, the para-nitro-chlorobenzene can be reacted with the sodium salt of ethylacetoacetate and with the subsequent careful hydrolysis and simultaneous decarboxylation in acidic media you could get the para-nitro-P2P. Unfortunately with the addition of electron donating groups like the methoxy the ring gets again a little deactivated toward NAS. Luckily there is a catalyst for such occasions, the copper (I) chloride.

3.)   The nitro group makes a para- or ortho-methyl group relatively acidic, even so much that it can be deprotonated with NaOH. At least in theory, it should be possible to use the so formed C-nucleophile to alkylate some activated acetic acid derivatives, like ethylacetate, acetanhydride or acylchloride to form the para- or ortho-nitro-P2P. I know this type of reaction works perfectly with oxalic esters and triethylformate. I guess there is no need to remember that the ortho- and para-nitro-toluene are so easy to make and consider also that the carbonyl can be reductively aminated with the sodium borohydrides, a reagent that does not reduce the nitro group.

To make this post relevant for the nitration of 1,4-dimethoxy benzenes, I will add my lab notes for the nitration of a similar compound, the 2-bromo-1,4-dimethoxy-benzene.

In a 25ml beaker there were added 1g of 2-bromo-1,4-methoxy-benzene, 4ml of acetic acid and while stirring with a magnetical stirrer in an ice bath there was added, drop by drop a nitrating mixture consisting of 0.5ml 65% HNO3 and 0.5ml H2SO4. A yellow solid immediately started forming. After the addition the mixture was left stirring for 45 minutes and then it was poured in 30ml of cold water. The solids were vacuum filtered and washed with 2×5ml of ethanol. The product was recrystallized from 30ml of ethanol. This gave 0.96g of crystalline mass of “green-olive-yellow” kind of color (80%).

This product was part of the project roughly described under the point 2.) but since other projects had more priority it still waits for better times. The 1,4-dimethoxy-benzene is more reactive and the temperature control must be taken seriously to avoid dinitration.