I.

INTRODUCTION

Nucleophilic aromatic substitution (SNAr) occurs readily with aryl halides when strong electron-
withdrawing groups (EWGs) are in ortho or para position relative to the carbon bonded to the
halogen (ipso carbon), as it becomes susceptible to nucleophiic attack; in contrast, those EWGs
in the meta position do not produce a similar activating effect, as the delocalization would
become hindered and not undergo an SnAr reaction (Solomons & Fryhle 2000). The over-all
mechanism for this reaction can be seen in Figure 1.1.

[FIGURE 1.1. SnAr mechanism]

More specifically, one of the mechanisms involved in the SnAr reaction is addition-elimination,
which involves the formation of resonance-stabilized carbanion with delocalized electrons called
a Meisenheimer complex (see Figure 1.2.). This carbanion intermediate may either remove the
nucleophile generating the reactants or remove the halide giving the product; this removal of
substituents on the ipso carbon is based on excess electron density and aromaticity regeneration
of the ring.

[FIGURE 1.2. Formation of Meisenheimer complex]

In this experiment, 2,4-dinitropheylhydrazine (2,4-DNP) will be synthesized from a hydrazine

solution consisting of hydrazine sulfate and sodium acetate mixed with 1-chloro-2,4-
dinitrobenzene, through a SnAr reaction (see Figure 1.3.). This will be achieved through the
reflux and subsequent filtration of the nucleophilic reagent, the hydrazine solution, and the
electrophile, 1-chloro-2,4-dinitrobenzene.

[FIGURE 1.3. Over-all mechanism for synthesis of 2,4-DNP]

It is possible, however, that 2,4-dinitrophenol may form if the hydrazine group does not
substitute the halide leaving group, and hydroxide instead takes its place (see Figure 1.4.). In
order to avoid this, it is important to avoid an increasingly basic medium or a basic nucleophilic
reagent.

[FIGURE 1.4. Possible side reaction: formation of 2,4-dinitrophenol]

Once the dried product is obtained, it will be characterized by melting point determination
(Fisher-Johns Melting Point Apparatus or Oil Bath Method), reaction with carbonyl compounds,
and Beilstein's test.

2,4-DNP is known to be used for qualitative tests of aldehydes and ketones, thus these carbonyl
compounds may also be used as evidence to identify the product. In this experiment,
benzaldehyde and acetone will be used as the test compounds. Upon contact with the carbonyl
compound, a bright orange or yellow precipitate indicates the presence of the C-O double bond
in an aldehyde or ketone (Clark 2004); the formed product is a hydrazone derivative (see Figure
1.5.).
[FIGURE 1.5. 2,4-DNP and benzaldehyde; 2,4-DNP and acetone]

Beilstein's test is used to qualitatively identify halides. Using a clean copper wire that will be
heated with a Bunsen burner until there is no evidence of green coloration, the wire will be
dipped in the substances to be tested (1-chloro-2,4-dinitrobenzene and the obtained product)
and place back into the burner flame; a positive result is indicative of a green color returning to
the flame, due to the formation of volatile copper halides (Richter 1951).

With this experiment, the student aims to:

1. properly synthesize 2,4-DNP by utilizing the SnAr mechanism; and
2. characterize the obtained product through determination of melting point and
chemical tests.

VI. DISCUSSION

In this exercise, 2,4-dinitrophenylhydrazine (2,4-DNP) was synthesized from 1-chloro-2,4-

dinitrobenzene through nucleophilic aromatic substitution (SnAr) (see Figure 1.10.). As the
benzene ring in this exercise is activated by nitro groups, electron withdrawing groups (EWGs)
which render the aromatic ring suspectible to reaction with nucleophiles, and chlorine acts as a
good leaving group, nucleophilic substitution is possible (Smith 2008).

[Figure 1.10. Mechanism for synthesis of 2,4-DNP]

Regarding nucleophilic aromatic substitution, its rate of reaction is dependent on the groups
bonded to the aromatic ring. Electron withdrawing groups increase the rate of reaction due to
their stabilization of the carbanion, while electron releasing groups decrease the rate of reaction
due to destabilization of the carbanion (Lynch 2015). For example, in reacting with 1-chloro-2,4-
dinitrobenzene, aniline, sodium methoxide, and ammonia will form the following compounds:

[Figure 1.11. Over-all reactions with 1-chloro-2,4-dinitrobenzene.]

In terms of rate of reaction, the reaction with sodium methoxide would occur fastest due to its
exposed lone pairs, followed by ammonia then aniline, due to steric hindrance. All three
compounds are electron releasing groups (ERGs), thus their rates of reaction are slower.

Similarly, in aqueous NaOH solution, 4-chloroanisole would react slower than 4-

chloronitrobenzene due to the nitro group present in the latter being an EWG, therefore its rate
of reaction is faster than that of 4-chloroanisole, whose methoxide group is an ERG. Not only
that, but from their reaction mechanisms, 4-chloronitrobenzene has more resonance structures
and its carbanion is therefore more stable than that of 4-chloroanisole (see Figure 1.12.).

[Figure 1.12. Reaction mechanisms of 4-chloronitrobenzene and 4-chloroanisole in aqueous

NaOH.]

Preceeding the synthesis in the exercise, the hydrazine solution was prepared by suspension of
hydrazine sulfate powder in water, which was then followed by addition of sodium acetate. The
mixture was boiled for five minutes, then cooled slightly. Afterwards, ethanol was added
(Equation 1.2.) and the mixture was filtered to remove the formed sodium sulfate (Na2SO4),
which, if hydrazine sulfate had not been initially dissolved in water and instead mixed directly
with the starting material, may have precipitated out and contaminated the product.

[Equation 1.2.]

The filtrate was kept for the synthesis proper, wherein it was added to 1-chloro-2,4-
dinitrobenzene dissolved in ethanol, and then the mixture underwent reflux for an hour. During
so, the pale yellow color of the reaction mixture changed to a deep orange color, indicating the
presence of possible 2,4-DNP formed by SnAr, which is a red to orange substance. After cooling
the mixture, it is filtered through suction, where it is continuously washed with warm ethanol
and warm water in order to dissolve any remaining starting material present in the residue.
Suction filtration was also repeated with the recovered filtrate, as some of the product
precipitated out upon the addition of warm ethanol.

The retrieved product, presumably 2,4-DNP, had a 45.4% yield and had the appearance of a deep
red solid (see Table 1.3.). This somewhat low yield could be attributed to the fact that some of
the washing could not be done quantitatively, thus amounting to less product being retrieved.

In order to properly identify the synthesized product as 2,4-DNP, it underwent characterization in

the form of melting point determination and two chemical tests.

The first chemical test was the reaction with carbonyl compounds (ketones or aldehydes), as 2,4-
DNP is known to be used for qualitative tests regarding them; upon contact with the carbonyl
compound, a bright orange or yellow precipitate indicates the presence of the C-O double bond
in an aldehyde or ketone (Clark 2004). Aromatic amines are less reactive than aliphatic amines
because of their reduced nucleophilicity (Baxter and Reitz 2004), however 2,4-DNP contains one
more amine group than 2,4-dinitroaniline (see Figure 1.13.), creating a longer branch with more
resonance stability, thus despite some structural similarities, 2,4-DNP is capable of reacting with
carbonyl compounds while 2,4-dinitroaniline is not.

[Figure 1.13. Structures of 2,4-dinitroaniline and 2,4-DNP.]

In relation to reactions with carbonyl compounds, aldehydes and ketons are known to react with
ammonia derivatives to form analogous adducts or analogous addition products. For example,
acetophone reacts with ammonia, hydrazine, hydroxylamine, and phenylhydrazine to form the
following:

[Figure 1.14. Products of acetophone reactions with ammonia derivatives.]

Each product has a corresponding functional group containing nitrogen, such as amide for the
first two, a nitrogen bonded to a hydroxyl group, and aniline for the last.
Returning to the characterization of the synthesized product, according to the data in Table 1.5.,
the synthesized product reacted positively with the test compounds of benzaldehyde and
acetone, causing the formation of a bright orange and yellow precipitate, respectively; the
colored precipitate come from the formation of a dinitrophenylhydrazone following the reaction
mechanism in Figure 1.15. A yellow precipitate, given by acetone, is indicative of an
unconjugated compound, unlike benzaldehyde, which resulted in an orange precipitate due to its
aromaticity (Jackson-Hotchkiss 2014).

[Figure 1.15. Reaction mechanism for the reaction of carbonyl compounds with 2,4-DNP.]

The second chemical test, known as Beilstein's test, is used to detect the presence of halide
groups. A copper wire was burned under a flame until no green color was observed, and then
after touching to the sample to be tested, the copper wire is placed under the flame again; a
positive result is indicative of a green color returning to the flame, due to the formation of
volatile copper halides (Richter 1951) (see Equation 1.1.). According to the data in Table 1.6., 1-
chloro-2,4-dinitrobenzene gave a positive result due to the presence of chlorine reacting with
the copper oxides, while the synthesized product gave no green color under the flame, which
indicates no presence of halogens.

However, while the chemical tests followed results that 2,4-DNP would have similarly presented,
the determined melting point range at 93-109degC (see Table 1.4.) indicated that the product
was impure. The true melting point value for 2,4-DNP is around 200degC, while the melting
point for 1-chloro-2,4-dinitrobenzene is at a low 53degC. Therefore, this low melting point range
could be attributed to small portions of starting material that may have also made its way to the
final product, due to insufficient washing with warm ethanol and warm water. Accidental cooling
of the ethanol and water from its required 60degC may have also caused the starting material to
be unable to dissolve properly and remain in the residue.

VII. APPLICATIONS

Ibrahim et al. (2013) conducted an experiment on the leaving group and solvent effects of 2,4-
dinitrobenzene derivatives with hydrazine, wherein hydrazine acted as the nucleophile in an
nucleophilic aromatic substitution with 2,4-dinitrobenzene derivatives.

In their results, 1-chloro-2,4-dinitrobenzene reacts with hydrazine in methanol, acetonitrile and

dimethyl sulfoxide through an uncatalyzed substitution where formation of the zwitterionic (also
known as a dipolar ion whose net charge is zero) intermediate, while the remaining 2,4-
dinitrobenzene derivatives reacts with hydrazine in DMSO also uncatalyzed substitution,
however the departure of the leaving group is the rate-determining step.

Each process is dependent on the basicity of the leaving group as well as its steric hindrance and
any possible intramolecular hydrogen bonds in the transition state; also, the reactivity of certain
compounds depend on the substituent of the aromatic ring.
XI. REFERENCES

A. Books

RICHTER GH. 1951. Laboratory Manual of Elementary Organic Chemistry. 2nd ed. New York: John
Wiley & Sons, Inc. p. 10.

SMITH 2008.

SOLOMONS TWG, CB FRYHLE. 2000. Organic Chemistry. 7th ed. New York: John Wiley & Sons,
Inc. 1032-1034 pp.

B. Journals

BAXTER EW, AB REITZ. 2004. ChemInform 34(19): 10.1002/0471264180.

IBRAHIM MF, HA ABDEL-REHEEM, SN KHATTAB, EA HAMED. 2013. International Journal of

Chemistry 5(3): 33-45.

C. Web Sources

CLARK J. 2004. Addition-elimination reactions of aldehydes and ketones. Retrieved January 25,
2018, from: https://www.chemguide.co.uk/organicprops/carbonyls/addelim.html

JACKSON-HOTCHKISS S. 2014. Lab Photo: The 2,4-Dinitrophenylhydrazine Test for Aldehydes and
Ketones. Retrieved February 4, 2018, from: http://www.stempunk.com/2014/09/05/lab-photo-
the-24-dinitrophenylhydrazine-test-for-aldehydes-and-ketones/

LYNCH K. 2015. Nucleophilic Aromatic Substitution. Retrieved February 4, 2018, from:

https://www.masterorganicchemistry.com/tips/nucleophilic-aromatic-substitution/