Lab 8: Nitration Chemistry

Objective: The purpose of this lab is to gain a deeper understanding of nitration chemistry with aromatics. We will do this by first synthesizing 5-nitrosalicylic acid from salicylic acid and then by adding a carbene to a phenol. The success of our experiment will be determined through TLC analysis, the quality of the TLC sample, melting point, and a RI.

Methods:

Activity #1 - Nitration of Salicylic Acid to Nitro-salicylic acid

•  Added 4 mL of concentrated sulfuric acid to an Erlenmeyer flask.

• The reaction flask was placed in an ice bath to chill until sulfuric acid reached 2 degrees Celsius.

• 2 g of salicylic acid was added in three separate portions to the Erlenmeyer flask.  Each portion was added slowly, allowing the reaction mixture to return to 2 degrees Celsius between each portion addition. The flask was swirled to combine all of the contents.

• Added approximately 1.4 mL of concentrated nitric acid drop by drop, carefully monitoring the reaction temperature to prevent the reaction mixture from rising above 10 degrees Celsius. 

• Removed the flask from the ice bath and placed the flask on the bench top to allow the solution to warm to room temperature (approximately 20 degrees Celsius).

•  Added 16.67 g of ice to the reaction mixture.

• After 10 minutes, the bulk of the melted water was drained off into the acid waste container. 

• The final product was collected via vacuum filtration. The yellow crystal product remained at the top of the vacuum filter, which will be used for the remainder of the purification.

•  Added 2M NaOH one drop at a time to the crude solid nitrosalicylic acid product until the pH of the product reached 8.0.

•  Added 3M HCL one drop at a time to the crude product until the pH was brought back to 6.0.

• The remainder of the product was vacuum filtered and washed with very cold water.

Activity 2- Electrophilic Addition to Phenol to Synthesize Salicylaldehyde

Our Lab Group Chose to do Activity #1: Conducted the lab exactly as written at ⅓ scale.

• 2 g of phenol, 2.1 g of sodium hydroxide, and 3.3 mL of water were combined in a 50 mL round-bottom flask, resulting in a brilliant red appearing solution.

• The reaction flask was placed in a heating mantle and heated to 50 degrees Celsius.

• 1.0 mL of chloroform was added to the reaction mixture drop by drop, and the flask was shaken vigorously to mix the contents.

• Another 1.0 mL of chloroform was added to the solution, and the round-bottom flask containing the reaction mixture was connected to a condenser and allowed to reflux for 1 hour.

•  After the reflux had run for an hour, the product was allowed to cool before being poured over 13.3 g of ice. 

• The reaction mixture was swirled until the ice was fully melted.

• 3M HCL was added until the reaction mixture reached a pH of 6. The solution now appeared a bright orange color.

• The solution was filtered by gravity filtration to remove excess NaOH.

• The organic layer was separated in a separatory funnel and washed with 1M HCL, followed by water, and a saturated salt solution.

• Any chloroform remaining in the solution was evaporated using low heat.

• The product was then transferred to an Erlenmeyer flask and capped.

• Capped flask placed in a lab drawer for analysis next week. When flask was removed the solution was noted to be a brilliant red color.  

Activity #3 - Lab Cleanup

• A warm, soapy bath was created in the sink to soak all glassware used in experimental proceedings today.

• All the glassware was scrubbed and placed back in the lab drawer to dry.

• The inside of the lab hood was wiped down with a soapy rag.

• The rag was rinsed and the hood was wiped a second time.

• The communal area around the scales was cleaned to ensure no acid lingered in the open within the lab.

• The inside of the chemical hood was tidied, making sure to tightly close all containers and refill the DI water bottle. 

Activity #4 - Purification and Analysis of Nitro-salicylic acid - Product Purification Performed Using Kirsten Kirkham and Thea Meyer's Product due to the absence of usual Lab Partner, Justin Young-Bach

• Retrieved the bright yellow, oily, nitro-salicylic acid solution from the lab drawer and placed the flask on a hot plate set to 5. 

• Covered the flask with a watch glass and heated the solution until solution came to a boil.

• Removed solution from heat and placed on bench top, and monitored solution until thin, yellow crystals began to form.

• Placed flask in an ice bath to allow for further recrystallization. 

• Allowed solution to sit for 15 minutes before vacuum filtering the solid from the solution.

• Used a small amount of the final product for TLC analysis. 

• After the product was fully dry, analyzed by % yield and IR.

Discussion:

% yield:  The percent yield for the synthesis of nitrosalicylic acid was 74%,  indicating high yield and a likely successful synthesis. The bright red color of the nitrosalicylic acid product is contrary to the off white colored product anticipated for this lab. It's believed that the stir bar used had a contaminant on it as color change was only noted after the addition of the stir bar. All analyses will be conducted with this interpretation in mind.  The percent yield for salicylic acid was 81%, another high yield experiment and indicating a successful experimental procedure. 

TLC: TLC for nitro salicylic acid had one distinct spot with obvious "dragging", indicating that the spot may have been too concentrated and needed to be further diluted for increased TLC accuracy.  The presence of only one spot on the plate is reassuring for product purity, indicating that only one compound is present within the solution.  As no lab standard was provided, no sample is available for comparison, which would provide further confirmation on the identity of our synthesized compound and its purity. 

IR: The observed IR for nitrosalicylic acid is generally consistent with what we would expect for nitrosalicylic acid. A very broad peak between 1800–3000 cm⁻¹ likely represents the carboxylic acid C=O stretch, possibly overlapping with alkane and/or alkene C–H stretches around 2900–3100 cm⁻¹. A peak near 3200 cm⁻¹ suggests the presence of an O–H stretch, typical for both carboxylic acids and phenols, while the sharp peak around 3500 cm⁻¹ may indicate an N–H stretch, consistent with an amine group, although this is less typical for nitrosalicylic acid unless shifts are significant. The broad peak from 3700–4000 cm⁻¹ could reflect a highly shifted O–H stretch of the carboxylic acid, though this is higher than normally expected, possibly due to experimental conditions. Shifting of peaks may be caused by the stir bar contaminant. Peaks in the fingerprint region further support the complex functional groups present. The unusually intense peaks are likely due to enhanced IR sensitivity settings needed to capture a readable spectrum for the sample.

The observed IR data are generally consistent with a possible salicylaldehyde product. The very broad peak between 3000–3600 cm⁻¹ likely corresponds to the O–H stretch of the phenol group, which typically appears broad and strong around 3300 cm⁻¹. Some contribution from C–H stretches of aromatic (alkene-like) character near 3000–3100 cm⁻¹ is also possible, though these are usually narrower. A peak observed around 1600 cm⁻¹ likely represents aromatic C=C stretching vibrations, common in benzene rings, though it appears broader than typical. Several prominent peaks in the fingerprint region support the presence of complex aromatic and alcohol functionalities. Overall, these findings could indicate the presence of salicylaldehyde.

Mass Spec: Salicylaldehyde’s expected molecular weight (122 amu) is substantially lower than the observed true molecular mass (236 amu), indicating that the product analyzed via mass spec is not pure salicylaldehyde. Strong fragment peaks were observed at 172, 183, 198, 215, and 225 amu, these fragment masses are consistent with the breakdown of a larger, more complex molecule, rather than a small molecule like salicylaldehyde. Typical fragmentation of salicylaldehyde would produce smaller fragments corresponding to benzene ring cleavage or simple side-chain losses rather than the larger fragment masses recorded on the mass spec data.

Post Lab:

1. Different functional groups are said to “direct” nitration to different locations on a benzene ring.  What would be the directing effects of a –CH3 (a donating group)?  Of a carboxylic acid (an electron-withdrawing group)?  You must refer to your Wade text or class notes for your answer.

The –CH₃ group is an activating group with electron-donating properties through inductive effects. The methyl group increases electron density on the ring, especially at the ortho and para positions. In nitration, the incoming nitro group (NO₂⁺) will prefer to attach to the ortho or para positions of the methyl group due to increased electron density.

The –COOH group is a deactivating group and electron-withdrawing through resonance and inductive effects.
It pulls electron density away from the ring, especially from the ortho and para positions, making it a meta director
During nitration chemistry, the nitro group will preferentially add to the meta position relative to the carboxylic acid group because those positions retain slightly more electron density.

2. Why does the nitro group most likely add to the 5 position of salicylic acid and the carbene add to the 2 or 4 positions of phenol?  You must refer to your Wade text or class notes for your answer.  

The Salicylic acid product has two functional groups on the benzene ring: a hydroxyl group (–OH) at the 2-position and a carboxylic acid (–COOH) at the 1-position. The –OH is ortho/para directing and activating, while –COOH is meta directing and deactivating. The 5-position is ortho to –OH and meta to –COOH, which aligns with the directing effects of both groups. This makes the 5-position the most favorable site for electrophilic attack (e.g., by NO₂⁺), due to resonance stabilization and relatively higher electron density.

Carbenes react via electrophilic substitution, and phenol (–OH on a benzene ring) strongly activates the ring.
The –OH group donates electrons via resonance, increasing electron density at the ortho (2,6) and para (4) positions. This makes the 2 and 4 positions the most reactive toward electrophilic attack (like with a carbene).
Steric hindrance may make the 4-position slightly more favorable in some cases, but both 2 and 4 are highly activated.