Price Lists for 2023 Projects

The current projects we are working on in 2023 include the following:

- Aspirin production on a pilot plant scale

- Aspirin qualification

- Phenylacetic acid production

- Lab upgrades

As such, this page compiles the price lists of the various analyses done on each of these topics.

Aspirin Pilot Plant Production

Here we can find the price list of reagents needed for large-scale aspirin production:

Pilot Plant Scale Aspirin Production
Reagent	Quantity per cycle	Quantity ordered	Price	Reference
Salicylic acid	1013.5 g	2 kg	$101.64	Biosynth	Alternatively	5 kg	$241.40	Biosynth
Acetic anhydride	2.5 L	5 L	$238.87	VWR
Sulfuric acid(We have 440 mL)	125 mL	-	-	-
Total			$340.51

Aspirin Qualification

Here we can find the price list of chemicals needed for testing:

Aspirin quality control standard tests according to the Ph.Eur.
Test	Reagent	Quantity per experiment	Quantity ordered	Price	Reference	Missing Apparatus
IR absorption	Potassium bromide	300-400 mg				IR Spectrophotometer, hydraulic press
Color test	Calcium hydroxide	0.5 g	500 g	$63.53	Biosynth
Color test	2-Nitrobenzaldehyde solution	0.05 mL	0.25 kg	$50.82	Biosynth
Appearance of solution	Reference solution B9	For comparision	100 mL	$107.70	Reagecon
Related substances	Phosphoric acid					HPLC
Related substances	Acetonitrile					HPLC
Heavy metals	Thioacetamide solution	1.20 mL	25 g (19.7 mL)	$69.00	Sigma
Heavy metals	Buffer solution	2 mL	1 L	$63.49	Reagecon
Heavy metals	Lead standard solution	10 mL of 1 ppm	100 mL of 100 ppm	$127.42	Reagecon		Note: needs to be in water
Loss on drying	Diphosphorus pentoxide	Amount depends on size of desiccator	500 g	$154.00	Sigma	vacuum desiccator, weighing bottle
Sulphated ash	Silica gel					crucible, muffle furnace, desiccator
Assay	Phenolphthalein	As an indicator	50 g	$44.84	VWR
Total				$680.80

Finalized Price List

In order to work according to priorities, the first involves ordering large amounts of salicylic acid and acetic anhydride. As for the aspirin qualification, due to the specific apparatus that is required, we have decided to move forward with conducting a melting point test and therefore purchasing that apparatus. As for the remaining tests, those will be done at specialized laboratories, such as the university labs listed by the MOPH in order to register and certify a drug. In addition, this table includes components that are missing from the lab but are vital to the projects we are conducting, both now and in the future. Finally, we have also included the reagents required for phenylacetic acid production.

Title	Reagent	Quantity ordered	Price	Reference	Total
Aspirin production	Acetic anhydride	5 L	$150.00	VTC (VWR)/in stock	$150.00
Lab Equipment	Separatory funnel (1000 mL)		$32.00	VTC	$713.00
	Complete Buchner filtration apparatus (1000 mL)		$150.00	VTC
	Stand		$16.00	VTC
	Capillary tubes	100 units	$5.00	VTC
	Separatory funnel (500 mL)		$20.00	City Med Lab
	Safety goggles	3 units	$18.00	City Med Lab
	Fire Extinguisher	2 kg	$12.00
	Distillation (Vacuum)		$90.00	Amazon
	Shipping:		$40.00
	Melting point apparatus		$200.00	Alibaba
	Shipping:		$130.00
PAA production	Methyphenyl acetate	1 kg	$210.00	VTC	$357.00
	Sodium hydroxide (2M)	1 kg	$5.00
	Ether	2.5 L	$125.00	VTC
	Na2SO4	1 kg	$17.00	VTC
Total			$1,220.00		$1,220.00

Aspirin Optimization

Introduction

With the arrival of the melting point apparatus, the sample that had originally been produced on 25/11/2022 during the aspirin production protocol was tested for its melting point. Its range was approximately 114-116oC. In light of the impurities that have lowered the melting point, trials were conducted varying different parameters to both test the effect these parameters have on yield as well as on purity.

Results

Trial	Volume	Molarity of Acid	Recrystallization solvent	Reaction time	Mass of Product	% Yield	FeCl3 test	Melting Point
1	5 mL acetic anhydride	1M (sulfuric acid)	warm water	10 min 10min 10min 15min 15min	1.96g - - 1.56g 1.21g	75.1% 60% 46.3%	+ + + + +	120.6-121.4 °C 121.5-124.0 °C 120.8-124 °C 125-127 °C 126.7-130.5 °C
2	5 mL acetic anhydride	6M	water	10 min	1.60g 2.42g 1.07g	61.3% 92.7% 41.15%	+ + +	117.7-119.6 °C 121-128 °C 123.7-125.8 °C
3	5 mL acetic anhydride	6M	ethanol and water ethanol and cold water ethanol and warm water ethanol and warm water ethanol and warm water ethanol (10ml) and warm water ethanol 5%, distilled water at room temperature ethanol (10ml) and warm water	10 min 15 min 10min 15 min 15min 15min 15min 15min	0.85g 0.68g 0.88g 0.37g 0.94g 0.65g 1.28g (unkown residue milky-oily mass) 2.08g (98% concentrated acid)	32.6% 26.6% 33.7% 14.1% 36% 24.9% 49.1% 79.6%	- + + + + + + +	118.6-119.7 °C 119.5-122.1 °C 125.3-128.2 °C 126.5-128 °C 125.7-128.8 °C 121-122 °C 119.4-123.1 °C
4a	1.56 mL acetic anhydride 1.29 mL acetic acid	1M	water	10 min	1.85g	70.9%	+	119.2-120.9 °C
4b	1.56 mL acetic anhydride 1.29 mL acetic acid	6M	water	10 min	2.37 g	90.8%	+	108.0-108.5 °C
5	5 mL acetic anhydride	6M	water	2 hr	-	-	-	Some melted at around 90 °C. Finished melting at 118 °C.
6	5 mL acetic anhydride	6M	water	20 min	2.39 g	91.5%	-	120.0-120.7 °C
7	1.56 mL acetic anhydride 3.44 mL acetic acid	6M	water	10 min	1.57g	60.2%	+	114-116 °C
8*	5 mL acetic anhydride	6M	water	10 min	1.80g	69.0%	-	114-116 °C
9	5 mL acetic anhydride	6M	Room temp distilled water	10 min	2.97g	114%	+	114-123.3 °C
	4 ml acetic anhydride	6M	- ()	15 min	1g	40%	-	132-134 °C

*Using Biosynth salicylic acid. Based on visual appearance alone, the crystals are much larger than those of Xilong Scientific, the other supplier of salicylic acid. Seeing as the large scale production would utilize the salicylic acid purchased from Biosynth, we decided to conduct a trail using it.

Discussion

The theoretical yield of aspirin is 2.61g for excess acetic anhydride and 2g of salicylic acid. This was determined based on the following calculation: mass of aspirin = 180 g/mol (molar mass of aspirin) x 2 g salicylic acid / 138 g/mol (molar mass of salicylic acid).

Trial 2 was repeated a second time due to the positive ferric chloride test for the first sample. The second sample had a much higher yield and tested negative in the ferric chloride test.

The result of trial 5 was a yellowish putty, as though the product it contained had burnt. This might be due to the extended exposure to heat, or it might be due to the small quantity used within a large round bottomed flask. It was not possible to determine its exact mass due to its dampness, nor did it fit any of the characteristics of aspirin. For continuity purposes, it was included within the table along with its ferric chloride test and had its melting point crudely measured.

As hot water induces the hydrolysis of aspirin into acetic and salicylic acids, trial 9 was designed to observe whether using room temperature water would lead to an increase in the purity. However, as evident from its sizable mass and ferric chloride test, it prevented the salicylic acid from being washed away completely, meaning this was not a suitable step to take.

Trial 4 was designed based on the following patent: https://patents.google.com/patent/US3235583A/en. This patent describes how an 18% molar excess of acetic anhydride is sufficient to arrive at a good yield of aspirin. Based on this quantity, the following calculations were made:

nacetic anhydride = 1.18 nsalicylic acid = 1.18 x 2 g / 138 g/mol = 0.0165 mol

Vacetic anhydride = n x MM / d = 0.0165 mol x 102 g/mol / 1.08 g/mL = 1.56 mL

In order to dilute the reaction mixture, it was calculated using the proportion that for 140 g of salicylic acid, 95 g of acetic acid were used. This calculation netted that for 2 g of salicylic acid, 1.36 g of acetic acid should be used, which equates to a volume of 1.29 mL.

The ferric chloride test indicated that both trials 4a and 4b contained salicylic acid. One possible reason behind this is the combined volume of the solvents is approximately 3 mL, and the increased concentration relative to the other trials may have prevented the salicylic acid from being washed away completely. Trial 7 was therefore designed to account for this possibility, yet its result was also positive for salicylic acid. This may imply that a repetition is required. Regardless, this allows for the opportunity to conserve the usage of the reactants.

The melting point is relatively low for all the trials regardless of whether they tested positive or negative for the ferric chloride test. It was also measured after leaving the samples to dry overnight in the refrigerator. To attempt to purify 4b, two trials for a third recrystallization were conducted. 0.5g of crude aspirin were used. The first trial involved adding 2 mL of ethanol and 15 mL of water and heating until all aspirin had dissolved. The second trial involved adding 17 mL of warm water only. Both trials resulted in samples that still tested positive in the ferric chloride test, with a melting point that was not significantly different from the parent material.

Trial	Solvent	Agitation	Mass obtained	Melting Point
4b	2mL ethanol and 15mL water	No	0.39 g	108.0-108.5
4b	17mL water	No	0.40 g	107.1-107.8

Conclusive Remarks:

Overall, using an increased concentration of sulfuric acid has a positive effect on results by significantly increasing the yield. This is expected due to its catalytic activity expediting the reaction and driving it closer to completion. However, most samples had a relatively low melting point compared to the reported melting point of pure aspirin (135oC), as well as the melting point of medicinal aspirin (~130oC). Medicinal aspirin contains impurities such as maize starch, cellulose powder, methacrylic acid, and other coating reagents or those that aid in the absorption of aspirin. As such, it is expected that its melting point is depressed.

Following steps include using toluene as a recrystallization agent instead of water. This would preclude the hydrolysis of aspirin. Extra recrystallization steps may also be conducted on the samples obtained, particularly those that tested negative for the ferric chloride test.

Noting the inconsistencies across the two tests in trial 2, in order to ensure validity and reproducibility of these tests, it is worth repeating each trial three times.