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[ CAS No. 16633-50-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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2D 3D

Chemical Structure| 16633-50-4

Chemical Structure| 16633-50-4

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Quality Control of [ 16633-50-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 16633-50-4 ]

SDS Specification

Alternatived Products of [ 16633-50-4 ]

Product Details of [ 16633-50-4 ]

CAS No. :	16633-50-4	MDL No. :	MFCD06208279
Formula :	C₉H₉FO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PQYFAAZGSGZNGG-UHFFFAOYSA-N
M.W :	168.17	Pubchem ID :	8167074
Synonyms :

Calculated chemistry of [ 16633-50-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.29
TPSA :	37.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.71 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.64
Log Po/w (XLOGP3) :	2.28
Log Po/w (WLOGP) :	2.56
Log Po/w (MLOGP) :	2.67
Log Po/w (SILICOS-IT) :	2.56
Consensus Log Po/w :	2.34

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.62
Solubility :	0.401 mg/ml ; 0.00238 mol/l
Class :	Soluble
Log S (Ali) :	-2.7
Solubility :	0.335 mg/ml ; 0.00199 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.82
Solubility :	0.256 mg/ml ; 0.00152 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.31

Safety of [ 16633-50-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 16633-50-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 16633-50-4 ]
Downstream synthetic route of [ 16633-50-4 ]

[ 16633-50-4 ] Synthesis Path-Upstream 1~9

1
[ 186581-53-3 ]
[ 16633-50-4 ]
[ 14659-60-0 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

2
[ 14659-60-0 ]
[ 16633-50-4 ]

Yield	Reaction Conditions	Operation in experiment
31%	With potassium hydroxide; water In methanol; dichlorobenzene, 1,2-	4-Amino-2,6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1,2-dichlorobenzene at 100 °C for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 °C and acidified with conc. HCl (pH = 1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31 percent) of the acid as a tan solid.

Reference： [1] Patent: EP1175401, 2005, B1, . Location in patent: Page/Page column 30
[2] Patent: US6391865, 2002, B1, . Location in patent: Page column 46

3
[ 16643-19-9 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

4
[ 3095-38-3 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

5
[ 315-12-8 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

6
[ 34761-82-5 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

7
[ 19023-45-1 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

8
[ 14659-61-1 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

9
[ 392-70-1 ]
[ 16633-50-4 ]

Reference： [1] Journal of the American Chemical Society, 1967, vol. 89, # 2, p. 390 - 394

[ 16633-50-4 ] Synthesis Path-Downstream 1~21

1
[ 186581-53-3 ]
[ 16633-50-4 ]
[ 14659-60-0 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

2
[ 16643-19-9 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

3
[ 3095-38-3 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

4
[ 315-12-8 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

5
[ 34761-82-5 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

6
[ 14659-61-1 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

7
[ 19023-45-1 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

8
[ 392-70-1 ]
[ 16633-50-4 ]

Reference： [1]Journal of the American Chemical Society,1967,vol. 89,p. 390 - 394

9
C₂₀H₃₀F₃N₃*3ClH [ No CAS ]
[ 16633-50-4 ]
C₂₉H₃₇F₄N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine;	8CC The trihydrochloride salt of the product of Example 8, step 3 (127 mg, 0.27 mmol) and <strong>[16633-50-4]4-fluoro-2,6-dimethyl benzoic acid</strong> (58 mg, 0.35 mmol) (see preparation below) were coupled according to the general procedure (EDC/HOBT/IPr2NEt).. Purification via preparative TLC (2/1 hexanes/EtOAc, SiO2) gave 8CC as a colorless oil (87 mg bis-HCl salt, 54%).

Reference： [1]Patent: US6391865,2002,B1 .Location in patent: Page column 46, 59-60

10
[ 14659-60-0 ]
[ 16633-50-4 ]

Yield	Reaction Conditions	Operation in experiment
31%	With potassium hydroxide; water; In methanol; dichlorobenzene, 1,2-;	4-Amino-2,6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1,2-dichlorobenzene at 100 C for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 C and acidified with conc. HCl (pH = 1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31 %) of the acid as a tan solid.
		4-Amino-2,6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1,2-dichlorobenzene at 100 C. for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 C. and acidified with conc. HCl (pH=1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31%) of the acid as a tan solid.

Reference： [1]Patent: EP1175401,2005,B1 .Location in patent: Page/Page column 30
[2]Patent: US6391865,2002,B1 .Location in patent: Page column 46

11
C₂₀H₃₀F₃N₃*3ClH [ No CAS ]
[ 16633-50-4 ]
C₂₉H₃₇F₄N₃O*2ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine;	The trihydrochloride salt of the product of Example 8, step 3 (127 mg, 0.27 mmol) and <strong>[16633-50-4]4-fluoro-2,6-dimethyl benzoic acid</strong> (58 mg, 0.35 mmol) (see preparation below) were coupled according to the general procedure (EDC/HOBT/iPr2NEt). Purification via preparative TLC (2/1 hexanes/EtOAc, SiO2) gave 8CC as a colorless oil (87 mg bis-HCl salt, 54 %).

Reference： [1]Patent: EP1175401,2005,B1 .Location in patent: Page/Page column 30

Yield	Reaction Conditions	Operation in experiment
		Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, S.C. 29172, USA. TCI America, 9211 N. Harborgate Street, Portland, Oreg. 97203, USA ... 3,5-difluorobenzoic acid; 2,6-difluoro-3-nitrobenzoic acid; 2,6-dihydroxy-4-methylbenzoic acid; 3,4-dimethylbenzoic acid; 2,6-dimethyl-4-fluorobenzoic acid; 3,5-dinitrosalicylic acid; 4-fluorobenzoic acid; 2-fluoro-6-hydroxybenzoic acid; ...

13
C₂₁H₂₈N₄O₂*3ClH [ No CAS ]
[ 16633-50-4 ]
C₃₀H₃₅FN₄O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 65 - 68

14
[ 578-66-5 ]
[ 16633-50-4 ]
[ 1609401-44-6 ]

Yield	Reaction Conditions	Operation in experiment
91%		General procedure: A solution of 8-aminoquinoline (0.3950 g, 2.74 mmol) and Et3N (0.42 mL, 3 mmol) in CH2Cl2 (5 mL) was cooled to 0 C, then an acyl chloride (2.74 mmol) was added (the acyl chloride was prepared by reaction of the appropriate carboxylic acid with SOCl2). After addition, the reaction mixture was warmed to room temperature and stirred for 24 h. The reaction mixture was washed with water (1 mL), brine (1.5 mL × 3), and dried over Na2SO4. The solvent was removed and theproduct was obtained by recrystallisation or flash chromatography.

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 606 - 610

15
[ 16633-50-4 ]
N⁵-{4-[(4-fluoro-2,6-dimethylbenzoyl)amino]phenyl}-N⁴-methyl-1H-imidazole-4,5-dicarboxamide [ No CAS ]

Reference： [1]Patent: WO2015/150449,2015,A2

16
[ 16633-50-4 ]
4-fluoro-2,6-dimethylbenzoyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
187 mg	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 2h;Inert atmosphere;	To a so[ution of 169 mg (1.00 mmo[) 4-f[uoro-2,6-dimethy[benzoic acid and 112 j.iL (1.30 mmo[) oxa[y[ch[oride in 5 mL dry dich[oromethane, a few drops of DMF were added under an argon atmosphere. After stirring for 2 hours at room temperature the reaction mixture was concentrated in vacuo to give 187 mg of the tit[ecompound which was used without further purification.

Reference： [1]Patent: WO2015/150449,2015,A2 .Location in patent: Page/Page column 173; 174

17
[ 16633-50-4 ]
3,3’‐oxybis(tert‐butylbenzene) [ No CAS ]
3,6‐di‐tert‐butyl‐9‐(4‐fluoro‐2,6‐dimethylphenyl)‐10‐phenylacridin‐10‐ium tetrafluoroborate [ No CAS ]

Reference： [1]Synlett,2019,vol. 30,p. 827 - 832

18
[ 67969-82-8 ]
[ 13755-29-8 ]
[ 16633-50-4 ]
3,3’‐oxybis(tert‐butylbenzene) [ No CAS ]
3,6‐di‐tert‐butyl‐9‐(4‐fluoro‐2,6‐dimethylphenyl)xanthylium tetrafluoroborate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
493 mg		General procedure: To a flame-dried 250 mL round-bottom flask under argon wereadded 4 (8.02 g, 28.4 mmol, 1 equiv), TMEDA (8.71 mL, 58.2mmol, 2.05 equiv), and anhydrous n-hexane (28 mL). Theresulting solution was cooled in an ice bath and sec-butyllithium(1.4 M solution in cyclohexane, 42.0 mL, 58.2 mmol, 2.05equiv) was added dropwise. The ice bath was removed and thereaction mixture was stirred at room temperature for 4 h. Thereaction was cooled to -78 C and a solution of methyl 2,4,6-trimethylbenzoate (5.11 g, 28.7 mmol, 1.01 equiv) in anhydrousn-hexane (28 mL) was added slowly via cannula. After the addition,the mixture was allowed to slowly warm to room temperatureand stirred for 12 h. The reaction was quenched with water(25 mL) and the biphasic mixture was stirred vigorously for 30min. The mixture was diluted with Et2O (100 mL) and the layerswere separated. The organic layer was washed with water(2 × 150 mL) and brine (1 × 150 mL). The organic layer wastransferred to a 250 mL round-bottom flask equipped with astir bar. To the vigorously stirred solution was added conc. HCl(12 mL), resulting in a bright-yellow precipitate. The suspensionwas stirred vigorously for 30 min then diluted with water (150mL). The layers were separated and the organic layer wasextracted with water (3 × 150 mL or until the washings becomecolorless). To the combined aqueous layers was added solidNaBF4 (9.35 g, 85.2 mmol, 3 equiv), resulting in a bright-yellowprecipitate. The resulting suspension was extracted withdichloromethane (3 × 150 mL or until the washings become colorless).To the combined organic layers was added HBF4·Et2Ocomplex (3.46 mL, 28.4 mmol, 1 equiv). The solution wasswirled to achieve homogeneity then washed with water(1 × 100 mL) and aq. NaBF4 (1 M, 1 × 100 mL). The organic layerwas dried over solid NaBF4, filtered, and concentrated to dryness.The residue was purified by trituration with hexanes andfiltered. The solid was rinsed with n-pentane and dried in vacuoto give xanthylium 3 (10.6 g, 21.3 mmol, 75% yield) as a yelloworangesolid.

Reference： [1]Synlett,2019,vol. 30,p. 827 - 832

19
[ 16633-50-4 ]
[ 74-88-4 ]
[ 14659-60-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 24.0h;Inert atmosphere;	General procedure: To a 250 mL round bottom flask equipped with a stir barwere added 2,4,6-trimethylbenzoic acid (6.57 g, 40.0 mmol, 1 equiv), potassium carbonate (8.29g, 60.0 mmol, 1.5 equiv) and DMF (50 mL). Iodomethane (3.00 mL, 48.0 mmol, 1.2 equiv) wasslowly added to the reaction vessel and the resulting suspension was stirred vigorously at roomtemperature for 24 h. The reaction was poured onto 300 mL of H2O and extracted with 3 x 300mL portions of Et2O. The combined organic extracts were washed with 3 x 150 mL portions ofH2O and 2 x 150 mL portions of brine. The organic layer was dried over MgSO4, filtered, andconcentrated to dryness. The residue was purified by passing through a pad of silica eluting with1:1 EtOAc/hexanes to give methyl ester S4 (6.28 g, 35.2 mmol, 88% yield) as a pale yellow oil.Spectral data are in agreement with those previously published.4

Reference： [1]Synlett,2019,vol. 30,p. 827 - 832

20
[ 124-38-9 ]
[ 14659-58-6 ]
[ 16633-50-4 ]

Yield	Reaction Conditions	Operation in experiment
17%		4-fluoro-2,6-dimethylbenzoic acid (S6) was prepared using a modified version of a publishedprocedure.5 To an oven-dried 25 mL round bottom flask under argon atmosphere were added <strong>[14659-58-6]2-bromo-5-fluoro-1,3-dimethylbenzene</strong> (3.07 g, 15.1 mmol, 1 equiv) and dry Et2O (18.0 mL). Theresulting solution was cooled to 0 C and n-butyllithium (1.6 M solution in hexanes, 10.4 mL, 16.6mmol, 1.1 equiv) was added dropwise. The solution was stirred at 0 C for 1 h. The ice bath wasremoved and the reaction vessel was fitted with a balloon of CO2 (equipped with a calcium sulfatedrying tube) and a vent needle. Dry CO2 was then bubbled through the reaction for 1 h. Thereaction was quenched with 2 M HCl. The biphasic mixture was diluted with water and extractedwith 3 x 50 mL portions of Et2O. The combined organic layers were dried over MgSO4, filtered,and concentrated. The resulting residue was purified by trituration with hexanes to give 4-fluoro-2,6-dimethylbenzoic acid (437 mg, 2.60 mmol, 17% yield) as a white solid. The product was usedin the next step without any further purification.

Reference： [1]Synlett,2019,vol. 30,p. 827 - 832

21
[ 110-05-4 ]
[ 321-21-1 ]
[ 16633-50-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium acetate; palladium diacetate; at 80℃; under 760.051 Torr; for 24h;	0.6 mmol of potassium acetate, 0.3 mmol of 4-fluoro-2-methylbenzoic acid,Palladium acetate 0.03 mmol, peroxydi-tert-butyl ether 0.6 mmol,0.8 mL of hexafluoroisopropanol was added to a 15 mL reaction tubeThe mixture was placed in an oil bath at 80 C, and reacted in an air atmosphere at a pressure of 1 atm for 24 hours;After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed with water.The organic phase was dried over anhydrous Na2SO4, filtered and concentrated.Purification by thin layer chromatography gave 37.8 mg of the desired product as a white solid.The yield was 75%.

Reference： [1]Patent: CN109970551,2019,A .Location in patent: Paragraph 0052-0055

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Code	Phrase
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P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Ghs Hazard Statements

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere