[ CAS No. 118-12-7 ] {[proInfo.proName]}

Name: 118-12-7|1,3,3-Trimethyl-2-methyleneindoline|98%
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SKU: A374094
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2D 3D

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Quality Control of [ 118-12-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 118-12-7 ]

SDS Specification

Alternatived Products of [ 118-12-7 ]

Product Details of [ 118-12-7 ]

CAS No. :	118-12-7	MDL No. :	MFCD00005813
Formula :	C₁₂H₁₅N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZTUKGBOUHWYFGC-UHFFFAOYSA-N
M.W :	173.25	Pubchem ID :	8351
Synonyms :

Calculated chemistry of [ 118-12-7 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.33
Num. rotatable bonds :	0
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	60.27
TPSA :	3.24 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.93 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.49
Log Po/w (XLOGP3) :	3.42
Log Po/w (WLOGP) :	2.55
Log Po/w (MLOGP) :	2.85
Log Po/w (SILICOS-IT) :	2.89
Consensus Log Po/w :	2.84

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.41
Solubility :	0.0674 mg/ml ; 0.000389 mol/l
Class :	Soluble
Log S (Ali) :	-3.17
Solubility :	0.118 mg/ml ; 0.000679 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.82
Solubility :	0.0264 mg/ml ; 0.000152 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.0

Safety of [ 118-12-7 ]

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 [ 118-12-7 ]

* 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 [ 118-12-7 ]
Downstream synthetic route of [ 118-12-7 ]

[ 118-12-7 ] Synthesis Path-Upstream 1~17

1
[ 118-12-7 ]
[ 68-12-2 ]
[ 84-83-3 ]

Reference： [1] Journal of Materials Chemistry C, 2017, vol. 5, # 21, p. 5111 - 5118
[2] Journal of the American Chemical Society, 2017, vol. 139, # 48, p. 17301 - 17304
[3] Chemische Berichte, 1959, vol. 92, p. 1809,1810
[4] Organic and Biomolecular Chemistry, 2017, vol. 15, # 38, p. 8091 - 8101

2
[ 118-12-7 ]
[ 3724-43-4 ]
[ 84-83-3 ]

Reference： [1] Journal of the American Chemical Society, 2017, vol. 139, # 48, p. 17301 - 17304
[2] Patent: KR2016/22280, 2016, A, . Location in patent: Paragraph 0166; 0174-0176

3
[ 118-12-7 ]
[ 93-61-8 ]
[ 84-83-3 ]

Reference： [1] Patent: US2126852, 1934, ,
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 22, p. 336
[3] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 171
[4] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 171

4
[ 118-12-7 ]
[ 2834-92-6 ]
[ 27333-47-7 ]

Reference： [1] Tetrahedron, 1997, vol. 53, # 28, p. 9669 - 9678

5
[ 118-12-7 ]
[ 131-91-9 ]
[ 27333-47-7 ]

Reference： [1] Synthetic Communications, 2004, vol. 34, # 2, p. 315 - 322
[2] Bulletin des Societes Chimiques Belges, 1992, vol. 101, # 8, p. 719 - 740
[3] Bulletin des Societes Chimiques Belges, 1992, vol. 101, # 8, p. 719 - 740
[4] Patent: US5446151, 1995, A,
[5] Journal of Organic Chemistry, 2016, vol. 81, # 19, p. 8744 - 8758
[6] Canadian Journal of Chemistry, 1983, vol. 61, p. 300 - 305

6
[ 118-12-7 ]
[ 131-91-9 ]
[ 66943-05-3 ]
[ 27333-47-7 ]
[ 257282-10-3 ]

Reference： [1] Russian Chemical Bulletin, 2002, vol. 51, # 1, p. 58 - 66
[2] New Journal of Chemistry, 2002, vol. 26, # 9, p. 1137 - 1145

7
[ 118-12-7 ]
[ 27333-47-7 ]

Reference： [1] Synthesis, 2005, # 11, p. 1876 - 1880

8
[ 33941-15-0 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 27333-47-7 ]
[ 471908-22-2 ]

Reference： [1] New Journal of Chemistry, 2002, vol. 26, # 9, p. 1137 - 1145

9
[ 110-89-4 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 114747-45-4 ]

Reference： [1] Synthesis, 2010, # 20, p. 3418 - 3422

10
[ 110-89-4 ]
[ 118-12-7 ]
[ 1198-27-2 ]
[ 114747-45-4 ]

Reference： [1] Synthesis, 2005, # 11, p. 1876 - 1880

11
[ 118-12-7 ]
[ 149140-04-5 ]
[ 114747-45-4 ]

Reference： [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 1994, vol. 246, p. 17 - 24
[2] Tetrahedron, 2005, vol. 61, # 34, p. 8192 - 8198

12
[ 496-15-1 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 114747-44-3 ]

Reference： [1] Synthesis, 2010, # 20, p. 3418 - 3422
[2] Patent: US5446151, 1995, A,

13
[ 496-15-1 ]
[ 118-12-7 ]
[ 1198-27-2 ]
[ 114747-44-3 ]

Reference： [1] Synthesis, 2005, # 11, p. 1876 - 1880

14
[ 118-12-7 ]
[ 159256-79-8 ]
[ 114747-44-3 ]

15
[ 110-91-8 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 114747-48-7 ]

Reference： [1] Synthesis, 2010, # 20, p. 3418 - 3422
[2] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2000, vol. 345, p. 647/323 - 652/328
[3] Synthetic Communications, 2004, vol. 34, # 2, p. 315 - 322

16
[ 110-91-8 ]
[ 118-12-7 ]
[ 1198-27-2 ]
[ 114747-48-7 ]

Reference： [1] Synthesis, 2005, # 11, p. 1876 - 1880

17
[ 118-12-7 ]
[ 114747-48-7 ]

[ 118-12-7 ] Synthesis Path-Downstream 1~88

1
[ 1805-65-8 ]
[ 74-88-4 ]
[ 118-12-7 ]

Reference： [1]Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti,1902,vol. <5> 11 II,p. 185

2
[ 2460-58-4 ]
[ 118-12-7 ]
[ 20200-74-2 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 5605,5607, 5608

3
[ 118-12-7 ]
[ 16634-88-1 ]
[ 13034-70-3 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 5605,5607, 5608

5
[ 118-12-7 ]
[ 68-12-2 ]
[ 84-83-3 ]

Reference： [1]Journal of Materials Chemistry C,2017,vol. 5,p. 5111 - 5118
[2]Journal of the American Chemical Society,2017,vol. 139,p. 17301 - 17304
[3]Chemische Berichte,1959,vol. 92,p. 1809,1810
[4]Organic and Biomolecular Chemistry,2017,vol. 15,p. 8091 - 8101

6
[ 118-12-7 ]
[ 17028-61-4 ]
[ 1498-89-1 ]

Reference： [1]Magnetic Resonance in Chemistry,1992,vol. 30,p. 1128 - 1131
[2]Inorganic Chemistry,2019,vol. 58,p. 15479 - 15486
[3]Chemical Communications,2015,vol. 51,p. 4815 - 4818
[4]European Journal of Inorganic Chemistry,2008,p. 4951 - 4960
[5]Journal of the American Chemical Society,1959,vol. 81,p. 5605,5607, 5608

7
[ 118-12-7 ]
[ 13034-76-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With [P(H)t-Bu₂][B(C₆F₅)4]; 1,3-diisopropylimidazol-2-ylidene-9-borabicyclo[3.3.1]nonane; hydrogen In chlorobenzene at 100℃; for 4h; Glovebox;	3 General procedure: [001141 Reaction 2[001151 In a glovebox IiPr2-BBN(3.9 mg, 0.016 mmol, 1 eq), [tBu3PHj[B(C6F5)4j (14.0 mg, 0.0159 mmol, 1 eq) and N-benzylidene-tert-butylamine (255.4 mg, 1.584 mmol, 100 eq.) were weighed into vials. N-benzylidene-tert-butylamine and IiPr2-BBN were transferred to the vial containing [tBu3PHj[B(C6F5)4j using 0.6 mL toluene. The vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm hydrogen and ten times at 102 atm hydrogen. The reactor was sealed under 102 atm hydrogen and placed on a stir plate for 2 hours at room temperature. The reactor was then slowly vented and the sample was concentrated in vacuo. Conversion of N-benzylidene-tert-butylamine to N-benzyl-tert-butylamine was determined by ‘H-NMR in toluene-d8.
96%	With 2C₂H₃O₂^(1-)Pd⁽²⁺⁾3Na⁽¹⁺⁾*C₁₈H₁₂O₉PS₃^(3-); hydrogen; glycerol at 100℃; for 2h; Schlenk technique;
94%	With [1,3-diisopropylimidazol-2-ylidene-9-borabicyclo[3.3.1]nonane][tetrakis (pentafluorophenyl)borate]; hydrogen In chlorobenzene at 20℃; for 4h; Inert atmosphere;

93%	With hydrogenchloride; hydrogen; nickel In methanol at 100℃; for 3h;
91%	With C₁₃H₂₀BCl₂N₂⁽¹⁺⁾*C₂₄BF₂₀^(1-); hydrogen In dichloromethane at 20℃; for 0.5h;
80%	With sodium tetrahydroborate In methanol at 0 - 20℃; for 4h;	1-3 Example 1-3: Synthesis of Intermediate 3 compound Intermediate 2 (0.11 mol) and 450 ml of methanol were added,Sodium borohydride (0.26 mol) was slowly added at 0°C. Thereafter, the reaction was terminated after stirring at room temperature for 4 hours. Water was slowly added (PH 14->11), and separation was carried out with an aqueous sodium hydrogen carbonate solution (5 wt%) and ethyl acetate. After separation, the obtained organic layer was removed using a rotary evaporator, and the concentrated organic layer was purified by column chromatography to obtain a mixture containing the intermediate 3 compound as a yellow liquid in a yield of 80%.
73%	With aluminum (III) chloride In ethanol; water; acetonitrile at 20℃; for 6h; Irradiation; Inert atmosphere;
	With 1,4-dihydronicotinamide adenine dinucleotide; catalaze; putidaredoxin reductase; putidaredoxin; P₄₅₀_cam In ethanol at 25℃; for 1.5h;
	With hydrogenchloride; tin
	With methanesulfonic acid; triphenylmethane; oxygen
9 %Chromat.	With ethanol at 160℃; for 1h; Microwave irradiation;
98 %Spectr.	With tris(pentafluorophenyl)borate; diisopropylamine at 100℃; for 24h; Neat (no solvent);

Reference： [1]Current Patent Assignee: STEPHAN CONSULTING - WO2013/177708, 2013, A1 Location in patent: Paragraph 0020; 0021
[2]Chahdoura, Faouzi; Pradel, Christian; Gomez, Montserrat [Advanced Synthesis and Catalysis, 2013, vol. 355, # 18, p. 3648 - 3660]
[3]Farrell, Jeffrey M.; Hatnean, Jillian A.; Stephan, Douglas W. [Journal of the American Chemical Society, 2012, vol. 134, # 38, p. 15728 - 15731,4]
[4]Tolmachev, A. A.; Tolmacheva, V. S. [Chemistry of Heterocyclic Compounds, 1986, vol. 22, # 11, p. 1189 - 1192][Khimiya Geterotsiklicheskikh Soedinenii, 1986, vol. 22, # 11, p. 1474 - 1477]
[5]Farrell, Jeffrey M.; Posaratnanathan, Roy T.; Stephan, Douglas W. [Chemical Science, 2015, vol. 6, # 3, p. 2010 - 2015]
[6]Current Patent Assignee: UKSEUNG CHEMICAL CO LTD - KR2021/42029, 2021, A Location in patent: Paragraph 0107; 0117-0119
[7]Qiu, Chuntian; Sun, Yangyang; Xu, Yangsen; Zhang, Bing; Zhang, Xu; Yu, Lei; Su, Chenliang [ChemSusChem, 2021, vol. 14, # 16, p. 3344 - 3350]
[8]De Voss, James J.; Sibbesen, Ole; Zhang, Zhoupeng; Ortiz De Montellano, Paul R. [Journal of the American Chemical Society, 1997, vol. 119, # 24, p. 5489 - 5498]
[9]Fischer,E.; Steche [Justus Liebigs Annalen der Chemie, 1887, vol. 242, p. 356] Fischer,E.; Meyer [Chemische Berichte, 1890, vol. 23, p. 2630]
[10]Casades; Alvaro; Garcia; Espla [Chemical Communications, 2001, # 11, p. 982 - 983]
[11]Location in patent: scheme or table Cook, A. Gilbert [Tetrahedron Letters, 2010, vol. 51, # 29, p. 3762 - 3764]
[12]Location in patent: experimental part Farrell, Jeffrey M.; Heiden, Zachariah M.; Stephan, Douglas W. [Organometallics, 2011, vol. 30, # 17, p. 4497 - 4500]

8
[ 118-12-7 ]
[ 20200-86-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With air In 1,2-dimethoxyethane at 20℃; Irradiation;
	With chromium(III) oxide; sulfuric acid
	With alkaline potassium permanganate solution

	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 3 steps 1: Fischer base 2: POCl₃ / dioxane / 4 h / 80 °C 3: aq. NaOH / Ambient temperature
	Multi-step reaction with 2 steps 1: 71 percent / triethylamine / benzene / 2 h / 40 °C / 20 degC, overnight 2: 1. POCl₃; 2. 10percent aq. NaOH / 1. dioxane, 80 degC, 4h
	Multi-step reaction with 2 steps 1: 69 percent / sodium carbonate / CHCl₃ / 1.) 50 deg C, 2.) R_.T_., overnight. 2: phosphorus oxychloride / dioxane / 7 h / 85 °C

Reference： [1]Yang, Shuai; Li, Pinhua; Wang, Zhihui; Wang, Lei [Organic Letters, 2017, vol. 19, # 13, p. 3386 - 3389]
[2]Ciamician; Piccinini [Chemische Berichte, 1896, vol. 29, p. 2469][Gazzetta Chimica Italiana, 1897, vol. 27 I, p. 341]
[3]Ciamician; Piccinini [Chemische Berichte, 1896, vol. 29, p. 2469][Gazzetta Chimica Italiana, 1897, vol. 27 I, p. 341]
[4]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[5]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[6]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[7]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[8]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[9]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[10]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[11]Kon'kov, L. I.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Doklady Chemistry, 1984, vol. 278, p. 350 - 352][Dokl. Akad. Nauk SSSR Ser. Khim., 1984, vol. 278, # 5, p. 1130 - 1133]
[12]Prizhiyalgovskaya, N. M.; Kon'kov, L. I.; Tarshits, D. L.; Salmina, S. V.; Segizova, N. T.; Suvorov, N. N. [Chemistry of Heterocyclic Compounds, 1987, vol. 23, # 7, p. 751 - 754][Khimiya Geterotsiklicheskikh Soedinenii, 1987, # 7, p. 915 - 918]
[13]Tarshits, D. L.; Przhiyalgovskaya, N. M.; Suvorov, N. N. [Chemistry of Heterocyclic Compounds, 1988, vol. 24, # 11, p. 1217 - 1221][Khimiya Geterotsiklicheskikh Soedinenii, 1988, vol. 24, # 11, p. 1472 - 1475]

9
[ 672-13-9 ]
[ 118-12-7 ]
[ 20200-73-1 ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 8744 - 8758
[2]Journal of Pharmaceutical Sciences,1987,vol. 76,p. 892 - 897
[3]Heterocycles,2014,vol. 89,p. 1017 - 1024
[4]Tetrahedron Letters,1968,p. 5097 - 5099

10
[ 672-13-9 ]
[ 118-12-7 ]
6-methoxy-1',3',3'-trimethyl-4-(1,3,3-trimethyl-2,3-dihydro-indol-2-ylidenemethyl)-1',3'-dihydro-spiro[chroman-2,2'-indole] [ No CAS ]
[ 20200-73-1 ]

Reference： [1]Tetrahedron Letters,1968,p. 5097 - 5099

11
[ 118-12-7 ]
[ 3328-71-0 ]
[ 17965-24-1 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol

Reference： [1]Schiele,C. et al. [Tetrahedron Letters, 1967, p. 4983 - 4984]

12
[ 118-12-7 ]
[ 74901-29-4 ]
[ 19253-37-3 ]

Reference： [1]Journal of the American Chemical Society,2000,vol. 122,p. 6594 - 6600
[2]Tetrahedron Letters,1968,p. 5097 - 5099

13
[ 118-12-7 ]
[ 74901-29-4 ]
1',3',3'-trimethyl-4-(1,3,3-trimethyl-1,3-dihydro-indol-2-ylidenemethyl)-1',3'-dihydro-spiro[chroman-2,2'-indole]-6-carbonitrile [ No CAS ]
[ 19253-37-3 ]

Reference： [1]Tetrahedron Letters,1968,p. 5097 - 5099

14
[ 118-12-7 ]
[ 90-02-8 ]
[ 1485-92-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	In ethanol for 5h; Reflux;
93%	In neat (no solvent) for 0.166667h; Microwave irradiation; Green chemistry;
90%	In isopropyl alcohol Inert atmosphere; Reflux;	3.10 General Method B General procedure: Add Salicylaldehyde to a solution of 1,3,3-trimethyl-2-methyleneindolin 5 (1 equivalent) in isopropanol (15 V relative to indole) , naphthaldehyde or nitros naphthol (1 equivalent). Then under nitrogen protection, Stir under reflux overnight, cool to room temperature and spin dry. The residue was purified by column (eluent petroleum ether / ethyl acetate) to give the desired product.

60%	In isopropyl alcohol for 4h; Heating;
47%	In ethanol Heating;
	In chloroform for 2.33333h; Reflux;

Reference： [1]Balmond, Edward I.; Tautges, Brandon K.; Faulkner, Andrea L.; Or, Victor W.; Hodur, Blanka M.; Shaw, Jared T.; Louie, Angelique Y. [Journal of Organic Chemistry, 2016, vol. 81, # 19, p. 8744 - 8758]
[2]Rohadi, Atisya; Hasbullah, Siti Aishah; Lazim, Azwan Mat; Nordin, Rumaisa [Heterocycles, 2014, vol. 89, # 4, p. 1017 - 1024]
[3]Current Patent Assignee: SUZHOU CHIEN SHIUNG INST TECH - CN109180693, 2019, A Location in patent: Paragraph 0074; 0077; 0078; 0079
[4]Connors; Jozwiakowski [Journal of Pharmaceutical Sciences, 1987, vol. 76, # 12, p. 892 - 897]
[5]Keum, Sam-Rok; Lee, Ki-Bong; Kazmaier, Peter M.; Manderville, Richard A.; Buncel, Erwin [Magnetic Resonance in Chemistry, 1992, vol. 30, # 11, p. 1128 - 1131]
[6]Balny,C. et al. [Tetrahedron Letters, 1968, p. 5097 - 5099] Yuzawa, Tetsuro; Ebihara, Ken; Hiura, Hidefumi; Ohzeki, Tomoyuki; Takahashi, Hiroaki [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 1994, vol. 50, # 8/9, p. 1487 - 1498]
[7]Nourmohammadian, Farahnaz; Abdi, Ali Ashtiani [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2016, vol. 153, p. 53 - 62]

15
[ 16789-84-7 ]
[ 118-12-7 ]
[ 10558-52-8 ]

Reference： [1]Magnetic Resonance in Chemistry,1992,vol. 30,p. 1128 - 1131

16
[ 118-12-7 ]
[ 7310-95-4 ]
[ 133592-38-8 ]

Yield	Reaction Conditions	Operation in experiment
67%	In ethanol for 12h; Reflux;
61%	In ethanol at 70℃; for 14h; Reflux;
56%	In ethanol for 2h; Heating;

	In ethanol for 12h; Reflux;
	Stage #1: 1,3,3-Trimethyl-2-methyleneindoline Stage #2: 2-Hydroxy-5-methylisophthalaldehyde With triethylamine In isopropyl alcohol for 0.25h; Reflux;	8-Formyl-1,3,3,6'-tetramethylspiro[indoline-2,2'-2H-chromene](1). Triethylamine (0.28 mL, one molar equivalent) wasadded dropwise under heating to a mixture of 1,2,3,3-tetramethyl-3H-indolium perchlorate (3) (0.547 g, 0.002 mol) and 2-hydroxy-3-formyl-5-methylbenzaldehyde (4a) (0.328 g, 0.002 mol)in propan-2-ol (15 mL). The reaction mixture was refl uxed for15 min, cooled, poured into water (60 mL), and extracted withbenzene. The organic layer was separated, washed with water,dried with anhydrous sodium sulfate, concentrated using a waterjet vacuum pump to 15 mL, and chromatographed on a silica gelcolumn (chloroform as the eluent). The solvent was distilled off ,and the residue was crystalized from ethanol. The yield was 0.357 g(56%), m.p. 107 C (cf. lit. data44: 105-106 C). IR, ν/cm-1:1667 (C=O); 1646, 1598 (C=C); 927 (Cspiro-O). 1H NMR,δ: 10.10 (s, 1 H, CHO); 7.43 (d, 1 H, C(7)H, J = 1.7 Hz); 7.15(td, 1 H, C(6)H, J = 7.7 Hz, J = 1.0 Hz); 7.08 (d, 1 H, C(5)H,J = 2.1 Hz); 7.04 (d, 1 H, C(4)H, J = 7.0 Hz); 6.88-6.79 (m, 2 H,C(5)H, C(4)H); 6.51 (d, 1 H, C(7)H, J = 7.7 Hz); 5.77 (d, 1 H,C(3)H, J = 10.3 Hz); 2.73 (s, 3 H, N-CH3); 2.25 (s, 3 H,C(6)-CH3); 1.31 (s, 3 H, C(3)-CH3); 1.18 (s, 3 H, C(3)-CH3). 13C NMR, δ: 189.00 (s, CHO); 155.53 (s, C(9)); 147.76(s, C(8)); 136.32 (s, C(9)); 133.45 (s, C(5)); 129.27 (s, C(10));128.78 (s, C(4)); 127.64 (s, C(6)); 127.36 (s, C(7)); 122.23(s, C(8)); 121.39 (s, C(4)); 120.34 (s, C(3)); 119.95 (s, C(6));119.51 (s, C(5)); 106.91 (s, C(7)); 105.42 (s, C(22)); 51.98 (s, C(3)); 28.93 (s, NCH3); 25.71 (s, C(3)-CH3); 20.40(s, C(3)-CH3); 20.24 (s, C(6)-CH3). 15N NMR, δ: 92.40.Found (%): C, 79.08; H, 6.59; N, 4.41. C21H21NO2. Calculated(%): C, 79.03; H, 6.63; N, 4.39.

Reference： [1]Goswami, Shymaprosad; Aich, Krishnendu; Das, Sangita; Das, Avijit Kumar; Sarkar, Deblina; Panja, Sukanya; Mondal, Tapan Kumar; Mukhopadhyay, Subhrakanti [Chemical Communications, 2013, vol. 49, # 91, p. 10739 - 10741]
[2]Goswami, Shyamaprosad; Das, Avijit Kumar; Maity, Anup Kumar; Manna, Abhishek; Aich, Krishnendu; Maity, Sibaprasad; Saha, Partha; Mandal, Tarun Kanti [Dalton Transactions, 2014, vol. 43, # 1, p. 231 - 239]
[3]Luk'yanov, B. S.; Nivorozhkin, L. I.; Minkin, V. I.; Metelitsa, A. V. [Chemistry of Heterocyclic Compounds, 1990, vol. 26, # 12, p. 1416 - 1446][Khimiya Geterotsiklicheskikh Soedinenii, 1990, # 12, p. 1700 - 1701]
[4]Goswami, Shyamaprosad; Das, Sangita; Aich, Krishnendu [RSC Advances, 2015, vol. 5, # 37, p. 28996 - 29001]
[5]Aldoshin, S. M.; Lukyanov, B. S.; Lukyanova, M. B.; Metelitsa, A. V.; Minkin, V. I.; Mukhanov, E. L.; Ozhogin, I. V.; Pugachev, A. D.; Stankevich, N. V.; Tkachev, V. V. [Russian Chemical Bulletin, 2021, vol. 70, # 11, p. 2090 - 2099][Izv. Akad. Nauk, Ser. Khim., 2021, # 11, p. 2090 - 2099]

17
[ 118-12-7 ]
[ 55969-94-3 ]
[ 85000-11-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide In ethanol for 10h; Reflux;
75%	With piperidine In ethanol for 5h; Reflux;
35%	In ethanol

15%

In ethanol for 3h; Heating;

Reference： [1]Shiraishi, Yasuhiro; Tanaka, Kazuya; Shirakawa, Eri; Sugano, Yoshitsune; Ichikawa, Satoshi; Tanaka, Shunsuke; Hirai, Takayuki [Angewandte Chemie - International Edition, 2013, vol. 52, # 32, p. 8304 - 8308][Angew. Chem., 2013, vol. 125, # 32, p. 8462 - 8466,5]
[2]Liu, Zhenzhen; Liu, Tao; Lin, Qiuning; Bao, Chunyan; Zhu, Linyong [Angewandte Chemie - International Edition, 2015, vol. 54, # 1, p. 174 - 178][Angew. Chem., 2015, vol. 127, # 1, p. 176 - 180,5][Angewandte Chemie, 2015, vol. 127, # 1, p. 176 - 180,5]
[3]Arakawa, Sei'ichi; Kondo, Hirofumi; Seto, Jun'etsu [Chemistry Letters, 1985, p. 1805 - 1808]
[4]Lyubimov, A. V.; Marevtsev, V. S.; Ermakova, V. D.; Cherkashin, M. I. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1985, vol. 34, # 7, p. 1380 - 1383][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1985, # 7, p. 1509 - 1512]

18
[ 118-12-7 ]
[ 149140-04-5 ]
[ 114747-45-4 ]

Reference： [1]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,1994,vol. 246,p. 17 - 24
[2]Tetrahedron,2005,vol. 61,p. 8192 - 8198

19
[ 118-12-7 ]
1-nitroso-4-morpholinyl-2-naphthol [ No CAS ]
[ 114747-48-7 ]

20
[ 118-12-7 ]
[ 159256-79-8 ]
[ 114747-44-3 ]

21
[ 118-12-7 ]
[ 131-91-9 ]
[ 27333-47-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	In ethanol;	COMPARATIVE EXAMPLE 4 1,3-Dihydro-1,3,3-trimethylspiro[2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine] A mixture 1,3-dihydro-1,3,3-trimethyl-2-methyleneindoline (3.62 g; 0.021 mol) and 1-nitroso-2-naphthol (3.46 g; 0.02 mol) in ethanol (80.0 ml) was heated under reflux for 2 h. The solution was evaporated and the residue flash-chromatographed over silica (dichloromethane) to give 1,3-Dihydro-1,3,3-trimethylspiro[2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine] as a pale yellow solid (3-96 g; 60%). m.p. 127-30 C. STR16

Reference： [1]Synthetic Communications,2004,vol. 34,p. 315 - 322
[2]Bulletin des Societes Chimiques Belges,1992,vol. 101,p. 719 - 740
[3]Bulletin des Societes Chimiques Belges,1992,vol. 101,p. 719 - 740
[4]Patent: US5446151,1995,A
[5]Journal of Organic Chemistry,2016,vol. 81,p. 8744 - 8758
[6]Canadian Journal of Chemistry,1983,vol. 61,p. 300 - 305

22
[ 118-12-7 ]
[ 6872-17-9 ]
[ 75560-72-4 ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 843 - 852

23
[ 118-12-7 ]
[ 36429-14-8 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium nitrate; sulfuric acid below 0 deg C;
35%	With nitric acid In sulfuric acid	1.10 Synthesis of 5-Nitro-1,3,3-Trimethyl-2-Methyleneindoline Example 1.10 Synthesis of 5-Nitro-1,3,3-Trimethyl-2-Methyleneindoline This compound was prepared by the general synthesis method 1d) from a solution of 20 g of 1,3,3-trimethyl-2-methyleneindoline in 50 mL of 97% sulfuric acid and 23.5 mL of nitrating acid (a mixture of 3.5 mL of fuming 99% nitric acid and 20 mL of 97% sulfuric acid). The crude product was crystallized from hexane/methylene chloride. Yield: 8.8 g of 5-nitro-1,3,3-trimethyl-2-methyleneindoline (35% of the theoretical). Melting point: 89-91° C. 1H-NMR (CDCl3): δ=1.35 ppm (s, 6H); 3.11 ppm (s,3H); 4.09 ppm (d, 2J=3 Hz, 1H); 4.11 ppm (d, 2J=2.5 Hz, 1H); 6.51 ppm (d, 3J=9 Hz, 1H); 7.91 ppm (d, 4J=2.5 Hz, 1H); 8.11 ppm (dd, 2J=9 Hz, 4J=2.5 Hz, 1H); El mass spectrum: 218 (85, M+); 203 (100); 188 (6); 171 (16); 157 (91); 145 (32); 1.45 (32); 1.28 (24); 115 (44); 103 (10); 89 (15); 77 (14); 63 (12).
	With sulfuric acid; nitric acid for 3h;	S1 S1: Synthesis of 5-nitro-3,3-dimethyl-1'-methyl-2-methyleneindole Specific structural formulas are as follows, 8.00 g of 3,Dimethyl-1'-methyl-2-methyleneindole was slowly added dropwise to a 250 ml three-necked round bottom flask containing 20 ml of concentrated sulfuric acid,Dropping process continuously stirring,After the completion of this operation to the flask dropping fuming nitric acid and concentrated sulfuric acid mixed solution, after the completion of the reaction to continue after 3h,Seal overnight.The reaction solution was poured into a 1000 ml large beaker containing ice cubes,To the beaker slowly dropping saturated NaOH solution while stirring constantly,Until a large number of red fluffy solid appears, and then vacuum filtration,Washed thoroughly with a large amount of distilled water, dried,Recrystallization gave bright yellow crystals, mp 84.2-85.1 ° C.

Reference： [1]Pottier, E.; Sergent, M.; Luu, R. Phan Tan; Guglielmetti, R. [Bulletin des Societes Chimiques Belges, 1992, vol. 101, # 8, p. 719 - 740]
[2]Current Patent Assignee: Coty (in: JAB Holding); AGNATEN SE; KKR & CO LP - US2003/79301, 2003, A1
[3]Current Patent Assignee: EASTERN BRANCH INNER MONGOLIA SCIENCE AND TECH INS - CN105541855, 2016, A Location in patent: Paragraph 0032; 0033; 0034; 0035; 0036

24
[ 5418-63-3 ]
[ 118-12-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide In water at 20℃; for 4h;	1-2 Example 1-2: Synthesis of Intermediate 2 compound An aqueous sodium hydroxide solution (10 wt%) was added to Intermediate 1 (0.09 mol), followed by stirring at room temperature for 4 hours.After the reaction was completed, the organic layer obtained after separation of the reaction mixture and dichloromethane was dried over magnesium sulfate, and the solvent was removed using a rotary evaporator to obtain a mixture containing the intermediate 2 compound as a red liquid in a yield of 90%. .
71%	With sodium hydroxide In diethyl ether; water for 0.5h;
55%	With potassium hydroxide at 20℃; for 1h;

	With potassium hydroxide Ambient temperature;
	With sodium hydroxide
	With potassium hydroxide In water; toluene
	With sodium hydroxide at 20℃;
	With sodium hydroxide In diethyl ether
	Multi-step reaction with 2 steps 1: durch Destillation im Kohlensaeurestrom oder im Vakuum 2: 100 °C
	With potassium hydroxide	2 EXAMPLE 2 EXAMPLE 2 In an aqueous solution of potassium hydroxide (0.7 mol/l, 107 mmol) was suspended 1,2,3,3-tetramethylindolenium iodide (1.5133 g, 5.03 mmol) and the suspension was stirred at room temperature for 1 hour, whereby a yellow oil was produced in the reaction system. This oil was extracted with diethyl ether and the extract was washed with saturated aqueous sodium chloride solution until a neutral aqueous wash was obtained. Then, the extract was dried by addition of anhydrous sodium sulfate and the ether was distilled off to give 1,3,3-trimethyl-2-methyleneindoline as a red liquid. Yield 807.2 mg, 93% 1 H-NMR (CDCl3): 6ppm 1.3 (s, 6H, 3-CH3), 3.1 (s, 3H, N-CH3), 4.0 (s, 2H, =CH2), 6.5-7.2 (m, 4H, aromatic H)
	With sodium hydroxide In water; acetone	1 Preparation of compound 3: After the crude solid of compound 2 is washed with acetone, a portion of the solid is dissolved in NaOH aqueous solution (1 M). The resultant 1,3,3-trimethyl-2-methyleneindoline is extracted with chloroform. The organic layer is dried with anhydrous Na2SO4 and the solvent was evaporated.
	With sodium carbonate In water at 20℃;	General procedure: To a stirred solution of the corresponding iodide (5a-c, 5 mmol) in distilled water (15 mL), sodium carbonate (1.06 g, 10 mmol) was added at rt. The mixture became turbid and was extracted with diethyl ether (3*20 mL). The combined organic phase was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to afford the corresponding 2-methylidene-2,3-dihydro-1H-indole (6a, 6b, and 6c, respectively) as an oil.
	With sodium hydroxide In water	1 Preparation of Compound 3: Preparation of Compound 3: [0111] After the crude solid of compound 2 is washed with acetone, a portion of the solid is dissolved in NaOH aqueous solution (1 M). The resultant 1,3,3-trimethyl-2-methyleneindoline is extracted with chloroform. The organic layer is dried with anhydrous Na2SO4 and the solvent was evaporated.
	With sodium carbonate In water at 20℃; for 0.0166667h;
	With sodium hydroxide In diethyl ether for 0.5h;	1 Manufacturing example 1 4 g (13.28 mol) of the compound 1c was dissolved in 320 ml of diethyl ether: 2M NaOH = 1: 3 and stirred for 30 minutes. The organic layer was passed through MgSO4,solvent was removed under reduced pressure. 3 g (17.32 mmol, 1 eq) of the compound 1d,was dissolved in 30 ml of MC and the solution dissolved in 35 ml of MC ((Chloroethylene) dimethyliminium chloride) 2.5 g (1.953 mol, 1.13 eq) was slowly added. After stirring for 15 minutes, 75 ml of 10% aqueous NaOH solution in an ice bath was slowly added. The mixture was stirred for 1 hour and 30 minutes, and the organic layer was separated, washed with brine and dried over MgSO4. The solvent was removed under reduced pressure and used in the next reaction without further separation.
	With triethylamine In ethanol at 70℃; for 1h;	3 7-hydroxy-2-mercaptonaphthalene (Compound 4c, 1.76 g, 10 mmol) was completely dissolved in 21 mL of a 1.2 mol / L aqueous solution of sodium hydroxide,The system was cooled to -5 ° C using an ice bath,And keep low temperature conditions.NaNO2 (828 mg, 12 mmol) was added to the system to complete dissolution.Subsequently, 6 g of dilute sulfuric acid at a concentration of 45% was slowly added under constant stirring,Add after the low temperature stirring 1 hour, after filtration,Wash the filter cake into a neutral vacuum and then dry,The intermediate product (6c) was obtained.The newly prepared N-methyl iodide (compound 5c, 3.01 g, 10 mmol) was then added to a flask containing 40 mL of absolute ethanol,After adding triethylamine (3 mL), the mixture was heated at 70 ° C for 1 hour to give the intermediate product (5c ').While the reaction was carried out in the intermediate (5c), the intermediate product (6c) (compound 6c, 2.46 g, 12 mmol) was added to another flask containing 60 mL of absolute ethanol and heated at 70 ° C.After 1 hour, the solution in the flask containing the intermediate (6c) was added dropwise to another flask containing the intermediate (5c '), heating was continued, and the reaction was monitored by thin layer chromatography (TLC) until the reaction was completed.
	With sodium hydroxide at 20℃; for 0.166667h;	1.b b) Synthesis of 1,3,3-trimethyl-2-methyleneindolinine (7): 1,2,3,3-tetramethyl-3H-indol-1-ium iodide (2 g, 6.63 mmol) was dissolved in a stirred 40% of 10 NaOH (60 mL) and 11 diethyl ether (150 mL) was added into the reaction mixture vigorous and stirred at 25-30° C. for 15-30 mis. After this period of time diethyl ether was separated and dried with anhydrous sodium sulphate. It was filtrated and evaporated under reduced pressure. The yield of 12 compound was yellow oil in nature. It was characterized by 1H-NMR by using CDCl3 solvent it was given below (δ,ppm., J(Hz)): J=1.27 (6H, s, (CH3)2); J=4.31(3H, s, (CH3); J=2.96 (3H, s, N-CH3); J=6.44 (1H d, CH); J=6.68 (1H, t, CH); J=6.72-7.18 (2H, m, CH).
	With piperidine In butanone for 0.0833333h; Reflux; Inert atmosphere;

Reference： [1]Current Patent Assignee: UKSEUNG CHEMICAL CO LTD - KR2021/42029, 2021, A Location in patent: Paragraph 0107; 0113-0115
[2]Natali, Manuel; Giordani, Silvia [Organic and Biomolecular Chemistry, 2012, vol. 10, # 6, p. 1162 - 1171]
[3]Hirano, Masafumi; Osakada, Kohtaro; Nohira, Hiroyuki; Miyashita, Akira [Journal of Organic Chemistry, 2002, vol. 67, # 2, p. 533 - 540]
[4]Hirano, Masafumi; Miyashita, Akira; Nohira, Hiroyuki [Chemistry Letters, 1991, # 2, p. 209 - 212]
[5]Arakawa, Sei'ichi; Kondo, Hirofumi; Seto, Jun'etsu [Chemistry Letters, 1985, p. 1805 - 1808] Traven; Miroshnikov; Chibisova; Barachevsky; Venidiktova; Strokach [Russian Chemical Bulletin, 2005, vol. 54, # 10, p. 2417 - 2424]
[6]Henning, Hans-Georg; Thanh, Le Hoang; Laue, Joerg; Urban, Barbara; Reck, Guenter [Monatshefte fur Chemie, 1994, vol. 125, # 1, p. 95 - 106]
[7]Tan, Ting-Feng; Chen, Pei-Li; Huang, Hua-Ming; Meng, Ji-Ben [Tetrahedron, 2005, vol. 61, # 34, p. 8192 - 8198]
[8]Roxburgh, Craig J.; Sammes, Peter G. [European Journal of Organic Chemistry, 2006, # 4, p. 1050 - 1056]
[9]Ciamician; Boeris [Gazzetta Chimica Italiana, 1894, vol. 24 II, p. 301][Gazzetta Chimica Italiana, 1897, vol. 27 I, p. 78]
[10]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - US5288592, 1994, A
[11]Current Patent Assignee: KOREA UNIVERSITY - US2011/198546, 2011, A1 Location in patent: Page/Page column 12
[12]Dagiliene, Migle; Martynaitis, Vytas; Vengris, Mikas; Redeckas, Kipras; Voiciuk, Vladislava; Holzer, Wolfgang; Šačkus, Algirdas [Tetrahedron, 2013, vol. 69, # 44, p. 9309 - 9315]
[13]Current Patent Assignee: KOREA UNIVERSITY - US2014/191168, 2014, A1 Location in patent: Paragraph 0110-0111
[14]Dagiliene, Migle; Martynaitis, Vytas; Kriščiu¯niene, Vilija; Krikštolaityte, Sonata; Šačkus, Algirdas [ChemistryOpen, 2015, vol. 4, # 3, p. 363 - 369]
[15]Current Patent Assignee: LG CHEM CO.,LTD. - KR2016/22280, 2016, A Location in patent: Paragraph 0166; 0174-0176
[16]Current Patent Assignee: Institute of Chemistry (in: CAS); CHINESE ACADEMY OF SCIENCES - CN104130269, 2017, B Location in patent: Paragraph 0082; 0083; 0086
[17]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - US2018/163053, 2018, A1 Location in patent: Paragraph 0061; 0063
[18]Ajiro, Hiroharu; Ando, Tsuyoshi; Murase, Nobuo [Journal of Materials Chemistry B, 2020, vol. 8, # 7, p. 1489 - 1495]

25
[ 672-13-9 ]
[ 118-12-7 ]
[ 17487-82-0 ]
[ 20200-73-1 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 105 - 110

26
[ 118-12-7 ]
[ 97-51-8 ]
[ 1498-88-0 ]
C₃₁H₃₃N₃O₃ [ No CAS ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 105 - 110

27
[ 118-12-7 ]
[ 3328-70-9 ]
[ 20200-69-5 ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 3915 - 3917
[2]Russian Journal of Bioorganic Chemistry,2008,vol. 34,p. 252 - 260
[3]Russian Chemical Bulletin,2014,vol. 63,p. 2026 - 2035
Izv. Akad. Nauk, Ser. Khim.,2014,p. 2026 - 2035,10
[4]Tetrahedron,1996,vol. 52,p. 8755 - 8762
[5]Chemical Communications,2002,p. 1398 - 1399

28
[ 118-12-7 ]
[ 2834-92-6 ]
[ 27333-47-7 ]

Reference： [1]Tetrahedron,1997,vol. 53,p. 9669 - 9678

29
[ 118-12-7 ]
[ 16644-30-7 ]
[ 38147-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; for 4h;Heating / reflux;	A THF solution (10 ml) of <strong>[16644-30-7]3-chloromethyl-5-nitrosalicylaldehyde</strong> (50 mg, 0.23 mmol) and 1,3,3-trimethyl-2-methyleneindoline (40 mg, 0.23 mmol) was refluxed for 4 hours. Evaporation of the solvent gave 2 as a crude product, which was used for the subsequent reaction without further purification. MS(EI): 370(M+, 45), 336(72), 159(73); HRMS(EI): M+370.1096 (Calc. 370.1084); 1H NMR (CDCl3) delta1.22 (s, 3H), 1.32 (s, 3H), 2.71, (s, 3H), 4.32 (d, J=11.7 Hz, 1H), 4.38 (d, J=11.7 Hz, 1H), 5.92 (d, J=10.3 Hz, 1H), 6.55 (d, J=7.3 Hz, 1H), 6.89 (dd, J=7.3, 7.3 Hz, 1H), 6.95 (d, J=10.3 Hz, 1H), 7.09(d, J=7.3 Hz, 1H), 7.19(dd, J=7.3, 7.3 Hz, 1H), 8.00 (d, J=2.8, 1H), 8.14 (d, J=2.8 Hz, 1H).

Reference： [1]New Journal of Chemistry,2002,vol. 26,p. 554 - 559
[2]Dyes and Pigments,2010,vol. 86,p. 74 - 80
[3]Journal of Organic Chemistry,2005,vol. 70,p. 2009 - 2013
[4]Journal of Organic Chemistry,2001,vol. 66,p. 1533 - 1537
[5]Patent: US2007/195309,2007,A1 .Location in patent: Page/Page column 45; 47

30
[ 118-12-7 ]
3-(hydroxymethyl)-1-nitroso-2-naphthol [ No CAS ]
[ 126633-36-1 ]

Yield	Reaction Conditions	Operation in experiment
63%	In ethanol at 75℃; for 4h; Reflux;	5’-Hydroxymethyl-1,3,3-trimethylspiro[indoline-2-3’-naphtho[2,1-b][1,4]oxazine] (1c) To a solution of 3-(hydroxymethyl)-1-nitroso-2-naphthol (4.00 g, 19.7 mmol) in ketone-free EtOH (200 mL) was added freshly distilled 1,3,3-trimethyl-2-methyleneindoline (3.76 g,21.7 mmol, 3.8 mL) at 75 °C, and the reaction mixture was stirred under reflux for 4 h. Aftercooling to rt, the solvent was removed under reduced pressure. The product 1c was isolatedby flash column chromatography (SiO2; eluent: n-hexane/EtOAc 8/2, Rf = 0.37), crystallizedfrom EtOH, and obtained as green, crystalline solid (4.43 g, 12.4 mmol, 63%)
55%	In ethanol for 5h; Heating;
	In ethanol	2 EXAMPLE 2 EXAMPLE 2 In 100 ml of ethanol, 7.0 g (40 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 8.0 g (40 mmol) of 3-hydroxymethyl-1-nitroso-2-naphthol were dissolved and the solution was heated to reflux for 3 hours. After removal of the solvent, purification was conducted by column chromatography and recrystallization from hexane to obtain 3.0 g of 1,3,3-trimethyl-5'-hydroxymethylspiro [indoline-2,3'-[3H]-naphtho[2,1-b](1,4)oxazine] as a white solid.

Reference： [1]Ihmels, Heiko; Pithan, Phil M.; Steup, Sören [Beilstein Journal of Organic Chemistry, 2020, vol. 16, p. 904 - 916]
[2]Samat, André; Lokshin, Vladimir; Chamontin, Karine; Levi, David; Pepe, Gérard; Guglielmetti, Robert [Tetrahedron, 2001, vol. 57, # 34, p. 7349 - 7359]
[3]Current Patent Assignee: TORAY INDUSTRIES INC - US5166345, 1992, A

31
[ 118-12-7 ]
[ 131-91-9 ]
[ 66943-05-3 ]
[ 27333-47-7 ]
[ 257282-10-3 ]

Reference： [1]Russian Chemical Bulletin,2002,vol. 51,p. 58 - 66
[2]New Journal of Chemistry,2002,vol. 26,p. 1137 - 1145

32
[ 33941-15-0 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 27333-47-7 ]
[ 471908-22-2 ]

Reference： [1]New Journal of Chemistry,2002,vol. 26,p. 1137 - 1145

33
[ 110-91-8 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 114747-48-7 ]

Reference： [1]Synthesis,2010,p. 3418 - 3422
[2]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,2000,vol. 345,p. 647/323 - 652/328
[3]Synthetic Communications,2004,vol. 34,p. 315 - 322

34
[ 118-12-7 ]
[ 584-87-2 ]
(8RS,10RS,21E)-4-(2-methylene-1,3,3-trimetylindoline-2'-yl)-6-carboxylic-1',2',3'-trimethyl-spiro[3,4-dihydro-2H-1-benzopyran-2,2'-indoline] [ No CAS ]
[ 23022-08-4 ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 6720 - 6725
[2]Magnetic Resonance in Chemistry,2006,vol. 44,p. 90 - 94

35
[ 110-89-4 ]
[ 118-12-7 ]
[ 1198-27-2 ]
[ 114747-45-4 ]

Reference： [1]Synthesis,2005,p. 1876 - 1880

36
[ 110-91-8 ]
[ 118-12-7 ]
[ 1198-27-2 ]
[ 114747-48-7 ]

Reference： [1]Synthesis,2005,p. 1876 - 1880

37
[ 496-15-1 ]
[ 118-12-7 ]
[ 1198-27-2 ]
[ 114747-44-3 ]

Reference： [1]Synthesis,2005,p. 1876 - 1880

38
[ 118-12-7 ]
[ 121314-69-0 ]
C₄₆H₄₀N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	In ethanol for 3h; Heating;

Reference： [1]Zhou, Yucheng; Zhang, Deqing; Zhang, Yazhou; Tang, Yalin; Zhu, Daoben [Journal of Organic Chemistry, 2005, vol. 70, # 16, p. 6164 - 6170]

39
[ 118-12-7 ]
[ 125366-78-1 ]
C₃₈H₃₆N₂O₂ [ No CAS ]

Reference： [1]Magnetic Resonance in Chemistry,2005,vol. 43,p. 873 - 876

40
[ 118-12-7 ]
[ 97-51-8 ]
C₃₁H₃₃N₃O₃ [ No CAS ]
[ 1498-88-0 ]

Reference： [1]Magnetic Resonance in Chemistry,2006,vol. 44,p. 90 - 94

41
[ 110-86-1 ]
[ 118-12-7 ]
[ 16644-30-7 ]
[ 16150-39-3 ]

Reference： [1]Russian Chemical Bulletin,2006,vol. 55,p. 1605 - 1611

42
[ 118-12-7 ]
[ 27333-47-7 ]

Reference： [1]Synthesis,2005,p. 1876 - 1880

43
[ 118-12-7 ]
[ 20200-73-1 ]

Reference： [1]Synthesis,1997,p. 1137 - 1139

44
[ 1122-58-3 ]
[ 118-12-7 ]
[ 63857-00-1 ]
2-[2-[2-(4-dimethylaminopyridinium)-3-[2-(1,3-dihydro-1,3,3-trimethyl-2H-indole-2-ylidene)-ethylidene]-1-cyclohexene-1-yl]-ethenyl]-1,3,3-trimethyl-3H-indolium dichloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%		3.6 g 4-dimethylaminopyridine and 11. 8 g dye A (both available from Aldrich) were added under stirring to 60 ml Downanol PM in a 0. 5 1 three-necked flask equipped with a stirrer and a reflux condenser. Then 11.8 g 2-methylene-1, 3,3-trimethylindoline (Fischer base, available from Aldrich) was added under stirring for one minute to this suspension. The reaction mixture was heated to 80C for 2 hours. Then the reaction mixture was left to cool to room temperature and 200 ml of a 1 wt. -% hydrochloric acid were added. After the reaction mixture had cooled to room temperature, the insoluble portion was separated by filtration and washed with 0.5 1 of water. Then the product was dried for one day at 50C in a circulating air oven. Yield: 15.6 g (81.0 % based on dye A). The dried product was suspended in 150 ml methyl ethyl ketone and heated to 80C for one hour. Subsequently, the solution with a temperature of about 40C was filtered and the solid portion was washed with ethyl acetate. The product was air-dried. The yield after clean-up WAS 78 WT. -%; UV/VIS SPECTRUM IN METHANOL : 786 NM, EXTINCTION COEFFICIENT E = 381 1/G X CM.

Reference： [1]Patent: WO2004/52995,2004,A1 .Location in patent: Page 23

45
[ 118-12-7 ]
[ 63857-00-1 ]
[ 108-98-5 ]
2-[2-[2-thiophenyl-3-[2-(1,3-dihydro-1,3,3-trimethyl-2H-indole-2-ylidene)-ethylidene]-1-cyclohexene-1-yl]-ethenyl]-1,3,3-trimethyl-3H-indolinium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%		110 g thiophenol and 360 g dye A (both available from Aldrich) were added under stirring to 2,000 ml 1-methoxy-2-propanol (Downanol PM) in a 101 three-necked flask equipped with a stirrer and a reflux condenser. Then a solution of 40 g sodium hydroxide and 365 g 2- methylene-1, 3, 3-trimethylindoline (Fischer base, available from Aldrich) in 350 ml ethanol was added under stirring for one minute to this suspension. The reaction mixture warmed up to about 40C without the addition of external heat. Then the reaction mixture was left to cool to room temperature and 6 1 of a 2 wt. -% hydrochloric acid were added. After the reaction mixture had cooled to room temperature, the insoluble portion was separated by filtration and washed with 21 of water. Then the product was dried for one day at 50C in a circulating air oven. Yield: 556 g (94 % based on dye A), IR dye content: 90 wt. -% (determined by measuring the optical density at 788 nm in methanol using an extinction coefficient E of 435 1/G x cm for the pure IR dye), moisture content: 3.2 wt. -%. The dried product was suspended in 5 1 methyl ethyl ketone and heated to 80C for one hour. Subsequently, the solution with a temperature of about 40C was filtered and the solid portion was washed with ethyl acetate. The product was air-dried. Yield: 462 g (78 wt.-% BASED ON DYE A), IR DYE CONTENT: 97. 8 WT. -% (DETERMINED BY MEASURING THE OPTICAL DENSITY AT 788 nm in methanol using an extinction coefficient £ of 435 1/G x cm for the pure IR dye), moisture content: 1.1 wt. -%, melting point: 222-223C (decomposition). For determining whether an aniline-substituted dye D had been formed, a thin-layer chromatography was carried out with the following parameters: TLC plates: Silica gel 60 F254 (available from Merck) Eluent: Solvent mixture of 60 vol. -% n-butanol, 20 vol. -% water, 10 vol. -% ethanol and 0.5 vol. -% acetic acid 3 samples (non-purified dye, purified dye and dye D (available from Hayashibara, Japan)) were dissolved in methanol and applied to the plate. After elution with the solvent mixture, the spot corresponding to dye D was not observed in the non-purified or in the purified dye samples.

Reference： [1]Patent: WO2004/52995,2004,A1 .Location in patent: Page 17-18

46
[ 118-12-7 ]
[ 873-55-2 ]
[ 63857-00-1 ]
2-[2-[2-phenylsulfonyl-3-[2-(1,3-dihydro-1,3,3-trimethyl-2H-indole-2-ylidene)-ethylidene]-1-cyclohexene-1-yl]-ethenyl]-1,3,3-trimethyl-3H-indolium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82.5%		16.4 g sodium salt of benzenesulfinic acid and 36.0 g dye A (both available from Aldrich) were added under stirring to 200 ml Downanol PM in a 11 three-necked flask equipped with a stirrer and a reflux condenser. Then a solution of 4.0 g sodium hydroxide and 36.5 g 2- methylene-1, 3, 3-TRIMETHYLINDOLINE (Fischer base, available from Aldrich) in 35 ml ethanol was added under stirring for one minute to this suspension. The reaction mixture was heated to 50C for one hour. Then the reaction mixture was left to cool to room temperature and 600 ML of a 2 wt. -% hydrochloric acid were added. After the reaction mixture had cooled to room temperature, the insoluble portion was separated by filtration and washed with 2 1 of water. Then the product was dried for one day at 50C in a circulating air oven. Yield: 56.2 g (92. 9% based on dye A). The dried product was suspended in 450 ml methyl ethyl ketone and heated to 80C for one hour. Subsequently, the solution with a temperature of 40C was filtered and the solid portion was washed with ethyl acetate. The product was air-dried. The yield after clean-up was 82.5 wt. -%; UV/Vis spectrum in methanol : 828 nm, extinction coefficient E = 251 1/G X CM.

Reference： [1]Patent: WO2004/52995,2004,A1 .Location in patent: Page 21

47
[ 118-12-7 ]
[ 63857-00-1 ]
C₃₈H₄₂N₃⁽¹⁺⁾*Cl^(1-) [ No CAS ]
[ 199444-11-6 ]

Yield	Reaction Conditions	Operation in experiment
48%	With acetic anhydride; at 50℃; for 3h;	792 g dye A were added under stirring to 2,650 g acetic acid anhydride (both available from Aldrich) in a 301 three-necked flask equipped with a stirrer and a reflux condenser. Then 770 g 2-methylene-1, 3,3-trimethylindoline (Fischer base, available from Aldrich) was added under stirring for one minute to this suspension. Within one hour, the reaction mixture warmed up to about 50C. After two more hours of stirring, 18 1 water were added to the reaction mixture. Then the reaction mixture was left to cool to room temperature and 20 g sodium chloride were added. Subsequently, the insoluble portion was separated by filtration and washed with 2 1 water. Then the product was dried for one day at 50C in a circulating air vacuum oven. Yield: 1,063 g (95% based on dye A), IR dye content: 72.0 wt. -% (determined by measuring the optical density at 775 nm in methanol using an extinction coefficient for the pure IR dye of 5001/G x CM), moisture content: 3 wt.-%. The dried product was suspended in 2 1 ethyl acetate and heated to 76C for one hour. Subsequently, the solution with a temperature of about 50C was filtered and the isolated product was air-dried. The remaining solution was strongly colored. The yield of solid product after the first purification step was 925 g (81 wt. -%) with a content of dye B of 80%. The dried product was suspended in 1 1 methyl ethyl ketone and heated to 80C for one hour. Subsequently, the solution with a temperature of about 40C was filtered and the isolated solid substance was air-dried. The yield after this second purification step was 705 g (62 wt. -%) with a purity of dye B of 89.2%. For further clean-up, the second purification step was repeated and 552 g dye B (48%) with a purity of 96.3% dye B were obtained (moisture content: 0.7 wt. -%).

Reference： [1]Patent: WO2004/52995,2004,A1 .Location in patent: Page 24

48
2-mercapto-5-thiomethyl-1,3,4-thiadiazole [ No CAS ]
[ 118-12-7 ]
[ 63857-00-1 ]
2-[2-[2-(thio-5-thiomethyl-1,3,4-thiadiazole)-3-[2-(1,3-dihydro-1,3,3-trimethyl-2H-indole-2-ylidene)-ethylidene]-1-cyclohexene-1-yl]-ethenyl]-1,3,3-trimethyl-3H-indolinium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.3%		16.4 g 2-mercapto-5-thiomethyl-1, 3, 4-THIADIAZOLE (available from FEW, Wolfen/Germany) and 36.0 g dye A (available from Aldrich) were added under stirring to 200 ML Downanol PM in a 11 three-necked flask equipped with a stirrer and a reflux condenser. Then a solution of 4.0 g sodium hydroxide and 36.5 g 2-methylene-1, 3, 3-trimethylindoline (Fischer base, available from Aldrich) in 35 ml ethanol was added under stirring for one minute to this suspension. The reaction mixture warmed up to about 40C without the addition of external heat. Then the reaction mixture was left to cool to room temperature and 600 ml of a 2 wt.-% hydrochloric acid were added. After the reaction mixture had cooled to room temperature, the insoluble portion was separated by filtration and washed with 21 of water. Then the product was dried for one day at 50C in a circulating air oven. Yield: 56.2 g (92.9% based on dye A). The dried product was suspended in 500 ML methyl ethyl ketone and heated to 80C for one hour. Subsequently, the solution with a temperature of about 40C was filtered and the solid portion was washed with ethyl acetate. The product was air-dried. Yield: 48.6 g (80.3 wt. - % based on dye A), W/VIS spectrum in methanol : No.MAX = 796 nm, extinction coefficient E = 3321/G X CM.

Reference： [1]Patent: WO2004/52995,2004,A1 .Location in patent: Page 18-19

49
[ 118-12-7 ]
[ 131-91-9 ]
1,3,3-trimethyl-6'-(4-ethoxycarbonyl)-piperidin-1-yl-spiro[indoline-2,3'-3H-naphtho[2,1-b][1,4]oxazine]. [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With 4-carbethoxypiperidine; In methanol; for 2.16667h;	Example 14 [0516] A mixture of 1-nitroso-2-naphthol (12.32 g, 71 mmol), ethyl isonipecotate (11.2 g, 71 mmol) and methanol (200 ml) was refluxed for 2 hours. Neat 1,3,3-trimethyl-2-methyleneindoline was added in one portion. The mixture was kept refluxing for 10 more minutes and then the solvent was removed by vacuum. Flash chromatography was used to separate the product. An NMR spectrum showed that the final product, a yellow solid (9 g, yield 25%) had a structure consistent with 1,3,3-trimethyl-6'-(4-ethoxycarbonyl)-piperidin-1-yl)-spiro[indoline-2,3'-3H-naphtho[2,1-b][1,4]oxazine].

Reference： [1]Patent: US2005/4361,2005,A1 .Location in patent: Page 50

50
[ 496-15-1 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 114747-44-3 ]

Yield	Reaction Conditions	Operation in experiment
10%	In Trichloroethylene; acetone;	COMPARATIVE EXAMPLE 1 1,3-Dihydro-1,3,3-trimethyl-6'-(2,3-dihydroindol-1-yl) spiro[2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine] A mixture of 1-nitroso-2-naphthol (17.3 g; 0.10 mol) and indoline (23.8 g; 0.20 mol) in trichloroethylene (150 ml) was heated under reflux for 10 min. A solution of 1,3-dihydro-1,3,3-trimethyl-2-methyleneindoline (17.3 g; 0.1 mol) in trichloroethylene (100 ml) was added in one batch and the resulting mixture heated under reflux for 1 h. The solution was evaporatedand the oily residue treated with acetone to yield 1,3-Dihydro-1,3,3-trimethyl-6'-(2,3-dihydroindol-1-yl)spiro [2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine] as a yellow solid (4.44 g; 10%). m.p 255-7 C. STR10

Reference： [1]Synthesis,2010,p. 3418 - 3422
[2]Patent: US5446151,1995,A

51
[ 118-12-7 ]
[ 23731-06-8 ]
6-Chloromethyl-1',3',3'-trimethylspiro[2H-1-benzopyran-2,2'-indoline] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In magnesium sulfate; benzene	1.a (a) (a) 6-Chloromethyl-1',3',3'-trimethylspiro[2H-1-benzopyran-2,2'-indoline] A solution of 1.6 g (9.3 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 1.6 g of 5-chloromethylsalicylaldehyde dissolved in 100 ml of benzene was heated under reflux for 2 hours in a reaction vessel provided with a Soxlet extractor, in which anhydrous magnesium sulfate was packed in a cylindrical filter paper. After completion of the reaction, the solvent was distilled off under reduced pressure to give crude product. This product was purified by gel permeation chromatography through a column (30cm-length) packed with polystyrene beads (a product of Nihon Bunseki Kogyo Co.: JAIGEL-2H) to give the title compound in a pure state. NMR (δ),(CDCl3): 6.8-7.2 (7H, m), 6.5 (1H, d), 5.7(1H,d), 4.6 (2H, s), 2.8 (3H, s), 1.3 (3H, s), 1.2 (3H, s).

Reference： [1]Current Patent Assignee: SOJITZ CORPORATION - EP738728, 1996, A2

52
[ 118-12-7 ]
[ 118-29-6 ]
[ 312961-81-2 ]

Yield	Reaction Conditions	Operation in experiment
68%		8.1 5-[1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1,2,3,3-tetramethyl-3H-indolium 2-Methylene-1,3,3-trimethylindolenine (100g, 0.575mol) was slowly added to concentrated sulphuric acid (500ml) at 0C. This was stirred for 1 hour and N-(hydroxymethyl)-phthalimide (100g, 0.565mol) was added in 10g portions over two hours at 0C. The reaction was then stirred for 70 hours to give an orange solution.. This was poured onto 500g of ice.. concentrated ammonia solution (750ml) was diluted with distilled water (750ml) and slowly added to the quenched reaction mixture at 0C. Upon neutralisation the aqueous solution became yellow.. This was extracted with chloroform and the organic layer dried with sodium sulfate, filtered and the solvent removed in vacuo. The product was recrystallized from methanol/chloroform to give 130g of product.. Yield = 68%.1H-NMR (CDCl3) delta 7.9-7.8 (m, 2H Ar-phthalimide), delta 7.75-7.65(m, 2H Ar-phthalimide), delta 7.3 (d, 1H, 6-H), delta 7.2 (S, 1H, 4-H), delta 6.5 (d, 1H, 7-H), delta 4.8 (s, 2H, beta-CH2), delta 3.9(s, 2H, Ar-CH2) delta 3.0 (s, 3H, N-CH3), delta 1.33 (s, 6H, (CH3)2). MALDI-TOF m/z = 332 (100%), M+ = 334 for C21H22N2O2.

Reference： [1]Patent: EP1394219,2004,A1 .Location in patent: Page 24

53
[ 118-12-7 ]
[ 29261-33-4 ]
[ 500285-21-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,2008,vol. 81,p. 1131 - 1146

54
[ 118-12-7 ]
[ 94-31-5 ]
[ 911709-30-3 ]

Yield	Reaction Conditions	Operation in experiment
		Example 11a: Preparation of the compound of formula (101a) (a) Condensation35.7 g 1,3,3 trimethyl-2-methylene-indoline are added to 60 g acetic acid.The equivalent amount (35.0 g) of 2-chloroethyl-methylamino-benzaldehyde is added and the reaction mixture stirred for 6 h at 30-40 C.The reaction product is precipitated by cooling, diluted with 375 ml water and salted out with 40 g sodium chloride, then separated by filtration and dried in vacuum to obtain 65 g of a reddish violet solid product.The product is recrystallized twice from methanol.The product is characterized by 1H-NMR data in deuterated chloroform (128 scans)/360 MHz:(b) AlkylationOne equivalent (10.0 g) sodium thiosulfate is dissolved in 30 g of the alkylating dye (101c) with 75 ml ethanol as solvent.The temperature is raised to reflux and maintained at 80 C. during the following 4 hours.The product of formula (101b) is obtained.The product is characterized by 1H-NMR data in deuterated chloroform (128 scans)/360 MHz

Reference： [1]Patent: US2009/113639,2009,A1 .Location in patent: Page/Page column 21

55
[ 110-89-4 ]
[ 118-12-7 ]
[ 131-91-9 ]
[ 114747-45-4 ]

Reference： [1]Synthesis,2010,p. 3418 - 3422

56
[ 118-12-7 ]
[ 150-13-0 ]
[ 1309374-44-4 ]

Yield	Reaction Conditions	Operation in experiment
31.1%	Stage #1: 4-amino-benzoic acid With sodium carbonate; sodium nitrite In water at 15℃; Stage #2: With hydrogenchloride Cooling with ice; Stage #3: 1,3,3-Trimethyl-2-methyleneindoline	1 Synthesis of 2-(5-(5-(4-carboxyphenylazo)-1,3,3-trimethyl-2-yliden)prop-1-enyl)-1,3,3-trimethyl-3H-indolium acetate (4). ; The synthesis was as shown in Scheme 1.5-(4-carboxyphenylazo)-1,3,3-trimethyl-2-methyleneindoline (2). To a cold solution of 10 g (72.9 mmol) of p-aminobezoic acid and 2.4 g (22.6 mmol) of sodium carbonate in 100 mL of DI water was added a solution of 3.5 g (50.7 mmol) of NaNO2 in 10 mL of DI water at 15° C. with stirring. The above mixture was poured into a mixture of 10 mL of concentrated HCl and 60 gm of crashed ice with stirring. Then of 10.8 g (62.4 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 6 ml of acetic acid were added to the reaction mixture. After 10 min the reaction mixture was neutralized with 8 mL of 20% NaOH solution in water. The precipitant was filtered. Flash chromatography with chloroform/hexanes/acetone 5:3:2 mobile system provided 7.3 g (31.1%) of azo bezoate (2) as orange solid. TLC Rf 0.26 (chloroform/hexanes/acetone 5:3:2). UV/Vis (methanol) λmax (nm) 455 (ε=32,600 M-1cm-1). ESMS 322.3 [C19H19N3O2 (M+H)+ requires 322.4].
31.1%	Stage #1: 4-amino-benzoic acid With hydrogenchloride; sodium carbonate; sodium nitrite In water at 15℃; Cooling with ice; Stage #2: 1,3,3-Trimethyl-2-methyleneindoline With acetic acid In water for 0.166667h;	2 To a cold solution of 10 g (72.9 mmol) ofp-aminobezoic acid and 2.4 g (22.6 mmol) of sodium carbonate in 100 mL of DI water was added a solution of 3.5 g (50.7 mmol) of NaNO2 in 10 mL of DI water at 15 °C with stirring. The above mixture was poured into a mixture of 10 mL of concentrated HCl and 60 gm of crashed ice with stirring. Then of 10.8 g (62.4 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 6 ml of acetic acid were added to the reaction mixture. After 10 min the reaction mixture was neutrolized with 8 mL of 20% NaOH solution in water. The precipitant was filtered. Flash chromatography with chloroform/hexanes/acetone 5:3:2 mobile system provided 7.3 g (31.1 %) of azo bezoate (2) as orange solid. TLC Rf 0.26 (chloroform/hexanes/acetone 5:3:2). UV/Vis (methanol) λmax (nm) 455 (ε =32,600 M-1cm-1). ESMS 322.3 [C19H19N3O2 (M+H)+ requires 322.4].

Reference： [1]Current Patent Assignee: CHEMGENES - US7956169, 2011, B1 Location in patent: Page/Page column 9-10; 15
[2]Current Patent Assignee: CHEMGENES - EP2397464, 2011, A1 Location in patent: Page/Page column 13-14

57
[ 118-12-7 ]
[ 1588-83-6 ]
[ 1309374-43-3 ]

Yield	Reaction Conditions	Operation in experiment
34.7%		EXPERIMENTALExamplesExample 1; Synthesis of 5-(2-nitro-4-carboxyphenylazo)-1,3,3-trimethyl-2-methyleneindoline (6). To a cold solution of 10 g (54.9 mmol) of 2-nitro-4-aminobezoic acid (5) and 2.4 g (22.6 mmol) of sodium carbonate in 100 mL of DI water was added a solution of 3.5 g (50.7 mmol) of NaNO2 in 10 mL of DI water at 15 C. with stirring. The above mixture was poured into a mixture of 10 mL of concentrated HCl and 60 gm of crashed ice with stirring. Then of 9.5 g (54.9 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 6 ml of acetic acid were added to the reaction mixture. After 10 min the reaction mixture was neutralized with 8 mL of 20% NaOH solution in water. The precipitant was filtered. Flash chromatography with chloroform/hexanes/acetone 5:3:2 mobile system provided 7 g (34.7%) of azo bezoate (6) as orange solid. TLC Rf 0.23 (chloroform/hexanes/acetone 5:3:2). UV/Vis (buffer pH=11) lambdamax (nm) 490 (epsilon=38,200 M-1cm-1). ESIMS 367.6 [C19H18N4O4 (M+H)+ requires 367.4].
34.7%		EXAMPLE 1 Synthesis of 5-(2-nitro-4-carboxyphenylazo)-1,3,3-trimethyl-2-methyleneindoline (6). To a cold solution of 10 g (54.9 mmol) of 2-nitro-4-aminobezoic acid (5) and 2.4 g (22.6 mmol) of sodium carbonate in 100 mL of DI water was added a solution of 3.5 g (50.7 mmol) of NaNO2 in 10 mL of DI water at 15C with stirring. The above mixture was poured into a mixture of 10 mL of concentrated HCl and 60 gm of crashed ice with stirring. Then of 9.5 g (54.9 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 6 ml of acetic acid were added to the reaction mixture. After 10 min the reaction mixture was neutrolized with 8 mL of 20% NaOH solution in water. The precipitant was filtered. Flash chromatography with chloroform/hexanes/acetone 5:3:2 mobile system provided 7 g (34.7%) of azo bezoate (6) as orange solid. TLC Rf 0.23 (chloroform/hexanes/acetone 5:3:2). UV/Vis (buffer pH=11) lambdamax (nm) 490 (epsilon =38,200 M-1cm-1). ESIMS 367.6 [C19H18N4O4 (M+H)+ requires 367.4].

Reference： [1]Patent: US7956169,2011,B1 .Location in patent: Page/Page column 14-15
[2]Patent: EP2397464,2011,A1 .Location in patent: Page/Page column 13

58
[ 118-12-7 ]
[ 1309374-47-7 ]
[ 1309374-48-8 ]

Yield	Reaction Conditions	Operation in experiment
68.2%	Stage #1: 4-(4-carboxyphenylazo)-2,5-dimethoxyaniline With sodium carbonate; sodium nitrite In water at 15℃; Stage #2: With hydrogenchloride Cooling with ice; Stage #3: 1,3,3-Trimethyl-2-methyleneindoline	3 5-(4-(4-carboxyphenylazo)-2,5-dimethoxyphenylazo)-1,3,3-trimethyl-2-methyleneindoline (9). To a cold solution of 5 g (16.6 mmol) of 4-(4-carboxy-phenylazo)-2,5-dimethoxyaniline (8) and 1.25 g (11.8 mmol) of sodium carbonate in 50 mL of DI water was added a solution of 1.75 g (25.4 mmol) of NaNO2 in 5 mL of DI water at 15° C. with stirring. The above mixture was poured into a mixture of 5 mL of concentrated HCl and 30 gm of crashed ice with stirring. Then of 2.9 g (16.6 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 1.5 ml of acetic acid were added to the reaction mixture. After 10 min the reaction mixture was neutralized with 6 mL of 20% NaOH solution in water. The precipitant was filtered. Flash chromatography with chloroform/hexanes/acetone 5:3:2 mobile system provided 5.5 g (68.2%) of azo bezoate (9) as dark blue solid. TLC Rf 0.48 (1:9 MeOH-DCM). UV/Vis (buffer pH=11) λmax (nm) 585 (ε=48,500 M-1cm-1). 486.6 [C27H27N5O4 (M+H)+ requires 486.5].
68.2%	Stage #1: 4-(4-carboxyphenylazo)-2,5-dimethoxyaniline With hydrogenchloride; sodium carbonate; sodium nitrite In water at 15℃; Cooling with ice; Stage #2: 1,3,3-Trimethyl-2-methyleneindoline With acetic acid In water for 0.166667h;	3 5-(4-(4-carboxyphenylazo)-2,5-dimethoxyphenylazo)-1,3,3-trimethyl-2-methyleneindoline (9). To a cold solution of 5 g (16.6 mmol) of 4-(4-carboxy-phenylazo)-2,5-dimethoxyaniline (8) and 1.25 g (11.8 mmol) of sodium carbonate in 50 mL of DI water was added a solution of 1.75 g (25.4 mmol) of NaNO2 in 5 mL of DI water at 15 °C with stirring. The above mixture was poured into a mixture of 5 mL of concentrated HCl and 30 gm of crashed ice with stirring. Then of 2.9 g (16.6 mmol) of 1,3,3-trimethyl-2-methyleneindoline and 1.5 ml of acetic acid were added to the reaction mixture. After 10 min the reaction mixture was neutrolized with 6 mL of 20% NaOH solution in water. The precipitant was filtered. Flash chromatography with chloroform/hexanes/acetone 5:3:2 mobile system provided 5.5 g (68.2%) of azo bezoate (9) as dark blue solid. TLC Rf 0.48 (1:9 MeOH-DCM). UV/Vis (buffer pH=11) λmax (nm) 585 (ε =48,500 M-1cm-1).

Reference： [1]Current Patent Assignee: CHEMGENES - US7956169, 2011, B1 Location in patent: Page/Page column 15-18
[2]Current Patent Assignee: CHEMGENES - EP2397464, 2011, A1 Location in patent: Page/Page column 14

59
[ 30169-25-6 ]
[ 118-12-7 ]
[ 1322027-46-2 ]

Reference： [1]Heterocycles,2011,vol. 83,p. 1363 - 1370

60
[ 30169-25-6 ]
[ 118-12-7 ]
2-((6-(3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazin-3-yl)methylene)-1,3,3-trimethylindoline [ No CAS ]
[ 1322027-46-2 ]

Reference： [1]Heterocycles,2011,vol. 83,p. 1363 - 1370

61
[ 118-12-7 ]
[ 84501-28-0 ]
[ 1370284-34-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	In ethanol; at 85℃; for 12h;	To the solution of 4-tert-butyl-2,6-diformyl phenol (500 mg, 2.42 mmol) in 50 ml ethanol was added 1,3,3-trimethyl-2-methyleneindoline in another 50 ml ethanol through a drop funnel in 2 h (415 mg, 2.40 mmol) at reflux condition. The reaction mixture was then stirred at 85 0C for 12 h. The mixture was concentrated and purified by column chromatography on silica gel (PE/EA 20:1 v/v) to afford 2 (694 mg, 1.92 mmol, yield: 80% ) as yellow oil.1H NMR (400 MHz, CDCl3) delta 10.13 (s, 1H), 7.65 (d, J = 2.4 Hz, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.16 (td, J = 7.2, 1.2 Hz, 1H), 7.06 (dd, J = 7.2, 0.8 Hz, 1H), 6.90 (d, J = 10.4 Hz, 1H), 6.85 (td, J = 7.6, 0.8 Hz, 1H), 6.52 (d, J = 7.6 Hz, 1H), 5.79 (d, J = 10.4 Hz, 1H), 2.75 (s, 3H), 1.33 (s, 3H), 1.30 (s, 9H), 1.20 (s, 3H).; 13C NMR (100 MHz, CDCl3) delta 189.2, 147.8, 142.8, 136.3, 130.2, 129.1, 127.6, 123.8, 121.8, 121.4, 120.1, 119.5, 106.9, 105.5, 51.9, 34.1, 31.2, 29.0, 25.7, 20.4. HRMS (ESI) for C24H27NO2 calcd 362.2120 (M+H+), found, 362.2115.

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 13882 - 13886
Angew. Chem.,2016,vol. 128,p. 14086 - 14090,5
[2]Tetrahedron Letters,2012,vol. 53,p. 2001 - 2004

62
[ 118-12-7 ]
4-(4-bromophenyl)naphthalene-1,2-dione [ No CAS ]
[ 1365120-11-1 ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: 4-(4-bromophenyl)naphthalene-1,2-dione With hydroxylamine hydrochloride In ethanol at 20℃; for 18h; Stage #2: 1,3,3-Trimethyl-2-methyleneindoline In ethanol at 100℃; for 3h;	General procedure for the synthesis of novel spirooxazine photochromics (6a-6f and 7) General procedure: A mixture of 3-substituted naphthalene-1,2-dione (1.71 mmol) and hydroxylamine hydrochloride (0.24 g, 3.42 mmol) in EtOH (15 mL) was stirred at room temperature for 18 h. The mixture was then evaporated in-vacuo, suspended between CH2Cl2 (30 mL) and H2O (30 mL), the organic phase separated, dried (MgSO4) and evaporated in-vacuo. The residue was then suspended in EtOH (10 mL), treated with 1,3,3-trimethyl-2-methyleneindoline (0.385 g, 2.22 mmol) and heated in a sealed tube at 100 °C for 3 h. The mixture was then evaporated in-vacuo and the residue purified by column chromatography eluting with 0-10% v/v EtOAc / petroleum ether to furnish the desired product.

Reference： [1]York, Mark [Tetrahedron Letters, 2012, vol. 53, # 17, p. 2226 - 2230]

63
[ 118-12-7 ]
[ 1449790-49-1 ]
[ 1449790-54-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	In chloroform for 2h; Reflux;	Preparation of Compounds 4a-e. General procedure: A solution of 3a-e (1 mmol) in 50 mL CHCl3 was heated under reflux conditions, and then 2-methylene-1,3,3-trimethylindoline (0.352 mL, 2 mmol) in 5mL CHCl3 was added dropwise. The mixture was refluxed for 2 h and then cooled to rt. The precipitate solid was filtered and crystallized in EtOH to afford pure 4.
89%	In chloroform for 2.33333h; Reflux;	2.3 2.3.2.1. Synthesis of Mono-azo Spiropyran 5 and Symmetrical Bis-azoSpiropyran 6 General procedure: 2-Methylene-1,3,3-trimethylindoline (1 mmol for monospiropyranand 2 mmol for bis-spiropyran compounds) in 5 ml CHCl3was added dropwise to a refluxing solution of salicylaldehyde derivatives2 or 3 (1 mmol) in 20 ml chloroform, in 20 min. The mixturewas refluxed for 2 h, and then cooled to room temperature. Then theprecipitate was filtered and washed out with distilled water, and crystallizedin EtOH to afford the pure spiropyran compounds 5 and 6 accordingly.

Reference： [1]Nourmohammadian, Farahnaz; Abdi, Ali Ashtiani [Bulletin of the Korean Chemical Society, 2013, vol. 34, # 6, p. 1727 - 1734]
[2]Nourmohammadian, Farahnaz; Abdi, Ali Ashtiani [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2016, vol. 153, p. 53 - 62]

64
[ 1612-65-3 ]
[ 118-12-7 ]
zinc(II) 1-nitroso-2-naphtholate [ No CAS ]
[ 1587261-01-5 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 2-methyl-1,2,3,4-tetrahydroisoquinoline; zinc(II) 1-nitroso-2-naphtholate In ethanol for 3h; Reflux; Stage #2: 1,3,3-Trimethyl-2-methyleneindoline In ethanol for 16h; Inert atmosphere; Reflux;	2.2 General method for synthesis of spirooxazines containing nitrogen heterocycle (entries 1-7) General procedure: 1.36g (10mmol) ZnCl2 in 50mL aqueous solution was added to the 150mL mixed solution of tetrahydrofuran and water (1:1v/v) containing 4.18g (24mmol) 5-nitroso-6-hydroxyquinoline while stirring. The reaction was completed after 30min at room temperature, the raw product of 5-nitroso-6-hydroxyquinoline zinc salt was filtered, then washed with water, and dried under an infrared heat lamp. Yield: 98%. (0005) 5-nitroso-6-hydroxyquinoline zinc salt (1.0mmol) and nitrogen-containing heterocycles compounds (2.8mmol) were added to 20mL ethanol. The resulting mixture was stirred for 3h under reflux. Indoline base (1.8mmol) in 20mL ethanol was added to the solution under nitrogen atmosphere, and stirred for additional 16h at reflux. After removal of the solvent, the residue was purified by column chromatography on silica gel with petroleum ether/ethyl acetate (5:1v/v) as the eluent. The derivatives of spiro[indoline-quinolineoxazine] 1-7 were obtained in modest yields.

Reference： [1]Zhou, Yan; Pang, Meili; Li, Jingjing; Li, Hong [Dyes and Pigments, 2014, vol. 105, p. 130 - 136]

65
[ 845958-95-4 ]
[ 118-12-7 ]
[ 536-74-3 ]
(E)-3-((2Z,4Z)-1,3-diphenyl-4-(1,3,3-trimethylindolin-2-ylidene)but-2-en-1-ylidene)-1-tosylindolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: N-(2-iodo-phenyl)-4-methyl-N-(3-phenyl-propynoyl)-benzenesulfonamide; phenylacetylene With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 16h; Inert atmosphere; Stage #2: 1,3,3-Trimethyl-2-methyleneindoline With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; ethanol at 80℃; for 48h; Inert atmosphere; Sealed tube; diastereoselective reaction;	3. General Procedure for the synthesis of 4-(1,3,3-trimethylindolin-2-ylidene)but-2-en-1-ylideneindolones 10 General procedure: In a flame-dried and argon-flushed Schlenk tube iodo phenylanilide 5 (1.00 mmol), alkyne 6 (1.10 mmol), and dry, degassed THF (5 mL) were placed (for experimental details see Table 2). After the addition of PdCl2(PPh3)2 (35 mg, 0.05 mmol) and CuI (10 mg, 0.05 mmol), diisopropylethylamine (1.7 mL, 10 mmol) was added and the reaction mixture was stirred at rt for 16 h. Then, the enamine 7 (2.00 mmol) or the benzothiazolium salt 9 (2.00 mmol and 1.1 mmol of diisopropylethylamine), and EtOH (2 mL) were added. The sealed reaction vessel was placed in a thermostatted oil bath at 80 °C and stirred for 48 h. After cooling to rt the solvents were removed in vacuo and the residue was chromatographed on silica gel (hexane/EtOAc) to give the 4-(1,3,3-trimethylindolin-2-ylidene)but-2-en-1-ylideneindolones 10 as bluish-black or darkgreen solids.