GB2338955A

GB2338955A - Method of Making 3,3-disubstituted Oxazine Compounds

Info

Publication number: GB2338955A
Application number: GB9814184A
Authority: GB
Inventors: Georges Tennant; Martin Rickwood; David Rowe; Martin PRITCHARD
Original assignee: Gentex Optics Inc
Current assignee: Gentex Optics Inc
Priority date: 1998-06-30
Filing date: 1998-06-30
Publication date: 2000-01-12
Also published as: GB9814184D0

Description

1 2338955 METHOD OF PHOTOCHROMIC MAKING 3,3-DISUBSTITUTED OXAZINE

COMPOUNDS The present invention relates to a novel method of making photochromic oxazine compounds and in particular photochromic 3,3 disubstituted oxazine compounds.

Photochromic oxazine compounds are useful in the optical field for manufacturing lenses having photochromic properties.

Several methods are known in the art for preparing photochromic oxazine compounds and in particular, photochromic 3,3 disubstituted oxazine compounds.

A first synthesis route is disclosed in document WO 95/00500. In a first step of the disclosed synthesis, 1-nitroso-2 naphtol is reduced into 1-amino-2-naphtol hydrochloride. The I amino-2-naphtol hydrochloride is then reacted with a bromoacetaldehyde in the presence of p-toluolsulfonic acid to obtain the expected photochromic oxazine compound.

The above synthesis may be illustrated as follows:

2 N=O NH2, HCI OH -OH te sodium dithioni -06 HCI 1-nitroso-2-naphtol I-amino-2-naphtol hydrocbloride NH2, HC1 OH OHC,,, Br 1--, 1-0 Diphenylbromoacetaldehyde "",10 p-toluolsulfonic acid 30 06C"O This synthesis necessitates the intermediatepreparationofan aminophenol derivative. This synthesis route allows only a limited class of substituents to be used for the phenyl groups and the yield in the expected product is not as high as wishable.

A second synthesis route is disclosed in document JP-7 25862. This synthesis comprises in a first step reacting a nitrophenol with an halogenated acetaldehyde to form the amine derivative and then cyclising the amine derivative.

This second synthesis route may be illustrated as follows:

3 02 CHO 2 1 + X_ -R, CHO H R2 o-nitrophenol a -halogenated aldebyde R2 WH2 N catalytic hydrogenation ICHO acid catalist,,, O_ C_ R, cyclization 01 -R I I R2 2 R, and R2 being alkyl groups, and X being an halogen such as a bromo group This second synthesis route is also a two steps method necessitating the obtention of the corresponding amino compound. This second synthesis route suffers from the same drawbacks as the first synthesis route.

Besides, unwanted side reactions can happen between unconnected amino and aldehyde groups leading to unwanted polymerization and not to the desired photochromic compound.

In document DDR-0153690, there is disclosed a one step method for obtaining 1,4-2H-oxazine compounds.

In this third synthesis route a nitroso o-naphtol or o- phenantrol is reacted with a 1,1-diarylethylene compound. This third synthesis route may be illustrated as follows:

R N=O R Yk,-N R 1:6C \ Zza 0 8 + C=C R bH H / R Nitrosonaphtol 1, 1 -diarylethylene 1,4-2H-oxazine where R are amine or alkoxy groups and R' is H, an alkyl or 4 an aryl group.

In this third method, the yield in the expected product is not as high as wishable and the class of possible substituents for the phenyl groups is rather limited.

Thus, the aim of the present invention is to obtain a one step method for making photochromic 3,3-disubstituted oxazine compounds which avoids the step of obtention of an amine derivative, exhibits improved yield in the expected product as well as allows the use of a wide range of substituents, in particular on phenyl groups.

According to the invention, there is provided a method for making photochromic 3,3-disubstituted oxazines which comprises reacting a salt of a dione monoxime cyclic aromatic compound with a 1,1-disubstituted cc-halogenated aldehyde and recovering the expected 3,3-disubstituted oxazine compound.

The preferred dione monoxime cyclic aromatic compounds are the compounds comprising a benzene- 1,2-dione oxime, a naphthalene- 1,2-dione oxime and a phenanthrene-9,10-dione oxime base structure.

The method of the present invention may be schematically illustrated as follows:

1-10 R \ C / Hal C 0 X R ' -imp N R' M + 4' -- G1 R' CHO OHC R" R" wherein C is an aromatic cycle, preferably a condensed aromatic cycle, MI is a cation, preferably a metallic cation, Hal is an halogene, and R' and R" are independently from each other an alkyl group, a phenyl, a substituted phenyl group, or R' and R" together form a divalent aromatic or non-aromatic cyclic group.

In the method of the invention, the intermediary product may or may not be isolated. It is preferably isolated before cyclisation.

Dione monoxime cyclic aromatic starting compounds in the form of their salts, useful in the method of the present invention may be represented by the formula 0 <.1 MID wherein C is an aromatic ring and MI is a cation.

The aromatic ring C is preferably selected from rings having the formula:

C, C, M I&, and (R)m (R)n (R)m wherein R is, independently, a hydrogen atom, an alkyl group, preferably a CI-C4 alkyl group, an aryl group, preferably a phenyl group, a substituted aryl group, preferably a substituted phenyl group and in particular a CI-C4 alkyl substituted phenyl group, a group -(CH2)xORI, -SRI, -CORI or -COORI in which R, is H or an alkyl group, preferably a CI-C4 alkyl group, or an aryl group, preferably a phenyl group and x is an integer ranging from 0 to 10, an amino group of formula -NR2R3 in which R2 and R3 respresent, independently from each other, H, an alkyl group, preferably a C1_C4 alkyl group, a cyclo alkyl group, or an aryl group, preferably a phenyl group, R2 and R3 forming eventually with the nitrogen atom an heterocycle having 4 to 7 links that may include one or more intracyclic heteroatoms selected from nitrogen, oxygen and sulfur, a halogen atom, a mono- or polyhaloalkyl group, preferably a trifluoromethyl group, a -N02, -CN, -SCN or -S03R4 group, in which R4 is H or an alkaline metal, a _S02R5 group where R5 is a phenyl or tolyl group, or a (meth)acrylic, vinylic or allylic polymerizable group, and C' is an aromatic hydrocarbon cycle or an aromatic heterocycle having 4 to 7 links, 6 preferably 5 to 6 links, the heterocycle comprising one or more intracyclic heteroatoms selected from nitrogen, oxygen and sulfur that may be substituted by one or more groups, such that those defined for R.

When C' is an aromatic hydrocarbon cycle, it is preferably a phenyl ring, or a subsituted phenyl ring. Among the preferred substituted phenyl rings there can be cited (CI_C4) alkyl and polyhalo (CI-C4) alkyl substituted phenyl rings. The most preferred aromatic hydrocarbon rings for C' are 0 O-CF, and 00 _CH, When C' is an heterocycle, it is preferably an heterocycle having 5 to 6 links.

Preferably, the Cheterocycle will have formula:

Mi__ (X)b ()c in which:

X, Y, and Z represent independently from each other, a CR7 group where R7 is H or a CI"C6 alkyl group or a phenyl group, the carbon atom being linked to one of the adjacent atoms through a double bond; a nitrogen atom linked to one of the adjacent atoms by a double bond, an oxygen or sulfur atom; a, b and c being integers equal to 0 or 1; R6 is H, a CI-C6 alkyl group, a phenyl group, or R6 and X or R6 and Z conjointly form an aromatic or non-aromatic, preferably a benzene or naphtalene ring, eventually susbstituted by one or more (R8)p groups, where R8 has the same meanings as R and p is an integer from I to 4 for a benzene ring or I to 6 for a naphtalene ring, X, Y, Z 7 and CR7 being selected in order to ascertain the aromaticity of the condensed heterocycle on the phenyl ring.

A preferred heterocycle represented by C' is:

1 MOD Among the preferred dione monoxime cyclic aromatic starting compounds, there can be cited the salts of the following compounds:

(aN = 0 N=O OH OH 0 0H The cation M+ is preferably a metallic cation, in particular an alkaline metallic cation such as Li+, Na+, K+ and more specifically Li+.

Metallic salts, in particular lithium salts, of 1,2-dione-l oxime cyclic aromatic compounds and their preparation processes are known. In particular, lithium salts of naphtalene-1,2-dione-l-oxime and naphtalene-1,2-dione-2-oxime and their preparation processes are disclosed by A.K. Banerjee et al, in J. Indian Chem. Soc., 1987, 64 p. 53 and J. Indian Chem. Soc.', 1977, 53 p. 273.

Phenantrene-9,10-dione monoxime salt may be synthesized using similar procedures.

The 1,1-disubstituted (x-halogenated aldehydes useful in the process of the present invention may be represented by the formula:

8 R Hal C R" CHO 5 wherein R' and R" represent, independently from each other, an alkyl group, preferably a CI_C6 alkyl group, a phenyl group, or a substituted phenyl group, preferably a (CI_C4) alkyl substituted or a mono or polyhaloalkyl phenyl group such as a methyl phenyl or a trifluoromethyl phenyl group.

Among the substituted phenyl alkyl group substituted phenyl groups and haloalkyl substituted phenyl groups are preferred.

Also, R' and R" may conjointly represent a divalent cyclic aromatic or non-aromatic group preferably having 5 to 16 links.

The most preferred R' and R" groups are -CH 3, (0 -_VCH3, _O-CF3 Ud (0 07,0- Hal may be any halogen atom such as 1, Br, Cl and F, but is preferably Br.

Among the most preferred 1,1-disubstituted cx-halogenated aldehyde, there may be cited:

9 CH \ C / CHO 1-11 CHO CH- CHO CH / \ B, 11Br 'Br 3 COY CH3-0/ CF3- 0--1C z CHO and 0 CHO C CF3 N"Br 0 r In the method of the present invention, the starting materials are ususally reacted in stoechiometric amounts.

The reaction is effected using the general following procedure:

the (x-halogenated aldehyde is slowly added at room temperature to a stirred anhydrous solution of a salt of the 1,2-dione 1-oxime cyclic aromatic compound.

At this stage, an intermediate reaction product as described hereinunder may be isolated, for example by crystallisation, and purified. The isolated intermediate product is then dissolved in an appropriate anhydrous solvent and heated to reflux to obtain the expected 3,3-disubstituted oxazine which is then isolated 'and enventually purified in a classical manner, or the mixture containing the intermediate product may be directly heated to reflux and the expected oxazine isolated and purified.

The expected 3,3 -di substituted compound is recovered and purified using usual procedures such as for example crystallisation, filtration and flash chromatography.

In the implementation of the method according to the invention as mentioned above, it has been found that the following intermediate compounds are formed and may be isolated:

(R)m R' 0\ C C.

(R)M 0 OHC R";CK 0 OHC R C, 0\ R and C N-0 C / R' / OHC R" ORC R" (R)n SK (R)M where C', R, R', R", n and m are defined as above.

Among the preferred intermediate compounds, there can be cited the following compounds:

CH3 N 0\ c 0\ CXO 0 OHC CH3 0 OHC N-(\ CH3 N-\ CF, c X0 - H3 c lec -CF, 0 OHC \O-C 0 OHC \0 - \ /CH, ( N-o\ g?o< gYo o 0 0 OHC CH3 0 0 OHC N-(\ CH3 N-C\ --CF3 /a X0 gYo c \H3 g?o c \, I -CF 0 0 OHC 0 0 OHC 3 N%(N - 01\ c XN-C\ c 0 0 OHC \"(0 0 OHC 0 Nr - /--CH3 N-C\ c AO C/o 0 OHC OHC 0 0 12 N - (XX 3 CF3 /0- CF3 0 OHC (O-- N-0 C and N - 0 OHC N460( X(io OHC The invention is further illustrated by the following examples. 15 Example I 3,3-diphenyl-3H-naphth[2,1-b]-1,4-oxazine N %YO 11<90 Step 1 2-bromo-2,2-diphenylethanal A solution of 2,2 ' -diphenylethanal (9.8g; 0.05mol)in anhydrous dichloromethane (190CM3) was stirred and treated dropwise at room temperature with a solution of bromine (12.0g; 0.075mol) in anhydrous dichloromethane (60.Ocm3). The mixture was then stirred at room temperature with the exclusion of atmospheric moisture for th. The mixture was treated with 1% w/v aqueous sodium metabisulfite solution (200 cm3), and the layers were separated and the aqueous layer extracted three times with dichloromethane 13 Q x 100 cm3). Rotary evaporation of the combined and dried (MgS04) dichloromethane extracts gave 2-bromo-2,2-diphenylethanal (93%) as a waxy solid which was used without further purification.

0 Br 0 CHO 8X 10 Step 2 Naphthalene- 1,2-dione- 1 -oxime- 1, 1 -diphenyl1 - formylmethyl ether A suspension of naphthalene- 1,2-dione- 1-oxime lithium salt (8.96g; 0.05mol) in anhydrous 1,2-dimethoxyethane (400cm3) was stirred and treated at room temperature in a slow stream with a solution of 2-bromo-2,2-diphenylethanal (13.71g; 0.05mol) in anhydrous 1,2-dimethoxyethane (100cm3). The mixture was then stirred at room temperature with exclusion of atmospheric moisture for 24h. The mixture was rotary evaporated and the residue was treated with water (50.0 cm3) and extracted four times with dichloromethane (4 x 50.0 cm3). Rotary evaporation of the combined and dried (MgSO4) extracts gave naphthalene1,2-dione- 1-oxime 1,1-diphenyl-l formy1methyl ether as a brown gum. Purification by flash chromatography over silica, elution with hexane-ether (1:4), gave syn naphthalene- 1,2-dione 1-oxime 1,1-diphenyl-l-formylmethyl ether as orange crystals (29%), mp 154-157'C (from 1,2-dimethoxyethaneethanol).

Elemental analysis Found Theoretical C% 78.4 78.5 H% 4.6 4.6 N% 3.7 3.8 The structure was confirmed by NMR and by crystal X-ray analysis.

14 Elution with hexane-ether (1:9) gave antinaphthalene1,2dione-l-oxime-1, 1-diphenyl-l-formylmethyI ether as yellow plates (50%), mp, 155-157'C (from 1,2-dimethoxyethane-ethanol). Elemental analysis 5 Found Theoretical C% 78.4 78.5 H% 4.6 4.6 N% 3.7 3.8 The structure was confirmed by NMR and by crystal X-ray analysis.

0 CHO I N 'o anti- syn Step 3 3,3-diphenyl-3H-naphth[2,1-b]-1,4-oxazine (a) a stirred solution of anti- naphth alene- 1, 2-dione- 1 -oxime 1,1-diphenyl-l-formylmethyl ether (4.78g; 0.013mol) in anhydrous 1,2-dimethoxyethane (65.0 cm3) was treated with a solution of triphenylphosphine (6.8g; 0.026 mol) in anhdrous 1,2 dimethoxyethane (65.0 cm3) and the resulting yellow solution was stirred and heated under reflux with the exclusion of atmospheric moisture for 24h. The mixture was allowed to cool then rotary evaporated. The resulting brown gum was washed with ether and the washings rotary evaporated to give a brown gum which was flashchromatographed over silica. Elution with hexane-ether (9:1) gave a brown gum which was triturated with light petroleum (bp 60-800C) to yield prisms, mp 124-125'C (from hexane-ethyl acetate).

Elemental analysis Found Theoretical C% 85.9 86.0 H% 4.9 5.0 N% 4.2 4.2 The structure was confirmed by NMR and by crystal X-ray analysis.

(b) Syn-naphthalene-1,2-dione-l-oxime-1,1-diphenyl-l- formyl-mehtyl ether under the same conditions as in step 3a gave 3,3 diphenyl-3H-naphth[2,1-b]-1,4-oxazine (yield 78%).

(c) A mixture of unresolved syn and anti naphthalene- 1,2 dione 1-oxime 1,1-diphenyl-l-formylmethyl ether under the same conditions as in step 3a gave 3,3-diphenyl-3H-naphth[2,1-b]-1,4- oxazine (yield 79%).

Example 2 2,2-di-(4-methylphenyl)-2H-naphth[1,2-b]-1,4-oxazine MMe Step 1 2-bromo-2,2-di(4-methylphenyl)ethanaI A solution of the 2,2-di-(4-methylphenyl)ethanal (I 1.22g; 16 0.05mol) in anhydrous dichloromethane (190 cm3) was stirred and treated dropwise at room temperature with a solution of bromine (12.0g; 0.075mol) in anhydrous dichloromethane (60.Ocm3). The mixture was then stirred at room temperature with the exclusion of atmospheric moisture for lh. The mixture was treated with 1% w/v aqueous sodium metabisulfite solution (200 cm3), and the layers were separated and the aqueous layer extracted three times with dichloromethane Q x 100 cm3). Rotary evaporation of the combined and dried (MgSO4) dichloromethane extracts gave the 2-bromo-2,2-di (4-methylphenyl)ethanal (100%), bp 188'C/0.02 mm Hg.

Nt 0Br CHO 0 Nt Step 2 Naphthalene1,2-dione-2-oidme-1,1-di-(4-methylphenyl)- I - formylmethyl ether A suspension of naphthalene- 1,2-dione 2-monoxime lithium salt (8.96g; 0.05mol) in anhydrous 1,2-dimethoxyethane (400cm3) was stirred and treated at room temperature in a slow stream with a solution of 2-bromo-2,2-di-(4-methylphenyl)ethanaI (15.16g; 0.05mol) in anhydrous 1,2-dimethoxyethane (100 cm3). The mixture was then stirred at room temperature with exclusion of atmospheric moisture for 24h. The mixture was rotary evaporated and the residue was treated with water (50.0 cm3) and extracted four times with dichloromethane (4 x 50.Ocm3). Rotary evaporation and trituration with ether of the combined and dried (MgS04) extracts gave naphthalene- 1,2-dione-2 oxime-1,1-di-(4-methylphenyl)-l-formylmethyI ether (62%) as a brownsolid which formed yellow crystals, mp 177-1800C (from 17 toluene-light petroleum bp 80-1000Q.

i5 c I 18 Elemental analysis Found Theoretical C% 79.4 79.1 H% 5.5 5.3 N% 3.5 3.5 "Me structure was confirmed by NMR.

Me N 0 CHO 0 Step 3 2,2-di-(4-methylphenyl)-2H-naphth[1,2-b]-1,4-oxazine A stirred solution of naphthalene- 1,2-dione 2-oxime 2,2-di(4methylphenyl)-l-formylmethyl ether (7.9g; 0.02mol) in anhydrous 1,2-dimethoxyethane (100cm3) was treated with a solution of triphenylphosphine (10.0g; 0.04mol) in anhydrous 1,2dimethoxyethane (100 cm3) and the resulting solution was stirred and heated under reflux. with the exclusion of atmospheric moisture for 24h. The mixture was allowed to cool, then rotary evaporated to give a brown gum which was flash-chromatographed over silica. Elution with hexane-dichloromethane (2:3) gave 2,2-di-(4-methylphenyl)-2Hnaphth[1,2-bl- 1,4-oxazine (40%) which formed cream prisms, mp 173176'C (from ethyl acetate).

19 Elemental analysis Found Theoretical C% 85.7 86.0 H% 5.8 5.8 N% 3.6 3.9 The structure was confirmed by NMR. Example 3 2,2-di-(4-trifluoromethyIphenyl)-2H-phenanthr[9,10-b]-1,4-oxazine N CF3 F., 3 Step 1 2-bromo-2,2-di-(4-trifluoromethylphenyl)ethanaI A solution of the 2,2-di-(4-trifluoromethylphenyl)ethanaI (16.61g; 0. 05mol) in anhydrous dichloromethane (190 cm3) was stirred and treated dropwise at room temperature with a solution of bromine (12. 0g; 0.075mol) in anhydrous dichloromethane (60.Ocm3). The mixture was then stirred at room temperature with the exclusion of atmopsheric moisture for lh. The mixture was treated with 1% w/v aqueous sodium metabisulfite solution (200cm3), and the layers were separated and the aqueous layer extracted three times with dichloromehtane (3 x 100cm3). Rotary evaporation of the combined and dried (MgSO4) dichloromethane extracts gave 2-bromo-2,2-di(4trifluoromethylphenyl)ethanal as a pale brown oil (90%).

CF3 0 Br I CHO 0 CF3 Step 2 Phenanthrene-9,10-dione 9-oxime 1,1-di-(4 trifluoromethyl-phenyl)-l-formylmethyI ether A suspension of phenanthrene-9,10-dione monoxime lithium salt (11.49g; 0.05mol) in anhydrous 1,2-dimethoxyethane (400cm3) was stirred and treated at room temperature in a slow stream with a solution of 2-bromo-2,2-di-(4-trifluoromethylphenyl)eth anal (20.56g; 0.05mol) in anhydrous 1,2-dimethoxyethane (100cm3). The mixture was then stirred at room temperature with exclusion of atmospheric moisture for 24h. The mixture was rotary evaporated and the residue was treated with water (50.Ocm3) and extracted four times with dichloromethane (4 x 50.Ocm3). Rotary evaporation of the combined and dried (MgS04) extracts gave phenanthrene-9,10-dione-9-oxime1,1-di-(4-trifluoromethylphenyl)-l-formylmethyI ether (61%) as a brown semisolid, which formed yellow crystals, mp 165-1670C (from toluene).

Elemental analysis Found Theoretical C% 65.8 65.1 11% 3.2 3.1 N% 2.5 2.5 The structure was confirmed by NMR.

21 CF3-",, CF3 2?0 N 0 CHO 0 Step 3 2,2-di-(4-trifluoromethylphenyl)-2H-phenanthr[9,10-b]- 1,4-oxazine A stirred solution of phenanthrene-9,10-dione-9-oxime-1,1d-(4-trifluoromethyl-phenyl)-l-formylmethyI ether (11.07g; 0.02mol) i in anhydrous 1,2-dimethoxyethane (100cm3) was treated with a solution of triphenylphosphine (10.0g; 0.04mol) in anhydrous 1,2 dimethoxyethane (100 cm3) and the resulting solution was stirred and heated under reflux with the exclusion of atmospheric moisture for 24h. The mixture was allowed to cool, then rotary evaporated to give a red-brown gum which was flash-chromatographed over silica.

Elution with hexane-ether (9:1) gave 2,2-di-(4-me:thylphenyl)-2H phenanthr[9,10-b]-1,4-oxazine (10%) which formed cream crystals, mp 198-201'C (from toluene-light petroleum bp 80-100'C).

Elemental analysis Found Theoretical C% 69.3 69.1 H% 3.3 3.3 N% 2.5 2.7 The structure was confirmed by NMR.

22 Example 4 3,3-di-(4-methylphenyl)-3H-naphth[2,1-b]-1,4-oxazine %70 N Me Step I Naphthalene-1,2-dione-l-o3dme-1,1-di-(4-methylphenyl)-lformylmethyl ether A suspension of naphthalene- 1,2-dione- 1-monoxime lithium Cc salt (8.96g; 0.05mol) in anhydrous 1,2-dimethoxyethane (400cm3) was C stirred and treated at room temperature in a slow stream with a solution of 2-bromo-2,2-di-(4-methylphenyl)ethanaI (15.16g; 0.05mol) in anhydrous 1,2-dimethoxyethane (100 cm3). The mixture was then stirred at room temperature with exclusion of atmospheric moisture for 24h. The mixture was rotary evaporated and the residue was treated with water (50.0 cm3) and extracted four times with dichloromethane, (4 x 50.Ocm3). Rotary evaporation of the combined and dried (MgS04) extracts gave naphthalene1,2-dione-l-oxime- 1, 1-di-(4-methylphenyl) 1-formylmethyl ether (62%) which formed a orange-yellow crystals, mp 145-147'C (from toluene-light petroleum bp 80-100'C).

Elemental analysis Found Theoretical C% 79.3 79.0 H% 5.6 5.3 N% 3.4 3.5 The structure was confirmed by NMR.

23 Nkl' NI k N 0 CHO 0 Step 2 3,3-di-(4-methylphenyl)-3H-naphth[1,2-b]-1,4-oxazine A stirred solution of naphthalene- 1,2-dione- 1-oxime- 1, 1 -di- (4-methylphenyl)-l-formylmethyl ether (7.9g; 0.02mol) in anhydrous 1,2- dimethoxyethane (100cm3) was treated with a solution of triphenylphosphine (10.0g; 0.04mol) in anhydrous 1,2dimethoxyethane (100 cm3) and the resulting solution was stirred and heated under reflux with the exclusion of atmospheric moisture for 24h. The mixture was allowed to cool, then rotary evaporated to give a red semisolid. Flash-chromatography over silica, clution with hexanedichloromethane (3:2) gave 3,3-di-(4-methylphenyl)-3Hnaphth[1,2-b]-1,4oxazine (82%) which formed tan crystals, mp 157- 159'C (from light petroleum bp 80-100'C).

Elemental analysis Found Theoretical C% 86.0 86.0 H17c 5.9 5.8 N% 3.6 3.9 The structure was confirmed by NMR.

The visible absorbance maximal wavelengths of the photochromic 3,3-di substituted oxazines of examples I to 4 were 24 measured at 25'C ( VQ in solution in tetrahydrofuran using a spectrophotometer.

Results are given below Example 1 2 3 4 Xmu (nm) 472 497 428 498 CLAFqS 1. A method for making a photochromic 3,3-disubstituted oxazine compound which comprises reacting a salt of a dione monoxime cyclic aromatic compound with a 1,1-disubstituted (X halogenated aldehyde and recovering the expected 3,3 -di substituted oxazine compound.

2. The method of claim 1, wherein the salt of dione monoxime cyclic aromatic compound has formula:

0 Me where C is an aromatic cycle and M+ is a cation.

3. The method of claim 2 wherein the 1,1-disubstituted oc- halogenated aIdehyde has formula:

R' 14al \ C / R' \ CHO where Hal represents an halogen atom, and R' and R" respresent, independently from each other, an alkyl group, a phenyl group, a substituted phenyl group, or R' and R" together form a divalent aromatic or non-aromatic cyclic group.

4. The method according to claim 2 or 3, wherein the aromatic ring C is selected from rings of formula:

tct C, ( and (R)m (R)n (R)m I 26 wherein R is, independently, a hydrogen atom, an alkyl group, preferably a CI-C4 alkyl group, an aryl group, preferably a phenyl group, a substituted aryl group, preferably a substituted phenyl group and in particular a Cj-C4 alkyl substituted phenyl group, a group -(CH2)xORI, -SRI, -COR, or -COORI in which R, is H or an alkyl group, preferably a CI-C4 alkyl group, or an aryl group, preferably a phenyl group and x is an integer ranging from 0 to 10, an amino group of formula -NR2R3 in which R2 and R3 respresent, independently from each other, H, an alkyl group, preferably a CFC4 alkyl group, a cyclo alkyl group, or an aryl group, preferably a phenyl group, R2 and R3 forming eventually with the nitrogen atom an heterocycle having 4 to 7 links that may include one or more intracyclic heteroatoms selected from nitrogen, oxygen and sulfur, an halogen atom, a mono- or polyhaloalkyl group, preferably a trifluoromethyl group, a -N02, -CN, -SCN or -S03R4 group in which R4 is H or an alkaline metal, a -S02R5 group where R5 is a phenyl or tolyl group, or a (meth)acrylic, vinylic or allylic polymerizable group, and C' is an aromatic hydrocarbon cycle or an aromatic heterocycle having 4 to 7 links, preferably 5 to 6 links, the heterocycle comprising one or more intracyclic heteroatoms selected from nitrogen, oxygen and sulfur that may be substituted by one or more groups, such that those defined for R.

5. The method of claim 4, wherein where C' is an heterocycle it is preferably a heterocycle having 5 to 6 links.

6. The method of claim 5, wherein C' has formula (Y)__ Mb (Z)c in which:

X, Y, and Z represent independently from each other, a CR7 group where R7 is H or a C1_C6 alkyl group or a phenyl group, the 27 carbon atom being linked to one of the adjacent atoms through a double bond; a nitrogen atom linked to one of the adjacent atoms by a double bond, an oxygen or sulfur atom; a, b and c being integers equal to 0 or 1; R6 is H, a CI_C6 alkyl group, a phenyl group, or R6 and X or R6 and Z conjointly form an aromatic or non-aromatic, preferably a benzene or naphtalene ring, eventually susbstituted by one or more (R8)P groups, where R8 has the same meanings as R and p is an integer from 1 to 4 for a benzene ring or 1 to 6 for a naphtalene ring, X, Y, Z and CR7 being selected in order to ascertain the aromaticity of the condensed heterocycle on the phenyl ring.

7. The method of claim 4, wherein C' is or NOO and R is H.

8. The method according to anyone of claims 3 to 6, wherein R' and R" represent, independently from each other, an alkyl group, preferably a C1_C6 alkyl group, a phenyl group, a substituted phenyl group, a haloalkyl substituted phenyl group or R' and R" conjointly represent a divalent cyclic aromatic or non aromatic group.

9. The method of claim 7, wherein R' and R" represent, independently from each other -CH3, 0,, -0--cF.

or R' and R" represent together 0O - 10. The method according to anyone of claims 1 to 7, wherein the salt of the dione monoxime cyclic aromatic compound is an alkaline metal salt.

11. The method of claim 9, wherein the alkaline metal is lithium.

12. Novel intermediate compounds having the formulae:

28 /R' (R)M N - 0\ /R' C N\ / C \ 0 R" 0 OHC R" (Rim OHC;< C. O\ / R' and C, N-o \ C / R t< / \ R" OHC R" (R)n OHC ' SK (R where C', R, m, n, R' and R" are as defined in claim 4.

13. Novel intermediate compounds of claim 12, having the formulae 0 N-(\ 0 OHC o& N - 0 /a,-CH3 N-(\ CH3 H3 /,\(o---and C/o- 0 OHC ffo( -C 0 OHCCH3 2yn 0 - o\ C /-C- CF3 0 0 OHC \O-CF3